Interventional Cardiology & Surgery

A second trial has shown benefit of stopping aspirin 3 months after stenting and continuing solely with ticagrelor monotherapy.

The Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI (TICO) study shows very similar results as the TWILIGHT trial reported last year. But whereas TWILIGHT enrolled a more general PCI population, TICO included only patients with acute coronary syndrome (ACS).

The South Korean TICO trial was presented today at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology.

Presenting the study, senior investigator Yangsoo Jang, MD, PhD, professor of cardiology at Yonsei University College of Medicine in Seoul, South Korea, concluded: “Ticagrelor monotherapy after 3-month dual antiplatelet therapy  showed a significantly lower risk of net adverse clinical events than currently recommended ticagrelor-based 12-month dual antiplatelet therapy. The reduced risk was mainly due to decreased major bleeding.”

These findings indicate that ticagrelor monotherapy “could be an optimal strategy that balances both ischemic and bleeding risks for patients with ACS,” he added.

Discussant of the TICO study, Deepak Bhatt, MD, Brigham and Women’s Hospital, Boston, said: “This is an independent confirmation of TWILIGHT. To have two independent trials reaching the same conclusion — that the regimen of ticagrelor monotherapy after 3 months dual antiplatelet therapy essentially cuts major bleeding in half — is very comforting.”

Michelle O’Donoghue, MD, also from Brigham and Women’s and chair of the ACC session at which the study was presented, added, “A particular strength of this trial was that you had an all-ACS population.”

Enough to Change Guidelines?

Discussing the trial at an ACC press conference, Claire Duvernoy, MD, University of Michigan, Ann Arbor, suggested that the results from TICO and TWILIGHT together are “enough evidence to change the guidelines. I think we are there,” she added.  

“TICO adds to our expanding body of evidence for newer, more potent, P2Y12 inhibitors as monotherapy. This trial stands out as the only exclusive ACS study looking at this and the only trial enrolling a significant population of STEMI patients,” Duvernoy said.

She pointed out one caveat — the need to discontinue ticagrelor because of dyspnea, which she said occurs in around 10%-15% of patients in her practice.

“Also, both TICO and TWILIGHT used the latest second-generation drug-eluting stents, which may have better safety and allows us to get away with less antiplatelet therapy,” Duvernoy noted.  

The TICO trial, conducted at 38 centers in South Korea, enrolled 3056 patients with ACS (average age 61 years) undergoing PCI and stenting with the second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stents (Biotronik).

All patients received ticagrelor plus aspirin for 3 months, then were randomly assigned to continue treatment with ticagrelor and aspirin or ticagrelor alone.

The primary study endpoint was a net clinical benefit composite of death, MI, stroke, stent thrombosis, revascularization, or TIMI major bleeding at 12 months. This occurred in 3.9% of those randomly assigned to ticagrelor alone vs 5.9% of those who continued on dual antiplatelet therapy, giving a hazard ratio of 0.66 (P = .01).

The curves separated early with a marked difference in event rate being seen at 3 months after randomization. At this point, rates of the composite endpoint were 1.4% in the ticagrelor monotherapy group vs 3.5% in the dual antiplatelet therapy group (HR, 0.41; P = .001). 

The benefit was driven by a reduced risk of major bleeding in the ticagrelor monotherapy group. At 1 year, the rate of TIMI major bleeding was 1.7% in the ticagrelor alone group vs 3% in the dual antiplatelet group (HR, 0.56; P = .02).

There was no difference in ischemic events between the two groups. The rate of death/MI/ stroke/stent thrombosis/revascularization at 1 year was 2.3% in the ticagrelor alone group vs 3.4% for those on dual antiplatelet therapy (P = .09)

Yang noted that limitations of the study included an open-label design, no placebo used, and exclusion of patients with an elevated risk for bleeding (defined as aged 80 years or older, having had a stroke within the past year, or having had brain surgery or a traumatic brain injury within the past 6 months).

As part of his discussion, Bhatt asked how these results can be reconciled with trials such as CHARISMA and PEGASUS, which showed higher rates of MI with abbreviated durations of dual antiplatelet therapy

Jang replied: “Maybe for STEMI patients, if the duration of [dual antiplatelet therapy] is prolonged ischemic events may be reduced, especially if clopidogrel is used. But my opinion is when ticagrelor or prasugrel are used — they are very strong P2Y12 inhibitors — you can reduce duration of dual therapy by dropping aspirin. I think aspirin just makes the bleeding.”

Also commenting on the TICO study, Jacqueline Tamis-Holland, MD, Mount Sinai Saint Luke’s Hospital, New York City, pointed out that there was an interaction between the number of diseased vessels, and asked for more information on the complexity of disease in the patients in this trial.

“We had very few CTOs (total chronic occlusions) and left main disease,” Jang replied. “Dual antiplatelet duration is related to total atherosclerotic burden I think, so if you have very high atherosclerotic burden and multivessel disease, dual therapy may be more important. But our data show that the ticagrelor monotherapy group is not inferior to conventional dual therapy, so this suggests that even in multivessel disease, 3 months dual antiplatelet therapy is enough if you use a potent agent like ticagrelor as monotherapy after.”

This study was funded by Biotronik, manufacturer of the stents used. Jang has disclosed no relevant financial relationships. Bhatt reports consultant fees/honoraria from Elsevier Practice Update Cardiology, Medtelligence/WebMD, MJH Life Sciences, and WebMD; and research grants from Abbott, Afimmune, Amarin, Amgen, Astra Zeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, Eisai, Eli Lilly, Ethicon, FlowCo, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Medtronic, Novo Nordisk, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, sanofi-aventis, Synaptic, Takeda, The Medicines Company.

This article first appeared on Medscape.com.

A second trial has shown benefit of stopping aspirin 3 months after stenting and continuing solely with ticagrelor monotherapy.

The Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI (TICO) study shows very similar results as the TWILIGHT trial reported last year. But whereas TWILIGHT enrolled a more general PCI population, TICO included only patients with acute coronary syndrome (ACS).

The South Korean TICO trial was presented today at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology.

Presenting the study, senior investigator Yangsoo Jang, MD, PhD, professor of cardiology at Yonsei University College of Medicine in Seoul, South Korea, concluded: “Ticagrelor monotherapy after 3-month dual antiplatelet therapy  showed a significantly lower risk of net adverse clinical events than currently recommended ticagrelor-based 12-month dual antiplatelet therapy. The reduced risk was mainly due to decreased major bleeding.”

These findings indicate that ticagrelor monotherapy “could be an optimal strategy that balances both ischemic and bleeding risks for patients with ACS,” he added.

Discussant of the TICO study, Deepak Bhatt, MD, Brigham and Women’s Hospital, Boston, said: “This is an independent confirmation of TWILIGHT. To have two independent trials reaching the same conclusion — that the regimen of ticagrelor monotherapy after 3 months dual antiplatelet therapy essentially cuts major bleeding in half — is very comforting.”

Michelle O’Donoghue, MD, also from Brigham and Women’s and chair of the ACC session at which the study was presented, added, “A particular strength of this trial was that you had an all-ACS population.”

Enough to Change Guidelines?

Discussing the trial at an ACC press conference, Claire Duvernoy, MD, University of Michigan, Ann Arbor, suggested that the results from TICO and TWILIGHT together are “enough evidence to change the guidelines. I think we are there,” she added.  

“TICO adds to our expanding body of evidence for newer, more potent, P2Y12 inhibitors as monotherapy. This trial stands out as the only exclusive ACS study looking at this and the only trial enrolling a significant population of STEMI patients,” Duvernoy said.

She pointed out one caveat — the need to discontinue ticagrelor because of dyspnea, which she said occurs in around 10%-15% of patients in her practice.

“Also, both TICO and TWILIGHT used the latest second-generation drug-eluting stents, which may have better safety and allows us to get away with less antiplatelet therapy,” Duvernoy noted.  

The TICO trial, conducted at 38 centers in South Korea, enrolled 3056 patients with ACS (average age 61 years) undergoing PCI and stenting with the second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stents (Biotronik).

All patients received ticagrelor plus aspirin for 3 months, then were randomly assigned to continue treatment with ticagrelor and aspirin or ticagrelor alone.

The primary study endpoint was a net clinical benefit composite of death, MI, stroke, stent thrombosis, revascularization, or TIMI major bleeding at 12 months. This occurred in 3.9% of those randomly assigned to ticagrelor alone vs 5.9% of those who continued on dual antiplatelet therapy, giving a hazard ratio of 0.66 (P = .01).

The curves separated early with a marked difference in event rate being seen at 3 months after randomization. At this point, rates of the composite endpoint were 1.4% in the ticagrelor monotherapy group vs 3.5% in the dual antiplatelet therapy group (HR, 0.41; P = .001). 

The benefit was driven by a reduced risk of major bleeding in the ticagrelor monotherapy group. At 1 year, the rate of TIMI major bleeding was 1.7% in the ticagrelor alone group vs 3% in the dual antiplatelet group (HR, 0.56; P = .02).

There was no difference in ischemic events between the two groups. The rate of death/MI/ stroke/stent thrombosis/revascularization at 1 year was 2.3% in the ticagrelor alone group vs 3.4% for those on dual antiplatelet therapy (P = .09)

Yang noted that limitations of the study included an open-label design, no placebo used, and exclusion of patients with an elevated risk for bleeding (defined as aged 80 years or older, having had a stroke within the past year, or having had brain surgery or a traumatic brain injury within the past 6 months).

As part of his discussion, Bhatt asked how these results can be reconciled with trials such as CHARISMA and PEGASUS, which showed higher rates of MI with abbreviated durations of dual antiplatelet therapy

Jang replied: “Maybe for STEMI patients, if the duration of [dual antiplatelet therapy] is prolonged ischemic events may be reduced, especially if clopidogrel is used. But my opinion is when ticagrelor or prasugrel are used — they are very strong P2Y12 inhibitors — you can reduce duration of dual therapy by dropping aspirin. I think aspirin just makes the bleeding.”

Also commenting on the TICO study, Jacqueline Tamis-Holland, MD, Mount Sinai Saint Luke’s Hospital, New York City, pointed out that there was an interaction between the number of diseased vessels, and asked for more information on the complexity of disease in the patients in this trial.

“We had very few CTOs (total chronic occlusions) and left main disease,” Jang replied. “Dual antiplatelet duration is related to total atherosclerotic burden I think, so if you have very high atherosclerotic burden and multivessel disease, dual therapy may be more important. But our data show that the ticagrelor monotherapy group is not inferior to conventional dual therapy, so this suggests that even in multivessel disease, 3 months dual antiplatelet therapy is enough if you use a potent agent like ticagrelor as monotherapy after.”

This study was funded by Biotronik, manufacturer of the stents used. Jang has disclosed no relevant financial relationships. Bhatt reports consultant fees/honoraria from Elsevier Practice Update Cardiology, Medtelligence/WebMD, MJH Life Sciences, and WebMD; and research grants from Abbott, Afimmune, Amarin, Amgen, Astra Zeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, Eisai, Eli Lilly, Ethicon, FlowCo, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Medtronic, Novo Nordisk, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, sanofi-aventis, Synaptic, Takeda, The Medicines Company.

This article first appeared on Medscape.com.

A second trial has shown benefit of stopping aspirin 3 months after stenting and continuing solely with ticagrelor monotherapy.

The Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI (TICO) study shows very similar results as the TWILIGHT trial reported last year. But whereas TWILIGHT enrolled a more general PCI population, TICO included only patients with acute coronary syndrome (ACS).

The South Korean TICO trial was presented today at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology.

Presenting the study, senior investigator Yangsoo Jang, MD, PhD, professor of cardiology at Yonsei University College of Medicine in Seoul, South Korea, concluded: “Ticagrelor monotherapy after 3-month dual antiplatelet therapy  showed a significantly lower risk of net adverse clinical events than currently recommended ticagrelor-based 12-month dual antiplatelet therapy. The reduced risk was mainly due to decreased major bleeding.”

These findings indicate that ticagrelor monotherapy “could be an optimal strategy that balances both ischemic and bleeding risks for patients with ACS,” he added.

Discussant of the TICO study, Deepak Bhatt, MD, Brigham and Women’s Hospital, Boston, said: “This is an independent confirmation of TWILIGHT. To have two independent trials reaching the same conclusion — that the regimen of ticagrelor monotherapy after 3 months dual antiplatelet therapy essentially cuts major bleeding in half — is very comforting.”

Michelle O’Donoghue, MD, also from Brigham and Women’s and chair of the ACC session at which the study was presented, added, “A particular strength of this trial was that you had an all-ACS population.”

Enough to Change Guidelines?

Discussing the trial at an ACC press conference, Claire Duvernoy, MD, University of Michigan, Ann Arbor, suggested that the results from TICO and TWILIGHT together are “enough evidence to change the guidelines. I think we are there,” she added.  

“TICO adds to our expanding body of evidence for newer, more potent, P2Y12 inhibitors as monotherapy. This trial stands out as the only exclusive ACS study looking at this and the only trial enrolling a significant population of STEMI patients,” Duvernoy said.

She pointed out one caveat — the need to discontinue ticagrelor because of dyspnea, which she said occurs in around 10%-15% of patients in her practice.

“Also, both TICO and TWILIGHT used the latest second-generation drug-eluting stents, which may have better safety and allows us to get away with less antiplatelet therapy,” Duvernoy noted.  

The TICO trial, conducted at 38 centers in South Korea, enrolled 3056 patients with ACS (average age 61 years) undergoing PCI and stenting with the second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stents (Biotronik).

All patients received ticagrelor plus aspirin for 3 months, then were randomly assigned to continue treatment with ticagrelor and aspirin or ticagrelor alone.

The primary study endpoint was a net clinical benefit composite of death, MI, stroke, stent thrombosis, revascularization, or TIMI major bleeding at 12 months. This occurred in 3.9% of those randomly assigned to ticagrelor alone vs 5.9% of those who continued on dual antiplatelet therapy, giving a hazard ratio of 0.66 (P = .01).

The curves separated early with a marked difference in event rate being seen at 3 months after randomization. At this point, rates of the composite endpoint were 1.4% in the ticagrelor monotherapy group vs 3.5% in the dual antiplatelet therapy group (HR, 0.41; P = .001). 

The benefit was driven by a reduced risk of major bleeding in the ticagrelor monotherapy group. At 1 year, the rate of TIMI major bleeding was 1.7% in the ticagrelor alone group vs 3% in the dual antiplatelet group (HR, 0.56; P = .02).

There was no difference in ischemic events between the two groups. The rate of death/MI/ stroke/stent thrombosis/revascularization at 1 year was 2.3% in the ticagrelor alone group vs 3.4% for those on dual antiplatelet therapy (P = .09)

Yang noted that limitations of the study included an open-label design, no placebo used, and exclusion of patients with an elevated risk for bleeding (defined as aged 80 years or older, having had a stroke within the past year, or having had brain surgery or a traumatic brain injury within the past 6 months).

As part of his discussion, Bhatt asked how these results can be reconciled with trials such as CHARISMA and PEGASUS, which showed higher rates of MI with abbreviated durations of dual antiplatelet therapy

Jang replied: “Maybe for STEMI patients, if the duration of [dual antiplatelet therapy] is prolonged ischemic events may be reduced, especially if clopidogrel is used. But my opinion is when ticagrelor or prasugrel are used — they are very strong P2Y12 inhibitors — you can reduce duration of dual therapy by dropping aspirin. I think aspirin just makes the bleeding.”

Also commenting on the TICO study, Jacqueline Tamis-Holland, MD, Mount Sinai Saint Luke’s Hospital, New York City, pointed out that there was an interaction between the number of diseased vessels, and asked for more information on the complexity of disease in the patients in this trial.

“We had very few CTOs (total chronic occlusions) and left main disease,” Jang replied. “Dual antiplatelet duration is related to total atherosclerotic burden I think, so if you have very high atherosclerotic burden and multivessel disease, dual therapy may be more important. But our data show that the ticagrelor monotherapy group is not inferior to conventional dual therapy, so this suggests that even in multivessel disease, 3 months dual antiplatelet therapy is enough if you use a potent agent like ticagrelor as monotherapy after.”

This study was funded by Biotronik, manufacturer of the stents used. Jang has disclosed no relevant financial relationships. Bhatt reports consultant fees/honoraria from Elsevier Practice Update Cardiology, Medtelligence/WebMD, MJH Life Sciences, and WebMD; and research grants from Abbott, Afimmune, Amarin, Amgen, Astra Zeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, Eisai, Eli Lilly, Ethicon, FlowCo, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Medtronic, Novo Nordisk, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, sanofi-aventis, Synaptic, Takeda, The Medicines Company.

This article first appeared on Medscape.com.

