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ESC’s new lipid guidelines keep LDL-cholesterol targets
ROME – LDL cholesterol treatment targets remain alive and well in non-U.S. lipid management guidelines.
New dyslipidemia management guidelines from the European Society of Cardiology, issued in late August, retain the same LDL cholesterol targets as the prior, 2011 guidelines, a sharp and purposeful departure from the “risk-based” U.S. guidelines introduced in 2013 that eliminated treating patients to specific LDL cholesterol targets.
The new ESC guidelines also incorporated the new class of lipid-lowering drugs, PCSK9 inhibitors (evolocumab [Repatha] and alirocumab [Praluent]), into the treatment algorithm, and carved out a role for ezetimibe (Zetia) following its proven success as an add-on agent to statins (Eur Heart J. 2016. doi: 10.1093/eurheartj/ehw272).
But it’s retention of LDL cholesterol targets as a cornerstone of dyslipidemia management in the new ESC report, written jointly with the European Atherosclerosis Society, that especially distinguishes the new guidelines.
“It seemed to us logical that if you have drugs [statins] that lower LDL cholesterol, then you target LDL cholesterol,” explained Ian M. Graham, MD, professor of cardiovascular medicine at Trinity College in Dublin and cochair of the guidelines panel. “If a patient’s risk is high, they still need to lower LDL cholesterol. It’s not really contradictory to the U.S. approach,” Dr. Graham said in an interview.
The ESC panel’s discussions about the LDL cholesterol targets were “difficult and long,” said Guy De Backer, MD, a member of the guidelines committee and professor of cardiology at the University of Ghent, Belgium, in a session devoted to the new guidelines during the annual congress of the ESC.
The ESC’s decision to retain the 2011 LDL cholesterol targets won praise from U.S. cardiologist Eugene Braunwald, MD. “I think that not measuring and following LDL cholesterol is silly. I don’t agree” with current U.S. guidelines, he said in a talk during the congress. “If you don’t follow LDL cholesterol then you don’t know a patient’s compliance.
Regularly measuring LDL cholesterol is important,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston. But he questioned the LDL cholesterol targets set by the ESC panel, specifically the LDL cholesterol goal of less than 70 mg/dL for very-high-risk patients.
“I don’t think the ESC went low enough; the goal should be less than 50 mg/dL,” declared Dr. Braunwald, who added “anything above 50 mg/dL is toxic.”
The new guidelines also made the definition of “very-high-risk” patients “stricter and more precise,” said Alberico L. Catapano, MD, cochair of the panel and professor of pharmacology at the University of Milan.
The guideline’s detailed list defining very-high-risk patients includes those with either clinical or “unequivocal” imaging evidence for cardiovascular disease, as well as patients with diabetes and target-organ damage, severe chronic kidney disease, or a 10% or greater 10-year risk for fatal cardiovascular disease calculated by the European Score risk formula.
The potent lipid-lowering PCSK9 inhibitors came onto the U.S. and European markets in 2015, labeled in the United States specifically for patients with familial hypercholesterolemia.
In July 2016, an American College of Cardiology Task Force issued a model clinical-decision pathway for lowering LDL cholesterol levels that for the first time included the PCSK9 inhibitors, specified as a “may be considered” option for selected patients (J Am Coll Cardiol. 2016 Jul;68[1]:92-125). This consensus decision pathway was not a set of actual guidelines, which means the ESC revision is the first guideline to include the PCSK9 inhibitors. The panel took the same stance as the U.S. decision pathway and designated the PCSK9 inhibitors as a “may be considered” option.
Dr. Graham explained that this designation was driven by the current absence of evidence for clinical benefit from the large lipid-lowering effect of the PCSK9 antibodies, although trial results that address this are expected to appear very soon. Experts not on the guidelines panel agreed with this decision.
“We know that it’s crucial to await results from the clinical endpoint studies” before the guidelines committee makes a more forceful recommendation, commented Erik S.G. Stroes, MD, professor of vascular medicine at the Academic Medical Center in Amsterdam. He added, however, that many clinicians, himself included, have been pleased to offer PCSK9-inhibitor treatment to very-high-risk patients with no good alternatives for effectively lowering their LDL cholesterol to target levels, such as statin-intolerant patients or those with LDL cholesterol levels that remain high despite maximal therapy.
The current ESC guideline’s statement on when to use a PCSK9 inhibitor “is vague” said Dr. Braunwald. “Within the next year, we’ll have results from two huge trials that will show clinical outcomes. We know that PCSK9 inhibitors are extremely powerful at lowering LDL cholesterol, but I would like to see the loop closed” with proven effects on clinical outcomes. “I would bet 100 to 1 that they will be effective, but LDL cholesterol is just a surrogate marker, and you need to look in large populations before you make a guideline recommendation to use these drugs, so we’ll wait.”
Once the clinical value of treatment with PCSK9 inhibitors is settled, the next issue will be the cost of these drugs, something that will become a big consideration once they become more widely used, Dr. Braunwald added.
Dr. De Backer and Dr. Graham had no disclosures. Dr. Catapano has been a consultant to Aegerion, Amgen, AstraZeneca, Merck, Pfizer, and Sigma-Tau. Dr. Braunwald has been a consultant to Bayer, Daiichi Sankyo, the Medicines Company, Merck, Novartis, and Sanofi. Dr. Stroes has been a consultant to Amgen, Bristol-Myers Squibb, Merck, and Sanofi.
On Twitter @mitchelzoler
ROME – LDL cholesterol treatment targets remain alive and well in non-U.S. lipid management guidelines.
New dyslipidemia management guidelines from the European Society of Cardiology, issued in late August, retain the same LDL cholesterol targets as the prior, 2011 guidelines, a sharp and purposeful departure from the “risk-based” U.S. guidelines introduced in 2013 that eliminated treating patients to specific LDL cholesterol targets.
The new ESC guidelines also incorporated the new class of lipid-lowering drugs, PCSK9 inhibitors (evolocumab [Repatha] and alirocumab [Praluent]), into the treatment algorithm, and carved out a role for ezetimibe (Zetia) following its proven success as an add-on agent to statins (Eur Heart J. 2016. doi: 10.1093/eurheartj/ehw272).
But it’s retention of LDL cholesterol targets as a cornerstone of dyslipidemia management in the new ESC report, written jointly with the European Atherosclerosis Society, that especially distinguishes the new guidelines.
“It seemed to us logical that if you have drugs [statins] that lower LDL cholesterol, then you target LDL cholesterol,” explained Ian M. Graham, MD, professor of cardiovascular medicine at Trinity College in Dublin and cochair of the guidelines panel. “If a patient’s risk is high, they still need to lower LDL cholesterol. It’s not really contradictory to the U.S. approach,” Dr. Graham said in an interview.
The ESC panel’s discussions about the LDL cholesterol targets were “difficult and long,” said Guy De Backer, MD, a member of the guidelines committee and professor of cardiology at the University of Ghent, Belgium, in a session devoted to the new guidelines during the annual congress of the ESC.
The ESC’s decision to retain the 2011 LDL cholesterol targets won praise from U.S. cardiologist Eugene Braunwald, MD. “I think that not measuring and following LDL cholesterol is silly. I don’t agree” with current U.S. guidelines, he said in a talk during the congress. “If you don’t follow LDL cholesterol then you don’t know a patient’s compliance.
Regularly measuring LDL cholesterol is important,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston. But he questioned the LDL cholesterol targets set by the ESC panel, specifically the LDL cholesterol goal of less than 70 mg/dL for very-high-risk patients.
“I don’t think the ESC went low enough; the goal should be less than 50 mg/dL,” declared Dr. Braunwald, who added “anything above 50 mg/dL is toxic.”
The new guidelines also made the definition of “very-high-risk” patients “stricter and more precise,” said Alberico L. Catapano, MD, cochair of the panel and professor of pharmacology at the University of Milan.
The guideline’s detailed list defining very-high-risk patients includes those with either clinical or “unequivocal” imaging evidence for cardiovascular disease, as well as patients with diabetes and target-organ damage, severe chronic kidney disease, or a 10% or greater 10-year risk for fatal cardiovascular disease calculated by the European Score risk formula.
The potent lipid-lowering PCSK9 inhibitors came onto the U.S. and European markets in 2015, labeled in the United States specifically for patients with familial hypercholesterolemia.
In July 2016, an American College of Cardiology Task Force issued a model clinical-decision pathway for lowering LDL cholesterol levels that for the first time included the PCSK9 inhibitors, specified as a “may be considered” option for selected patients (J Am Coll Cardiol. 2016 Jul;68[1]:92-125). This consensus decision pathway was not a set of actual guidelines, which means the ESC revision is the first guideline to include the PCSK9 inhibitors. The panel took the same stance as the U.S. decision pathway and designated the PCSK9 inhibitors as a “may be considered” option.
Dr. Graham explained that this designation was driven by the current absence of evidence for clinical benefit from the large lipid-lowering effect of the PCSK9 antibodies, although trial results that address this are expected to appear very soon. Experts not on the guidelines panel agreed with this decision.
“We know that it’s crucial to await results from the clinical endpoint studies” before the guidelines committee makes a more forceful recommendation, commented Erik S.G. Stroes, MD, professor of vascular medicine at the Academic Medical Center in Amsterdam. He added, however, that many clinicians, himself included, have been pleased to offer PCSK9-inhibitor treatment to very-high-risk patients with no good alternatives for effectively lowering their LDL cholesterol to target levels, such as statin-intolerant patients or those with LDL cholesterol levels that remain high despite maximal therapy.
The current ESC guideline’s statement on when to use a PCSK9 inhibitor “is vague” said Dr. Braunwald. “Within the next year, we’ll have results from two huge trials that will show clinical outcomes. We know that PCSK9 inhibitors are extremely powerful at lowering LDL cholesterol, but I would like to see the loop closed” with proven effects on clinical outcomes. “I would bet 100 to 1 that they will be effective, but LDL cholesterol is just a surrogate marker, and you need to look in large populations before you make a guideline recommendation to use these drugs, so we’ll wait.”
Once the clinical value of treatment with PCSK9 inhibitors is settled, the next issue will be the cost of these drugs, something that will become a big consideration once they become more widely used, Dr. Braunwald added.
Dr. De Backer and Dr. Graham had no disclosures. Dr. Catapano has been a consultant to Aegerion, Amgen, AstraZeneca, Merck, Pfizer, and Sigma-Tau. Dr. Braunwald has been a consultant to Bayer, Daiichi Sankyo, the Medicines Company, Merck, Novartis, and Sanofi. Dr. Stroes has been a consultant to Amgen, Bristol-Myers Squibb, Merck, and Sanofi.
On Twitter @mitchelzoler
ROME – LDL cholesterol treatment targets remain alive and well in non-U.S. lipid management guidelines.
New dyslipidemia management guidelines from the European Society of Cardiology, issued in late August, retain the same LDL cholesterol targets as the prior, 2011 guidelines, a sharp and purposeful departure from the “risk-based” U.S. guidelines introduced in 2013 that eliminated treating patients to specific LDL cholesterol targets.
The new ESC guidelines also incorporated the new class of lipid-lowering drugs, PCSK9 inhibitors (evolocumab [Repatha] and alirocumab [Praluent]), into the treatment algorithm, and carved out a role for ezetimibe (Zetia) following its proven success as an add-on agent to statins (Eur Heart J. 2016. doi: 10.1093/eurheartj/ehw272).
But it’s retention of LDL cholesterol targets as a cornerstone of dyslipidemia management in the new ESC report, written jointly with the European Atherosclerosis Society, that especially distinguishes the new guidelines.
“It seemed to us logical that if you have drugs [statins] that lower LDL cholesterol, then you target LDL cholesterol,” explained Ian M. Graham, MD, professor of cardiovascular medicine at Trinity College in Dublin and cochair of the guidelines panel. “If a patient’s risk is high, they still need to lower LDL cholesterol. It’s not really contradictory to the U.S. approach,” Dr. Graham said in an interview.
The ESC panel’s discussions about the LDL cholesterol targets were “difficult and long,” said Guy De Backer, MD, a member of the guidelines committee and professor of cardiology at the University of Ghent, Belgium, in a session devoted to the new guidelines during the annual congress of the ESC.
The ESC’s decision to retain the 2011 LDL cholesterol targets won praise from U.S. cardiologist Eugene Braunwald, MD. “I think that not measuring and following LDL cholesterol is silly. I don’t agree” with current U.S. guidelines, he said in a talk during the congress. “If you don’t follow LDL cholesterol then you don’t know a patient’s compliance.
Regularly measuring LDL cholesterol is important,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston. But he questioned the LDL cholesterol targets set by the ESC panel, specifically the LDL cholesterol goal of less than 70 mg/dL for very-high-risk patients.
