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Evolocumab doesn’t make patients dumb
WASHINGTON – Concerns about possible adverse cognitive effects from the new lipid-lowering drug evolocumab and from aggressive lowering of LDL cholesterol were largely put to rest with results from a nearly 2,000-patient study showing that a median 20 months of treatment with evolocumab caused no cognitive or memory decline, either compared with baseline measures or compared with similar patients randomized to placebo treatment.
A subgroup analysis in the study also showed that, even among patients who achieved and sustained LDL cholesterol below 25 mg/dL, no hint arose of an adverse effect on memory or cognition, said Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston.
“Every day in my office, patients tell me that statins make you dumb. Now I can comfortably tell my patients that we studied whether this drug [evolocumab] makes you dumb, and it doesn’t; nor did having an LDL cholesterol level below 25 mg/dL,” commented Sandra J. Lewis, MD, chief of cardiology at Legacy Good Samaritan Hospital in Portland, Ore.
The primary assessment tool Dr. Giugliano and his associates used in EBBINGHAUS was the Cambridge Neuropsychological Test Automated Battery (CANTAB) Assessments, a computer-based test of spatial working memory strategy index of executive function, and 1,204 patients underwent CANTAB testing both before they received their first dose of their assigned agent and also at the end of treatment. The scores of the patients on evolocumab virtually superimposed on those of patients in the placebo group, both at baseline and at the end of treatment, easily meeting the study’s prespecified definition of noninferiority, Dr. Giugliano reported at the annual meeting of the American College of Cardiology.
The CANTAB scores also showed no change from baseline over time in the individual subgroups of both evolocumab-treated and placebo-treated patients. The total absence of a signal of mental deterioration in the placebo patients who remained on statin treatment throughout the study provided new evidence that medium-term treatment with a statin was not linked with any change in memory or cognition.
EBBINGHAUS also assessed participants using several other memory and cognition tests, had patients complete an end-of-study survey of their perceptions of their mental function, and questioned participating physicians about patients’ mental performance. None of these measures showed any signals of impairment. A full description of the range of assessments used in EBBINGHAUS appeared recently in a published article (Clin Cardiol. 2017 Feb;40[2]:59-65).
Dr. Giugliano conceded that what remains unknown at this point is the possible impact of further prolonged treatment with a PCSK9 drug or from extended maintenance of LDL cholesterol levels at very low levels, effects that could continue for decades in the routine treatment of selected patients. He noted that patients who participated in FOURIER and in EBBINGHAUS are undergoing continued follow-up to gain better insight into the longer-term effects of their treatment.
EBBINGHAUS was sponsored by Amgen, the company that markets evolocumab (Repatha). Dr. Giugliano has been a consultant to and received research support from Amgen and from several other drug companies. Dr. Bhatt has received research support from Amgen, from Sanofi Regeneron associated with research on another PCSK9 inhibitor, and from several other drug companies, Dr. Lewis had no disclosures.
[email protected]
On Twitter @mitchelzoler
WASHINGTON – Concerns about possible adverse cognitive effects from the new lipid-lowering drug evolocumab and from aggressive lowering of LDL cholesterol were largely put to rest with results from a nearly 2,000-patient study showing that a median 20 months of treatment with evolocumab caused no cognitive or memory decline, either compared with baseline measures or compared with similar patients randomized to placebo treatment.
A subgroup analysis in the study also showed that, even among patients who achieved and sustained LDL cholesterol below 25 mg/dL, no hint arose of an adverse effect on memory or cognition, said Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston.
“Every day in my office, patients tell me that statins make you dumb. Now I can comfortably tell my patients that we studied whether this drug [evolocumab] makes you dumb, and it doesn’t; nor did having an LDL cholesterol level below 25 mg/dL,” commented Sandra J. Lewis, MD, chief of cardiology at Legacy Good Samaritan Hospital in Portland, Ore.
The primary assessment tool Dr. Giugliano and his associates used in EBBINGHAUS was the Cambridge Neuropsychological Test Automated Battery (CANTAB) Assessments, a computer-based test of spatial working memory strategy index of executive function, and 1,204 patients underwent CANTAB testing both before they received their first dose of their assigned agent and also at the end of treatment. The scores of the patients on evolocumab virtually superimposed on those of patients in the placebo group, both at baseline and at the end of treatment, easily meeting the study’s prespecified definition of noninferiority, Dr. Giugliano reported at the annual meeting of the American College of Cardiology.