The guidelines allow for the addition of short-term clopidogrel to an oral anticoagulant (OAC) in patients with an established OAC indication, such as atrial fibrillation (AF), who undergo transcatheter aortic valve replacement (TAVR). But does the extra antithrombotic protection come with safety issues?

It apparently did in the POPULAR-TAVI trial, which saw an excess of major and minor bleeding in such patients already on an OAC when they underwent TAVR and who then took the antiplatelet agent for the next 3 months.

The patients who instead continued on their OAC as the only post-TAVR antithrombotic, compared with those on double therapy, showed a 37% lower 1-year risk of any bleeding, including major and disabling bleeding.

Importantly, they didn’t seem to pay a price in excess ischemic events, such as stroke or myocardial infarction (MI).

The trial argues against adding clopidogrel on top of OAC in TAVR patients with an OAC indication in order to reduce their risk of bleeding, Jurriën ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands, told theheart.org | Medscape Cardiology.

Whether the ischemic event risk was comparable with and without clopidogrel is less clear. “As the study is not powered for the ischemic end points, the answer is less definite. But we did not see a hint of a higher ischemic event rate, especially stroke, in the OAC-alone group,” ten Berg said.

“So we are pretty confident in saying that OAC alone is the optimal treatment.”

The results of POPULAR-TAVI were presented by Vincent Nijenhuis, MD, also from St. Antonius Hospital, on March 29 during the virtual presentation of the American College of Cardiology 2020 Scientific Session/World Congress of Cardiology. Nijenhuis is also first author on the trial’s simultaneous publication in the New England Journal of Medicine.

The only reason to add an antiplatelet in TAVR patients who need to be on an OAC for another indication is to prevent ischemic events like MI, stroke, or death, agreed George D. Dangas, MD, PhD, Mount Sinai Hospital, New York City, for theheart.org | Medscape Cardiology.

But that protection apparently wasn’t needed; for patients on OAC only, “the overall risk–benefit ratio was favorable for them both ways. Although the study is small, I think the findings would be clinically meaningful,” said Dangas, who was not involved in POPULAR-TAVI but was lead author on the GALILEO trial publication.

GALILEO tested a direct oral anticoagulant (DOAC) against dual antiplatelet therapy in patients undergoing TAVR but without a conventional OAC indication. The trial was halted because the DOAC group started to show an excess of bleeding, thromboembolic events, and mortality.

Most POPULAR-TAVI patients were on vitamin K antagonists, but about a quarter were taking DOACs. Clopidogrel was given on an open-label basis.

The trial suggests that, for TAVR patients with an indication for lifelong OAC, “it does appear to be safe to give only an anticoagulant, whether it’s warfarin or a DOAC, and not add clopidogrel,” Robert O. Bonow, MD, Northwestern University, Chicago, told theheart.org | Medscape Cardiology.

“The bottom line appears to be that it’s no worse, and is probably better in terms of bleeding events,” said Bonow, who wasn’t involved in POPULAR-TAVI.

But there are difficulties in interpreting the trial that stem from its design and other issues, he said. For example, it can’t really be concluded that adding an antiplatelet agent to OAC in such patients who undergo TAVR, according to commonly practiced techniques, will increase the risk of bleeding compared with OAC alone.

To begin with, Bonow said, substituting aspirin for clopidogrel might have produced better double-therapy results. But the bigger issues, Bonow said, center on the discretion its operators had in whether to maintain or suspend the patients’ OAC during the TAVR procedure, as well as the unusual bleeding definitions used in the trial.

The first POPULAR-TAVI primary end point was any bleeding that met Valve Academic Research Consortium (VARC) criteria; the second was nonprocedural bleeding that met the Bleeding Academic Research Consortium (BARC) definition.

“Because the VARC-2 classification does not distinguish between procedure-related and nonprocedure-related bleeding events, procedure-related events were defined as BARC type 4 severe bleeding,” the trial’s journal report states. Therefore, “most bleeding at the puncture site was counted as nonprocedure-related.”

It may be Bonow’s biggest issue with the trial, he said. “They’re terming these events that occurred periprocedurally, in the first day or first hours of the procedure, as being ‘nonprocedural’ because they didn’t represent severe BARC bleeding, where you have a subarachnoid hemorrhage or require transfusions.”

An editorial accompanying the trial report also knocks this aspect of the trial design. Although the trial “confirmed” a higher incidence of any bleeding in the double-therapy group, “there are concerns regarding the classification of bleeding and the reliability of secondary outcome analysis,” writes Frederick Feit, MD, NYU Grossman School of Medicine, New York City.

“Bleeding occurring during TAVI or the index hospitalization was unadvisedly defined as non-procedure related, even if it occurred at the access site,” the editorial notes.

Ten Berg noted that procedural bleeding is frequent in TAVI, but the VARC-2 definition doesn’t accommodate them. So “we also used the BARC definition for procedural bleeding, BARC-4,” he told theheart.org | Medscape Cardiology.

“However, BARC-4 describes bleeding during surgery, and it turned out that in POPULAR- TAVI only one patient had BARC-4 bleeding. So we do not at all agree with the editorial.”

Still, the trial’s reported event-rate curves show that “most of the step-up in bleeding, in either arm of the trial, occurred immediately,” Bonow observed. A more consistent, flat trend followed thereafter out to 3 months.

“So half of the bleeding in both arms of the trial occurred at the site of the arterial puncture. Though it wasn’t considered severe, it was indeed periprocedural,” Bonow said, interpreting the results.

The POPULAR-TAVI journal report says the procedures were performed according to local site protocols, and site physicians were allowed to decide whether to continue or suspend OAC. But “the trial protocol advised physicians to continue oral anticoagulation during admission for the TAVI procedure.”

Many of the patients, regardless of randomization group, “went through the procedure under full anticoagulation,” Dangas agreed. POPULAR-TAVI, it seems, “is the first anticoagulation study ever to start anticoagulation before the procedure.”

Bleeding event rates in the trial “are somewhat high because of this unusual procedural feature of the study,” Dangas said.

“It’s therefore not surprising that so much of the bleeding occurred in the first hours of the procedure itself,” observed Bonow.

The trial enrolled 313 patients in four European countries who were on OAC for an approved indication, predominantly AF, and underwent TAVR. Their mean age was about 81 years, and 45.4% were women. They were randomly assigned to receive or not receive clopidogrel in a loading dose, followed by 75 mg/d on top of their OAC for 3 months, and were followed out to a year.

All bleeding that met VARC-2 criteria, the first primary end point, occurred in 21.7% of the 157 patients on OAC alone and 34.6% of the 156 who received double therapy (risk ratio [RR], 0.63; 95% CI, 0.43 - 0.90; P = .011).

The second primary end point, “nonprocedural” bleeding that met BARC-4 criteria, occurred in 21.7% and 34.0%, respectively, of patients (RR, 0.64; 95% CI, 0.44 - 0.92; P = .015).

There were also two secondary composite outcomes. The first consisted of nonprocedural bleeding, cardiovascular (CV) death, any stroke, and MI, and was seen in 31.2% of patients on OAC alone and 45.5% of those on OAC plus clopidogrel (RR, 0.69; 95% CI, 0.51 - 0.92), an absolute difference that was within the prospectively defined noninferiority margins.

The other secondary end point — CV death, ischemic stroke, and MI — occurred in 13.4% of those receiving only OAC and 17.3% on added clopidogrel (RR, 0.77; 95% CI, 0.46 - 1.31), which was nonsignificant for superiority.

“Could they have done better by holding the anticoagulation, whether warfarin or a DOAC, during that time? That’s what I think many centers might do if they’re performing a TAVR,” Bonow said.

“It seems to me that could have been done in this trial as well: they could have stopped the anticoagulation, done the procedure, and started the anticoagulation after, the way you would normally in a patient getting a TAVR.”

Such a practice might have reduced the risk of procedural bleeding as it is usually defined in TAVR in both groups, thereby potentially blunting any difference in bleeding rate between the two groups.

“That’s my take on it.” Still, he said, the trial’s message remains: OAC without clopidogrel is safe in POPULAR-TAVI-like patients.

Nijenhuis had no disclosures. Ten Berg disclosed no industry ties. Disclosures for the other authors are in the report. Bonow has previously reported no disclosures. Dangas has previously disclosed receiving grants and fees from Bayer, fees from Janssen; grants and personal fees from Daiichi-Sankyo; and other compensation from Medtronic. Feit discloses personal fees from Abbott Vascular and other relationships with Medtronic, Boston Scientific, and Sapheon.

This article first appeared on Medscape.com.

The guidelines allow for the addition of short-term clopidogrel to an oral anticoagulant (OAC) in patients with an established OAC indication, such as atrial fibrillation (AF), who undergo transcatheter aortic valve replacement (TAVR). But does the extra antithrombotic protection come with safety issues?

It apparently did in the POPULAR-TAVI trial, which saw an excess of major and minor bleeding in such patients already on an OAC when they underwent TAVR and who then took the antiplatelet agent for the next 3 months.

The patients who instead continued on their OAC as the only post-TAVR antithrombotic, compared with those on double therapy, showed a 37% lower 1-year risk of any bleeding, including major and disabling bleeding.

Importantly, they didn’t seem to pay a price in excess ischemic events, such as stroke or myocardial infarction (MI).

The trial argues against adding clopidogrel on top of OAC in TAVR patients with an OAC indication in order to reduce their risk of bleeding, Jurriën ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands, told theheart.org | Medscape Cardiology.

Whether the ischemic event risk was comparable with and without clopidogrel is less clear. “As the study is not powered for the ischemic end points, the answer is less definite. But we did not see a hint of a higher ischemic event rate, especially stroke, in the OAC-alone group,” ten Berg said.

“So we are pretty confident in saying that OAC alone is the optimal treatment.”

The results of POPULAR-TAVI were presented by Vincent Nijenhuis, MD, also from St. Antonius Hospital, on March 29 during the virtual presentation of the American College of Cardiology 2020 Scientific Session/World Congress of Cardiology. Nijenhuis is also first author on the trial’s simultaneous publication in the New England Journal of Medicine.

The only reason to add an antiplatelet in TAVR patients who need to be on an OAC for another indication is to prevent ischemic events like MI, stroke, or death, agreed George D. Dangas, MD, PhD, Mount Sinai Hospital, New York City, for theheart.org | Medscape Cardiology.

But that protection apparently wasn’t needed; for patients on OAC only, “the overall risk–benefit ratio was favorable for them both ways. Although the study is small, I think the findings would be clinically meaningful,” said Dangas, who was not involved in POPULAR-TAVI but was lead author on the GALILEO trial publication.

GALILEO tested a direct oral anticoagulant (DOAC) against dual antiplatelet therapy in patients undergoing TAVR but without a conventional OAC indication. The trial was halted because the DOAC group started to show an excess of bleeding, thromboembolic events, and mortality.

Most POPULAR-TAVI patients were on vitamin K antagonists, but about a quarter were taking DOACs. Clopidogrel was given on an open-label basis.

The trial suggests that, for TAVR patients with an indication for lifelong OAC, “it does appear to be safe to give only an anticoagulant, whether it’s warfarin or a DOAC, and not add clopidogrel,” Robert O. Bonow, MD, Northwestern University, Chicago, told theheart.org | Medscape Cardiology.

“The bottom line appears to be that it’s no worse, and is probably better in terms of bleeding events,” said Bonow, who wasn’t involved in POPULAR-TAVI.

But there are difficulties in interpreting the trial that stem from its design and other issues, he said. For example, it can’t really be concluded that adding an antiplatelet agent to OAC in such patients who undergo TAVR, according to commonly practiced techniques, will increase the risk of bleeding compared with OAC alone.

To begin with, Bonow said, substituting aspirin for clopidogrel might have produced better double-therapy results. But the bigger issues, Bonow said, center on the discretion its operators had in whether to maintain or suspend the patients’ OAC during the TAVR procedure, as well as the unusual bleeding definitions used in the trial.

The first POPULAR-TAVI primary end point was any bleeding that met Valve Academic Research Consortium (VARC) criteria; the second was nonprocedural bleeding that met the Bleeding Academic Research Consortium (BARC) definition.

“Because the VARC-2 classification does not distinguish between procedure-related and nonprocedure-related bleeding events, procedure-related events were defined as BARC type 4 severe bleeding,” the trial’s journal report states. Therefore, “most bleeding at the puncture site was counted as nonprocedure-related.”

It may be Bonow’s biggest issue with the trial, he said. “They’re terming these events that occurred periprocedurally, in the first day or first hours of the procedure, as being ‘nonprocedural’ because they didn’t represent severe BARC bleeding, where you have a subarachnoid hemorrhage or require transfusions.”

An editorial accompanying the trial report also knocks this aspect of the trial design. Although the trial “confirmed” a higher incidence of any bleeding in the double-therapy group, “there are concerns regarding the classification of bleeding and the reliability of secondary outcome analysis,” writes Frederick Feit, MD, NYU Grossman School of Medicine, New York City.

“Bleeding occurring during TAVI or the index hospitalization was unadvisedly defined as non-procedure related, even if it occurred at the access site,” the editorial notes.

Ten Berg noted that procedural bleeding is frequent in TAVI, but the VARC-2 definition doesn’t accommodate them. So “we also used the BARC definition for procedural bleeding, BARC-4,” he told theheart.org | Medscape Cardiology.

“However, BARC-4 describes bleeding during surgery, and it turned out that in POPULAR- TAVI only one patient had BARC-4 bleeding. So we do not at all agree with the editorial.”

Still, the trial’s reported event-rate curves show that “most of the step-up in bleeding, in either arm of the trial, occurred immediately,” Bonow observed. A more consistent, flat trend followed thereafter out to 3 months.

“So half of the bleeding in both arms of the trial occurred at the site of the arterial puncture. Though it wasn’t considered severe, it was indeed periprocedural,” Bonow said, interpreting the results.

The POPULAR-TAVI journal report says the procedures were performed according to local site protocols, and site physicians were allowed to decide whether to continue or suspend OAC. But “the trial protocol advised physicians to continue oral anticoagulation during admission for the TAVI procedure.”

Many of the patients, regardless of randomization group, “went through the procedure under full anticoagulation,” Dangas agreed. POPULAR-TAVI, it seems, “is the first anticoagulation study ever to start anticoagulation before the procedure.”

Bleeding event rates in the trial “are somewhat high because of this unusual procedural feature of the study,” Dangas said.

“It’s therefore not surprising that so much of the bleeding occurred in the first hours of the procedure itself,” observed Bonow.

The trial enrolled 313 patients in four European countries who were on OAC for an approved indication, predominantly AF, and underwent TAVR. Their mean age was about 81 years, and 45.4% were women. They were randomly assigned to receive or not receive clopidogrel in a loading dose, followed by 75 mg/d on top of their OAC for 3 months, and were followed out to a year.

All bleeding that met VARC-2 criteria, the first primary end point, occurred in 21.7% of the 157 patients on OAC alone and 34.6% of the 156 who received double therapy (risk ratio [RR], 0.63; 95% CI, 0.43 - 0.90; P = .011).

The second primary end point, “nonprocedural” bleeding that met BARC-4 criteria, occurred in 21.7% and 34.0%, respectively, of patients (RR, 0.64; 95% CI, 0.44 - 0.92; P = .015).

There were also two secondary composite outcomes. The first consisted of nonprocedural bleeding, cardiovascular (CV) death, any stroke, and MI, and was seen in 31.2% of patients on OAC alone and 45.5% of those on OAC plus clopidogrel (RR, 0.69; 95% CI, 0.51 - 0.92), an absolute difference that was within the prospectively defined noninferiority margins.

The other secondary end point — CV death, ischemic stroke, and MI — occurred in 13.4% of those receiving only OAC and 17.3% on added clopidogrel (RR, 0.77; 95% CI, 0.46 - 1.31), which was nonsignificant for superiority.

“Could they have done better by holding the anticoagulation, whether warfarin or a DOAC, during that time? That’s what I think many centers might do if they’re performing a TAVR,” Bonow said.

“It seems to me that could have been done in this trial as well: they could have stopped the anticoagulation, done the procedure, and started the anticoagulation after, the way you would normally in a patient getting a TAVR.”

Such a practice might have reduced the risk of procedural bleeding as it is usually defined in TAVR in both groups, thereby potentially blunting any difference in bleeding rate between the two groups.

“That’s my take on it.” Still, he said, the trial’s message remains: OAC without clopidogrel is safe in POPULAR-TAVI-like patients.

Nijenhuis had no disclosures. Ten Berg disclosed no industry ties. Disclosures for the other authors are in the report. Bonow has previously reported no disclosures. Dangas has previously disclosed receiving grants and fees from Bayer, fees from Janssen; grants and personal fees from Daiichi-Sankyo; and other compensation from Medtronic. Feit discloses personal fees from Abbott Vascular and other relationships with Medtronic, Boston Scientific, and Sapheon.