“I don’t think the ESC went low enough; the goal should be less than 50 mg/dL,” declared Dr. Braunwald, who added “anything above 50 mg/dL is toxic.”
The new guidelines also made the definition of “very-high-risk” patients “stricter and more precise,” said Alberico L. Catapano, MD, cochair of the panel and professor of pharmacology at the University of Milan.
The guideline’s detailed list defining very-high-risk patients includes those with either clinical or “unequivocal” imaging evidence for cardiovascular disease, as well as patients with diabetes and target-organ damage, severe chronic kidney disease, or a 10% or greater 10-year risk for fatal cardiovascular disease calculated by the European Score risk formula.
The potent lipid-lowering PCSK9 inhibitors came onto the U.S. and European markets in 2015, labeled in the United States specifically for patients with familial hypercholesterolemia.
In July 2016, an American College of Cardiology Task Force issued a model clinical-decision pathway for lowering LDL cholesterol levels that for the first time included the PCSK9 inhibitors, specified as a “may be considered” option for selected patients (J Am Coll Cardiol. 2016 Jul;68[1]:92-125). This consensus decision pathway was not a set of actual guidelines, which means the ESC revision is the first guideline to include the PCSK9 inhibitors. The panel took the same stance as the U.S. decision pathway and designated the PCSK9 inhibitors as a “may be considered” option.
Dr. Graham explained that this designation was driven by the current absence of evidence for clinical benefit from the large lipid-lowering effect of the PCSK9 antibodies, although trial results that address this are expected to appear very soon. Experts not on the guidelines panel agreed with this decision.
“We know that it’s crucial to await results from the clinical endpoint studies” before the guidelines committee makes a more forceful recommendation, commented Erik S.G. Stroes, MD, professor of vascular medicine at the Academic Medical Center in Amsterdam. He added, however, that many clinicians, himself included, have been pleased to offer PCSK9-inhibitor treatment to very-high-risk patients with no good alternatives for effectively lowering their LDL cholesterol to target levels, such as statin-intolerant patients or those with LDL cholesterol levels that remain high despite maximal therapy.
The current ESC guideline’s statement on when to use a PCSK9 inhibitor “is vague” said Dr. Braunwald. “Within the next year, we’ll have results from two huge trials that will show clinical outcomes. We know that PCSK9 inhibitors are extremely powerful at lowering LDL cholesterol, but I would like to see the loop closed” with proven effects on clinical outcomes. “I would bet 100 to 1 that they will be effective, but LDL cholesterol is just a surrogate marker, and you need to look in large populations before you make a guideline recommendation to use these drugs, so we’ll wait.”
Once the clinical value of treatment with PCSK9 inhibitors is settled, the next issue will be the cost of these drugs, something that will become a big consideration once they become more widely used, Dr. Braunwald added.
Dr. De Backer and Dr. Graham had no disclosures. Dr. Catapano has been a consultant to Aegerion, Amgen, AstraZeneca, Merck, Pfizer, and Sigma-Tau. Dr. Braunwald has been a consultant to Bayer, Daiichi Sankyo, the Medicines Company, Merck, Novartis, and Sanofi. Dr. Stroes has been a consultant to Amgen, Bristol-Myers Squibb, Merck, and Sanofi.
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE ESC CONGRESS 2016
Simtuzumab did not help IPF patients
LONDON – Despite very promising activity in animal models of idiopathic pulmonary fibrosis (IPF), a monoclonal antibody targeted at an enzyme considered to be important to collagen cross-linking did not produce any improvement in progression-free survival (PFS), according to results of a multicenter study presented at the annual congress of the European Respiratory Society.
“This was such a negative study, there is no point in doing another,” reported Ganesh Raghu, MD, director of the Pulmonary Fibrosis Program at the University of Washington Medical Center, Seattle.
The focus of this study was simtuzumab, a monoclonal antibody targeted at lysyl oxidase like 2 (LOXL2), an enzyme which catalyzes a step in the formation of collagen crosslinks, which are thought to be important in fibrosis formation. Simtuzumab has been entered into clinical trials for treatment of several forms of fibrosis, including fibrosis in the liver.
“In animal models, simtuzumab has demonstrated efficacy in reducing fibrosis when administered prior to fibrosis formation or after the process has already begun,” Dr. Raghu explained. He said a large trial was initiated in IPF because the agent seemed so promising and because a large study was thought to be the best strategy to arrive at a definitive answer regarding safety and efficacy.
The drug was found safe but not effective. The independent data monitoring and safety committee terminated the trial early for futility.
In the study, 544 IPF patients were randomized to 125 mg simtuzumab or placebo administered subcutaneously once weekly. The primary endpoint was PFS, but there were a large number of secondary endpoints including hospitalization for progressive disease, change in 6-minute walk distance (6MWD), and overall survival.
For the endpoint of PFS, “there was absolutely no difference” between the groups receiving simtuzumab or placebo. When the patients were stratified for demonstrating above or below median expression of LOXL2, which was a prespecified analysis for the trial, there was still no difference between groups. Even when those in the top quarter percentile of LOXL2 expression were compared with those with less [expression of the enzyme], there was still “absolutely no difference.”
There was also no significant evidence of benefit for simtuzumab observed on key secondary endpoints, such as overall survival. When patients were stratified by baseline lung function as expressed by percentage of predicted forced expiratory volume in 1 second (FEV1), there was no signal of benefit for those with severe, moderate, or mild impairment.
One criticism of this study raised after the presentation was that patients with 26% or greater of predicted FEV1 were permitted into the study. It was suggested that such patients would be expected to already have a high degree of fibrosis and therefore would be less likely to benefit from an antifibrosis therapy. Dr. Raghu acknowledged this criticism, but he said it was important to include patients with advanced disease in order to generate an adequate event rate. Even with inclusion of patients with severe lung impairment, the mortality rate was less than 10%.
He concluded that there was no signal of benefit even among those with the greatest expression of the target.
“We absolutely need better markers for IPF,” Dr. Raghu maintained. While other members of the LOXL family of enzymes may still prove to be valuable markers of IPF risk and targets of therapy, these data appear to rule out a therapeutic role for blocking LOXL2.
Dr. Raghu is a consultant for Boehringer Ingelheim, Biogen, FibroGen, Gilead, Janssen, MedImmune, Promedior, Sanofi-Aventis, and Veracyte.
LONDON – Despite very promising activity in animal models of idiopathic pulmonary fibrosis (IPF), a monoclonal antibody targeted at an enzyme considered to be important to collagen cross-linking did not produce any improvement in progression-free survival (PFS), according to results of a multicenter study presented at the annual congress of the European Respiratory Society.
“This was such a negative study, there is no point in doing another,” reported Ganesh Raghu, MD, director of the Pulmonary Fibrosis Program at the University of Washington Medical Center, Seattle.
The focus of this study was simtuzumab, a monoclonal antibody targeted at lysyl oxidase like 2 (LOXL2), an enzyme which catalyzes a step in the formation of collagen crosslinks, which are thought to be important in fibrosis formation. Simtuzumab has been entered into clinical trials for treatment of several forms of fibrosis, including fibrosis in the liver.
“In animal models, simtuzumab has demonstrated efficacy in reducing fibrosis when administered prior to fibrosis formation or after the process has already begun,” Dr. Raghu explained. He said a large trial was initiated in IPF because the agent seemed so promising and because a large study was thought to be the best strategy to arrive at a definitive answer regarding safety and efficacy.
The drug was found safe but not effective. The independent data monitoring and safety committee terminated the trial early for futility.
In the study, 544 IPF patients were randomized to 125 mg simtuzumab or placebo administered subcutaneously once weekly. The primary endpoint was PFS, but there were a large number of secondary endpoints including hospitalization for progressive disease, change in 6-minute walk distance (6MWD), and overall survival.
For the endpoint of PFS, “there was absolutely no difference” between the groups receiving simtuzumab or placebo. When the patients were stratified for demonstrating above or below median expression of LOXL2, which was a prespecified analysis for the trial, there was still no difference between groups. Even when those in the top quarter percentile of LOXL2 expression were compared with those with less [expression of the enzyme], there was still “absolutely no difference.”
There was also no significant evidence of benefit for simtuzumab observed on key secondary endpoints, such as overall survival. When patients were stratified by baseline lung function as expressed by percentage of predicted forced expiratory volume in 1 second (FEV1), there was no signal of benefit for those with severe, moderate, or mild impairment.
One criticism of this study raised after the presentation was that patients with 26% or greater of predicted FEV1 were permitted into the study. It was suggested that such patients would be expected to already have a high degree of fibrosis and therefore would be less likely to benefit from an antifibrosis therapy. Dr. Raghu acknowledged this criticism, but he said it was important to include patients with advanced disease in order to generate an adequate event rate. Even with inclusion of patients with severe lung impairment, the mortality rate was less than 10%.
He concluded that there was no signal of benefit even among those with the greatest expression of the target.
“We absolutely need better markers for IPF,” Dr. Raghu maintained. While other members of the LOXL family of enzymes may still prove to be valuable markers of IPF risk and targets of therapy, these data appear to rule out a therapeutic role for blocking LOXL2.
Dr. Raghu is a consultant for Boehringer Ingelheim, Biogen, FibroGen, Gilead, Janssen, MedImmune, Promedior, Sanofi-Aventis, and Veracyte.
LONDON – Despite very promising activity in animal models of idiopathic pulmonary fibrosis (IPF), a monoclonal antibody targeted at an enzyme considered to be important to collagen cross-linking did not produce any improvement in progression-free survival (PFS), according to results of a multicenter study presented at the annual congress of the European Respiratory Society.
“This was such a negative study, there is no point in doing another,” reported Ganesh Raghu, MD, director of the Pulmonary Fibrosis Program at the University of Washington Medical Center, Seattle.
The focus of this study was simtuzumab, a monoclonal antibody targeted at lysyl oxidase like 2 (LOXL2), an enzyme which catalyzes a step in the formation of collagen crosslinks, which are thought to be important in fibrosis formation. Simtuzumab has been entered into clinical trials for treatment of several forms of fibrosis, including fibrosis in the liver.
“In animal models, simtuzumab has demonstrated efficacy in reducing fibrosis when administered prior to fibrosis formation or after the process has already begun,” Dr. Raghu explained. He said a large trial was initiated in IPF because the agent seemed so promising and because a large study was thought to be the best strategy to arrive at a definitive answer regarding safety and efficacy.
The drug was found safe but not effective. The independent data monitoring and safety committee terminated the trial early for futility.
In the study, 544 IPF patients were randomized to 125 mg simtuzumab or placebo administered subcutaneously once weekly. The primary endpoint was PFS, but there were a large number of secondary endpoints including hospitalization for progressive disease, change in 6-minute walk distance (6MWD), and overall survival.
For the endpoint of PFS, “there was absolutely no difference” between the groups receiving simtuzumab or placebo. When the patients were stratified for demonstrating above or below median expression of LOXL2, which was a prespecified analysis for the trial, there was still no difference between groups. Even when those in the top quarter percentile of LOXL2 expression were compared with those with less [expression of the enzyme], there was still “absolutely no difference.”
There was also no significant evidence of benefit for simtuzumab observed on key secondary endpoints, such as overall survival. When patients were stratified by baseline lung function as expressed by percentage of predicted forced expiratory volume in 1 second (FEV1), there was no signal of benefit for those with severe, moderate, or mild impairment.
One criticism of this study raised after the presentation was that patients with 26% or greater of predicted FEV1 were permitted into the study. It was suggested that such patients would be expected to already have a high degree of fibrosis and therefore would be less likely to benefit from an antifibrosis therapy. Dr. Raghu acknowledged this criticism, but he said it was important to include patients with advanced disease in order to generate an adequate event rate. Even with inclusion of patients with severe lung impairment, the mortality rate was less than 10%.
He concluded that there was no signal of benefit even among those with the greatest expression of the target.
“We absolutely need better markers for IPF,” Dr. Raghu maintained. While other members of the LOXL family of enzymes may still prove to be valuable markers of IPF risk and targets of therapy, these data appear to rule out a therapeutic role for blocking LOXL2.
Dr. Raghu is a consultant for Boehringer Ingelheim, Biogen, FibroGen, Gilead, Janssen, MedImmune, Promedior, Sanofi-Aventis, and Veracyte.
AT THE ERS CONGRESS 2016
Key clinical point: A large multicenter trial with simtuzumab in idiopathic pulmonary fibrosis failed to generate a hint of benefit.
Major finding: In this study, efficacy was not seen even in those with high expression of the simtuzumab target, lysyl oxidase like 2 (LOXL2).
Data source: Phase II multicenter, placebo-controlled trial.
Disclosures: Dr. Raghu is a consultant for Boehringer Ingelheim, Biogen, FibroGen, Gilead, Janssen, MedImmune, Promedior, Sanofi-Aventis, and Veracyte.