The CANTAB scores also showed no change from baseline over time in the individual subgroups of both evolocumab-treated and placebo-treated patients. The total absence of a signal of mental deterioration in the placebo patients who remained on statin treatment throughout the study provided new evidence that medium-term treatment with a statin was not linked with any change in memory or cognition.
EBBINGHAUS also assessed participants using several other memory and cognition tests, had patients complete an end-of-study survey of their perceptions of their mental function, and questioned participating physicians about patients’ mental performance. None of these measures showed any signals of impairment. A full description of the range of assessments used in EBBINGHAUS appeared recently in a published article (Clin Cardiol. 2017 Feb;40[2]:59-65).
Dr. Giugliano conceded that what remains unknown at this point is the possible impact of further prolonged treatment with a PCSK9 drug or from extended maintenance of LDL cholesterol levels at very low levels, effects that could continue for decades in the routine treatment of selected patients. He noted that patients who participated in FOURIER and in EBBINGHAUS are undergoing continued follow-up to gain better insight into the longer-term effects of their treatment.
EBBINGHAUS was sponsored by Amgen, the company that markets evolocumab (Repatha). Dr. Giugliano has been a consultant to and received research support from Amgen and from several other drug companies. Dr. Bhatt has received research support from Amgen, from Sanofi Regeneron associated with research on another PCSK9 inhibitor, and from several other drug companies, Dr. Lewis had no disclosures.
[email protected]
On Twitter @mitchelzoler
WASHINGTON – Concerns about possible adverse cognitive effects from the new lipid-lowering drug evolocumab and from aggressive lowering of LDL cholesterol were largely put to rest with results from a nearly 2,000-patient study showing that a median 20 months of treatment with evolocumab caused no cognitive or memory decline, either compared with baseline measures or compared with similar patients randomized to placebo treatment.
A subgroup analysis in the study also showed that, even among patients who achieved and sustained LDL cholesterol below 25 mg/dL, no hint arose of an adverse effect on memory or cognition, said Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston.
“Every day in my office, patients tell me that statins make you dumb. Now I can comfortably tell my patients that we studied whether this drug [evolocumab] makes you dumb, and it doesn’t; nor did having an LDL cholesterol level below 25 mg/dL,” commented Sandra J. Lewis, MD, chief of cardiology at Legacy Good Samaritan Hospital in Portland, Ore.
The primary assessment tool Dr. Giugliano and his associates used in EBBINGHAUS was the Cambridge Neuropsychological Test Automated Battery (CANTAB) Assessments, a computer-based test of spatial working memory strategy index of executive function, and 1,204 patients underwent CANTAB testing both before they received their first dose of their assigned agent and also at the end of treatment. The scores of the patients on evolocumab virtually superimposed on those of patients in the placebo group, both at baseline and at the end of treatment, easily meeting the study’s prespecified definition of noninferiority, Dr. Giugliano reported at the annual meeting of the American College of Cardiology.
The CANTAB scores also showed no change from baseline over time in the individual subgroups of both evolocumab-treated and placebo-treated patients. The total absence of a signal of mental deterioration in the placebo patients who remained on statin treatment throughout the study provided new evidence that medium-term treatment with a statin was not linked with any change in memory or cognition.
EBBINGHAUS also assessed participants using several other memory and cognition tests, had patients complete an end-of-study survey of their perceptions of their mental function, and questioned participating physicians about patients’ mental performance. None of these measures showed any signals of impairment. A full description of the range of assessments used in EBBINGHAUS appeared recently in a published article (Clin Cardiol. 2017 Feb;40[2]:59-65).
Dr. Giugliano conceded that what remains unknown at this point is the possible impact of further prolonged treatment with a PCSK9 drug or from extended maintenance of LDL cholesterol levels at very low levels, effects that could continue for decades in the routine treatment of selected patients. He noted that patients who participated in FOURIER and in EBBINGHAUS are undergoing continued follow-up to gain better insight into the longer-term effects of their treatment.
EBBINGHAUS was sponsored by Amgen, the company that markets evolocumab (Repatha). Dr. Giugliano has been a consultant to and received research support from Amgen and from several other drug companies. Dr. Bhatt has received research support from Amgen, from Sanofi Regeneron associated with research on another PCSK9 inhibitor, and from several other drug companies, Dr. Lewis had no disclosures.
[email protected]
On Twitter @mitchelzoler
AT ACC 17
Key clinical point:
Major finding: Patients on evolocumab for 20 months had noninferior memory and executive function test scores, compared with patients on placebo.