This article first appeared on Medscape.com.

The guidelines allow for the addition of short-term clopidogrel to an oral anticoagulant (OAC) in patients with an established OAC indication, such as atrial fibrillation (AF), who undergo transcatheter aortic valve replacement (TAVR). But does the extra antithrombotic protection come with safety issues?

It apparently did in the POPULAR-TAVI trial, which saw an excess of major and minor bleeding in such patients already on an OAC when they underwent TAVR and who then took the antiplatelet agent for the next 3 months.

The patients who instead continued on their OAC as the only post-TAVR antithrombotic, compared with those on double therapy, showed a 37% lower 1-year risk of any bleeding, including major and disabling bleeding.

Importantly, they didn’t seem to pay a price in excess ischemic events, such as stroke or myocardial infarction (MI).

The trial argues against adding clopidogrel on top of OAC in TAVR patients with an OAC indication in order to reduce their risk of bleeding, Jurriën ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands, told theheart.org | Medscape Cardiology.

Whether the ischemic event risk was comparable with and without clopidogrel is less clear. “As the study is not powered for the ischemic end points, the answer is less definite. But we did not see a hint of a higher ischemic event rate, especially stroke, in the OAC-alone group,” ten Berg said.

“So we are pretty confident in saying that OAC alone is the optimal treatment.”

The results of POPULAR-TAVI were presented by Vincent Nijenhuis, MD, also from St. Antonius Hospital, on March 29 during the virtual presentation of the American College of Cardiology 2020 Scientific Session/World Congress of Cardiology. Nijenhuis is also first author on the trial’s simultaneous publication in the New England Journal of Medicine.

The only reason to add an antiplatelet in TAVR patients who need to be on an OAC for another indication is to prevent ischemic events like MI, stroke, or death, agreed George D. Dangas, MD, PhD, Mount Sinai Hospital, New York City, for theheart.org | Medscape Cardiology.

But that protection apparently wasn’t needed; for patients on OAC only, “the overall risk–benefit ratio was favorable for them both ways. Although the study is small, I think the findings would be clinically meaningful,” said Dangas, who was not involved in POPULAR-TAVI but was lead author on the GALILEO trial publication.

GALILEO tested a direct oral anticoagulant (DOAC) against dual antiplatelet therapy in patients undergoing TAVR but without a conventional OAC indication. The trial was halted because the DOAC group started to show an excess of bleeding, thromboembolic events, and mortality.

Most POPULAR-TAVI patients were on vitamin K antagonists, but about a quarter were taking DOACs. Clopidogrel was given on an open-label basis.

The trial suggests that, for TAVR patients with an indication for lifelong OAC, “it does appear to be safe to give only an anticoagulant, whether it’s warfarin or a DOAC, and not add clopidogrel,” Robert O. Bonow, MD, Northwestern University, Chicago, told theheart.org | Medscape Cardiology.

“The bottom line appears to be that it’s no worse, and is probably better in terms of bleeding events,” said Bonow, who wasn’t involved in POPULAR-TAVI.

But there are difficulties in interpreting the trial that stem from its design and other issues, he said. For example, it can’t really be concluded that adding an antiplatelet agent to OAC in such patients who undergo TAVR, according to commonly practiced techniques, will increase the risk of bleeding compared with OAC alone.

To begin with, Bonow said, substituting aspirin for clopidogrel might have produced better double-therapy results. But the bigger issues, Bonow said, center on the discretion its operators had in whether to maintain or suspend the patients’ OAC during the TAVR procedure, as well as the unusual bleeding definitions used in the trial.

The first POPULAR-TAVI primary end point was any bleeding that met Valve Academic Research Consortium (VARC) criteria; the second was nonprocedural bleeding that met the Bleeding Academic Research Consortium (BARC) definition.

“Because the VARC-2 classification does not distinguish between procedure-related and nonprocedure-related bleeding events, procedure-related events were defined as BARC type 4 severe bleeding,” the trial’s journal report states. Therefore, “most bleeding at the puncture site was counted as nonprocedure-related.”

It may be Bonow’s biggest issue with the trial, he said. “They’re terming these events that occurred periprocedurally, in the first day or first hours of the procedure, as being ‘nonprocedural’ because they didn’t represent severe BARC bleeding, where you have a subarachnoid hemorrhage or require transfusions.”

An editorial accompanying the trial report also knocks this aspect of the trial design. Although the trial “confirmed” a higher incidence of any bleeding in the double-therapy group, “there are concerns regarding the classification of bleeding and the reliability of secondary outcome analysis,” writes Frederick Feit, MD, NYU Grossman School of Medicine, New York City.

“Bleeding occurring during TAVI or the index hospitalization was unadvisedly defined as non-procedure related, even if it occurred at the access site,” the editorial notes.

Ten Berg noted that procedural bleeding is frequent in TAVI, but the VARC-2 definition doesn’t accommodate them. So “we also used the BARC definition for procedural bleeding, BARC-4,” he told theheart.org | Medscape Cardiology.

“However, BARC-4 describes bleeding during surgery, and it turned out that in POPULAR- TAVI only one patient had BARC-4 bleeding. So we do not at all agree with the editorial.”

Still, the trial’s reported event-rate curves show that “most of the step-up in bleeding, in either arm of the trial, occurred immediately,” Bonow observed. A more consistent, flat trend followed thereafter out to 3 months.

“So half of the bleeding in both arms of the trial occurred at the site of the arterial puncture. Though it wasn’t considered severe, it was indeed periprocedural,” Bonow said, interpreting the results.

The POPULAR-TAVI journal report says the procedures were performed according to local site protocols, and site physicians were allowed to decide whether to continue or suspend OAC. But “the trial protocol advised physicians to continue oral anticoagulation during admission for the TAVI procedure.”

Many of the patients, regardless of randomization group, “went through the procedure under full anticoagulation,” Dangas agreed. POPULAR-TAVI, it seems, “is the first anticoagulation study ever to start anticoagulation before the procedure.”

Bleeding event rates in the trial “are somewhat high because of this unusual procedural feature of the study,” Dangas said.

“It’s therefore not surprising that so much of the bleeding occurred in the first hours of the procedure itself,” observed Bonow.

The trial enrolled 313 patients in four European countries who were on OAC for an approved indication, predominantly AF, and underwent TAVR. Their mean age was about 81 years, and 45.4% were women. They were randomly assigned to receive or not receive clopidogrel in a loading dose, followed by 75 mg/d on top of their OAC for 3 months, and were followed out to a year.

All bleeding that met VARC-2 criteria, the first primary end point, occurred in 21.7% of the 157 patients on OAC alone and 34.6% of the 156 who received double therapy (risk ratio [RR], 0.63; 95% CI, 0.43 - 0.90; P = .011).

The second primary end point, “nonprocedural” bleeding that met BARC-4 criteria, occurred in 21.7% and 34.0%, respectively, of patients (RR, 0.64; 95% CI, 0.44 - 0.92; P = .015).

There were also two secondary composite outcomes. The first consisted of nonprocedural bleeding, cardiovascular (CV) death, any stroke, and MI, and was seen in 31.2% of patients on OAC alone and 45.5% of those on OAC plus clopidogrel (RR, 0.69; 95% CI, 0.51 - 0.92), an absolute difference that was within the prospectively defined noninferiority margins.

The other secondary end point — CV death, ischemic stroke, and MI — occurred in 13.4% of those receiving only OAC and 17.3% on added clopidogrel (RR, 0.77; 95% CI, 0.46 - 1.31), which was nonsignificant for superiority.

“Could they have done better by holding the anticoagulation, whether warfarin or a DOAC, during that time? That’s what I think many centers might do if they’re performing a TAVR,” Bonow said.

“It seems to me that could have been done in this trial as well: they could have stopped the anticoagulation, done the procedure, and started the anticoagulation after, the way you would normally in a patient getting a TAVR.”

Such a practice might have reduced the risk of procedural bleeding as it is usually defined in TAVR in both groups, thereby potentially blunting any difference in bleeding rate between the two groups.

“That’s my take on it.” Still, he said, the trial’s message remains: OAC without clopidogrel is safe in POPULAR-TAVI-like patients.

Nijenhuis had no disclosures. Ten Berg disclosed no industry ties. Disclosures for the other authors are in the report. Bonow has previously reported no disclosures. Dangas has previously disclosed receiving grants and fees from Bayer, fees from Janssen; grants and personal fees from Daiichi-Sankyo; and other compensation from Medtronic. Feit discloses personal fees from Abbott Vascular and other relationships with Medtronic, Boston Scientific, and Sapheon.

This article first appeared on Medscape.com.

Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Mohammed Haneefa Nizamudeen/Getty Images

“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.

That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.

The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.

The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.

Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.

These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.

A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.

The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.

A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.

That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”

While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.

Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.

“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.

Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.

“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.

Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).

The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.

[email protected]

SOURCE: Boehm M. ACC 2020, Abstract 406-15.

Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Mohammed Haneefa Nizamudeen/Getty Images

“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.

That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.

The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.

The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.

Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.

These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.

A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.

The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.

A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.

That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”

While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.

Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.

“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.

Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.

“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.

Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).

The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.

[email protected]

SOURCE: Boehm M. ACC 2020, Abstract 406-15.

Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Mohammed Haneefa Nizamudeen/Getty Images

“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.

That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.

The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.

The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.

Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.

These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.

A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.

The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.

A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.

That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”

While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.

Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.

“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.

Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.

“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.

Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).

The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.

[email protected]

SOURCE: Boehm M. ACC 2020, Abstract 406-15.

The long-sought goal of measuring the quality of U.S. transcatheter aortic valve replacement (TAVR) programs by patient outcomes rather than by the surrogate measure of case volume is about to be realized.

Starting more or less immediately, the U.S. national register for all TAVR cases that’s mandated by Food and Drug Administration labeling of these devices and run through a collaboration of the American College of Cardiology and the Society of Thoracic Surgeons will start applying a newly developed and validated five-item metric for measuring 30-day patient outcomes and designed to gauge the quality of TAVR programs.

At first, the only recipients of the data will be the programs themselves, but starting in about a year, by sometime in 2021, the STS/ACC TVT (transcatheter valve therapy) Registry will start to make its star-based rating of TAVR programs available to the public, Nimesh D. Desai, MD, said on March 29 at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. These societies already make star-based ratings of U.S. programs available to the public for several other types of cardiac interventions, including coronary artery bypass surgery and MI management.

The new, composite metric based on 30-day outcome data “is appropriate for high-stakes applications such as public reporting,” said Dr. Desai, a thoracic surgeon and director of thoracic aortic surgery research at the University of Pennsylvania in Philadelphia. “We’re confident this model can be used for public reporting. It’s undergone extensive testing of its validity.” The steering committee of the STS/ACC TVT Registry commissioned development of the metric, and it’s now “considered approved,” and ready for use, he explained.

To create the new metric, Dr. Desai and his associates used data from 52,561 patients who underwent transfemoral TAVR during 2015-2017 at any of 301 U.S. sites. These data came from a total pool of more than 114,000 patients at 556 sites, but data from many sites weren’t usable because they were not adequately complete. The researchers then identified the top four measures taken during the 30 days following intervention (hospitalization included) that best correlated with 1-year survival and patients’ quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire: stroke; major, life-threatening, or disabling bleed; acute kidney injury (stage III); and moderate or severe paravalvular leak. These outcomes “matter most to patients,” Dr. Desai said.

They used these four outcomes plus 30-day mortality to calculate the programs’ ratings. Among the 52,561 patients, 14% had at least one of these adverse outcomes. The researchers then used a logistic regression model that adjusted for 46 measured variables to calculate how each program performed relative to the average performance of all the programs. Programs with outcomes that fell within the 95% confidence intervals of average performance were rated as performing as expected; those outside rated as performing either better or worse than expected. The results showed 34 centers (11%) had worse than expected outcomes and 25 (8%) had better than expected outcomes, Dr. Desai said.

“This is a major step forward in measuring TAVR quality,” commented Michael Mack, MD, a cardiac surgeon with Baylor Scott & White Health in Dallas who has been very active in studying TAVR. “Until now, we used volume as a surrogate for quality, but the precision was not great. This is an extremely welcome metric.” The next step is to eventually use 1-year follow-up data instead of 30-day outcomes, he added.

“With the rapid expansion of TAVR over the past 6-8 years, we’re now at the point to start to do this. It’s an ethical obligation This will be one of the most high-fidelity, valid models for public reporting” of clinical outcomes,” said Joseph Cleveland, MD, a professor of surgery at the University of Colorado at Denver in Aurora. “It’s reassuring that about 90% of the program performed as expected or better than expected,” he added.

“Transparency and outcomes should drive how TAVR is delivered,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medicine Heart Institute in Phoenix who estimated that he performs about 150 TAVR procedures annually. “This is a step forward. I’ve been waiting for this for a long time. Until now, volume has been used as a surrogate outcome, but we know it’s not accurate. I’m confident that this model is a good starting point.” But Dr. Pershad also had concern that this new approach “can lend itself to some degree of gaming,” like a bleeding event getting classified as minor when it was really major, or outlier patients getting dropped from reports.

The temptation to cut corners may be higher for TAVR than it’s been for the cardiac-disease metrics that already get publicly reported, like bypass surgery and myocardial infarction management, because of TAVR’s higher cost and higher profile, Dr. Pershad said. Existing measures “have not been as linked to financial disincentive as TAVR might be” because TAVR reimbursements can run as high as $50,000 per case. “The stakes with TAVR are higher,” he said.

Ultimately, the reliable examination of TAVR outcomes that this new metric allows may lead to a shake-up of TAVR programs, Dr. Pershad predicted. “This is clearly a step toward closing down some programs that [consistently] underperform.”

The STS/ACC TVT Registry receives no commercial funding. Dr. Desai has been a consultant to, speaker on behalf of, and received research funding from Gore, and he has also spoken on behalf of Cook, Medtronic, and Terumo Aortic. Dr. Cleveland, Dr. Mack, and Dr. Pershad had no disclosures.

[email protected]

The long-sought goal of measuring the quality of U.S. transcatheter aortic valve replacement (TAVR) programs by patient outcomes rather than by the surrogate measure of case volume is about to be realized.

Starting more or less immediately, the U.S. national register for all TAVR cases that’s mandated by Food and Drug Administration labeling of these devices and run through a collaboration of the American College of Cardiology and the Society of Thoracic Surgeons will start applying a newly developed and validated five-item metric for measuring 30-day patient outcomes and designed to gauge the quality of TAVR programs.

At first, the only recipients of the data will be the programs themselves, but starting in about a year, by sometime in 2021, the STS/ACC TVT (transcatheter valve therapy) Registry will start to make its star-based rating of TAVR programs available to the public, Nimesh D. Desai, MD, said on March 29 at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. These societies already make star-based ratings of U.S. programs available to the public for several other types of cardiac interventions, including coronary artery bypass surgery and MI management.

The new, composite metric based on 30-day outcome data “is appropriate for high-stakes applications such as public reporting,” said Dr. Desai, a thoracic surgeon and director of thoracic aortic surgery research at the University of Pennsylvania in Philadelphia. “We’re confident this model can be used for public reporting. It’s undergone extensive testing of its validity.” The steering committee of the STS/ACC TVT Registry commissioned development of the metric, and it’s now “considered approved,” and ready for use, he explained.

To create the new metric, Dr. Desai and his associates used data from 52,561 patients who underwent transfemoral TAVR during 2015-2017 at any of 301 U.S. sites. These data came from a total pool of more than 114,000 patients at 556 sites, but data from many sites weren’t usable because they were not adequately complete. The researchers then identified the top four measures taken during the 30 days following intervention (hospitalization included) that best correlated with 1-year survival and patients’ quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire: stroke; major, life-threatening, or disabling bleed; acute kidney injury (stage III); and moderate or severe paravalvular leak. These outcomes “matter most to patients,” Dr. Desai said.

They used these four outcomes plus 30-day mortality to calculate the programs’ ratings. Among the 52,561 patients, 14% had at least one of these adverse outcomes. The researchers then used a logistic regression model that adjusted for 46 measured variables to calculate how each program performed relative to the average performance of all the programs. Programs with outcomes that fell within the 95% confidence intervals of average performance were rated as performing as expected; those outside rated as performing either better or worse than expected. The results showed 34 centers (11%) had worse than expected outcomes and 25 (8%) had better than expected outcomes, Dr. Desai said.

“This is a major step forward in measuring TAVR quality,” commented Michael Mack, MD, a cardiac surgeon with Baylor Scott & White Health in Dallas who has been very active in studying TAVR. “Until now, we used volume as a surrogate for quality, but the precision was not great. This is an extremely welcome metric.” The next step is to eventually use 1-year follow-up data instead of 30-day outcomes, he added.