More TOPCAT flaws back spironolactone’s HFpEF efficacy
ORLANDO – Spironolactone inched a little closer toward becoming the first and only agent with proven efficacy for treating patients with heart failure with preserved ejection fraction based on further evidence for the drug’s efficacy in a subgroup of patients enrolled in the TOPCAT trial.
In 2014, the initial TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) report showed that spironolactone treatment of patients with heart failure with preserved ejection fraction (HFpEF) for 3 years produced a small, 11% relative reduction in the primary risk endpoint, compared with placebo that was not statistically significant (N Engl J Med. 2014 Apr 10;370[15]:1383-92).
But a follow-up post hoc analysis a year later showed evidence that the roughly half of patients in TOPCAT enrolled at centers in Russia and the Republic of Georgia may not have had HFpEF and also may not have received the planned dosage of spironolactone (Circulation. 2015 Jan 6;131[1]:34-42). An analysis that focused only on the 1,767 HFpEF patients (51% of the total TOPCAT cohort) enrolled in the Americas (United States, Canada, Argentina, and Brazil) showed that, compared with placebo, treatment with spironolactone cut the combined rate of cardiovascular death, nonfatal cardiac arrest, and heart failure hospitalization by 4.5 percentage points, an 18% relative risk reduction that was statistically significant. In the Americas, spironolactone also cut cardiovascular death alone by a relative 26%, and reduced heart failure hospitalization by a relative 18%, both statistically significant.
Additional analysis reported at the annual scientific meeting of the Heart Failure Society of America further supported the idea that many TOPCAT patients enrolled in Russia did not receive a physiologically meaningful dosage of spironolactone. Among 66 Russian patients randomized to the spironolactone arm who reported taking their drug as prescribed and who participated in a random draw of blood specimens 1 year into the study, 20 (30%) failed to show detectable blood levels of canrenone, a characteristic spironolactone metabolite, reported Eileen O’Meara, MD, at the meeting. In contrast, 2 (3%) of 76 enrolled U.S. patients failed to show detectable blood levels of the canrenone metabolite, a 10-fold difference said Dr. O’Meara, a cardiologist at the Montreal Heart Institute.The tested U.S. patients also showed a clear dose-response relationship between their reported spironolactone dosage and their canrenone levels, something not seen in the Russian patients. These new findings, plus the evidence cited in the 2015 analysis, create a compelling case that “actual use of spironolactone in Russia was lower than reported” by the trial participants in Russia and probably in Georgia as well, Dr. O’Meara said. The implication is that spironolactone’s real impact on HFpEF patients is best represented in the 51% of TOPCAT patients from the Americas, she added.
“We believe these findings emphasize the reliability of the Americas data,” said Marc A. Pfeffer, MD, a coinvestigator for TOPCAT and lead author of the 2015 post hoc analysis. “Until someone comes up with a better treatment for patients with HFpEF, we should pay attention to this. People need to get this message. And spironolactone costs 7 cents a day,” said Dr. Pfeffer, professor of medicine at Harvard Medical School in Boston.Currently, no agent is considered proven effective for improving outcomes in HFpEF patients. The 2016 guidelinesfor heart failure treatment from the European Society of Cardiology said “no treatment has yet been shown, convincingly, to reduce morbidity or mortality in patients with HFpEF.”
After the TOPCAT results and post hoc analysis came out in 2014 and 2015 and word spread of spironolactone’s apparent efficacy in the American half of the trial, use of spironolactone to treat HFpEF patient has increased, commented Margaret M. Redfield, MD, a heart failure physician and professor at the Mayo Clinic in Rochester, Minn. She said she often prescribes spironolactone patients to HFpEF patients who require potassium supplementation, generally because of their diuretic treatment. These are the “safest” HFpEF patients for spironolactone treatment, she said, because they face the lowest risk for hyperkalemia, the major adverse effect from spironolactone.
On Twitter @mitchelzoler
This is extraordinarily important information from an extraordinarily important study. I’m strongly persuaded that the data from the Americas in TOPCAT show that spironolactone worked. The new data presented on canrenone levels make me even more ready to exclude from consideration the TOPCAT data from Russia and Georgia.
 |
| Mitchel L. Zoler/Frontline Medical News Dr. Barry H. Greenberg |
The heart failure community is left to decide what conclusions to draw from TOPCAT. I think guideline committees will struggle over what to make of the TOPCAT evidence. Any recommendation in favor of spironolactone needs to be somewhat guarded, but if a group made recommendations in support of spironolactone it would add an impetus for using it.
There has been long-standing interest in treating patients with heart failure with preserved ejection fraction with spironolactone. Currently, about a quarter of these patients take spironolactone. I’m not sure this level of use will increase dramatically because of what we now know about TOPCAT.
Dr. Barry H. Greenberg is professor of medicine and director of the advanced heart failure treatment program at the University of California, San Diego. He had no relevant disclosures. He made these comments in an interview.
This is extraordinarily important information from an extraordinarily important study. I’m strongly persuaded that the data from the Americas in TOPCAT show that spironolactone worked. The new data presented on canrenone levels make me even more ready to exclude from consideration the TOPCAT data from Russia and Georgia.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Barry H. Greenberg |
The heart failure community is left to decide what conclusions to draw from TOPCAT. I think guideline committees will struggle over what to make of the TOPCAT evidence. Any recommendation in favor of spironolactone needs to be somewhat guarded, but if a group made recommendations in support of spironolactone it would add an impetus for using it.
There has been long-standing interest in treating patients with heart failure with preserved ejection fraction with spironolactone. Currently, about a quarter of these patients take spironolactone. I’m not sure this level of use will increase dramatically because of what we now know about TOPCAT.
Dr. Barry H. Greenberg is professor of medicine and director of the advanced heart failure treatment program at the University of California, San Diego. He had no relevant disclosures. He made these comments in an interview.
This is extraordinarily important information from an extraordinarily important study. I’m strongly persuaded that the data from the Americas in TOPCAT show that spironolactone worked. The new data presented on canrenone levels make me even more ready to exclude from consideration the TOPCAT data from Russia and Georgia.
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| Mitchel L. Zoler/Frontline Medical News Dr. Barry H. Greenberg |
The heart failure community is left to decide what conclusions to draw from TOPCAT. I think guideline committees will struggle over what to make of the TOPCAT evidence. Any recommendation in favor of spironolactone needs to be somewhat guarded, but if a group made recommendations in support of spironolactone it would add an impetus for using it.
There has been long-standing interest in treating patients with heart failure with preserved ejection fraction with spironolactone. Currently, about a quarter of these patients take spironolactone. I’m not sure this level of use will increase dramatically because of what we now know about TOPCAT.
Dr. Barry H. Greenberg is professor of medicine and director of the advanced heart failure treatment program at the University of California, San Diego. He had no relevant disclosures. He made these comments in an interview.
ORLANDO – Spironolactone inched a little closer toward becoming the first and only agent with proven efficacy for treating patients with heart failure with preserved ejection fraction based on further evidence for the drug’s efficacy in a subgroup of patients enrolled in the TOPCAT trial.
In 2014, the initial TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) report showed that spironolactone treatment of patients with heart failure with preserved ejection fraction (HFpEF) for 3 years produced a small, 11% relative reduction in the primary risk endpoint, compared with placebo that was not statistically significant (N Engl J Med. 2014 Apr 10;370[15]:1383-92).
But a follow-up post hoc analysis a year later showed evidence that the roughly half of patients in TOPCAT enrolled at centers in Russia and the Republic of Georgia may not have had HFpEF and also may not have received the planned dosage of spironolactone (Circulation. 2015 Jan 6;131[1]:34-42). An analysis that focused only on the 1,767 HFpEF patients (51% of the total TOPCAT cohort) enrolled in the Americas (United States, Canada, Argentina, and Brazil) showed that, compared with placebo, treatment with spironolactone cut the combined rate of cardiovascular death, nonfatal cardiac arrest, and heart failure hospitalization by 4.5 percentage points, an 18% relative risk reduction that was statistically significant. In the Americas, spironolactone also cut cardiovascular death alone by a relative 26%, and reduced heart failure hospitalization by a relative 18%, both statistically significant.
Additional analysis reported at the annual scientific meeting of the Heart Failure Society of America further supported the idea that many TOPCAT patients enrolled in Russia did not receive a physiologically meaningful dosage of spironolactone. Among 66 Russian patients randomized to the spironolactone arm who reported taking their drug as prescribed and who participated in a random draw of blood specimens 1 year into the study, 20 (30%) failed to show detectable blood levels of canrenone, a characteristic spironolactone metabolite, reported Eileen O’Meara, MD, at the meeting. In contrast, 2 (3%) of 76 enrolled U.S. patients failed to show detectable blood levels of the canrenone metabolite, a 10-fold difference said Dr. O’Meara, a cardiologist at the Montreal Heart Institute.The tested U.S. patients also showed a clear dose-response relationship between their reported spironolactone dosage and their canrenone levels, something not seen in the Russian patients. These new findings, plus the evidence cited in the 2015 analysis, create a compelling case that “actual use of spironolactone in Russia was lower than reported” by the trial participants in Russia and probably in Georgia as well, Dr. O’Meara said. The implication is that spironolactone’s real impact on HFpEF patients is best represented in the 51% of TOPCAT patients from the Americas, she added.
“We believe these findings emphasize the reliability of the Americas data,” said Marc A. Pfeffer, MD, a coinvestigator for TOPCAT and lead author of the 2015 post hoc analysis. “Until someone comes up with a better treatment for patients with HFpEF, we should pay attention to this. People need to get this message. And spironolactone costs 7 cents a day,” said Dr. Pfeffer, professor of medicine at Harvard Medical School in Boston.Currently, no agent is considered proven effective for improving outcomes in HFpEF patients. The 2016 guidelinesfor heart failure treatment from the European Society of Cardiology said “no treatment has yet been shown, convincingly, to reduce morbidity or mortality in patients with HFpEF.”
After the TOPCAT results and post hoc analysis came out in 2014 and 2015 and word spread of spironolactone’s apparent efficacy in the American half of the trial, use of spironolactone to treat HFpEF patient has increased, commented Margaret M. Redfield, MD, a heart failure physician and professor at the Mayo Clinic in Rochester, Minn. She said she often prescribes spironolactone patients to HFpEF patients who require potassium supplementation, generally because of their diuretic treatment. These are the “safest” HFpEF patients for spironolactone treatment, she said, because they face the lowest risk for hyperkalemia, the major adverse effect from spironolactone.
On Twitter @mitchelzoler
ORLANDO – Spironolactone inched a little closer toward becoming the first and only agent with proven efficacy for treating patients with heart failure with preserved ejection fraction based on further evidence for the drug’s efficacy in a subgroup of patients enrolled in the TOPCAT trial.
In 2014, the initial TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) report showed that spironolactone treatment of patients with heart failure with preserved ejection fraction (HFpEF) for 3 years produced a small, 11% relative reduction in the primary risk endpoint, compared with placebo that was not statistically significant (N Engl J Med. 2014 Apr 10;370[15]:1383-92).
But a follow-up post hoc analysis a year later showed evidence that the roughly half of patients in TOPCAT enrolled at centers in Russia and the Republic of Georgia may not have had HFpEF and also may not have received the planned dosage of spironolactone (Circulation. 2015 Jan 6;131[1]:34-42). An analysis that focused only on the 1,767 HFpEF patients (51% of the total TOPCAT cohort) enrolled in the Americas (United States, Canada, Argentina, and Brazil) showed that, compared with placebo, treatment with spironolactone cut the combined rate of cardiovascular death, nonfatal cardiac arrest, and heart failure hospitalization by 4.5 percentage points, an 18% relative risk reduction that was statistically significant. In the Americas, spironolactone also cut cardiovascular death alone by a relative 26%, and reduced heart failure hospitalization by a relative 18%, both statistically significant.
Additional analysis reported at the annual scientific meeting of the Heart Failure Society of America further supported the idea that many TOPCAT patients enrolled in Russia did not receive a physiologically meaningful dosage of spironolactone. Among 66 Russian patients randomized to the spironolactone arm who reported taking their drug as prescribed and who participated in a random draw of blood specimens 1 year into the study, 20 (30%) failed to show detectable blood levels of canrenone, a characteristic spironolactone metabolite, reported Eileen O’Meara, MD, at the meeting. In contrast, 2 (3%) of 76 enrolled U.S. patients failed to show detectable blood levels of the canrenone metabolite, a 10-fold difference said Dr. O’Meara, a cardiologist at the Montreal Heart Institute.The tested U.S. patients also showed a clear dose-response relationship between their reported spironolactone dosage and their canrenone levels, something not seen in the Russian patients. These new findings, plus the evidence cited in the 2015 analysis, create a compelling case that “actual use of spironolactone in Russia was lower than reported” by the trial participants in Russia and probably in Georgia as well, Dr. O’Meara said. The implication is that spironolactone’s real impact on HFpEF patients is best represented in the 51% of TOPCAT patients from the Americas, she added.