Data source: EBBINGHAUS, a multicenter randomized trial with 1,974 patients.
Disclosures: EBBINGHAUS was sponsored by Amgen, the company that markets evolocumab (Repatha). Dr. Giugliano has been a consultant to and received research support from Amgen and from several other drug companies.
VIDEO: iFR outperforms FFR in two major trials
WASHINGTON – Instantaneous wave-free ratio (iFR) is the new evidence-based standard of care for invasive physiologic assessment of stable coronary lesions of intermediate angiographic severity, supplanting the older fractional flow reserve (FFR) technology, Matthias Gotberg, MD, said at the annual meeting of the American College of Cardiology.
The virtually identical results of these two trials should encourage more interventional cardiologists to incorporate physiologic assessment of stable coronary lesions into their clinical practice instead of relying solely on anatomic assessment by angiography, which abundant evidence shows is insufficiently accurate in identifying hemodynamically significant lesions warranting revascularization.
FFR never really caught on because of its limitations. DEFINE-FLAIR and iFR-SWEDEHEART show that iFR overcomes those limitations, said Dr. Gotberg, director of the cardiac catheterization laboratory at Skane University Hospital in Lund, Sweden.
The two studies showed that iFR was noninferior to FFR in the 1-year composite endpoint of all-cause mortality, nonfatal MI, or unplanned revascularization. And iFR was associated with significantly shorter procedure times, less stent utilization, and markedly less patient discomfort because, unlike FFR, it doesn’t require administration of adenosine to induce hyperemia.
Indeed, in iFR-SWEDEHEART, which included more than 2,000 randomized patients in three Scandinavian countries, only 3% of the iFR group reported experiencing chest pain, dyspnea, or other forms of discomfort during their procedure, compared with 68% of the FFR group, Dr. Gotberg explains in this video interview.[[{"fid":"192539","view_mode":"medstat_image_full_text","attributes":{"height":"390","width":"100%","class":"media-element file-medstat-image-full-text","data-delta":"1"},"fields":{"format":"medstat_image_full_text"},"type":"media","field_deltas":{"1":{"format":"medstat_image_full_text"}}}]]
WASHINGTON – Instantaneous wave-free ratio (iFR) is the new evidence-based standard of care for invasive physiologic assessment of stable coronary lesions of intermediate angiographic severity, supplanting the older fractional flow reserve (FFR) technology, Matthias Gotberg, MD, said at the annual meeting of the American College of Cardiology.
The virtually identical results of these two trials should encourage more interventional cardiologists to incorporate physiologic assessment of stable coronary lesions into their clinical practice instead of relying solely on anatomic assessment by angiography, which abundant evidence shows is insufficiently accurate in identifying hemodynamically significant lesions warranting revascularization.
FFR never really caught on because of its limitations. DEFINE-FLAIR and iFR-SWEDEHEART show that iFR overcomes those limitations, said Dr. Gotberg, director of the cardiac catheterization laboratory at Skane University Hospital in Lund, Sweden.
The two studies showed that iFR was noninferior to FFR in the 1-year composite endpoint of all-cause mortality, nonfatal MI, or unplanned revascularization. And iFR was associated with significantly shorter procedure times, less stent utilization, and markedly less patient discomfort because, unlike FFR, it doesn’t require administration of adenosine to induce hyperemia.
Indeed, in iFR-SWEDEHEART, which included more than 2,000 randomized patients in three Scandinavian countries, only 3% of the iFR group reported experiencing chest pain, dyspnea, or other forms of discomfort during their procedure, compared with 68% of the FFR group, Dr. Gotberg explains in this video interview.[[{"fid":"192539","view_mode":"medstat_image_full_text","attributes":{"height":"390","width":"100%","class":"media-element file-medstat-image-full-text","data-delta":"1"},"fields":{"format":"medstat_image_full_text"},"type":"media","field_deltas":{"1":{"format":"medstat_image_full_text"}}}]]
WASHINGTON – Instantaneous wave-free ratio (iFR) is the new evidence-based standard of care for invasive physiologic assessment of stable coronary lesions of intermediate angiographic severity, supplanting the older fractional flow reserve (FFR) technology, Matthias Gotberg, MD, said at the annual meeting of the American College of Cardiology.
The virtually identical results of these two trials should encourage more interventional cardiologists to incorporate physiologic assessment of stable coronary lesions into their clinical practice instead of relying solely on anatomic assessment by angiography, which abundant evidence shows is insufficiently accurate in identifying hemodynamically significant lesions warranting revascularization.