“With the rapid expansion of TAVR over the past 6-8 years, we’re now at the point to start to do this. It’s an ethical obligation This will be one of the most high-fidelity, valid models for public reporting” of clinical outcomes,” said Joseph Cleveland, MD, a professor of surgery at the University of Colorado at Denver in Aurora. “It’s reassuring that about 90% of the program performed as expected or better than expected,” he added.

“Transparency and outcomes should drive how TAVR is delivered,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medicine Heart Institute in Phoenix who estimated that he performs about 150 TAVR procedures annually. “This is a step forward. I’ve been waiting for this for a long time. Until now, volume has been used as a surrogate outcome, but we know it’s not accurate. I’m confident that this model is a good starting point.” But Dr. Pershad also had concern that this new approach “can lend itself to some degree of gaming,” like a bleeding event getting classified as minor when it was really major, or outlier patients getting dropped from reports.

The temptation to cut corners may be higher for TAVR than it’s been for the cardiac-disease metrics that already get publicly reported, like bypass surgery and myocardial infarction management, because of TAVR’s higher cost and higher profile, Dr. Pershad said. Existing measures “have not been as linked to financial disincentive as TAVR might be” because TAVR reimbursements can run as high as $50,000 per case. “The stakes with TAVR are higher,” he said.

Ultimately, the reliable examination of TAVR outcomes that this new metric allows may lead to a shake-up of TAVR programs, Dr. Pershad predicted. “This is clearly a step toward closing down some programs that [consistently] underperform.”

The STS/ACC TVT Registry receives no commercial funding. Dr. Desai has been a consultant to, speaker on behalf of, and received research funding from Gore, and he has also spoken on behalf of Cook, Medtronic, and Terumo Aortic. Dr. Cleveland, Dr. Mack, and Dr. Pershad had no disclosures.

[email protected]

The long-sought goal of measuring the quality of U.S. transcatheter aortic valve replacement (TAVR) programs by patient outcomes rather than by the surrogate measure of case volume is about to be realized.

Starting more or less immediately, the U.S. national register for all TAVR cases that’s mandated by Food and Drug Administration labeling of these devices and run through a collaboration of the American College of Cardiology and the Society of Thoracic Surgeons will start applying a newly developed and validated five-item metric for measuring 30-day patient outcomes and designed to gauge the quality of TAVR programs.

At first, the only recipients of the data will be the programs themselves, but starting in about a year, by sometime in 2021, the STS/ACC TVT (transcatheter valve therapy) Registry will start to make its star-based rating of TAVR programs available to the public, Nimesh D. Desai, MD, said on March 29 at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. These societies already make star-based ratings of U.S. programs available to the public for several other types of cardiac interventions, including coronary artery bypass surgery and MI management.

The new, composite metric based on 30-day outcome data “is appropriate for high-stakes applications such as public reporting,” said Dr. Desai, a thoracic surgeon and director of thoracic aortic surgery research at the University of Pennsylvania in Philadelphia. “We’re confident this model can be used for public reporting. It’s undergone extensive testing of its validity.” The steering committee of the STS/ACC TVT Registry commissioned development of the metric, and it’s now “considered approved,” and ready for use, he explained.

To create the new metric, Dr. Desai and his associates used data from 52,561 patients who underwent transfemoral TAVR during 2015-2017 at any of 301 U.S. sites. These data came from a total pool of more than 114,000 patients at 556 sites, but data from many sites weren’t usable because they were not adequately complete. The researchers then identified the top four measures taken during the 30 days following intervention (hospitalization included) that best correlated with 1-year survival and patients’ quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire: stroke; major, life-threatening, or disabling bleed; acute kidney injury (stage III); and moderate or severe paravalvular leak. These outcomes “matter most to patients,” Dr. Desai said.

They used these four outcomes plus 30-day mortality to calculate the programs’ ratings. Among the 52,561 patients, 14% had at least one of these adverse outcomes. The researchers then used a logistic regression model that adjusted for 46 measured variables to calculate how each program performed relative to the average performance of all the programs. Programs with outcomes that fell within the 95% confidence intervals of average performance were rated as performing as expected; those outside rated as performing either better or worse than expected. The results showed 34 centers (11%) had worse than expected outcomes and 25 (8%) had better than expected outcomes, Dr. Desai said.

“This is a major step forward in measuring TAVR quality,” commented Michael Mack, MD, a cardiac surgeon with Baylor Scott & White Health in Dallas who has been very active in studying TAVR. “Until now, we used volume as a surrogate for quality, but the precision was not great. This is an extremely welcome metric.” The next step is to eventually use 1-year follow-up data instead of 30-day outcomes, he added.

“With the rapid expansion of TAVR over the past 6-8 years, we’re now at the point to start to do this. It’s an ethical obligation This will be one of the most high-fidelity, valid models for public reporting” of clinical outcomes,” said Joseph Cleveland, MD, a professor of surgery at the University of Colorado at Denver in Aurora. “It’s reassuring that about 90% of the program performed as expected or better than expected,” he added.

“Transparency and outcomes should drive how TAVR is delivered,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medicine Heart Institute in Phoenix who estimated that he performs about 150 TAVR procedures annually. “This is a step forward. I’ve been waiting for this for a long time. Until now, volume has been used as a surrogate outcome, but we know it’s not accurate. I’m confident that this model is a good starting point.” But Dr. Pershad also had concern that this new approach “can lend itself to some degree of gaming,” like a bleeding event getting classified as minor when it was really major, or outlier patients getting dropped from reports.

The temptation to cut corners may be higher for TAVR than it’s been for the cardiac-disease metrics that already get publicly reported, like bypass surgery and myocardial infarction management, because of TAVR’s higher cost and higher profile, Dr. Pershad said. Existing measures “have not been as linked to financial disincentive as TAVR might be” because TAVR reimbursements can run as high as $50,000 per case. “The stakes with TAVR are higher,” he said.

Ultimately, the reliable examination of TAVR outcomes that this new metric allows may lead to a shake-up of TAVR programs, Dr. Pershad predicted. “This is clearly a step toward closing down some programs that [consistently] underperform.”

The STS/ACC TVT Registry receives no commercial funding. Dr. Desai has been a consultant to, speaker on behalf of, and received research funding from Gore, and he has also spoken on behalf of Cook, Medtronic, and Terumo Aortic. Dr. Cleveland, Dr. Mack, and Dr. Pershad had no disclosures.

[email protected]

Transcatheter aortic valve replacement (TAVR) was not inferior to conventional surgery with respect to death from any cause at 1 year in a new real-world study in patients age 70 years or older with severe symptomatic aortic stenosis at increased operative risk due to age or comorbidity.

The UK TAVI study was presented March 29 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC).

The trial involved a broad group of patients who were treated at every medical center that performs the transcatheter procedure across the United Kingdom.

“The importance of this trial is that it confirms the effectiveness of the TAVR strategy in a real-world setting,” said lead author, William D. Toff, MD, professor of cardiology at the University of Leicester, United Kingdom.

Previous clinical trials have found TAVR to be noninferior or superior to open-heart surgery for various patient groups, but most trials have been limited to medical centers that perform a high volume of procedures or focus on the use of specific types of replacement valves, he noted.

“Our results are concordant with those from earlier trials in intermediate- and low-risk patients, but those earlier trials were performed in the best centers and had many exclusion criteria. We have replicated those results in populations more representative of the real world.”

“I think it is a very important message that supports the findings in earlier trials that were focused on showing whether TAVR can work under ideal conditions, while our trial shows that it does work in real-world clinical practice,” he added.

The UK TAVI trial enrolled 913 patients referred for treatment of severe aortic stenosis at 34 UK sites from 2014 to 2018. They were randomly assigned to receive TAVR or open-heart surgery.

Enrollment was limited to participants age 70 years or older (with additional risk factors) or age 80 years or older (with or without additional risk factors). The average age was 81 years.

Overall, participants were at intermediate to low risk from surgery, with a median Society of Thoracic Surgeons (STS) risk score of 2.6%. However, researchers did not specify a particular risk score cutoff for enrollment.

“This allowed the trial to evolve along with changes in guidelines and practice regarding TAVR over the course of the study and to reflect physicians’ nuanced, real-world approach to considering risk in decision-making rather than taking a formulaic approach,” Toff said.

At 1 year, the rate of death from any cause (the primary endpoint) was 4.6% in the TAVR group and 6.6% in the surgery group, a difference that met the trial’s prespecified threshold for noninferiority of TAVR.

Rates of death from cardiovascular disease or stroke were also similar between the two groups.

Patients who received TAVR had a significantly higher rate of vascular complications (4.8%) than those receiving surgery (1.3%).

TAVR patients were also more likely to have a pacemaker implanted. This occurred in 12.2% of TAVR patients and 6.6% of those undergoing surgery.

In addition, patients who underwent TAVR had a higher rate of aortic regurgitation. Mild aortic regurgitation occurred at 1 year in 38.3% of the TAVR group and 11.7% of the surgery group, whereas moderate regurgitation occurred in 2.3% of TAVR patients and 0.6% of surgery patients.

On the other hand, patients undergoing TAVR had a significantly lower rate of major bleeding complications, which occurred in 6.3% of patients having TAVR and 17.1% of those undergoing surgery.

TAVR was also associated with a shorter hospital stay, fewer days in intensive care, and a faster improvement in functional capacity and quality of life. Functional capacity and quality-of-life measures at 6 weeks after the procedure were better in the TAVR group but by 1 year they were similar in the two groups.

“Longer follow-up is required to confirm sustained clinical benefit and valve durability to inform clinical practice, particularly in younger patients,” Toff concluded.

“The results from our trial and others are encouraging, but patients need to be fully informed and know that the long-term durability of the TAVR valves and the long-term implications of the increased risk of aortic regurgitation are still uncertain,” he added.

The researchers plan to continue to track outcomes for a minimum of 5 years.

Discussant of the UK TAVI trial at an ACC press conference, Julia Grapsa, MD, Guys and St Thomas NHS Trust, London, United Kingdom, said it was a well-designed study.

“It was impressive to see so many UK sites and the age range of patients from 70 to 91 years, and the shorter hospital stays and functional recoveries as well as reduced major bleeding in the TAVR group,” Grapsa said.

“But something that was very striking to me was the increase in moderate aortic regurgitation in the TAVR arm, 2.3% versus 0.6% in the surgical arm, so it is very important to keep following these patients long term,” she added.

In answer to a question during the main session about using age alone as an inclusion criterion in those over 80 years old, Toff said, “We were more comfortable taking all comers over 80 years of age because of the uncertainty about TAVR is more in relation to its durability and the clinical significance of the aortic regurgitation, which may have consequences in the longer term. But the longer term for the over 80s is obviously less of a problem than for those in their 70s.”

This study was funded by the UK National Institute for Health Research Health Technology Assessment Programme. Toff reports no disclosures.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20410-ACC. Presented March 29, 2020.

This article first appeared on Medscape.com.

Transcatheter aortic valve replacement (TAVR) was not inferior to conventional surgery with respect to death from any cause at 1 year in a new real-world study in patients age 70 years or older with severe symptomatic aortic stenosis at increased operative risk due to age or comorbidity.

The UK TAVI study was presented March 29 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC).

The trial involved a broad group of patients who were treated at every medical center that performs the transcatheter procedure across the United Kingdom.

“The importance of this trial is that it confirms the effectiveness of the TAVR strategy in a real-world setting,” said lead author, William D. Toff, MD, professor of cardiology at the University of Leicester, United Kingdom.

Previous clinical trials have found TAVR to be noninferior or superior to open-heart surgery for various patient groups, but most trials have been limited to medical centers that perform a high volume of procedures or focus on the use of specific types of replacement valves, he noted.

“Our results are concordant with those from earlier trials in intermediate- and low-risk patients, but those earlier trials were performed in the best centers and had many exclusion criteria. We have replicated those results in populations more representative of the real world.”

“I think it is a very important message that supports the findings in earlier trials that were focused on showing whether TAVR can work under ideal conditions, while our trial shows that it does work in real-world clinical practice,” he added.

The UK TAVI trial enrolled 913 patients referred for treatment of severe aortic stenosis at 34 UK sites from 2014 to 2018. They were randomly assigned to receive TAVR or open-heart surgery.

Enrollment was limited to participants age 70 years or older (with additional risk factors) or age 80 years or older (with or without additional risk factors). The average age was 81 years.

Overall, participants were at intermediate to low risk from surgery, with a median Society of Thoracic Surgeons (STS) risk score of 2.6%. However, researchers did not specify a particular risk score cutoff for enrollment.

“This allowed the trial to evolve along with changes in guidelines and practice regarding TAVR over the course of the study and to reflect physicians’ nuanced, real-world approach to considering risk in decision-making rather than taking a formulaic approach,” Toff said.

At 1 year, the rate of death from any cause (the primary endpoint) was 4.6% in the TAVR group and 6.6% in the surgery group, a difference that met the trial’s prespecified threshold for noninferiority of TAVR.

Rates of death from cardiovascular disease or stroke were also similar between the two groups.

Patients who received TAVR had a significantly higher rate of vascular complications (4.8%) than those receiving surgery (1.3%).

TAVR patients were also more likely to have a pacemaker implanted. This occurred in 12.2% of TAVR patients and 6.6% of those undergoing surgery.

In addition, patients who underwent TAVR had a higher rate of aortic regurgitation. Mild aortic regurgitation occurred at 1 year in 38.3% of the TAVR group and 11.7% of the surgery group, whereas moderate regurgitation occurred in 2.3% of TAVR patients and 0.6% of surgery patients.

On the other hand, patients undergoing TAVR had a significantly lower rate of major bleeding complications, which occurred in 6.3% of patients having TAVR and 17.1% of those undergoing surgery.

TAVR was also associated with a shorter hospital stay, fewer days in intensive care, and a faster improvement in functional capacity and quality of life. Functional capacity and quality-of-life measures at 6 weeks after the procedure were better in the TAVR group but by 1 year they were similar in the two groups.

“Longer follow-up is required to confirm sustained clinical benefit and valve durability to inform clinical practice, particularly in younger patients,” Toff concluded.

“The results from our trial and others are encouraging, but patients need to be fully informed and know that the long-term durability of the TAVR valves and the long-term implications of the increased risk of aortic regurgitation are still uncertain,” he added.

The researchers plan to continue to track outcomes for a minimum of 5 years.

Discussant of the UK TAVI trial at an ACC press conference, Julia Grapsa, MD, Guys and St Thomas NHS Trust, London, United Kingdom, said it was a well-designed study.

“It was impressive to see so many UK sites and the age range of patients from 70 to 91 years, and the shorter hospital stays and functional recoveries as well as reduced major bleeding in the TAVR group,” Grapsa said.

“But something that was very striking to me was the increase in moderate aortic regurgitation in the TAVR arm, 2.3% versus 0.6% in the surgical arm, so it is very important to keep following these patients long term,” she added.

In answer to a question during the main session about using age alone as an inclusion criterion in those over 80 years old, Toff said, “We were more comfortable taking all comers over 80 years of age because of the uncertainty about TAVR is more in relation to its durability and the clinical significance of the aortic regurgitation, which may have consequences in the longer term. But the longer term for the over 80s is obviously less of a problem than for those in their 70s.”

This study was funded by the UK National Institute for Health Research Health Technology Assessment Programme. Toff reports no disclosures.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20410-ACC. Presented March 29, 2020.

This article first appeared on Medscape.com.

Transcatheter aortic valve replacement (TAVR) was not inferior to conventional surgery with respect to death from any cause at 1 year in a new real-world study in patients age 70 years or older with severe symptomatic aortic stenosis at increased operative risk due to age or comorbidity.

The UK TAVI study was presented March 29 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC).

The trial involved a broad group of patients who were treated at every medical center that performs the transcatheter procedure across the United Kingdom.

“The importance of this trial is that it confirms the effectiveness of the TAVR strategy in a real-world setting,” said lead author, William D. Toff, MD, professor of cardiology at the University of Leicester, United Kingdom.

Previous clinical trials have found TAVR to be noninferior or superior to open-heart surgery for various patient groups, but most trials have been limited to medical centers that perform a high volume of procedures or focus on the use of specific types of replacement valves, he noted.

“Our results are concordant with those from earlier trials in intermediate- and low-risk patients, but those earlier trials were performed in the best centers and had many exclusion criteria. We have replicated those results in populations more representative of the real world.”

“I think it is a very important message that supports the findings in earlier trials that were focused on showing whether TAVR can work under ideal conditions, while our trial shows that it does work in real-world clinical practice,” he added.

The UK TAVI trial enrolled 913 patients referred for treatment of severe aortic stenosis at 34 UK sites from 2014 to 2018. They were randomly assigned to receive TAVR or open-heart surgery.