“We believe these findings emphasize the reliability of the Americas data,” said Marc A. Pfeffer, MD, a coinvestigator for TOPCAT and lead author of the 2015 post hoc analysis. “Until someone comes up with a better treatment for patients with HFpEF, we should pay attention to this. People need to get this message. And spironolactone costs 7 cents a day,” said Dr. Pfeffer, professor of medicine at Harvard Medical School in Boston.Currently, no agent is considered proven effective for improving outcomes in HFpEF patients. The 2016 guidelinesfor heart failure treatment from the European Society of Cardiology said “no treatment has yet been shown, convincingly, to reduce morbidity or mortality in patients with HFpEF.”
After the TOPCAT results and post hoc analysis came out in 2014 and 2015 and word spread of spironolactone’s apparent efficacy in the American half of the trial, use of spironolactone to treat HFpEF patient has increased, commented Margaret M. Redfield, MD, a heart failure physician and professor at the Mayo Clinic in Rochester, Minn. She said she often prescribes spironolactone patients to HFpEF patients who require potassium supplementation, generally because of their diuretic treatment. These are the “safest” HFpEF patients for spironolactone treatment, she said, because they face the lowest risk for hyperkalemia, the major adverse effect from spironolactone.
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point: A post hoc analysis of spironolactone use among TOPCAT participants further fueled the idea that spironolactone provides real benefit to patients with HFpEF.
Major finding: Among patients reportedly taking spironolactone, 30% of tested Russians and 3% of tested Americans did not have detectable canrenone levels.
Data source: TOPCAT, a multicenter, randomized trial with 3,445 HFpEF patients.
Disclosures: TOPCAT received no commercial funding. Dr. O’Meara, Dr. Pfeffer, and Dr. Redfield had no relevant disclosures.
International Coronary Congress Program Available
November 11-13, 2016
Hotel Taj Palace
New Delhi, India
Program Directors
John D. Puskas
David P. Taggart
Naresh Trehan
Kunal Sarkar
Course Overview
This highly practical interdisciplinary program is designed for surgeons, physicians, physician assistants and nurses from around the globe and will include a comprehensive simultaneous curriculum. Surgeons are encouraged to attend with their entire operative team to maximize the benefit of this unique course focused on state-of-the-art coronary surgery.
Share:
November 11-13, 2016
Hotel Taj Palace
New Delhi, India
Program Directors
John D. Puskas
David P. Taggart
Naresh Trehan
Kunal Sarkar
Course Overview
This highly practical interdisciplinary program is designed for surgeons, physicians, physician assistants and nurses from around the globe and will include a comprehensive simultaneous curriculum. Surgeons are encouraged to attend with their entire operative team to maximize the benefit of this unique course focused on state-of-the-art coronary surgery.
Share:
November 11-13, 2016
Hotel Taj Palace
New Delhi, India
Program Directors
John D. Puskas
David P. Taggart
Naresh Trehan
Kunal Sarkar
Course Overview
This highly practical interdisciplinary program is designed for surgeons, physicians, physician assistants and nurses from around the globe and will include a comprehensive simultaneous curriculum. Surgeons are encouraged to attend with their entire operative team to maximize the benefit of this unique course focused on state-of-the-art coronary surgery.
Share:
Four factors raise risk of post-TAVR endocarditis
Four factors – younger patient age, male sex, diabetes, and moderate to severe residual aortic regurgitation – are associated with a significantly increased risk of infective endocarditis after transcatheter aortic valve replacement, according to a report published online Sept. 13 in JAMA.
Until now, data pertaining to endocarditis following TAVR “have been limited to case reports and relatively small series with limited follow-up,” said Ander Regueiro, MD, of Laval University, Quebec City, and his associates.
They performed a retrospective analysis of data in a large international registry of TAVR cases to better characterize post-TAVR endocarditis.
Dr. Regueiro and his colleagues focused on 20,006 TAVR procedures done at 47 medical centers in Europe, North America, and South America during a 10-year period. The median time to symptom onset was 5.3 months after the procedure.
Infective endocarditis was definitively diagnosed in 250 of these cases. This incidence is similar to that reported for endocarditis following surgical aortic valve replacement, indicating that TAVR is no less predisposing to endocarditis despite being a less invasive approach.
The mean age of patients who developed post-TAVR endocarditis was 78.9 years, compared with 81.8 years for those who did not (HR, 0.97). The reason for this association is unclear, but it is possible that younger patients chosen for TAVR because of their prohibitive surgical risk carry a higher burden of comorbidity than do older patients. Similarly, 62% of endocarditis cases arose in men (HR, 1.69), and sex differences in comorbid conditions may explain the higher risk among men.
More patients who developed endocarditis had diabetes (41.7%), compared with those who did not develop endocarditis (30%), for an HR of 1.52. And patients who had moderate to severe residual aortic regurgitation after TAVR also were at much higher risk for endocarditis than were those who did not (HR, 2.05), the investigators noted (JAMA. 2016 Sep 13;316[10]:1083-92).
In contrast, factors that were not associated with endocarditis risk included chronic pulmonary disease, type of valve (self-expandable or balloon-expandable), and setting of the procedure (catheterization lab vs. operating room).
The bacteria that most commonly caused infective endocarditis were Enterococci species (24.6% of cases), Staphylococcus aureus (23.8%), and coagulase-negative staphylococci (16.8%). This should be taken into consideration when selecting antibiotics for prophylaxis before TAVR and when choosing empirical antibiotics for treatment while waiting for blood culture results, wrote Dr. Regueiro and his associates.
“This information may help clinicians identify patients at higher risk [for endocarditis] and aid in implementing appropriate preventive measures,” they noted.
This study was supported by a grant from the Alfonso Martin Escudero Foundation. Dr. Regueiro reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.
Four factors – younger patient age, male sex, diabetes, and moderate to severe residual aortic regurgitation – are associated with a significantly increased risk of infective endocarditis after transcatheter aortic valve replacement, according to a report published online Sept. 13 in JAMA.
Until now, data pertaining to endocarditis following TAVR “have been limited to case reports and relatively small series with limited follow-up,” said Ander Regueiro, MD, of Laval University, Quebec City, and his associates.
They performed a retrospective analysis of data in a large international registry of TAVR cases to better characterize post-TAVR endocarditis.
Dr. Regueiro and his colleagues focused on 20,006 TAVR procedures done at 47 medical centers in Europe, North America, and South America during a 10-year period. The median time to symptom onset was 5.3 months after the procedure.
Infective endocarditis was definitively diagnosed in 250 of these cases. This incidence is similar to that reported for endocarditis following surgical aortic valve replacement, indicating that TAVR is no less predisposing to endocarditis despite being a less invasive approach.
The mean age of patients who developed post-TAVR endocarditis was 78.9 years, compared with 81.8 years for those who did not (HR, 0.97). The reason for this association is unclear, but it is possible that younger patients chosen for TAVR because of their prohibitive surgical risk carry a higher burden of comorbidity than do older patients. Similarly, 62% of endocarditis cases arose in men (HR, 1.69), and sex differences in comorbid conditions may explain the higher risk among men.
More patients who developed endocarditis had diabetes (41.7%), compared with those who did not develop endocarditis (30%), for an HR of 1.52. And patients who had moderate to severe residual aortic regurgitation after TAVR also were at much higher risk for endocarditis than were those who did not (HR, 2.05), the investigators noted (JAMA. 2016 Sep 13;316[10]:1083-92).
In contrast, factors that were not associated with endocarditis risk included chronic pulmonary disease, type of valve (self-expandable or balloon-expandable), and setting of the procedure (catheterization lab vs. operating room).
The bacteria that most commonly caused infective endocarditis were Enterococci species (24.6% of cases), Staphylococcus aureus (23.8%), and coagulase-negative staphylococci (16.8%). This should be taken into consideration when selecting antibiotics for prophylaxis before TAVR and when choosing empirical antibiotics for treatment while waiting for blood culture results, wrote Dr. Regueiro and his associates.
“This information may help clinicians identify patients at higher risk [for endocarditis] and aid in implementing appropriate preventive measures,” they noted.
This study was supported by a grant from the Alfonso Martin Escudero Foundation. Dr. Regueiro reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.
Four factors – younger patient age, male sex, diabetes, and moderate to severe residual aortic regurgitation – are associated with a significantly increased risk of infective endocarditis after transcatheter aortic valve replacement, according to a report published online Sept. 13 in JAMA.
Until now, data pertaining to endocarditis following TAVR “have been limited to case reports and relatively small series with limited follow-up,” said Ander Regueiro, MD, of Laval University, Quebec City, and his associates.
They performed a retrospective analysis of data in a large international registry of TAVR cases to better characterize post-TAVR endocarditis.
Dr. Regueiro and his colleagues focused on 20,006 TAVR procedures done at 47 medical centers in Europe, North America, and South America during a 10-year period. The median time to symptom onset was 5.3 months after the procedure.
Infective endocarditis was definitively diagnosed in 250 of these cases. This incidence is similar to that reported for endocarditis following surgical aortic valve replacement, indicating that TAVR is no less predisposing to endocarditis despite being a less invasive approach.
The mean age of patients who developed post-TAVR endocarditis was 78.9 years, compared with 81.8 years for those who did not (HR, 0.97). The reason for this association is unclear, but it is possible that younger patients chosen for TAVR because of their prohibitive surgical risk carry a higher burden of comorbidity than do older patients. Similarly, 62% of endocarditis cases arose in men (HR, 1.69), and sex differences in comorbid conditions may explain the higher risk among men.
More patients who developed endocarditis had diabetes (41.7%), compared with those who did not develop endocarditis (30%), for an HR of 1.52. And patients who had moderate to severe residual aortic regurgitation after TAVR also were at much higher risk for endocarditis than were those who did not (HR, 2.05), the investigators noted (JAMA. 2016 Sep 13;316[10]:1083-92).
In contrast, factors that were not associated with endocarditis risk included chronic pulmonary disease, type of valve (self-expandable or balloon-expandable), and setting of the procedure (catheterization lab vs. operating room).
The bacteria that most commonly caused infective endocarditis were Enterococci species (24.6% of cases), Staphylococcus aureus (23.8%), and coagulase-negative staphylococci (16.8%). This should be taken into consideration when selecting antibiotics for prophylaxis before TAVR and when choosing empirical antibiotics for treatment while waiting for blood culture results, wrote Dr. Regueiro and his associates.
“This information may help clinicians identify patients at higher risk [for endocarditis] and aid in implementing appropriate preventive measures,” they noted.
This study was supported by a grant from the Alfonso Martin Escudero Foundation. Dr. Regueiro reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.
FROM JAMA
Key clinical point: Four factors raise the risk that patients undergoing transcatheter aortic valve replacement will develop infective endocarditis.
Major finding: The mean age of patients who developed post-TAVR endocarditis was 78.9 years, compared with 81.8 years for those who didn’t (HR, 0.97).
Data source: A retrospective analysis of data in an international registry involving 20,006 patients who underwent TAVR at 47 medical centers during a 10-year period.
Disclosures: This study was supported by a grant from the Alfonso Martin Escudero Foundation. Dr. Regueiro reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.
Smoking thickens LV wall, worsens function
Current smoking, as well as higher levels of cumulative cigarette exposure from past smoking, were both associated with higher left ventricular mass, a higher LV mass-to-volume ratio, and worse diastolic function in an elderly community-based population with no overt indications of coronary artery disease or heart failure, according to a report published online Sept. 13 in Circulation: Cardiovascular Imaging.
“These findings suggest that smoking is associated with subtle alterations in LV structure and function, which might help explain the higher risk of heart failure [HF] reported for smokers, independent of coronary artery disease [CAD],” said Wilson Nadruz Jr., MD, of the cardiovascular division, Brigham and Women’s Hospital, Boston, and his associates.
They analyzed links between smoking and echocardiographic features using data from the Atherosclerosis Risk in Communities (ARIC) study, an ongoing prospective observational study involving community-dwelling adults who were aged 45-64 years at baseline in 1987-1989. For their study, Dr. Nadruz and his colleagues assessed echocardiographic images taken for 4,580 ARIC participants at follow-up roughly 25 years later. None of these adults had any indication of CAD or HF; 287 (6.3%) were current smokers, 2,316 (50.5%) were former smokers, and 1,977 (43.2%) never smoked.
Compared with never smokers, current smokers showed a greater LV mass index (80.4 vs. 76.7), a greater LV mass-to-volume ratio (1.93 vs. 1.83), and a higher prevalence of LV hypertrophy (15% vs. 9%), as well as a higher prevalence of concentric LV hypertrophy and worse LV diastolic function. The same association was found between never smokers and former smokers who had higher levels of cumulative cigarette exposure, the investigators said (Circ Cardiovasc Imag. 2016 Sep 13. doi: 10.1161/circimaging.116.004950).