Enrollment was limited to participants age 70 years or older (with additional risk factors) or age 80 years or older (with or without additional risk factors). The average age was 81 years.

Overall, participants were at intermediate to low risk from surgery, with a median Society of Thoracic Surgeons (STS) risk score of 2.6%. However, researchers did not specify a particular risk score cutoff for enrollment.

“This allowed the trial to evolve along with changes in guidelines and practice regarding TAVR over the course of the study and to reflect physicians’ nuanced, real-world approach to considering risk in decision-making rather than taking a formulaic approach,” Toff said.

At 1 year, the rate of death from any cause (the primary endpoint) was 4.6% in the TAVR group and 6.6% in the surgery group, a difference that met the trial’s prespecified threshold for noninferiority of TAVR.

Rates of death from cardiovascular disease or stroke were also similar between the two groups.

Patients who received TAVR had a significantly higher rate of vascular complications (4.8%) than those receiving surgery (1.3%).

TAVR patients were also more likely to have a pacemaker implanted. This occurred in 12.2% of TAVR patients and 6.6% of those undergoing surgery.

In addition, patients who underwent TAVR had a higher rate of aortic regurgitation. Mild aortic regurgitation occurred at 1 year in 38.3% of the TAVR group and 11.7% of the surgery group, whereas moderate regurgitation occurred in 2.3% of TAVR patients and 0.6% of surgery patients.

On the other hand, patients undergoing TAVR had a significantly lower rate of major bleeding complications, which occurred in 6.3% of patients having TAVR and 17.1% of those undergoing surgery.

TAVR was also associated with a shorter hospital stay, fewer days in intensive care, and a faster improvement in functional capacity and quality of life. Functional capacity and quality-of-life measures at 6 weeks after the procedure were better in the TAVR group but by 1 year they were similar in the two groups.

“Longer follow-up is required to confirm sustained clinical benefit and valve durability to inform clinical practice, particularly in younger patients,” Toff concluded.

“The results from our trial and others are encouraging, but patients need to be fully informed and know that the long-term durability of the TAVR valves and the long-term implications of the increased risk of aortic regurgitation are still uncertain,” he added.

The researchers plan to continue to track outcomes for a minimum of 5 years.

Discussant of the UK TAVI trial at an ACC press conference, Julia Grapsa, MD, Guys and St Thomas NHS Trust, London, United Kingdom, said it was a well-designed study.

“It was impressive to see so many UK sites and the age range of patients from 70 to 91 years, and the shorter hospital stays and functional recoveries as well as reduced major bleeding in the TAVR group,” Grapsa said.

“But something that was very striking to me was the increase in moderate aortic regurgitation in the TAVR arm, 2.3% versus 0.6% in the surgical arm, so it is very important to keep following these patients long term,” she added.

In answer to a question during the main session about using age alone as an inclusion criterion in those over 80 years old, Toff said, “We were more comfortable taking all comers over 80 years of age because of the uncertainty about TAVR is more in relation to its durability and the clinical significance of the aortic regurgitation, which may have consequences in the longer term. But the longer term for the over 80s is obviously less of a problem than for those in their 70s.”

This study was funded by the UK National Institute for Health Research Health Technology Assessment Programme. Toff reports no disclosures.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20410-ACC. Presented March 29, 2020.

This article first appeared on Medscape.com.

The largest trial to date investigating the clinical utility of using genetic testing to detect clopidogrel loss-of-function genotype to guide antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) missed its primary endpoint of a 50% reduction in cardiovascular events at 1 year.

However, the TAILOR-PCI trial did show a 34% reduction in such events at 1 year, as well as a statistically significant 40% reduction in the total number of events per patient receiving genetically guided treatment compared with patients who received standard treatment.

In addition, a post hoc analysis found a significant 79% reduction in the rate of adverse events in the first 3 months of treatment among patients who received genetically guided therapy compared with those who did not.

The study was presented March 28 during the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology.

“Although these results fell short of the effect size that we predicted, they nevertheless provide a signal that offers support for the benefit of genetically guided therapy, with approximately one-third fewer adverse events in the patients who received genetically guided treatment compared with those who did not,” concluded Naveen L. Pereira, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota, and co-principal investigator of the study.

Pereira said the post hoc analysis of the first 3 months of treatment was particularly interesting. “This period immediately after PCI is when patients are at the highest risk for adverse events. We now know that antiplatelet drug therapy is critical during the first 3 months after PCI. Our findings suggest that the lion’s share of the benefit of genetically guided therapy may occur during this high-risk period,” he noted.

However, he added, “Because this wasn’t a preplanned analysis, we can’t draw firm conclusions from it, but it merits further study.”

Asked during an ACC virtual press conference how these results may influence clinical practice, Pereira said he hopes it changes practice toward genotyping.

“We set a very high standard in trying to achieve a 50% reduction in events, but we did see a 34% reduction. I think the probability of the results being true is very high,” he said. “I hope people pay attention to that. I’m not sure what the guidelines will do, but I believe if clopidogrel genetic information is made available to the physician, not changing therapy in a patient who has the loss-of-function gene will now be very difficult.”

Discussant of the trial, Roxana Mehran, MD, Mount Sinai Hospital, New York City, said she thought the results were good enough clinically to justify using genotyping to guide therapy.

“The trial showed an absolute 1.8% reduction and a relative 34% reduction in cardiovascular events, which did not quite meet the P value for significance, and they are supported by a significant reduction in multiple events, and a large difference at 3 months, although these are not primary analyses. So, for me this trial has shown that tailoring antiplatelet therapy by genetic testing is beneficial,” she said.

Another outside commentator, Patrick O’Gara, MD, Brigham and Women’s Hospital, Boston, Massachusetts, described TAILOR-PCI as a “terrific study.”

“Together with the study presented last year showing genotype-guided clopidogrel treatment was noninferior to ticagrelor/prasugrel in STEMI [non-ST-segment elevation myocardial infarction] patients, it chips away at the biologic appropriateness of targeting therapies based on genetic risk,” he said.

“I would hate people to focus on the fact the primary endpoint was missed by one hundredth of a percentage point but hope they would rather consider the bigger picture of making this genotype test more available and accessible to inform clinical decision making,” O’Gara added. “It just makes too much sense to ignore this potential.”

The TAILOR-PCI trial enrolled 5302 patients from 40 centers in the United States, Canada, Mexico, and South Korea who had undergone PCI with stenting. They were randomly assigned to genetic testing for the clopidogrel loss-of-function variant or a group that received standard treatment (clopidogrel) without genetic testing.

In the genetic testing group, 35% of patients were found to have the clopidogrel loss-of-function variant and were therefore prescribed ticagrelor, whereas those without the loss-of-function variant received clopidogrel.

After 1 year, the primary endpoint, a composite of cardiovascular death, MI, stroke, definite or probable stent thrombosis, and severe recurrent ischemia, occurred in 35 patients (4%) of the group that received genetically guided treatment, compared with 54 (5.9%) in the conventionally treated group (adjusted hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.43 - 1.02; P = .56).

A prespecified analysis of total events (rather than just analysis of first event per patient) showed a 40% reduction in the genotyped group (HR, 0.60; 95% CI, 0.41 - 0.89; P = .011).

“Multiple adverse events represent a higher burden on the patient, so it is encouraging to see a significant reduction in cumulative events with genetically guided therapy,” Pereira said.

There was no difference in the safety endpoint of TIMI major bleeding or minor bleeding between the two groups: 1.9% in the genetically guided group vs 1.6% in the conventional treatment group.

The results did not differ between various subgroups in the trial, including race or ethnicity. Although Asian patients have a higher occurrence of the clopidogrel loss-of-function gene, the event risk reductions were similar in Asian and white patients in the study.

Pereira said the study may have been underpowered because of recent improvements in care. When the TAILOR-PCI trial was designed in 2012, around 10% to 12% of patients who received a stent could be expected to have a major adverse event, but during the trial, greater use of drug-coated stents and other treatments significantly reduced the expected rate of adverse events and made it more difficult for the trial to reach its goal of a 50% reduction in adverse events with the number of patients enrolled, he explained.

As part of the discussion, Mehran pointed out that more than 80% of the patients in the trial had acute coronary syndrome (ACS) and yet were being sent home on clopidogrel, which she said she found “daunting.”

“This begs the question of whether they were lower-risk patients and not really the hot unstable ACS patients with large thrombus burden where we see higher event rates,” Mehran commented. She also noted the results must be considered in the new era of platelet monotherapy, where aspirin is being withdrawn, and asked whether clopidogrel monotherapy would be considered safe without aspirin on board.

The researchers are planning a cost-effectiveness analysis of genetically guided therapy based on these data, and they are also continuing to follow patients over the longer term.

The TAILOR-PCI study was funded by the Mayo Clinic in collaboration with the National Heart, Lung, and Blood Institute. Spartan Bioscience Inc supplied the genetic tests used. Pereira reports no relevant disclosures.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology. Abstract 20-LB-20309-ACC. Presented March 28, 2020.

This article first appeared on Medscape.com.

The largest trial to date investigating the clinical utility of using genetic testing to detect clopidogrel loss-of-function genotype to guide antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) missed its primary endpoint of a 50% reduction in cardiovascular events at 1 year.

However, the TAILOR-PCI trial did show a 34% reduction in such events at 1 year, as well as a statistically significant 40% reduction in the total number of events per patient receiving genetically guided treatment compared with patients who received standard treatment.

In addition, a post hoc analysis found a significant 79% reduction in the rate of adverse events in the first 3 months of treatment among patients who received genetically guided therapy compared with those who did not.

The study was presented March 28 during the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology.

“Although these results fell short of the effect size that we predicted, they nevertheless provide a signal that offers support for the benefit of genetically guided therapy, with approximately one-third fewer adverse events in the patients who received genetically guided treatment compared with those who did not,” concluded Naveen L. Pereira, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota, and co-principal investigator of the study.

Pereira said the post hoc analysis of the first 3 months of treatment was particularly interesting. “This period immediately after PCI is when patients are at the highest risk for adverse events. We now know that antiplatelet drug therapy is critical during the first 3 months after PCI. Our findings suggest that the lion’s share of the benefit of genetically guided therapy may occur during this high-risk period,” he noted.

However, he added, “Because this wasn’t a preplanned analysis, we can’t draw firm conclusions from it, but it merits further study.”

Asked during an ACC virtual press conference how these results may influence clinical practice, Pereira said he hopes it changes practice toward genotyping.

“We set a very high standard in trying to achieve a 50% reduction in events, but we did see a 34% reduction. I think the probability of the results being true is very high,” he said. “I hope people pay attention to that. I’m not sure what the guidelines will do, but I believe if clopidogrel genetic information is made available to the physician, not changing therapy in a patient who has the loss-of-function gene will now be very difficult.”

Discussant of the trial, Roxana Mehran, MD, Mount Sinai Hospital, New York City, said she thought the results were good enough clinically to justify using genotyping to guide therapy.

“The trial showed an absolute 1.8% reduction and a relative 34% reduction in cardiovascular events, which did not quite meet the P value for significance, and they are supported by a significant reduction in multiple events, and a large difference at 3 months, although these are not primary analyses. So, for me this trial has shown that tailoring antiplatelet therapy by genetic testing is beneficial,” she said.

Another outside commentator, Patrick O’Gara, MD, Brigham and Women’s Hospital, Boston, Massachusetts, described TAILOR-PCI as a “terrific study.”

“Together with the study presented last year showing genotype-guided clopidogrel treatment was noninferior to ticagrelor/prasugrel in STEMI [non-ST-segment elevation myocardial infarction] patients, it chips away at the biologic appropriateness of targeting therapies based on genetic risk,” he said.

“I would hate people to focus on the fact the primary endpoint was missed by one hundredth of a percentage point but hope they would rather consider the bigger picture of making this genotype test more available and accessible to inform clinical decision making,” O’Gara added. “It just makes too much sense to ignore this potential.”

The TAILOR-PCI trial enrolled 5302 patients from 40 centers in the United States, Canada, Mexico, and South Korea who had undergone PCI with stenting. They were randomly assigned to genetic testing for the clopidogrel loss-of-function variant or a group that received standard treatment (clopidogrel) without genetic testing.

In the genetic testing group, 35% of patients were found to have the clopidogrel loss-of-function variant and were therefore prescribed ticagrelor, whereas those without the loss-of-function variant received clopidogrel.

After 1 year, the primary endpoint, a composite of cardiovascular death, MI, stroke, definite or probable stent thrombosis, and severe recurrent ischemia, occurred in 35 patients (4%) of the group that received genetically guided treatment, compared with 54 (5.9%) in the conventionally treated group (adjusted hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.43 - 1.02; P = .56).

A prespecified analysis of total events (rather than just analysis of first event per patient) showed a 40% reduction in the genotyped group (HR, 0.60; 95% CI, 0.41 - 0.89; P = .011).

“Multiple adverse events represent a higher burden on the patient, so it is encouraging to see a significant reduction in cumulative events with genetically guided therapy,” Pereira said.

There was no difference in the safety endpoint of TIMI major bleeding or minor bleeding between the two groups: 1.9% in the genetically guided group vs 1.6% in the conventional treatment group.

The results did not differ between various subgroups in the trial, including race or ethnicity. Although Asian patients have a higher occurrence of the clopidogrel loss-of-function gene, the event risk reductions were similar in Asian and white patients in the study.

Pereira said the study may have been underpowered because of recent improvements in care. When the TAILOR-PCI trial was designed in 2012, around 10% to 12% of patients who received a stent could be expected to have a major adverse event, but during the trial, greater use of drug-coated stents and other treatments significantly reduced the expected rate of adverse events and made it more difficult for the trial to reach its goal of a 50% reduction in adverse events with the number of patients enrolled, he explained.

As part of the discussion, Mehran pointed out that more than 80% of the patients in the trial had acute coronary syndrome (ACS) and yet were being sent home on clopidogrel, which she said she found “daunting.”

“This begs the question of whether they were lower-risk patients and not really the hot unstable ACS patients with large thrombus burden where we see higher event rates,” Mehran commented. She also noted the results must be considered in the new era of platelet monotherapy, where aspirin is being withdrawn, and asked whether clopidogrel monotherapy would be considered safe without aspirin on board.

The researchers are planning a cost-effectiveness analysis of genetically guided therapy based on these data, and they are also continuing to follow patients over the longer term.

The TAILOR-PCI study was funded by the Mayo Clinic in collaboration with the National Heart, Lung, and Blood Institute. Spartan Bioscience Inc supplied the genetic tests used. Pereira reports no relevant disclosures.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology. Abstract 20-LB-20309-ACC. Presented March 28, 2020.

This article first appeared on Medscape.com.

The largest trial to date investigating the clinical utility of using genetic testing to detect clopidogrel loss-of-function genotype to guide antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) missed its primary endpoint of a 50% reduction in cardiovascular events at 1 year.

However, the TAILOR-PCI trial did show a 34% reduction in such events at 1 year, as well as a statistically significant 40% reduction in the total number of events per patient receiving genetically guided treatment compared with patients who received standard treatment.

In addition, a post hoc analysis found a significant 79% reduction in the rate of adverse events in the first 3 months of treatment among patients who received genetically guided therapy compared with those who did not.

The study was presented March 28 during the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology.

“Although these results fell short of the effect size that we predicted, they nevertheless provide a signal that offers support for the benefit of genetically guided therapy, with approximately one-third fewer adverse events in the patients who received genetically guided treatment compared with those who did not,” concluded Naveen L. Pereira, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota, and co-principal investigator of the study.

Pereira said the post hoc analysis of the first 3 months of treatment was particularly interesting. “This period immediately after PCI is when patients are at the highest risk for adverse events. We now know that antiplatelet drug therapy is critical during the first 3 months after PCI. Our findings suggest that the lion’s share of the benefit of genetically guided therapy may occur during this high-risk period,” he noted.

However, he added, “Because this wasn’t a preplanned analysis, we can’t draw firm conclusions from it, but it merits further study.”

Asked during an ACC virtual press conference how these results may influence clinical practice, Pereira said he hopes it changes practice toward genotyping.

“We set a very high standard in trying to achieve a 50% reduction in events, but we did see a 34% reduction. I think the probability of the results being true is very high,” he said. “I hope people pay attention to that. I’m not sure what the guidelines will do, but I believe if clopidogrel genetic information is made available to the physician, not changing therapy in a patient who has the loss-of-function gene will now be very difficult.”

Discussant of the trial, Roxana Mehran, MD, Mount Sinai Hospital, New York City, said she thought the results were good enough clinically to justify using genotyping to guide therapy.

“The trial showed an absolute 1.8% reduction and a relative 34% reduction in cardiovascular events, which did not quite meet the P value for significance, and they are supported by a significant reduction in multiple events, and a large difference at 3 months, although these are not primary analyses. So, for me this trial has shown that tailoring antiplatelet therapy by genetic testing is beneficial,” she said.

Another outside commentator, Patrick O’Gara, MD, Brigham and Women’s Hospital, Boston, Massachusetts, described TAILOR-PCI as a “terrific study.”

“Together with the study presented last year showing genotype-guided clopidogrel treatment was noninferior to ticagrelor/prasugrel in STEMI [non-ST-segment elevation myocardial infarction] patients, it chips away at the biologic appropriateness of targeting therapies based on genetic risk,” he said.

“I would hate people to focus on the fact the primary endpoint was missed by one hundredth of a percentage point but hope they would rather consider the bigger picture of making this genotype test more available and accessible to inform clinical decision making,” O’Gara added. “It just makes too much sense to ignore this potential.”

The TAILOR-PCI trial enrolled 5302 patients from 40 centers in the United States, Canada, Mexico, and South Korea who had undergone PCI with stenting. They were randomly assigned to genetic testing for the clopidogrel loss-of-function variant or a group that received standard treatment (clopidogrel) without genetic testing.

In the genetic testing group, 35% of patients were found to have the clopidogrel loss-of-function variant and were therefore prescribed ticagrelor, whereas those without the loss-of-function variant received clopidogrel.

After 1 year, the primary endpoint, a composite of cardiovascular death, MI, stroke, definite or probable stent thrombosis, and severe recurrent ischemia, occurred in 35 patients (4%) of the group that received genetically guided treatment, compared with 54 (5.9%) in the conventionally treated group (adjusted hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.43 - 1.02; P = .56).

A prespecified analysis of total events (rather than just analysis of first event per patient) showed a 40% reduction in the genotyped group (HR, 0.60; 95% CI, 0.41 - 0.89; P = .011).

“Multiple adverse events represent a higher burden on the patient, so it is encouraging to see a significant reduction in cumulative events with genetically guided therapy,” Pereira said.

There was no difference in the safety endpoint of TIMI major bleeding or minor bleeding between the two groups: 1.9% in the genetically guided group vs 1.6% in the conventional treatment group.

The results did not differ between various subgroups in the trial, including race or ethnicity. Although Asian patients have a higher occurrence of the clopidogrel loss-of-function gene, the event risk reductions were similar in Asian and white patients in the study.

Pereira said the study may have been underpowered because of recent improvements in care. When the TAILOR-PCI trial was designed in 2012, around 10% to 12% of patients who received a stent could be expected to have a major adverse event, but during the trial, greater use of drug-coated stents and other treatments significantly reduced the expected rate of adverse events and made it more difficult for the trial to reach its goal of a 50% reduction in adverse events with the number of patients enrolled, he explained.

As part of the discussion, Mehran pointed out that more than 80% of the patients in the trial had acute coronary syndrome (ACS) and yet were being sent home on clopidogrel, which she said she found “daunting.”

“This begs the question of whether they were lower-risk patients and not really the hot unstable ACS patients with large thrombus burden where we see higher event rates,” Mehran commented. She also noted the results must be considered in the new era of platelet monotherapy, where aspirin is being withdrawn, and asked whether clopidogrel monotherapy would be considered safe without aspirin on board.

The researchers are planning a cost-effectiveness analysis of genetically guided therapy based on these data, and they are also continuing to follow patients over the longer term.

The TAILOR-PCI study was funded by the Mayo Clinic in collaboration with the National Heart, Lung, and Blood Institute. Spartan Bioscience Inc supplied the genetic tests used. Pereira reports no relevant disclosures.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology. Abstract 20-LB-20309-ACC. Presented March 28, 2020.

This article first appeared on Medscape.com.

From the Society for Thoracic Surgeons (STS)/ACC Transcatheter Valve Therapy (TVT) Registry, the group identified 120,080 patients who had TAVR at 559 US sites, from January 2016 to March 2019.

During this time, the percentage of procedures that were done using conscious sedation almost doubled, plateauing in the final 6 months.

And the proportion of sites using any conscious sedation during TAVR increased from 50% to 76%.

The use of this procedure varied widely among the sites: 26% performed >80% of TAVR with conscious sedation, and 13% did not perform any TAVR cases with conscious sedation.

In hospitals in the lowest and highest quartiles of use of conscious sedation during TAVR, this type of sedation was used in a median of 0% of TAVR cases and 91% of cases, respectively.

The researchers used instrumental variable analysis to compare outcomes in patients whose type of anesthesia would differ if they went to a hospital with high or low use of conscious sedation.

Using this method, the use of conscious sedation was associated with a 0.2% absolute risk difference in in-hospital death, the primary study endpoint (P = .010).

And compared with general anesthesia, conscious sedation during TAVR was also associated with a lower rate of 30-day death (2.0% vs 2.5%, respectively), fewer days in the hospital (3.5 vs 4.3 days), and a higher rate of being discharged to home (88.9% vs 86.1%, all P < .001).

“Our results would not apply to those patients who always receive general anesthesia, even at high conscious sedation use centers (eg, patients with severe lung disease on oxygen or significant right ventricular dysfunction),” the authors caution.

Study limitations, next steps

A study limitation is that the registry data did not specify the type of conscious sedation that was used, Cohen acknowledged.

This could vary. For example, a patient could be given a very powerful sedative such as propofol (Diprivan), and his or her respiration and oxygen saturation would be monitored, and an anesthesiologist would be always present. Or the patient could receive sedation like that for angioplasty — diazepam (Valium) or midazolam (Versed) and a narcotic — without an anesthesiologist.

It would be useful to look at the TAVR volumes and compare outcomes within different TAVR volume quartiles, Tang suggested.

In low-volume centers, the anesthesiologist may be uncomfortable with complex cases, whereas larger academic centers would perform more complex procedures and may paradoxically have a slightly higher rate of complications, he speculated.

Future research should investigate what drives the differences in the use of conscious sedation, the authors suggest.

Cohen reports institutional grant support and consulting fees from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott. Butala is funded by the John S. LaDue Memorial Fellowship at Harvard Medical School and reports consulting fees and ownership interest in HiLabs, outside the submitted work. The disclosures of the other authors are listed with the original article.

This article first appeared on Medscape.com.

From the Society for Thoracic Surgeons (STS)/ACC Transcatheter Valve Therapy (TVT) Registry, the group identified 120,080 patients who had TAVR at 559 US sites, from January 2016 to March 2019.

During this time, the percentage of procedures that were done using conscious sedation almost doubled, plateauing in the final 6 months.

And the proportion of sites using any conscious sedation during TAVR increased from 50% to 76%.

The use of this procedure varied widely among the sites: 26% performed >80% of TAVR with conscious sedation, and 13% did not perform any TAVR cases with conscious sedation.

In hospitals in the lowest and highest quartiles of use of conscious sedation during TAVR, this type of sedation was used in a median of 0% of TAVR cases and 91% of cases, respectively.

The researchers used instrumental variable analysis to compare outcomes in patients whose type of anesthesia would differ if they went to a hospital with high or low use of conscious sedation.

Using this method, the use of conscious sedation was associated with a 0.2% absolute risk difference in in-hospital death, the primary study endpoint (P = .010).

And compared with general anesthesia, conscious sedation during TAVR was also associated with a lower rate of 30-day death (2.0% vs 2.5%, respectively), fewer days in the hospital (3.5 vs 4.3 days), and a higher rate of being discharged to home (88.9% vs 86.1%, all P < .001).

“Our results would not apply to those patients who always receive general anesthesia, even at high conscious sedation use centers (eg, patients with severe lung disease on oxygen or significant right ventricular dysfunction),” the authors caution.

Study limitations, next steps

A study limitation is that the registry data did not specify the type of conscious sedation that was used, Cohen acknowledged.

This could vary. For example, a patient could be given a very powerful sedative such as propofol (Diprivan), and his or her respiration and oxygen saturation would be monitored, and an anesthesiologist would be always present. Or the patient could receive sedation like that for angioplasty — diazepam (Valium) or midazolam (Versed) and a narcotic — without an anesthesiologist.

It would be useful to look at the TAVR volumes and compare outcomes within different TAVR volume quartiles, Tang suggested.

In low-volume centers, the anesthesiologist may be uncomfortable with complex cases, whereas larger academic centers would perform more complex procedures and may paradoxically have a slightly higher rate of complications, he speculated.

Future research should investigate what drives the differences in the use of conscious sedation, the authors suggest.

Cohen reports institutional grant support and consulting fees from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott. Butala is funded by the John S. LaDue Memorial Fellowship at Harvard Medical School and reports consulting fees and ownership interest in HiLabs, outside the submitted work. The disclosures of the other authors are listed with the original article.

This article first appeared on Medscape.com.

From the Society for Thoracic Surgeons (STS)/ACC Transcatheter Valve Therapy (TVT) Registry, the group identified 120,080 patients who had TAVR at 559 US sites, from January 2016 to March 2019.

During this time, the percentage of procedures that were done using conscious sedation almost doubled, plateauing in the final 6 months.

And the proportion of sites using any conscious sedation during TAVR increased from 50% to 76%.

The use of this procedure varied widely among the sites: 26% performed >80% of TAVR with conscious sedation, and 13% did not perform any TAVR cases with conscious sedation.

In hospitals in the lowest and highest quartiles of use of conscious sedation during TAVR, this type of sedation was used in a median of 0% of TAVR cases and 91% of cases, respectively.

The researchers used instrumental variable analysis to compare outcomes in patients whose type of anesthesia would differ if they went to a hospital with high or low use of conscious sedation.

Using this method, the use of conscious sedation was associated with a 0.2% absolute risk difference in in-hospital death, the primary study endpoint (P = .010).

And compared with general anesthesia, conscious sedation during TAVR was also associated with a lower rate of 30-day death (2.0% vs 2.5%, respectively), fewer days in the hospital (3.5 vs 4.3 days), and a higher rate of being discharged to home (88.9% vs 86.1%, all P < .001).

“Our results would not apply to those patients who always receive general anesthesia, even at high conscious sedation use centers (eg, patients with severe lung disease on oxygen or significant right ventricular dysfunction),” the authors caution.

Study limitations, next steps

A study limitation is that the registry data did not specify the type of conscious sedation that was used, Cohen acknowledged.

This could vary. For example, a patient could be given a very powerful sedative such as propofol (Diprivan), and his or her respiration and oxygen saturation would be monitored, and an anesthesiologist would be always present. Or the patient could receive sedation like that for angioplasty — diazepam (Valium) or midazolam (Versed) and a narcotic — without an anesthesiologist.

It would be useful to look at the TAVR volumes and compare outcomes within different TAVR volume quartiles, Tang suggested.

In low-volume centers, the anesthesiologist may be uncomfortable with complex cases, whereas larger academic centers would perform more complex procedures and may paradoxically have a slightly higher rate of complications, he speculated.

Future research should investigate what drives the differences in the use of conscious sedation, the authors suggest.

Cohen reports institutional grant support and consulting fees from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott. Butala is funded by the John S. LaDue Memorial Fellowship at Harvard Medical School and reports consulting fees and ownership interest in HiLabs, outside the submitted work. The disclosures of the other authors are listed with the original article.

This article first appeared on Medscape.com.

NATIONAL HARBOR, MD – Data presented at the 2020 CRT meeting, sponsored by MedStar Heart & Vascular Institute, show that transcatheter aortic valve replacement (TAVR) is safe and effective, at least in the short term, for low-risk patients with bicuspid aortic stenosis, which addresses a data gap.

Ted Bosworth/MDedge News

In an investigator-driven prospective study, called LRT, there was no mortality, no myocardial infarctions (MI), and no disabling strokes 30 days after the procedure, according to Ronald Waksman, MD, associate director of cardiology at Medstar Heart Institute in Washington.

TAVR was approved in 2019 for low-risk patients with symptomatic severe aortic stenosis regardless of aortic valve morphology, but the pivotal industry-led trials only enrolled patients with tricuspid valves, excluding the bicuspid population, according to Dr. Waksman.

However, bicuspid patients were enrolled in the investigator-led LRT study. The 1-year results with tricuspid values have been published previously (JACC Cardiovasc Interv. 2019;12:901-7), but new data from this same study provides the first prospective evaluation in low-risk bicuspid patients.

The LRT enrollment criteria were the same for the bicuspid patients as they were for those enrolled with tricuspid valves. These included a low surgical risk, defined as a Society of Thoracic Surgeons (STS) score of 3 or less; no high-risk criteria independent of STS score; and eligibility for a transfemoral percutaneous procedure. Patients were permitted to undergo TAVR with any commercially available device.

The 61 patients enrolled from August 2016 to September 2019 were compared at 30 days of follow-up with 211 low-risk bicuspid patients undergoing surgical aortic valve replacement (SAVR). Propensity matched, the two groups had generally similar baseline characteristics with some exceptions. Relative to the SAVR group, the TAVR group had an older median age (68.6 vs. 63.4 years) and a lower proportion of males (42.6% vs. 65.7%) and a lower proportion with New York Heart Association heart failure of class III or higher (15.8% vs. 24.6%).

For the primary outcome of all-cause mortality at 30 days, there were no deaths in the TAVR group versus one death in the SAVR group. TAVR was associated with a shorter length of stay (2.0 vs. 5.8 days) and a lower risk of new-onset atrial fibrillation (1.6% vs. 42.6%). However, pacemaker implantations were more common in the TAVR group (11.5% vs. 5.6%). There was one stroke in the TAVR group, but it was not disabling.

Following TAVR, there was one case of paravalvular leak, but it was of moderate severity, according to Dr. Waksman. Leaflet thrombosis in the form of hypoattenuated leaflet thickening (HALT), which occurred in 10.2% of patients; reduced leaflet motion (RELM), which occurred in 6.9%; and hypoattenuation affecting motion (HAM), which also occurred in 6.9%, was observed at 30 days following TAVR, but these have not so far been associated with any clinical consequences.

At baseline, only 4.9% of the bicuspid patients met criteria for NYHA class I function and 23% were in NYHA class III or higher. By 30 days, the proportion in NYHA class I had risen to 78.3%, and no patient was in NYHA class III or higher. Dr. Waksman characterized the improvement in hemodynamics – measured by mean aortic valve gradient and aortic valve area – as “excellent” at 30 days.

Further follow-up of bicuspid patients in the LRT study is needed to confirm long-term safety and efficacy, but Dr. Waksman indicated that the 30-day results are encouraging, in part because they show no greater risk of periprocedural complications than that observed in the tricuspid population.

NATIONAL HARBOR, MD – Data presented at the 2020 CRT meeting, sponsored by MedStar Heart & Vascular Institute, show that transcatheter aortic valve replacement (TAVR) is safe and effective, at least in the short term, for low-risk patients with bicuspid aortic stenosis, which addresses a data gap.

Ted Bosworth/MDedge News

In an investigator-driven prospective study, called LRT, there was no mortality, no myocardial infarctions (MI), and no disabling strokes 30 days after the procedure, according to Ronald Waksman, MD, associate director of cardiology at Medstar Heart Institute in Washington.

TAVR was approved in 2019 for low-risk patients with symptomatic severe aortic stenosis regardless of aortic valve morphology, but the pivotal industry-led trials only enrolled patients with tricuspid valves, excluding the bicuspid population, according to Dr. Waksman.

However, bicuspid patients were enrolled in the investigator-led LRT study. The 1-year results with tricuspid values have been published previously (JACC Cardiovasc Interv. 2019;12:901-7), but new data from this same study provides the first prospective evaluation in low-risk bicuspid patients.

The LRT enrollment criteria were the same for the bicuspid patients as they were for those enrolled with tricuspid valves. These included a low surgical risk, defined as a Society of Thoracic Surgeons (STS) score of 3 or less; no high-risk criteria independent of STS score; and eligibility for a transfemoral percutaneous procedure. Patients were permitted to undergo TAVR with any commercially available device.

The 61 patients enrolled from August 2016 to September 2019 were compared at 30 days of follow-up with 211 low-risk bicuspid patients undergoing surgical aortic valve replacement (SAVR). Propensity matched, the two groups had generally similar baseline characteristics with some exceptions. Relative to the SAVR group, the TAVR group had an older median age (68.6 vs. 63.4 years) and a lower proportion of males (42.6% vs. 65.7%) and a lower proportion with New York Heart Association heart failure of class III or higher (15.8% vs. 24.6%).

For the primary outcome of all-cause mortality at 30 days, there were no deaths in the TAVR group versus one death in the SAVR group. TAVR was associated with a shorter length of stay (2.0 vs. 5.8 days) and a lower risk of new-onset atrial fibrillation (1.6% vs. 42.6%). However, pacemaker implantations were more common in the TAVR group (11.5% vs. 5.6%). There was one stroke in the TAVR group, but it was not disabling.