This association between smoking and altered LV structure and function remained robust after the data were adjusted to account for numerous cardiac risk factors such as older age, higher BMI, diabetes, hypertension, greater alcohol consumption, and higher heart rate. It also didn’t vary by patient sex, race, or income level. In contrast, there was no association between smoking and right ventricular structure or function.
“These data suggest that smoking can independently lead to thickening of the heart and worsening of heart function, which may lead to a higher risk for heart failure, even in people who don’t have heart attacks,” Dr. Nadruz said in a statement.
Looking at the results in a more positive light, senior author Scott D. Solomon, MD, professor of medicine at Harvard University, Boston, said “The good news is that former smokers had similar heart structure and function, compared with never smokers,” suggesting that “the potential effects of tobacco on the myocardium might be reversible after smoking cessation.”
Current smoking, as well as higher levels of cumulative cigarette exposure from past smoking, were both associated with higher left ventricular mass, a higher LV mass-to-volume ratio, and worse diastolic function in an elderly community-based population with no overt indications of coronary artery disease or heart failure, according to a report published online Sept. 13 in Circulation: Cardiovascular Imaging.
“These findings suggest that smoking is associated with subtle alterations in LV structure and function, which might help explain the higher risk of heart failure [HF] reported for smokers, independent of coronary artery disease [CAD],” said Wilson Nadruz Jr., MD, of the cardiovascular division, Brigham and Women’s Hospital, Boston, and his associates.
They analyzed links between smoking and echocardiographic features using data from the Atherosclerosis Risk in Communities (ARIC) study, an ongoing prospective observational study involving community-dwelling adults who were aged 45-64 years at baseline in 1987-1989. For their study, Dr. Nadruz and his colleagues assessed echocardiographic images taken for 4,580 ARIC participants at follow-up roughly 25 years later. None of these adults had any indication of CAD or HF; 287 (6.3%) were current smokers, 2,316 (50.5%) were former smokers, and 1,977 (43.2%) never smoked.
Compared with never smokers, current smokers showed a greater LV mass index (80.4 vs. 76.7), a greater LV mass-to-volume ratio (1.93 vs. 1.83), and a higher prevalence of LV hypertrophy (15% vs. 9%), as well as a higher prevalence of concentric LV hypertrophy and worse LV diastolic function. The same association was found between never smokers and former smokers who had higher levels of cumulative cigarette exposure, the investigators said (Circ Cardiovasc Imag. 2016 Sep 13. doi: 10.1161/circimaging.116.004950).
This association between smoking and altered LV structure and function remained robust after the data were adjusted to account for numerous cardiac risk factors such as older age, higher BMI, diabetes, hypertension, greater alcohol consumption, and higher heart rate. It also didn’t vary by patient sex, race, or income level. In contrast, there was no association between smoking and right ventricular structure or function.
“These data suggest that smoking can independently lead to thickening of the heart and worsening of heart function, which may lead to a higher risk for heart failure, even in people who don’t have heart attacks,” Dr. Nadruz said in a statement.
Looking at the results in a more positive light, senior author Scott D. Solomon, MD, professor of medicine at Harvard University, Boston, said “The good news is that former smokers had similar heart structure and function, compared with never smokers,” suggesting that “the potential effects of tobacco on the myocardium might be reversible after smoking cessation.”
Current smoking, as well as higher levels of cumulative cigarette exposure from past smoking, were both associated with higher left ventricular mass, a higher LV mass-to-volume ratio, and worse diastolic function in an elderly community-based population with no overt indications of coronary artery disease or heart failure, according to a report published online Sept. 13 in Circulation: Cardiovascular Imaging.
“These findings suggest that smoking is associated with subtle alterations in LV structure and function, which might help explain the higher risk of heart failure [HF] reported for smokers, independent of coronary artery disease [CAD],” said Wilson Nadruz Jr., MD, of the cardiovascular division, Brigham and Women’s Hospital, Boston, and his associates.
They analyzed links between smoking and echocardiographic features using data from the Atherosclerosis Risk in Communities (ARIC) study, an ongoing prospective observational study involving community-dwelling adults who were aged 45-64 years at baseline in 1987-1989. For their study, Dr. Nadruz and his colleagues assessed echocardiographic images taken for 4,580 ARIC participants at follow-up roughly 25 years later. None of these adults had any indication of CAD or HF; 287 (6.3%) were current smokers, 2,316 (50.5%) were former smokers, and 1,977 (43.2%) never smoked.
Compared with never smokers, current smokers showed a greater LV mass index (80.4 vs. 76.7), a greater LV mass-to-volume ratio (1.93 vs. 1.83), and a higher prevalence of LV hypertrophy (15% vs. 9%), as well as a higher prevalence of concentric LV hypertrophy and worse LV diastolic function. The same association was found between never smokers and former smokers who had higher levels of cumulative cigarette exposure, the investigators said (Circ Cardiovasc Imag. 2016 Sep 13. doi: 10.1161/circimaging.116.004950).
This association between smoking and altered LV structure and function remained robust after the data were adjusted to account for numerous cardiac risk factors such as older age, higher BMI, diabetes, hypertension, greater alcohol consumption, and higher heart rate. It also didn’t vary by patient sex, race, or income level. In contrast, there was no association between smoking and right ventricular structure or function.
“These data suggest that smoking can independently lead to thickening of the heart and worsening of heart function, which may lead to a higher risk for heart failure, even in people who don’t have heart attacks,” Dr. Nadruz said in a statement.
Looking at the results in a more positive light, senior author Scott D. Solomon, MD, professor of medicine at Harvard University, Boston, said “The good news is that former smokers had similar heart structure and function, compared with never smokers,” suggesting that “the potential effects of tobacco on the myocardium might be reversible after smoking cessation.”
FROM CIRCULATION: CARDIOVASCULAR IMAGING
Key clinical point: Current smoking was associated with higher left ventricular mass, a higher LV mass-to-volume ratio, and worse diastolic function.
Major finding: Compared with never smokers, current smokers showed a greater LV mass index (80.4 vs. 76.7), a greater LV mass-to-volume ratio (1.93 vs. 1.83), and a higher prevalence of LV hypertrophy (15% vs. 9%).
Data source: A secondary analysis of data for 4,580 elderly participants in ARIC, a large community-based cohort.
Disclosures: This study was supported by Brigham and Women’s Hospital, Boston. Dr. Nadruz and his associates reported having no relevant financial disclosures.
Four-step screen IDs silent heart attack in type 2 diabetes
MUNICH – A four-component imaging/biomarker screen was highly accurate for identifying silent myocardial infarction among asymptomatic patients with type 2 diabetes.
The screen is far more accurate than the current standards of invasive imaging or only looking for pathologic Q waves, Peter Swoboda, MD, said at the annual meeting of the European Association for the Study of Diabetes.
“By combining these four factors we came up with a tool that has a diagnostic area under the curve [AUC] of 0.85,” said Dr. Swoboda of Leeds (England) University. “This is far better than the 0.58 AUC that we have with Q waves only – a sensitivity of just 25%.”
The study was published online in June in the Journal of Clinical Endocrinology and Metabolism (JCEM 2016. doi: 10.1210/jc.2016-1318).
The screen employs noninvasive imaging and biomarkers to tap multiple clinical hallmarks of silent MI. The components are:
• electrocardiogram.
• echocardiography.
• biomarker assessment.
• cardiac magnetic resonance imaging, focusing on left ventricular ejection fraction and late gadolinium enhancement.
The study cohort comprised 100 patients with type 2 diabetes without known heart disease and with no new cardiac symptoms. They underwent cardiac MRI, a 12-lead electrocardiogram, echocardiography, and serum biomarker assessment. Late gadolinium enhancement identified evidence of silent MI in 17 patients (17%).
There were few differences in the clinical characteristics of those who had experienced MI and those who had not, Dr. Swoboda noted. There were no differences at all in diabetes-related measures, including disease duration or hemoglobin A1c levels. Blood pressures were similar. Patients with MI were significantly older (65 vs. 60 years).
In cardiac-specific measures, left ventricular ejection fraction was similar, as was left ventricular mass, end diastolic volume, and left atrial volume. There were however, other very important differences, Dr. Swoboda noted.
Imaging included a measure called “feature tracking analysis,” which measured the peak global longitudinal strain, systolic strain rate, and early and late diastolic strain rates during contraction. This analysis noted a significant difference in global longitudinal strain between the MI and non-MI groups.
Ventricular filling velocities as measured by the E/A ratio on ECG were also significantly different between the MI and non-MI groups (0.75 vs. 0.89, respectively). ECG also found pathologic Q waves in significantly more MI patients (24% vs. 7%).
Finally, the serum biomarker panel showed a very strong increase in B-type natriuretic peptide (NT-proBNP) among MI patients, compared with non-MI patients (105 vs. 52 ng/L). There were no significant differences in the other biomarkers, including C-reactive protein and high-sensitive cardiac troponin.
Dr. Swoboda and his team then compiled these findings into a composite measure, assigning them optimum cutoff measures:
• Age older than 62 years.
• E/A ratio 0.72 or lower.
• Global longitudinal strain of at least 18.4%.
• NT-proBNP more than 29 ng/L.
The system resulted in a diagnostic accuracy AUC of 0.85 – significantly better than any of the AUCs generated by the individual components. All patients who scored 0 or 1 were free of MI. Among the 28 with a score of 2, only three had experienced a silent MI. Among the 21 with a score of 3, seven had experienced a silent MI and 14 had not. Among the 16 with a score of 4, seven had experienced a silent MI and nine had not.
While Dr. Swoboda called the screening method “simple” during discussion, a colleague in the audience disagreed with that.
“A simple test is something like a blood test only, not an MRI. Not imaging. That is expensive and takes time,” said Naveed Sattar, MD, of the University of Glasgow, Scotland. “However, I do think your data add more to the evidence that BNP can be a really valuable marker of cardiovascular risk in patients with diabetes.”
Dr. Sattar recently examined the value of cardiac serum biomarkers in predicting cardiovascular disease and mortality in nearly 100,000 people without a history of heart disease. In these subjects, he wrote, “NT-proBNP assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention.”
The paper appeared online in Lancet Diabetes in September (Lancet Diab. 2016. doi: 10.1016/S2213-8587[16]30196-6).
Dr. Swoboda agreed that data continue to support the increased use of NT-proBNP as a marker of heart disease.
“I think that in the future, diabetes medicine is moving toward individualized patient care, based on individualized risk factors. The future of assessing asymptomatic cardiac patients might be a combination of BNP and MRI.”
Dr. Swoboda had no financial disclosures. Some of Dr. Sattar’s coauthors reported relationships with pharmaceutical companies.
MUNICH – A four-component imaging/biomarker screen was highly accurate for identifying silent myocardial infarction among asymptomatic patients with type 2 diabetes.
The screen is far more accurate than the current standards of invasive imaging or only looking for pathologic Q waves, Peter Swoboda, MD, said at the annual meeting of the European Association for the Study of Diabetes.
“By combining these four factors we came up with a tool that has a diagnostic area under the curve [AUC] of 0.85,” said Dr. Swoboda of Leeds (England) University. “This is far better than the 0.58 AUC that we have with Q waves only – a sensitivity of just 25%.”
The study was published online in June in the Journal of Clinical Endocrinology and Metabolism (JCEM 2016. doi: 10.1210/jc.2016-1318).
The screen employs noninvasive imaging and biomarkers to tap multiple clinical hallmarks of silent MI. The components are:
• electrocardiogram.
• echocardiography.
• biomarker assessment.
• cardiac magnetic resonance imaging, focusing on left ventricular ejection fraction and late gadolinium enhancement.
The study cohort comprised 100 patients with type 2 diabetes without known heart disease and with no new cardiac symptoms. They underwent cardiac MRI, a 12-lead electrocardiogram, echocardiography, and serum biomarker assessment. Late gadolinium enhancement identified evidence of silent MI in 17 patients (17%).
There were few differences in the clinical characteristics of those who had experienced MI and those who had not, Dr. Swoboda noted. There were no differences at all in diabetes-related measures, including disease duration or hemoglobin A1c levels. Blood pressures were similar. Patients with MI were significantly older (65 vs. 60 years).
In cardiac-specific measures, left ventricular ejection fraction was similar, as was left ventricular mass, end diastolic volume, and left atrial volume. There were however, other very important differences, Dr. Swoboda noted.
Imaging included a measure called “feature tracking analysis,” which measured the peak global longitudinal strain, systolic strain rate, and early and late diastolic strain rates during contraction. This analysis noted a significant difference in global longitudinal strain between the MI and non-MI groups.
Ventricular filling velocities as measured by the E/A ratio on ECG were also significantly different between the MI and non-MI groups (0.75 vs. 0.89, respectively). ECG also found pathologic Q waves in significantly more MI patients (24% vs. 7%).
Finally, the serum biomarker panel showed a very strong increase in B-type natriuretic peptide (NT-proBNP) among MI patients, compared with non-MI patients (105 vs. 52 ng/L). There were no significant differences in the other biomarkers, including C-reactive protein and high-sensitive cardiac troponin.
Dr. Swoboda and his team then compiled these findings into a composite measure, assigning them optimum cutoff measures:
• Age older than 62 years.
• E/A ratio 0.72 or lower.
• Global longitudinal strain of at least 18.4%.
• NT-proBNP more than 29 ng/L.
The system resulted in a diagnostic accuracy AUC of 0.85 – significantly better than any of the AUCs generated by the individual components. All patients who scored 0 or 1 were free of MI. Among the 28 with a score of 2, only three had experienced a silent MI. Among the 21 with a score of 3, seven had experienced a silent MI and 14 had not. Among the 16 with a score of 4, seven had experienced a silent MI and nine had not.
While Dr. Swoboda called the screening method “simple” during discussion, a colleague in the audience disagreed with that.
“A simple test is something like a blood test only, not an MRI. Not imaging. That is expensive and takes time,” said Naveed Sattar, MD, of the University of Glasgow, Scotland. “However, I do think your data add more to the evidence that BNP can be a really valuable marker of cardiovascular risk in patients with diabetes.”
Dr. Sattar recently examined the value of cardiac serum biomarkers in predicting cardiovascular disease and mortality in nearly 100,000 people without a history of heart disease. In these subjects, he wrote, “NT-proBNP assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention.”
The paper appeared online in Lancet Diabetes in September (Lancet Diab. 2016. doi: 10.1016/S2213-8587[16]30196-6).
Dr. Swoboda agreed that data continue to support the increased use of NT-proBNP as a marker of heart disease.
“I think that in the future, diabetes medicine is moving toward individualized patient care, based on individualized risk factors. The future of assessing asymptomatic cardiac patients might be a combination of BNP and MRI.”
Dr. Swoboda had no financial disclosures. Some of Dr. Sattar’s coauthors reported relationships with pharmaceutical companies.
MUNICH – A four-component imaging/biomarker screen was highly accurate for identifying silent myocardial infarction among asymptomatic patients with type 2 diabetes.
The screen is far more accurate than the current standards of invasive imaging or only looking for pathologic Q waves, Peter Swoboda, MD, said at the annual meeting of the European Association for the Study of Diabetes.
“By combining these four factors we came up with a tool that has a diagnostic area under the curve [AUC] of 0.85,” said Dr. Swoboda of Leeds (England) University. “This is far better than the 0.58 AUC that we have with Q waves only – a sensitivity of just 25%.”
The study was published online in June in the Journal of Clinical Endocrinology and Metabolism (JCEM 2016. doi: 10.1210/jc.2016-1318).
The screen employs noninvasive imaging and biomarkers to tap multiple clinical hallmarks of silent MI. The components are:
• electrocardiogram.
• echocardiography.
• biomarker assessment.
• cardiac magnetic resonance imaging, focusing on left ventricular ejection fraction and late gadolinium enhancement.
The study cohort comprised 100 patients with type 2 diabetes without known heart disease and with no new cardiac symptoms. They underwent cardiac MRI, a 12-lead electrocardiogram, echocardiography, and serum biomarker assessment. Late gadolinium enhancement identified evidence of silent MI in 17 patients (17%).
There were few differences in the clinical characteristics of those who had experienced MI and those who had not, Dr. Swoboda noted. There were no differences at all in diabetes-related measures, including disease duration or hemoglobin A1c levels. Blood pressures were similar. Patients with MI were significantly older (65 vs. 60 years).
In cardiac-specific measures, left ventricular ejection fraction was similar, as was left ventricular mass, end diastolic volume, and left atrial volume. There were however, other very important differences, Dr. Swoboda noted.
Imaging included a measure called “feature tracking analysis,” which measured the peak global longitudinal strain, systolic strain rate, and early and late diastolic strain rates during contraction. This analysis noted a significant difference in global longitudinal strain between the MI and non-MI groups.
Ventricular filling velocities as measured by the E/A ratio on ECG were also significantly different between the MI and non-MI groups (0.75 vs. 0.89, respectively). ECG also found pathologic Q waves in significantly more MI patients (24% vs. 7%).
Finally, the serum biomarker panel showed a very strong increase in B-type natriuretic peptide (NT-proBNP) among MI patients, compared with non-MI patients (105 vs. 52 ng/L). There were no significant differences in the other biomarkers, including C-reactive protein and high-sensitive cardiac troponin.
Dr. Swoboda and his team then compiled these findings into a composite measure, assigning them optimum cutoff measures:
• Age older than 62 years.
• E/A ratio 0.72 or lower.
• Global longitudinal strain of at least 18.4%.
• NT-proBNP more than 29 ng/L.
The system resulted in a diagnostic accuracy AUC of 0.85 – significantly better than any of the AUCs generated by the individual components. All patients who scored 0 or 1 were free of MI. Among the 28 with a score of 2, only three had experienced a silent MI. Among the 21 with a score of 3, seven had experienced a silent MI and 14 had not. Among the 16 with a score of 4, seven had experienced a silent MI and nine had not.
While Dr. Swoboda called the screening method “simple” during discussion, a colleague in the audience disagreed with that.
“A simple test is something like a blood test only, not an MRI. Not imaging. That is expensive and takes time,” said Naveed Sattar, MD, of the University of Glasgow, Scotland. “However, I do think your data add more to the evidence that BNP can be a really valuable marker of cardiovascular risk in patients with diabetes.”
Dr. Sattar recently examined the value of cardiac serum biomarkers in predicting cardiovascular disease and mortality in nearly 100,000 people without a history of heart disease. In these subjects, he wrote, “NT-proBNP assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention.”
The paper appeared online in Lancet Diabetes in September (Lancet Diab. 2016. doi: 10.1016/S2213-8587[16]30196-6).
Dr. Swoboda agreed that data continue to support the increased use of NT-proBNP as a marker of heart disease.
“I think that in the future, diabetes medicine is moving toward individualized patient care, based on individualized risk factors. The future of assessing asymptomatic cardiac patients might be a combination of BNP and MRI.”
Dr. Swoboda had no financial disclosures. Some of Dr. Sattar’s coauthors reported relationships with pharmaceutical companies.
AT EASD 2016
Key clinical point: A four-component screen accurately identified silent myocardial infarction in asymptomatic patients with type 2 diabetes
Major finding: The tool had an 82% sensitivity and 72% specificity for silent MI.
Data source: It was created in a cohort of 100 patients with type 2 diabetes and no history of heart disease.
Disclosures: Dr. Swoboda had no financial disclosures.
WHO updates ranking of critically important antimicrobials
In light of increasing antibiotic resistance among pathogens, the World Health Organization has revised its global rankings of critically important antimicrobials used in human medicine, designating quinolones, third- and fourth-generation cephalosporins, macrolides and ketolides, and glycopeptides as among the highest-priority drugs in the world.
Peter C. Collignon, MBBS, of Canberra (Australia) Hospital and his colleagues on the WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance, created the rankings for use in developing risk management strategies related to antimicrobial use in food production animals. According to Dr. Collignon and his coauthors, the rankings are intended to help regulators and other stakeholders know which types of antimicrobials used in animals present potentially higher risks to human populations and help inform how this use might be better managed (e.g. restriction to single-animal therapy or prohibition of mass treatment and extra-label use) to minimize the risk of transmission of resistance to the human population.
WHO studies previously suggested that antimicrobials which currently have no veterinary equivalent (for example, carbapenems) “as well as any new class of antimicrobial developed for human therapy should not be used in animals.” Dr. Collignon’s WHO Advisory Group followed two essential criteria to designate antimicrobials of utmost importance to human health in the new study: 1. antimicrobials that are the sole, or one of limited available therapies, to treat serious bacterial infections in people and 2. antimicrobials used to treat infections in people caused by either (a) bacteria that may be transmitted to humans from nonhuman sources or (b) bacteria that may acquire resistance genes from nonhuman sources.
The highest-priority and most critically important antimicrobials are those which meet the criteria listed above and that are used in greatest volume or highest frequency by humans. Another criteria for prioritization involves antimicrobial classes where evidence suggests that the “transmission of resistant bacteria or resistance genes from nonhuman sources is already occurring, or has occurred previously.” Quinolones, third- and fourth-generation cephalosporins, macrolides and ketolides, and glycopeptides were the only antimicrobials that met all criteria for prioritization.
“Antimicrobial resistance remains a threat to human health and drivers of resistance act in all sectors; human, animal, and the environment,” the WHO Advisory Group concluded. “Prioritizing the antimicrobials that are critically important for humans is a valuable and strategic risk-management tool and will be improved with the evidence-based approach which is currently underway.”
Read the full study in Clinical Infectious Diseases (doi: 10.1093/cid/ciw475).
In light of increasing antibiotic resistance among pathogens, the World Health Organization has revised its global rankings of critically important antimicrobials used in human medicine, designating quinolones, third- and fourth-generation cephalosporins, macrolides and ketolides, and glycopeptides as among the highest-priority drugs in the world.
Peter C. Collignon, MBBS, of Canberra (Australia) Hospital and his colleagues on the WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance, created the rankings for use in developing risk management strategies related to antimicrobial use in food production animals. According to Dr. Collignon and his coauthors, the rankings are intended to help regulators and other stakeholders know which types of antimicrobials used in animals present potentially higher risks to human populations and help inform how this use might be better managed (e.g. restriction to single-animal therapy or prohibition of mass treatment and extra-label use) to minimize the risk of transmission of resistance to the human population.
WHO studies previously suggested that antimicrobials which currently have no veterinary equivalent (for example, carbapenems) “as well as any new class of antimicrobial developed for human therapy should not be used in animals.” Dr. Collignon’s WHO Advisory Group followed two essential criteria to designate antimicrobials of utmost importance to human health in the new study: 1. antimicrobials that are the sole, or one of limited available therapies, to treat serious bacterial infections in people and 2. antimicrobials used to treat infections in people caused by either (a) bacteria that may be transmitted to humans from nonhuman sources or (b) bacteria that may acquire resistance genes from nonhuman sources.
The highest-priority and most critically important antimicrobials are those which meet the criteria listed above and that are used in greatest volume or highest frequency by humans. Another criteria for prioritization involves antimicrobial classes where evidence suggests that the “transmission of resistant bacteria or resistance genes from nonhuman sources is already occurring, or has occurred previously.” Quinolones, third- and fourth-generation cephalosporins, macrolides and ketolides, and glycopeptides were the only antimicrobials that met all criteria for prioritization.
“Antimicrobial resistance remains a threat to human health and drivers of resistance act in all sectors; human, animal, and the environment,” the WHO Advisory Group concluded. “Prioritizing the antimicrobials that are critically important for humans is a valuable and strategic risk-management tool and will be improved with the evidence-based approach which is currently underway.”
Read the full study in Clinical Infectious Diseases (doi: 10.1093/cid/ciw475).
In light of increasing antibiotic resistance among pathogens, the World Health Organization has revised its global rankings of critically important antimicrobials used in human medicine, designating quinolones, third- and fourth-generation cephalosporins, macrolides and ketolides, and glycopeptides as among the highest-priority drugs in the world.
Peter C. Collignon, MBBS, of Canberra (Australia) Hospital and his colleagues on the WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance, created the rankings for use in developing risk management strategies related to antimicrobial use in food production animals. According to Dr. Collignon and his coauthors, the rankings are intended to help regulators and other stakeholders know which types of antimicrobials used in animals present potentially higher risks to human populations and help inform how this use might be better managed (e.g. restriction to single-animal therapy or prohibition of mass treatment and extra-label use) to minimize the risk of transmission of resistance to the human population.
WHO studies previously suggested that antimicrobials which currently have no veterinary equivalent (for example, carbapenems) “as well as any new class of antimicrobial developed for human therapy should not be used in animals.” Dr. Collignon’s WHO Advisory Group followed two essential criteria to designate antimicrobials of utmost importance to human health in the new study: 1. antimicrobials that are the sole, or one of limited available therapies, to treat serious bacterial infections in people and 2. antimicrobials used to treat infections in people caused by either (a) bacteria that may be transmitted to humans from nonhuman sources or (b) bacteria that may acquire resistance genes from nonhuman sources.