Following TAVR, there was one case of paravalvular leak, but it was of moderate severity, according to Dr. Waksman. Leaflet thrombosis in the form of hypoattenuated leaflet thickening (HALT), which occurred in 10.2% of patients; reduced leaflet motion (RELM), which occurred in 6.9%; and hypoattenuation affecting motion (HAM), which also occurred in 6.9%, was observed at 30 days following TAVR, but these have not so far been associated with any clinical consequences.

At baseline, only 4.9% of the bicuspid patients met criteria for NYHA class I function and 23% were in NYHA class III or higher. By 30 days, the proportion in NYHA class I had risen to 78.3%, and no patient was in NYHA class III or higher. Dr. Waksman characterized the improvement in hemodynamics – measured by mean aortic valve gradient and aortic valve area – as “excellent” at 30 days.

Further follow-up of bicuspid patients in the LRT study is needed to confirm long-term safety and efficacy, but Dr. Waksman indicated that the 30-day results are encouraging, in part because they show no greater risk of periprocedural complications than that observed in the tricuspid population.

NATIONAL HARBOR, MD – Data presented at the 2020 CRT meeting, sponsored by MedStar Heart & Vascular Institute, show that transcatheter aortic valve replacement (TAVR) is safe and effective, at least in the short term, for low-risk patients with bicuspid aortic stenosis, which addresses a data gap.

Ted Bosworth/MDedge News

In an investigator-driven prospective study, called LRT, there was no mortality, no myocardial infarctions (MI), and no disabling strokes 30 days after the procedure, according to Ronald Waksman, MD, associate director of cardiology at Medstar Heart Institute in Washington.

TAVR was approved in 2019 for low-risk patients with symptomatic severe aortic stenosis regardless of aortic valve morphology, but the pivotal industry-led trials only enrolled patients with tricuspid valves, excluding the bicuspid population, according to Dr. Waksman.

However, bicuspid patients were enrolled in the investigator-led LRT study. The 1-year results with tricuspid values have been published previously (JACC Cardiovasc Interv. 2019;12:901-7), but new data from this same study provides the first prospective evaluation in low-risk bicuspid patients.

The LRT enrollment criteria were the same for the bicuspid patients as they were for those enrolled with tricuspid valves. These included a low surgical risk, defined as a Society of Thoracic Surgeons (STS) score of 3 or less; no high-risk criteria independent of STS score; and eligibility for a transfemoral percutaneous procedure. Patients were permitted to undergo TAVR with any commercially available device.

The 61 patients enrolled from August 2016 to September 2019 were compared at 30 days of follow-up with 211 low-risk bicuspid patients undergoing surgical aortic valve replacement (SAVR). Propensity matched, the two groups had generally similar baseline characteristics with some exceptions. Relative to the SAVR group, the TAVR group had an older median age (68.6 vs. 63.4 years) and a lower proportion of males (42.6% vs. 65.7%) and a lower proportion with New York Heart Association heart failure of class III or higher (15.8% vs. 24.6%).

For the primary outcome of all-cause mortality at 30 days, there were no deaths in the TAVR group versus one death in the SAVR group. TAVR was associated with a shorter length of stay (2.0 vs. 5.8 days) and a lower risk of new-onset atrial fibrillation (1.6% vs. 42.6%). However, pacemaker implantations were more common in the TAVR group (11.5% vs. 5.6%). There was one stroke in the TAVR group, but it was not disabling.

Following TAVR, there was one case of paravalvular leak, but it was of moderate severity, according to Dr. Waksman. Leaflet thrombosis in the form of hypoattenuated leaflet thickening (HALT), which occurred in 10.2% of patients; reduced leaflet motion (RELM), which occurred in 6.9%; and hypoattenuation affecting motion (HAM), which also occurred in 6.9%, was observed at 30 days following TAVR, but these have not so far been associated with any clinical consequences.

At baseline, only 4.9% of the bicuspid patients met criteria for NYHA class I function and 23% were in NYHA class III or higher. By 30 days, the proportion in NYHA class I had risen to 78.3%, and no patient was in NYHA class III or higher. Dr. Waksman characterized the improvement in hemodynamics – measured by mean aortic valve gradient and aortic valve area – as “excellent” at 30 days.

Further follow-up of bicuspid patients in the LRT study is needed to confirm long-term safety and efficacy, but Dr. Waksman indicated that the 30-day results are encouraging, in part because they show no greater risk of periprocedural complications than that observed in the tricuspid population.

NATIONAL HARBOR, MD. – In a head-to-head comparison, the ultrathin-strut Orsiro drug-eluting stent (DES) is demonstrating a growing advantage over the thin-strut Xience DES stent in stable patients undergoing coronary revascularization, according to a presentation at the 2020 CRT meeting.

Ted Bostworth/MDedge News

“These results direct our attention to strut thickness and polymer composition as key attributes for stent design,” reported David E. Kandzari, MD, director of interventional cardiology at the Piedmont Heart Institute in Atlanta.

In the multinational BIOFLOW V trial, 1,334 patients were randomized in a two-to-one ratio to the Orsiro stent, which is composed of a bioabsorbable, sirolimus-eluting polymer, or to the Xience stent, which is composed of an everolimus-eluting durable polymer. Relative to the Xience device, which has thin struts of 81 microns in width, the struts of the Orsiro device, at 60 microns in width, are characterized as ultrathin.

In earlier published follow-up studies, the ultrathin device demonstrated a lower rate of target lesion (TL) failure at 1 year (5.9% vs. 9.2%; P = .032) and at 2 years (7.1% vs. 11.1%; P = .015), but the 3-year data are notable because they indicate that the relative advantage is continuing to grow, according to Dr. Kandzari.

At 3 years, with follow-up available for 94.8% and 94.2% of the Orsiro and Xience groups, respectively, the absolute relative difference in the primary endpoint of TL failure reached 5.4% (8.2% vs. 13.6%; P = .002) in favor of the Orsiro device.

For the components of the composite TL failure endpoint, which includes cardiovascular death, TL-related myocardial infarction, and TL revascularization, there were large relative advantages for every outcome except cardiovascular death, which did not differ between the Orsiro and Xience groups (1.1% vs. 1.2%, respectively; P = .1). Conversely, the TL-related MI (5.5% vs. 10.1%; P = .004) and ischemia-driven TL revascularization (3.4% vs. 6.9%; P = .008) rates were nearly cut in half in the Orsiro arm.

“The benefit appears to be bimodal in that there is a significant advantage in the periprocedural period [for the Orsiro device] and then a late advantage,” Dr. Kandzari reported.

Most TL-related MI in both groups, for example, occurred within the first 30 days of follow-up. Although there was a relative advantage for the Orsiro device in this early period (4.1% vs. 6.7%; P = .04), Dr. Kandzari indicated that the advantage between 30 days and 3 years was even more impressive (0.95% vs. 2.8%; P = .012).

Dr. Kandzari, showing a graph in which the line representing Orsiro device hugged the x axis as the line for the Xience device climbed, emphasized that the rate of target vessel MI at the end of follow-up was nearly three times greater for those randomized to the Xience device.

The patterns of ischemia-driven TL revascularization also diverged. In this case, the rates over the first 360 days were very similar for the two devices initially. At 1 year, the lower rate in the Orsiro device was not significantly different (2.0% vs. 2.3%; P = .72), but the lines began to separate at about 18 months. By the end of 3 years, the rate of ischemia-related TL revascularization was nearly 70% lower in the Orsiro arm (1.5% vs. 4.7%; P < .001).

The Orsiro device was also linked with a lower rate of definite or probable stent thrombosis when the two devices were compared from 30 days post implantation to 3 years of follow-up (0.1% vs. 1.2%; P = .018).

Noting that there are several features of the Orsiro device that might explain these results, including the width of the struts, the biodegradable polymer, and the type of anti-inflammatory coating, Dr. Kandzari said that it is difficult to determine which attributes account for the overall or the specific advantages observed for the Orsiro device in the BIOFLOW V trial.

However, he hypothesized that “there might be different time lines for different benefits” related to individual device characteristics. For example, the ultrathin struts might be important for the early relative advantages while the biodegradation of the strut might explain the reduced need for revascularization.

Overall, “there is an emerging evidence base consistent across clinical trials demonstrating a potential efficacy and safety difference in favor of ultrathin struts,” according to Dr. Kandzari.

The data are “remarkable,” according to James B. Hermiller, MD, an interventional cardiologist at the Heart Center of Indiana in Indianapolis. A panel member for the CRT late-breaking trial session where these data were presented, Dr. Hermiller was impressed by the very low rate of revascularization in the extended follow-up.

“We have all wanted to see a flattening of these event curves after a year,” Dr. Hermiller said. He indicated that the BIOFLOW V data represent a departure from the need for revascularization and other late events so commonly seen over lengthening follow-up with earlier generation devices.

SOURCE: Kandzari DE. CRT 2020, Late Breaking Trials session S300.

NATIONAL HARBOR, MD. – In a head-to-head comparison, the ultrathin-strut Orsiro drug-eluting stent (DES) is demonstrating a growing advantage over the thin-strut Xience DES stent in stable patients undergoing coronary revascularization, according to a presentation at the 2020 CRT meeting.

Ted Bostworth/MDedge News

“These results direct our attention to strut thickness and polymer composition as key attributes for stent design,” reported David E. Kandzari, MD, director of interventional cardiology at the Piedmont Heart Institute in Atlanta.

In the multinational BIOFLOW V trial, 1,334 patients were randomized in a two-to-one ratio to the Orsiro stent, which is composed of a bioabsorbable, sirolimus-eluting polymer, or to the Xience stent, which is composed of an everolimus-eluting durable polymer. Relative to the Xience device, which has thin struts of 81 microns in width, the struts of the Orsiro device, at 60 microns in width, are characterized as ultrathin.

In earlier published follow-up studies, the ultrathin device demonstrated a lower rate of target lesion (TL) failure at 1 year (5.9% vs. 9.2%; P = .032) and at 2 years (7.1% vs. 11.1%; P = .015), but the 3-year data are notable because they indicate that the relative advantage is continuing to grow, according to Dr. Kandzari.

At 3 years, with follow-up available for 94.8% and 94.2% of the Orsiro and Xience groups, respectively, the absolute relative difference in the primary endpoint of TL failure reached 5.4% (8.2% vs. 13.6%; P = .002) in favor of the Orsiro device.

For the components of the composite TL failure endpoint, which includes cardiovascular death, TL-related myocardial infarction, and TL revascularization, there were large relative advantages for every outcome except cardiovascular death, which did not differ between the Orsiro and Xience groups (1.1% vs. 1.2%, respectively; P = .1). Conversely, the TL-related MI (5.5% vs. 10.1%; P = .004) and ischemia-driven TL revascularization (3.4% vs. 6.9%; P = .008) rates were nearly cut in half in the Orsiro arm.

“The benefit appears to be bimodal in that there is a significant advantage in the periprocedural period [for the Orsiro device] and then a late advantage,” Dr. Kandzari reported.

Most TL-related MI in both groups, for example, occurred within the first 30 days of follow-up. Although there was a relative advantage for the Orsiro device in this early period (4.1% vs. 6.7%; P = .04), Dr. Kandzari indicated that the advantage between 30 days and 3 years was even more impressive (0.95% vs. 2.8%; P = .012).

Dr. Kandzari, showing a graph in which the line representing Orsiro device hugged the x axis as the line for the Xience device climbed, emphasized that the rate of target vessel MI at the end of follow-up was nearly three times greater for those randomized to the Xience device.

The patterns of ischemia-driven TL revascularization also diverged. In this case, the rates over the first 360 days were very similar for the two devices initially. At 1 year, the lower rate in the Orsiro device was not significantly different (2.0% vs. 2.3%; P = .72), but the lines began to separate at about 18 months. By the end of 3 years, the rate of ischemia-related TL revascularization was nearly 70% lower in the Orsiro arm (1.5% vs. 4.7%; P < .001).

The Orsiro device was also linked with a lower rate of definite or probable stent thrombosis when the two devices were compared from 30 days post implantation to 3 years of follow-up (0.1% vs. 1.2%; P = .018).

Noting that there are several features of the Orsiro device that might explain these results, including the width of the struts, the biodegradable polymer, and the type of anti-inflammatory coating, Dr. Kandzari said that it is difficult to determine which attributes account for the overall or the specific advantages observed for the Orsiro device in the BIOFLOW V trial.

However, he hypothesized that “there might be different time lines for different benefits” related to individual device characteristics. For example, the ultrathin struts might be important for the early relative advantages while the biodegradation of the strut might explain the reduced need for revascularization.

Overall, “there is an emerging evidence base consistent across clinical trials demonstrating a potential efficacy and safety difference in favor of ultrathin struts,” according to Dr. Kandzari.

The data are “remarkable,” according to James B. Hermiller, MD, an interventional cardiologist at the Heart Center of Indiana in Indianapolis. A panel member for the CRT late-breaking trial session where these data were presented, Dr. Hermiller was impressed by the very low rate of revascularization in the extended follow-up.

“We have all wanted to see a flattening of these event curves after a year,” Dr. Hermiller said. He indicated that the BIOFLOW V data represent a departure from the need for revascularization and other late events so commonly seen over lengthening follow-up with earlier generation devices.

SOURCE: Kandzari DE. CRT 2020, Late Breaking Trials session S300.

NATIONAL HARBOR, MD. – In a head-to-head comparison, the ultrathin-strut Orsiro drug-eluting stent (DES) is demonstrating a growing advantage over the thin-strut Xience DES stent in stable patients undergoing coronary revascularization, according to a presentation at the 2020 CRT meeting.

Ted Bostworth/MDedge News

“These results direct our attention to strut thickness and polymer composition as key attributes for stent design,” reported David E. Kandzari, MD, director of interventional cardiology at the Piedmont Heart Institute in Atlanta.

In the multinational BIOFLOW V trial, 1,334 patients were randomized in a two-to-one ratio to the Orsiro stent, which is composed of a bioabsorbable, sirolimus-eluting polymer, or to the Xience stent, which is composed of an everolimus-eluting durable polymer. Relative to the Xience device, which has thin struts of 81 microns in width, the struts of the Orsiro device, at 60 microns in width, are characterized as ultrathin.

In earlier published follow-up studies, the ultrathin device demonstrated a lower rate of target lesion (TL) failure at 1 year (5.9% vs. 9.2%; P = .032) and at 2 years (7.1% vs. 11.1%; P = .015), but the 3-year data are notable because they indicate that the relative advantage is continuing to grow, according to Dr. Kandzari.

At 3 years, with follow-up available for 94.8% and 94.2% of the Orsiro and Xience groups, respectively, the absolute relative difference in the primary endpoint of TL failure reached 5.4% (8.2% vs. 13.6%; P = .002) in favor of the Orsiro device.

For the components of the composite TL failure endpoint, which includes cardiovascular death, TL-related myocardial infarction, and TL revascularization, there were large relative advantages for every outcome except cardiovascular death, which did not differ between the Orsiro and Xience groups (1.1% vs. 1.2%, respectively; P = .1). Conversely, the TL-related MI (5.5% vs. 10.1%; P = .004) and ischemia-driven TL revascularization (3.4% vs. 6.9%; P = .008) rates were nearly cut in half in the Orsiro arm.

“The benefit appears to be bimodal in that there is a significant advantage in the periprocedural period [for the Orsiro device] and then a late advantage,” Dr. Kandzari reported.

Most TL-related MI in both groups, for example, occurred within the first 30 days of follow-up. Although there was a relative advantage for the Orsiro device in this early period (4.1% vs. 6.7%; P = .04), Dr. Kandzari indicated that the advantage between 30 days and 3 years was even more impressive (0.95% vs. 2.8%; P = .012).

Dr. Kandzari, showing a graph in which the line representing Orsiro device hugged the x axis as the line for the Xience device climbed, emphasized that the rate of target vessel MI at the end of follow-up was nearly three times greater for those randomized to the Xience device.

The patterns of ischemia-driven TL revascularization also diverged. In this case, the rates over the first 360 days were very similar for the two devices initially. At 1 year, the lower rate in the Orsiro device was not significantly different (2.0% vs. 2.3%; P = .72), but the lines began to separate at about 18 months. By the end of 3 years, the rate of ischemia-related TL revascularization was nearly 70% lower in the Orsiro arm (1.5% vs. 4.7%; P < .001).

The Orsiro device was also linked with a lower rate of definite or probable stent thrombosis when the two devices were compared from 30 days post implantation to 3 years of follow-up (0.1% vs. 1.2%; P = .018).

Noting that there are several features of the Orsiro device that might explain these results, including the width of the struts, the biodegradable polymer, and the type of anti-inflammatory coating, Dr. Kandzari said that it is difficult to determine which attributes account for the overall or the specific advantages observed for the Orsiro device in the BIOFLOW V trial.