The highest-priority and most critically important antimicrobials are those which meet the criteria listed above and that are used in greatest volume or highest frequency by humans. Another criteria for prioritization involves antimicrobial classes where evidence suggests that the “transmission of resistant bacteria or resistance genes from nonhuman sources is already occurring, or has occurred previously.” Quinolones, third- and fourth-generation cephalosporins, macrolides and ketolides, and glycopeptides were the only antimicrobials that met all criteria for prioritization.
“Antimicrobial resistance remains a threat to human health and drivers of resistance act in all sectors; human, animal, and the environment,” the WHO Advisory Group concluded. “Prioritizing the antimicrobials that are critically important for humans is a valuable and strategic risk-management tool and will be improved with the evidence-based approach which is currently underway.”
Read the full study in Clinical Infectious Diseases (doi: 10.1093/cid/ciw475).
FROM CLINICAL INFECTIOUS DISEASES
ANTARCTIC results chill enthusiasm for platelet monitoring
ROME – Measuring platelet function in order to tailor antiplatelet therapy in elderly patients undergoing percutaneous coronary intervention for acute coronary syndromes did not improve their clinical outcomes in the randomized ANTARCTIC trial, Gilles Montalescot, MD, reported at the annual congress of the European Society of Cardiology.
“We found absolutely no benefit for this strategy of adjustment of antiplatelet therapy based upon platelet function testing. The study was completely neutral on all types of endpoints, ischemic as well as bleeding,” said Dr. Montalescot, professor of cardiology at the University of Paris VI and director of the cardiac care unit at Pitié-Salpêtrière Hospital.
This was a disappointing result in what was the largest-ever randomized clinical trial involving PCI in elderly patients, he said. This was a high-risk population, not only by virtue of everyone being over age 75 years, but because they all presented with ACS. Indeed, one-third of ANTARCTIC participants underwent primary PCI for ST-segment elevation myocardial infarction.
ANTARCTIC (Assessment of a Normal Versus Tailored Dose of Prasugrel After Stenting in Patients Aged Over 75 Years to Reduce the Composite of Bleeding, Stent Thrombosis, and Ischemic Complications) was carried out as a follow-up to the earlier ARCTIC randomized trial, also conducted by Dr. Montalescot and his coinvestigators. Like ANTARCTIC, ARCTIC, too, showed no clinical benefit for platelet function testing in order to adjust antiplatelet therapy (N Engl J Med. 2012;367:2100-9). At the time, ARCTIC’s critics argued that this individualized strategy didn’t achieve the expected improved outcomes because the trial was conducted in low-risk, stable patients undergoing elective scheduled PCI. In contrast, if there was ever a high-risk population in which platelet function testing and tailored antiplatelet therapy should work, it was in the very high-risk ANTARCTIC population, he said.
ANTARCTIC included 877 elderly patients undergoing urgent PCI for ACS who were placed on low-dose aspirin and randomized to standard antiplatelet therapy with prasugrel (Effient) at 5 mg/day, the European approved dose for long-term maintenance therapy in elderly patients, or to tailored antiplatelet therapy.
Patients in the tailored therapy arm received prasugrel at 5 mg/day for the first 14 days, then underwent platelet function testing with the VerifyNow P2Y12 system. If they demonstrated high on-drug platelet activity, defined as at least 208 P2Y12 reaction units (PRU), their prasugrel was bumped up to 10 mg/day. If their PRU measurement was in what is considered the optimal range for quelling ischemia without promoting bleeding – that is, less than 208 but more than 85 PRU – they remained on prasugrel at 5 mg/day. And if they scored less than 85 PRU, exposing them to excess bleeding risk due to high suppression of platelets, they were switched to clopidogrel (Plavix) at 75 mg/day, a less potent antiplatelet regimen.
Two weeks after their first platelet function measurement, participants in the tailored therapy arm returned for a second round of platelet activity testing, with their antiplatelet regimen once again being adjusted on the basis of the results.
The primary study endpoint was net clinical benefit over a 12-month follow-up period. This was defined as the composite of cardiovascular death, MI, stroke, urgent revascularization, stent thrombosis, and Bleeding Academic Research Consortium (BARC) types 2, 3, or 5. This composite endpoint occurred in 27.6% of the platelet monitoring group and a near-identical 27.8% of conventionally managed patients.
Of note, 42% of patients in the actively monitored group were within the target platelet inhibition range when tested 14 days into the study. At study’s end, 55% of patients remained on prasugrel at 5 mg/day, 39% were on clopidogrel at 75 mg/day, and less than 4% were on prasugrel at 10 mg/day. Thus, most patients who underwent a dose adjustment on the basis of their VerifyNow results were downgraded to a less-potent antiplatelet regimen. Very few required enhanced platelet suppression in the form of 10 mg/day of prasugrel.
“Platelet function monitoring is difficult to use. Patients have to come back twice to be monitored. It’s costly. It’s time consuming. And platelet function monitoring clearly does not help,” the cardiologist said.
The ANTARCTIC results will likely lead to a revision of the American and European guidelines, which currently give a class IIb/level of evidence C recommendation for platelet function testing in high-risk situations.
“There is a huge literature showing that platelet reactivity affects clinical outcomes,” Dr. Montalescot continued. “One hypothesis now is that platelet reactivity may be only a marker of risk; you can modify it, but that has no impact on patient outcomes. We may be in the same situation here as with HDL cholesterol, for example.”
Discussant Steen Dalby Kristensen, MD, noted that ANTARCTIC is just the latest in a slew of negative randomized clinical trials of individualized antiplatelet therapy for coronary artery disease. In addition to ARCTIC, others include GRAVITAS, TRIGGER PCI, and ASCET. One study, the German/Austrian TROPICAL ACS trial, remains ongoing.
“It really is an intriguing concept that many of us have been fascinated by for years: to identify the sweet spot where, by measuring platelet aggregation and maybe changing the therapy, we can find just the right balance between bleeding and ischemia. The ANTARCTIC results are quite disappointing for platelet-monitoring enthusiasts. Is the whole concept wrong?” said Dr. Kristensen, professor of cardiology and head of the cardiovascular research center at Aarhus (Denmark) University Hospital.
“I think even more disappointing for me than the lack of impact on ischemic events was the bleeding. I would have anticipated that maybe bleeding could be avoided by adjusting the dose, but this was not the case,” he added.
But Stephan Gielen, MD, saw a silver lining in the negative results for ANTARCTIC.
“From my perspective as a clinical interventionalist, I’m happy that you ended up in the way you did. Putting things positively, this study confirms the safety of dual-platelet inhibition with prasugrel at the reduced dose of 5 mg in an elderly population. There is no need to go to the trouble of monitoring platelet function even in this elderly population, which I think for clinical practice is a good message,” said Dr. Gielen of Detmold (Germany) Hospital, who cochaired a press conference where Dr. Montalescot presented the ANTARCTIC results.
Simultaneously with Dr. Montalescot’s presentation at ESC 2016 in Rome, the ANTARCTIC results were published online (Lancet. 2016 Aug 26. doi: 10.1016/S0140-6736(16)31323-X).
ANTARCTIC was funded by Eli Lilly, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and the French Foundation for Heart Research. The presenter reported receiving research grants from and/or serving as a consultant to those organizations and numerous others.
ROME – Measuring platelet function in order to tailor antiplatelet therapy in elderly patients undergoing percutaneous coronary intervention for acute coronary syndromes did not improve their clinical outcomes in the randomized ANTARCTIC trial, Gilles Montalescot, MD, reported at the annual congress of the European Society of Cardiology.
“We found absolutely no benefit for this strategy of adjustment of antiplatelet therapy based upon platelet function testing. The study was completely neutral on all types of endpoints, ischemic as well as bleeding,” said Dr. Montalescot, professor of cardiology at the University of Paris VI and director of the cardiac care unit at Pitié-Salpêtrière Hospital.
This was a disappointing result in what was the largest-ever randomized clinical trial involving PCI in elderly patients, he said. This was a high-risk population, not only by virtue of everyone being over age 75 years, but because they all presented with ACS. Indeed, one-third of ANTARCTIC participants underwent primary PCI for ST-segment elevation myocardial infarction.
ANTARCTIC (Assessment of a Normal Versus Tailored Dose of Prasugrel After Stenting in Patients Aged Over 75 Years to Reduce the Composite of Bleeding, Stent Thrombosis, and Ischemic Complications) was carried out as a follow-up to the earlier ARCTIC randomized trial, also conducted by Dr. Montalescot and his coinvestigators. Like ANTARCTIC, ARCTIC, too, showed no clinical benefit for platelet function testing in order to adjust antiplatelet therapy (N Engl J Med. 2012;367:2100-9). At the time, ARCTIC’s critics argued that this individualized strategy didn’t achieve the expected improved outcomes because the trial was conducted in low-risk, stable patients undergoing elective scheduled PCI. In contrast, if there was ever a high-risk population in which platelet function testing and tailored antiplatelet therapy should work, it was in the very high-risk ANTARCTIC population, he said.
ANTARCTIC included 877 elderly patients undergoing urgent PCI for ACS who were placed on low-dose aspirin and randomized to standard antiplatelet therapy with prasugrel (Effient) at 5 mg/day, the European approved dose for long-term maintenance therapy in elderly patients, or to tailored antiplatelet therapy.
Patients in the tailored therapy arm received prasugrel at 5 mg/day for the first 14 days, then underwent platelet function testing with the VerifyNow P2Y12 system. If they demonstrated high on-drug platelet activity, defined as at least 208 P2Y12 reaction units (PRU), their prasugrel was bumped up to 10 mg/day. If their PRU measurement was in what is considered the optimal range for quelling ischemia without promoting bleeding – that is, less than 208 but more than 85 PRU – they remained on prasugrel at 5 mg/day. And if they scored less than 85 PRU, exposing them to excess bleeding risk due to high suppression of platelets, they were switched to clopidogrel (Plavix) at 75 mg/day, a less potent antiplatelet regimen.
Two weeks after their first platelet function measurement, participants in the tailored therapy arm returned for a second round of platelet activity testing, with their antiplatelet regimen once again being adjusted on the basis of the results.
The primary study endpoint was net clinical benefit over a 12-month follow-up period. This was defined as the composite of cardiovascular death, MI, stroke, urgent revascularization, stent thrombosis, and Bleeding Academic Research Consortium (BARC) types 2, 3, or 5. This composite endpoint occurred in 27.6% of the platelet monitoring group and a near-identical 27.8% of conventionally managed patients.
Of note, 42% of patients in the actively monitored group were within the target platelet inhibition range when tested 14 days into the study. At study’s end, 55% of patients remained on prasugrel at 5 mg/day, 39% were on clopidogrel at 75 mg/day, and less than 4% were on prasugrel at 10 mg/day. Thus, most patients who underwent a dose adjustment on the basis of their VerifyNow results were downgraded to a less-potent antiplatelet regimen. Very few required enhanced platelet suppression in the form of 10 mg/day of prasugrel.
“Platelet function monitoring is difficult to use. Patients have to come back twice to be monitored. It’s costly. It’s time consuming. And platelet function monitoring clearly does not help,” the cardiologist said.
The ANTARCTIC results will likely lead to a revision of the American and European guidelines, which currently give a class IIb/level of evidence C recommendation for platelet function testing in high-risk situations.
“There is a huge literature showing that platelet reactivity affects clinical outcomes,” Dr. Montalescot continued. “One hypothesis now is that platelet reactivity may be only a marker of risk; you can modify it, but that has no impact on patient outcomes. We may be in the same situation here as with HDL cholesterol, for example.”
Discussant Steen Dalby Kristensen, MD, noted that ANTARCTIC is just the latest in a slew of negative randomized clinical trials of individualized antiplatelet therapy for coronary artery disease. In addition to ARCTIC, others include GRAVITAS, TRIGGER PCI, and ASCET. One study, the German/Austrian TROPICAL ACS trial, remains ongoing.
“It really is an intriguing concept that many of us have been fascinated by for years: to identify the sweet spot where, by measuring platelet aggregation and maybe changing the therapy, we can find just the right balance between bleeding and ischemia. The ANTARCTIC results are quite disappointing for platelet-monitoring enthusiasts. Is the whole concept wrong?” said Dr. Kristensen, professor of cardiology and head of the cardiovascular research center at Aarhus (Denmark) University Hospital.
“I think even more disappointing for me than the lack of impact on ischemic events was the bleeding. I would have anticipated that maybe bleeding could be avoided by adjusting the dose, but this was not the case,” he added.
But Stephan Gielen, MD, saw a silver lining in the negative results for ANTARCTIC.
“From my perspective as a clinical interventionalist, I’m happy that you ended up in the way you did. Putting things positively, this study confirms the safety of dual-platelet inhibition with prasugrel at the reduced dose of 5 mg in an elderly population. There is no need to go to the trouble of monitoring platelet function even in this elderly population, which I think for clinical practice is a good message,” said Dr. Gielen of Detmold (Germany) Hospital, who cochaired a press conference where Dr. Montalescot presented the ANTARCTIC results.