However, he hypothesized that “there might be different time lines for different benefits” related to individual device characteristics. For example, the ultrathin struts might be important for the early relative advantages while the biodegradation of the strut might explain the reduced need for revascularization.

Overall, “there is an emerging evidence base consistent across clinical trials demonstrating a potential efficacy and safety difference in favor of ultrathin struts,” according to Dr. Kandzari.

The data are “remarkable,” according to James B. Hermiller, MD, an interventional cardiologist at the Heart Center of Indiana in Indianapolis. A panel member for the CRT late-breaking trial session where these data were presented, Dr. Hermiller was impressed by the very low rate of revascularization in the extended follow-up.

“We have all wanted to see a flattening of these event curves after a year,” Dr. Hermiller said. He indicated that the BIOFLOW V data represent a departure from the need for revascularization and other late events so commonly seen over lengthening follow-up with earlier generation devices.

SOURCE: Kandzari DE. CRT 2020, Late Breaking Trials session S300.

For patients undergoing transcatheter aortic valve replacement, using a specific orientation at deployment may optimize valve alignment and potentially preserve coronary access, at least for some devices, results of a pilot imaging study suggest.

In particular, positioning the Evolut THV (Medtronic) at a certain way at deployment led to an improvement in commissural alignment and a significant reduction in coronary artery overlap, according to authors of the study, led by Gilbert H. L. Tang, MD, MSc, MBA, surgical director of the structural heart program at Mount Sinai Health System, and associate professor of cardiovascular surgery, Mount Sinai Medical Center, New York.

Likewise, a specific positioning of the commissural post at deployment appeared to improve alignment and reduce coronary overlap when using the ACURATE-neo (Boston Scientific), though results with this transcatheter heart valve need to be considered preliminary because of the smaller number of cases, Dr. Tang said in an interview.

By contrast, initial deployment orientation of the SAPIEN 3 (Edwards Lifesciences) did not seem to have an impact on final orientation or neocommissural overlap with arteries in this study by Dr. Tang and colleagues, which was published in JACC: Cardiovascular Interventions and had been planned for presentation at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Improved positioning may have important future implications for patients undergoing transcatheter aortic valve replacement (TAVR), particularly if they are younger and therefore perhaps more likely than older patients to undergo a procedure requiring coronary access at some point in the future, according to Dr. Tang.

“Right now, device design does not permit us to have consistent commissural alignment,” said Dr. Tang in the interview. “What this study shows is that, with modification of delivery catheter insertion technique, at least for the EVOLUT valve, we can improve commissural alignment and hypothetically speaking, improve the likelihood of coronary access.”

While the technique modifications described by Dr. Tang and colleagues are commendable, the overall impact on commissural alignment and coronary overlap are “modest” and do not solve the problem, according to Hasan Jilaihawi, MD, associate professor of medicine and cardiothoracic surgery at NYU Langone Health, New York.

Instead, the onus should be on the device manufacturers to develop solutions that allow for better alignment between their devices and patients’ commissures, said Dr. Jilaihawi.

“We need really industry to focus wholeheartedly on this,” Dr. Jilaihawi said in an interview. “I think they will, and there will be some discussions about focusing on [commissural alignment], but I think it’s coming really very late.”

Dr. Tang agreed on the need for increased focus on achieving commissural alignment. Of note, he said, there are newer transcatheter heart valves under study that may be more likely to achieve alignment and reduce the possibility of severe coronary overlap, including the JenaValve (JenaValve Technology) and the J-Valve (JC Medical).

“We hope that manufacturers can design valves that would improve commissural alignment for these patients, so that in 10 or even 20 years’ time, when these patients require reintervention, we won’t have to do surgery because the valves are not aligned,” said Dr. Tang. “Ideally, we might have to do one surgical intervention in their lifetime, but really what we are talking about now is the lifetime management of these patients as the coronary artery disease progresses, and also the aortic valve disease returns with the prosthetic valve.”

The pilot imaging study by Dr. Tang and colleagues included a total of 828 patients undergoing TAVR, including 483 treated with SAPIEN 3, 245 with Evolut, and 100 with ACURATE-neo.

To track deployment orientation, the SAPIEN 3 cases had a commissure crimped at 3, 6, 9, or 12 o’clock orientation relative to the delivery catheter. However, crimping orientation at initial deployment did not appear to have an impact on the final orientation, with overall incidence of severe coronary overlap of 36.6% for the left main coronary artery (LMCA), 23.6% for the right coronary artery (RCA), and 51.3% for one or both, according to the report.

For 107 cases treated with Evolut, the investigators sought to have a marker on the device (known as the “hat” marker) oriented to the outer curve of the descending aorta; to do that, they inserted the delivery catheter with the flush port at the 3 o’clock position. Those cases with the hat marker at the outer curve or the center front had improved commissural alignment as compared to those with the hat at the inner curve or center back, according to investigators. The incidence of coronary overlap with the LMCA was 15.7% for those with the hat at the outer curve or center front, compared to 66.0% for those with the hat at the inner curve or center back (P < .001), and the differences in coronary overlap were likewise significantly different in favor of the outer curve/center front for the RCA or both coronaries.

Finally, the incidence of coronary overlap with the ACURATE-neo was much lower when the commissural post at initial deployment was at the center back or inner curve, and in a few cases where the operators tried to torque the delivery catheter to position the commissural post to the inner curve, commissural alignment was achieved in about three-quarters of the patients (five of seven cases).

This is believed to be the first study to systematically characterize how the initial orientation of different transcatheter heart valves impact commissural alignment and coronary overlap, according to Dr. Tang and coinvestigators.

Dr. Jilaihawi, who was not involved in the study, said the investigators studied this phenomenon in a “very detailed, methodical fashion,” but emphasized the need for new device innovations to improve alignment and overlap.

“Their efforts weren’t completely in vain, but they really made a small difference in something that is too important to be [addressed] in a kind of ‘MacGyver’ approach to this problem,” he said in the interview.

Disclosures reported by Dr. Tang were related to Edwards Lifesciences (physician proctor) and Medtronic (physician proctor, consultant). Coauthors reported disclosures related to Edwards, Medtronic, and Boston Scientific, among others.

SOURCE: ACC 20. Tang GHL et al. JACC Cardiovasc Interv. 2020 Mar 16. doi: 10.1016/j.jcin.2020.02.005.

For patients undergoing transcatheter aortic valve replacement, using a specific orientation at deployment may optimize valve alignment and potentially preserve coronary access, at least for some devices, results of a pilot imaging study suggest.

In particular, positioning the Evolut THV (Medtronic) at a certain way at deployment led to an improvement in commissural alignment and a significant reduction in coronary artery overlap, according to authors of the study, led by Gilbert H. L. Tang, MD, MSc, MBA, surgical director of the structural heart program at Mount Sinai Health System, and associate professor of cardiovascular surgery, Mount Sinai Medical Center, New York.

Likewise, a specific positioning of the commissural post at deployment appeared to improve alignment and reduce coronary overlap when using the ACURATE-neo (Boston Scientific), though results with this transcatheter heart valve need to be considered preliminary because of the smaller number of cases, Dr. Tang said in an interview.

By contrast, initial deployment orientation of the SAPIEN 3 (Edwards Lifesciences) did not seem to have an impact on final orientation or neocommissural overlap with arteries in this study by Dr. Tang and colleagues, which was published in JACC: Cardiovascular Interventions and had been planned for presentation at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Improved positioning may have important future implications for patients undergoing transcatheter aortic valve replacement (TAVR), particularly if they are younger and therefore perhaps more likely than older patients to undergo a procedure requiring coronary access at some point in the future, according to Dr. Tang.

“Right now, device design does not permit us to have consistent commissural alignment,” said Dr. Tang in the interview. “What this study shows is that, with modification of delivery catheter insertion technique, at least for the EVOLUT valve, we can improve commissural alignment and hypothetically speaking, improve the likelihood of coronary access.”

While the technique modifications described by Dr. Tang and colleagues are commendable, the overall impact on commissural alignment and coronary overlap are “modest” and do not solve the problem, according to Hasan Jilaihawi, MD, associate professor of medicine and cardiothoracic surgery at NYU Langone Health, New York.

Instead, the onus should be on the device manufacturers to develop solutions that allow for better alignment between their devices and patients’ commissures, said Dr. Jilaihawi.

“We need really industry to focus wholeheartedly on this,” Dr. Jilaihawi said in an interview. “I think they will, and there will be some discussions about focusing on [commissural alignment], but I think it’s coming really very late.”

Dr. Tang agreed on the need for increased focus on achieving commissural alignment. Of note, he said, there are newer transcatheter heart valves under study that may be more likely to achieve alignment and reduce the possibility of severe coronary overlap, including the JenaValve (JenaValve Technology) and the J-Valve (JC Medical).

“We hope that manufacturers can design valves that would improve commissural alignment for these patients, so that in 10 or even 20 years’ time, when these patients require reintervention, we won’t have to do surgery because the valves are not aligned,” said Dr. Tang. “Ideally, we might have to do one surgical intervention in their lifetime, but really what we are talking about now is the lifetime management of these patients as the coronary artery disease progresses, and also the aortic valve disease returns with the prosthetic valve.”

The pilot imaging study by Dr. Tang and colleagues included a total of 828 patients undergoing TAVR, including 483 treated with SAPIEN 3, 245 with Evolut, and 100 with ACURATE-neo.

To track deployment orientation, the SAPIEN 3 cases had a commissure crimped at 3, 6, 9, or 12 o’clock orientation relative to the delivery catheter. However, crimping orientation at initial deployment did not appear to have an impact on the final orientation, with overall incidence of severe coronary overlap of 36.6% for the left main coronary artery (LMCA), 23.6% for the right coronary artery (RCA), and 51.3% for one or both, according to the report.

For 107 cases treated with Evolut, the investigators sought to have a marker on the device (known as the “hat” marker) oriented to the outer curve of the descending aorta; to do that, they inserted the delivery catheter with the flush port at the 3 o’clock position. Those cases with the hat marker at the outer curve or the center front had improved commissural alignment as compared to those with the hat at the inner curve or center back, according to investigators. The incidence of coronary overlap with the LMCA was 15.7% for those with the hat at the outer curve or center front, compared to 66.0% for those with the hat at the inner curve or center back (P < .001), and the differences in coronary overlap were likewise significantly different in favor of the outer curve/center front for the RCA or both coronaries.

Finally, the incidence of coronary overlap with the ACURATE-neo was much lower when the commissural post at initial deployment was at the center back or inner curve, and in a few cases where the operators tried to torque the delivery catheter to position the commissural post to the inner curve, commissural alignment was achieved in about three-quarters of the patients (five of seven cases).

This is believed to be the first study to systematically characterize how the initial orientation of different transcatheter heart valves impact commissural alignment and coronary overlap, according to Dr. Tang and coinvestigators.

Dr. Jilaihawi, who was not involved in the study, said the investigators studied this phenomenon in a “very detailed, methodical fashion,” but emphasized the need for new device innovations to improve alignment and overlap.

“Their efforts weren’t completely in vain, but they really made a small difference in something that is too important to be [addressed] in a kind of ‘MacGyver’ approach to this problem,” he said in the interview.

Disclosures reported by Dr. Tang were related to Edwards Lifesciences (physician proctor) and Medtronic (physician proctor, consultant). Coauthors reported disclosures related to Edwards, Medtronic, and Boston Scientific, among others.

SOURCE: ACC 20. Tang GHL et al. JACC Cardiovasc Interv. 2020 Mar 16. doi: 10.1016/j.jcin.2020.02.005.

For patients undergoing transcatheter aortic valve replacement, using a specific orientation at deployment may optimize valve alignment and potentially preserve coronary access, at least for some devices, results of a pilot imaging study suggest.

In particular, positioning the Evolut THV (Medtronic) at a certain way at deployment led to an improvement in commissural alignment and a significant reduction in coronary artery overlap, according to authors of the study, led by Gilbert H. L. Tang, MD, MSc, MBA, surgical director of the structural heart program at Mount Sinai Health System, and associate professor of cardiovascular surgery, Mount Sinai Medical Center, New York.

Likewise, a specific positioning of the commissural post at deployment appeared to improve alignment and reduce coronary overlap when using the ACURATE-neo (Boston Scientific), though results with this transcatheter heart valve need to be considered preliminary because of the smaller number of cases, Dr. Tang said in an interview.

By contrast, initial deployment orientation of the SAPIEN 3 (Edwards Lifesciences) did not seem to have an impact on final orientation or neocommissural overlap with arteries in this study by Dr. Tang and colleagues, which was published in JACC: Cardiovascular Interventions and had been planned for presentation at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Improved positioning may have important future implications for patients undergoing transcatheter aortic valve replacement (TAVR), particularly if they are younger and therefore perhaps more likely than older patients to undergo a procedure requiring coronary access at some point in the future, according to Dr. Tang.

“Right now, device design does not permit us to have consistent commissural alignment,” said Dr. Tang in the interview. “What this study shows is that, with modification of delivery catheter insertion technique, at least for the EVOLUT valve, we can improve commissural alignment and hypothetically speaking, improve the likelihood of coronary access.”

While the technique modifications described by Dr. Tang and colleagues are commendable, the overall impact on commissural alignment and coronary overlap are “modest” and do not solve the problem, according to Hasan Jilaihawi, MD, associate professor of medicine and cardiothoracic surgery at NYU Langone Health, New York.

Instead, the onus should be on the device manufacturers to develop solutions that allow for better alignment between their devices and patients’ commissures, said Dr. Jilaihawi.

“We need really industry to focus wholeheartedly on this,” Dr. Jilaihawi said in an interview. “I think they will, and there will be some discussions about focusing on [commissural alignment], but I think it’s coming really very late.”

Dr. Tang agreed on the need for increased focus on achieving commissural alignment. Of note, he said, there are newer transcatheter heart valves under study that may be more likely to achieve alignment and reduce the possibility of severe coronary overlap, including the JenaValve (JenaValve Technology) and the J-Valve (JC Medical).

“We hope that manufacturers can design valves that would improve commissural alignment for these patients, so that in 10 or even 20 years’ time, when these patients require reintervention, we won’t have to do surgery because the valves are not aligned,” said Dr. Tang. “Ideally, we might have to do one surgical intervention in their lifetime, but really what we are talking about now is the lifetime management of these patients as the coronary artery disease progresses, and also the aortic valve disease returns with the prosthetic valve.”

The pilot imaging study by Dr. Tang and colleagues included a total of 828 patients undergoing TAVR, including 483 treated with SAPIEN 3, 245 with Evolut, and 100 with ACURATE-neo.

To track deployment orientation, the SAPIEN 3 cases had a commissure crimped at 3, 6, 9, or 12 o’clock orientation relative to the delivery catheter. However, crimping orientation at initial deployment did not appear to have an impact on the final orientation, with overall incidence of severe coronary overlap of 36.6% for the left main coronary artery (LMCA), 23.6% for the right coronary artery (RCA), and 51.3% for one or both, according to the report.

For 107 cases treated with Evolut, the investigators sought to have a marker on the device (known as the “hat” marker) oriented to the outer curve of the descending aorta; to do that, they inserted the delivery catheter with the flush port at the 3 o’clock position. Those cases with the hat marker at the outer curve or the center front had improved commissural alignment as compared to those with the hat at the inner curve or center back, according to investigators. The incidence of coronary overlap with the LMCA was 15.7% for those with the hat at the outer curve or center front, compared to 66.0% for those with the hat at the inner curve or center back (P < .001), and the differences in coronary overlap were likewise significantly different in favor of the outer curve/center front for the RCA or both coronaries.

Finally, the incidence of coronary overlap with the ACURATE-neo was much lower when the commissural post at initial deployment was at the center back or inner curve, and in a few cases where the operators tried to torque the delivery catheter to position the commissural post to the inner curve, commissural alignment was achieved in about three-quarters of the patients (five of seven cases).

This is believed to be the first study to systematically characterize how the initial orientation of different transcatheter heart valves impact commissural alignment and coronary overlap, according to Dr. Tang and coinvestigators.

Dr. Jilaihawi, who was not involved in the study, said the investigators studied this phenomenon in a “very detailed, methodical fashion,” but emphasized the need for new device innovations to improve alignment and overlap.

“Their efforts weren’t completely in vain, but they really made a small difference in something that is too important to be [addressed] in a kind of ‘MacGyver’ approach to this problem,” he said in the interview.

Disclosures reported by Dr. Tang were related to Edwards Lifesciences (physician proctor) and Medtronic (physician proctor, consultant). Coauthors reported disclosures related to Edwards, Medtronic, and Boston Scientific, among others.

SOURCE: ACC 20. Tang GHL et al. JACC Cardiovasc Interv. 2020 Mar 16. doi: 10.1016/j.jcin.2020.02.005.