Simultaneously with Dr. Montalescot’s presentation at ESC 2016 in Rome, the ANTARCTIC results were published online (Lancet. 2016 Aug 26. doi: 10.1016/S0140-6736(16)31323-X).
ANTARCTIC was funded by Eli Lilly, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and the French Foundation for Heart Research. The presenter reported receiving research grants from and/or serving as a consultant to those organizations and numerous others.
ROME – Measuring platelet function in order to tailor antiplatelet therapy in elderly patients undergoing percutaneous coronary intervention for acute coronary syndromes did not improve their clinical outcomes in the randomized ANTARCTIC trial, Gilles Montalescot, MD, reported at the annual congress of the European Society of Cardiology.
“We found absolutely no benefit for this strategy of adjustment of antiplatelet therapy based upon platelet function testing. The study was completely neutral on all types of endpoints, ischemic as well as bleeding,” said Dr. Montalescot, professor of cardiology at the University of Paris VI and director of the cardiac care unit at Pitié-Salpêtrière Hospital.
This was a disappointing result in what was the largest-ever randomized clinical trial involving PCI in elderly patients, he said. This was a high-risk population, not only by virtue of everyone being over age 75 years, but because they all presented with ACS. Indeed, one-third of ANTARCTIC participants underwent primary PCI for ST-segment elevation myocardial infarction.
ANTARCTIC (Assessment of a Normal Versus Tailored Dose of Prasugrel After Stenting in Patients Aged Over 75 Years to Reduce the Composite of Bleeding, Stent Thrombosis, and Ischemic Complications) was carried out as a follow-up to the earlier ARCTIC randomized trial, also conducted by Dr. Montalescot and his coinvestigators. Like ANTARCTIC, ARCTIC, too, showed no clinical benefit for platelet function testing in order to adjust antiplatelet therapy (N Engl J Med. 2012;367:2100-9). At the time, ARCTIC’s critics argued that this individualized strategy didn’t achieve the expected improved outcomes because the trial was conducted in low-risk, stable patients undergoing elective scheduled PCI. In contrast, if there was ever a high-risk population in which platelet function testing and tailored antiplatelet therapy should work, it was in the very high-risk ANTARCTIC population, he said.
ANTARCTIC included 877 elderly patients undergoing urgent PCI for ACS who were placed on low-dose aspirin and randomized to standard antiplatelet therapy with prasugrel (Effient) at 5 mg/day, the European approved dose for long-term maintenance therapy in elderly patients, or to tailored antiplatelet therapy.
Patients in the tailored therapy arm received prasugrel at 5 mg/day for the first 14 days, then underwent platelet function testing with the VerifyNow P2Y12 system. If they demonstrated high on-drug platelet activity, defined as at least 208 P2Y12 reaction units (PRU), their prasugrel was bumped up to 10 mg/day. If their PRU measurement was in what is considered the optimal range for quelling ischemia without promoting bleeding – that is, less than 208 but more than 85 PRU – they remained on prasugrel at 5 mg/day. And if they scored less than 85 PRU, exposing them to excess bleeding risk due to high suppression of platelets, they were switched to clopidogrel (Plavix) at 75 mg/day, a less potent antiplatelet regimen.
Two weeks after their first platelet function measurement, participants in the tailored therapy arm returned for a second round of platelet activity testing, with their antiplatelet regimen once again being adjusted on the basis of the results.
The primary study endpoint was net clinical benefit over a 12-month follow-up period. This was defined as the composite of cardiovascular death, MI, stroke, urgent revascularization, stent thrombosis, and Bleeding Academic Research Consortium (BARC) types 2, 3, or 5. This composite endpoint occurred in 27.6% of the platelet monitoring group and a near-identical 27.8% of conventionally managed patients.
Of note, 42% of patients in the actively monitored group were within the target platelet inhibition range when tested 14 days into the study. At study’s end, 55% of patients remained on prasugrel at 5 mg/day, 39% were on clopidogrel at 75 mg/day, and less than 4% were on prasugrel at 10 mg/day. Thus, most patients who underwent a dose adjustment on the basis of their VerifyNow results were downgraded to a less-potent antiplatelet regimen. Very few required enhanced platelet suppression in the form of 10 mg/day of prasugrel.
“Platelet function monitoring is difficult to use. Patients have to come back twice to be monitored. It’s costly. It’s time consuming. And platelet function monitoring clearly does not help,” the cardiologist said.
The ANTARCTIC results will likely lead to a revision of the American and European guidelines, which currently give a class IIb/level of evidence C recommendation for platelet function testing in high-risk situations.
“There is a huge literature showing that platelet reactivity affects clinical outcomes,” Dr. Montalescot continued. “One hypothesis now is that platelet reactivity may be only a marker of risk; you can modify it, but that has no impact on patient outcomes. We may be in the same situation here as with HDL cholesterol, for example.”
Discussant Steen Dalby Kristensen, MD, noted that ANTARCTIC is just the latest in a slew of negative randomized clinical trials of individualized antiplatelet therapy for coronary artery disease. In addition to ARCTIC, others include GRAVITAS, TRIGGER PCI, and ASCET. One study, the German/Austrian TROPICAL ACS trial, remains ongoing.
“It really is an intriguing concept that many of us have been fascinated by for years: to identify the sweet spot where, by measuring platelet aggregation and maybe changing the therapy, we can find just the right balance between bleeding and ischemia. The ANTARCTIC results are quite disappointing for platelet-monitoring enthusiasts. Is the whole concept wrong?” said Dr. Kristensen, professor of cardiology and head of the cardiovascular research center at Aarhus (Denmark) University Hospital.
“I think even more disappointing for me than the lack of impact on ischemic events was the bleeding. I would have anticipated that maybe bleeding could be avoided by adjusting the dose, but this was not the case,” he added.
But Stephan Gielen, MD, saw a silver lining in the negative results for ANTARCTIC.
“From my perspective as a clinical interventionalist, I’m happy that you ended up in the way you did. Putting things positively, this study confirms the safety of dual-platelet inhibition with prasugrel at the reduced dose of 5 mg in an elderly population. There is no need to go to the trouble of monitoring platelet function even in this elderly population, which I think for clinical practice is a good message,” said Dr. Gielen of Detmold (Germany) Hospital, who cochaired a press conference where Dr. Montalescot presented the ANTARCTIC results.
Simultaneously with Dr. Montalescot’s presentation at ESC 2016 in Rome, the ANTARCTIC results were published online (Lancet. 2016 Aug 26. doi: 10.1016/S0140-6736(16)31323-X).
ANTARCTIC was funded by Eli Lilly, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and the French Foundation for Heart Research. The presenter reported receiving research grants from and/or serving as a consultant to those organizations and numerous others.
AT THE ESC CONGRESS 2016
Key clinical point: Researchers have just about given up on the notion that monitoring platelet function in order to individualize antiplatelet therapy in patients undergoing PCI provides any clinical benefit.
Major finding: Individualized antiplatelet therapy based upon serial measurements of platelet function did not result in improved outcomes in elderly patients undergoing PCI for acute coronary syndrome (27.6% in the platelet monitoring group and 27.8% in conventionally managed patients).
Data source: ANTARCTIC was an open-label, blinded-endpoint randomized trial of tailored versus standard antiplatelet therapy in 877 elderly patients undergoing PCI for ACS.
Disclosures: ANTARCTIC was funded by Eli Lilly, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and the French Foundation for Heart Research. The presenter reported receiving research grants from and/or serving as a consultant to those organizations and numerous others.
New anticancer drugs linked to increased costs, life expectancy
New anticancer drugs are often expensive and have been accompanied by large increases in the cost of medical treatment, but they also are associated with gains in life expectancy, according to an analysis of Medicare data published online.
Investigators looked at four different types of cancer – breast, kidney, lung, and chronic myeloid leukemia (CML) – over two time periods: 1996-2000 and 2007-2011. Patients treated for CML during 2007-2011 had the largest increases in both average lifetime medical cost ($142,000) and months of life gained (22.1) over those treated during 1996-2000, reported David H. Howard, PhD, of Emory University, Atlanta, and his associates.
Breast cancer patients had the next-largest increases: 13.2 months of life expectancy and $72,000 in lifetime medical cost for those who received physician-administered intravenous drugs. For breast cancer patients who received only oral drugs, the increases were 2 months of life and $9,000 in lifetime cost, they noted.
Patients with kidney cancer had an average life-expectancy increase of 7.9 months and a cost increase of $45,000, but those estimates don’t fully reflect the effect of several oral drugs that were introduced after 2007 but did not come into widespread use during the entire study period, Dr. Howard and his associates noted (Health Aff. 2016 Sep 7;35[9]:1581-7).
Lung cancer patients experienced the smallest changes between the two time periods, with an increase in life expectancy of 3.9 months for those who received physician-administered anticancer drugs and a lifetime medical cost increase of $23,000. Patients with lung cancer who did not receive such drugs had increases of 0.7 months of life expectancy and $4,000 in lifetime medical costs.
The researchers used data from the Surveillance, Epidemiology, and End Results–Medicare database, and all costs are adjusted to 2012 dollars. Data collection was supported by the California Department of Health and funding for the study was provided by Pfizer. Three of Dr. Howard’s five coinvestigators are Pfizer employees.
New anticancer drugs are often expensive and have been accompanied by large increases in the cost of medical treatment, but they also are associated with gains in life expectancy, according to an analysis of Medicare data published online.
Investigators looked at four different types of cancer – breast, kidney, lung, and chronic myeloid leukemia (CML) – over two time periods: 1996-2000 and 2007-2011. Patients treated for CML during 2007-2011 had the largest increases in both average lifetime medical cost ($142,000) and months of life gained (22.1) over those treated during 1996-2000, reported David H. Howard, PhD, of Emory University, Atlanta, and his associates.
Breast cancer patients had the next-largest increases: 13.2 months of life expectancy and $72,000 in lifetime medical cost for those who received physician-administered intravenous drugs. For breast cancer patients who received only oral drugs, the increases were 2 months of life and $9,000 in lifetime cost, they noted.
Patients with kidney cancer had an average life-expectancy increase of 7.9 months and a cost increase of $45,000, but those estimates don’t fully reflect the effect of several oral drugs that were introduced after 2007 but did not come into widespread use during the entire study period, Dr. Howard and his associates noted (Health Aff. 2016 Sep 7;35[9]:1581-7).
Lung cancer patients experienced the smallest changes between the two time periods, with an increase in life expectancy of 3.9 months for those who received physician-administered anticancer drugs and a lifetime medical cost increase of $23,000. Patients with lung cancer who did not receive such drugs had increases of 0.7 months of life expectancy and $4,000 in lifetime medical costs.
The researchers used data from the Surveillance, Epidemiology, and End Results–Medicare database, and all costs are adjusted to 2012 dollars. Data collection was supported by the California Department of Health and funding for the study was provided by Pfizer. Three of Dr. Howard’s five coinvestigators are Pfizer employees.
New anticancer drugs are often expensive and have been accompanied by large increases in the cost of medical treatment, but they also are associated with gains in life expectancy, according to an analysis of Medicare data published online.
Investigators looked at four different types of cancer – breast, kidney, lung, and chronic myeloid leukemia (CML) – over two time periods: 1996-2000 and 2007-2011. Patients treated for CML during 2007-2011 had the largest increases in both average lifetime medical cost ($142,000) and months of life gained (22.1) over those treated during 1996-2000, reported David H. Howard, PhD, of Emory University, Atlanta, and his associates.
Breast cancer patients had the next-largest increases: 13.2 months of life expectancy and $72,000 in lifetime medical cost for those who received physician-administered intravenous drugs. For breast cancer patients who received only oral drugs, the increases were 2 months of life and $9,000 in lifetime cost, they noted.
Patients with kidney cancer had an average life-expectancy increase of 7.9 months and a cost increase of $45,000, but those estimates don’t fully reflect the effect of several oral drugs that were introduced after 2007 but did not come into widespread use during the entire study period, Dr. Howard and his associates noted (Health Aff. 2016 Sep 7;35[9]:1581-7).
Lung cancer patients experienced the smallest changes between the two time periods, with an increase in life expectancy of 3.9 months for those who received physician-administered anticancer drugs and a lifetime medical cost increase of $23,000. Patients with lung cancer who did not receive such drugs had increases of 0.7 months of life expectancy and $4,000 in lifetime medical costs.
The researchers used data from the Surveillance, Epidemiology, and End Results–Medicare database, and all costs are adjusted to 2012 dollars. Data collection was supported by the California Department of Health and funding for the study was provided by Pfizer. Three of Dr. Howard’s five coinvestigators are Pfizer employees.
FROM HEALTH AFFAIRS