FFR never really caught on because of its limitations. DEFINE-FLAIR and iFR-SWEDEHEART show that iFR overcomes those limitations, said Dr. Gotberg, director of the cardiac catheterization laboratory at Skane University Hospital in Lund, Sweden.
The two studies showed that iFR was noninferior to FFR in the 1-year composite endpoint of all-cause mortality, nonfatal MI, or unplanned revascularization. And iFR was associated with significantly shorter procedure times, less stent utilization, and markedly less patient discomfort because, unlike FFR, it doesn’t require administration of adenosine to induce hyperemia.
Indeed, in iFR-SWEDEHEART, which included more than 2,000 randomized patients in three Scandinavian countries, only 3% of the iFR group reported experiencing chest pain, dyspnea, or other forms of discomfort during their procedure, compared with 68% of the FFR group, Dr. Gotberg explains in this video interview.[[{"fid":"192539","view_mode":"medstat_image_full_text","attributes":{"height":"390","width":"100%","class":"media-element file-medstat-image-full-text","data-delta":"1"},"fields":{"format":"medstat_image_full_text"},"type":"media","field_deltas":{"1":{"format":"medstat_image_full_text"}}}]]
AT ACC 17
Cardiovascular disease most common cause of death in CRC survivors
SEATTLE – Improvements in diagnosis and treatment have lengthened the survival time of patients with colorectal cancer, but the majority of deaths from CRC occur within the first 5 years.
According to new findings presented at the annual Society of Surgical Oncology Cancer Symposium, CRC as a cause of death is surpassed by cardiovascular disease (CVD) and second primary cancers as time goes on.
Dr. Lewis explained that CRC as a cause of death begins to plateau over time and other causes become more important.
“As time goes on, colorectal cancer becomes less prominent, and by year 8, cardiovascular death surpasses it. By year 10, colorectal cancer is surpassed by second cancers and neurologic diseases.”
Information about long-term health problems in long-term colorectal cancer survivors is limited. To address this, Dr. Lewis and his colleagues sought to understand the trends and causes of death over time.
They analyzed causes of death in CRC patients who have survived 5 years and longer using the California Cancer Registry (2000-2011) that is linked to inpatient records. From this database, 139,743 patients with CRC were identified, with 97,604 (69.8%) having been treated for disease originating from the colon and 42,139 (30.2%) from the rectum.
The median age of the patients at the time of presentation was 68 years; at 5 years after diagnosis, 70 years; and at 10 years, 74 years. The 5-year overall survival was 59.1%, and it was during that 5 years that 95% of cancer-specific deaths occurred.
During the first 5 years, the major cause of death was CRC, accounting for nearly two-thirds of the mortality (n = 38,992, 65.4%). This was followed by cardiovascular disease (n = 7,140, 12.0%), second primary cancer (n = 3,775, 6.3%), neurologic disease (n = 2,329, 3.9%), and pulmonary disease (n = 2,307, 3.9%).
The most common second primary malignancies affecting CRC survivors were lung and hematologic cancers, followed by pancreatic and liver cancers.
Overall, in long-term survivors, cardiovascular disease was the major cause of death (n = 2,163, 24.0%) although nearly as many deaths were due to CRC (2,094, 23.2%). This was followed by neurologic disease (n = 1,174, 13.0%), secondary primary cancer (n = 1,146, 12.7%), and pulmonary disease (n = 765, 8.5%).
There was no funding source disclosed in the abstract. Dr. Lewis had no disclosures.
SEATTLE – Improvements in diagnosis and treatment have lengthened the survival time of patients with colorectal cancer, but the majority of deaths from CRC occur within the first 5 years.
According to new findings presented at the annual Society of Surgical Oncology Cancer Symposium, CRC as a cause of death is surpassed by cardiovascular disease (CVD) and second primary cancers as time goes on.
Dr. Lewis explained that CRC as a cause of death begins to plateau over time and other causes become more important.
“As time goes on, colorectal cancer becomes less prominent, and by year 8, cardiovascular death surpasses it. By year 10, colorectal cancer is surpassed by second cancers and neurologic diseases.”
Information about long-term health problems in long-term colorectal cancer survivors is limited. To address this, Dr. Lewis and his colleagues sought to understand the trends and causes of death over time.
They analyzed causes of death in CRC patients who have survived 5 years and longer using the California Cancer Registry (2000-2011) that is linked to inpatient records. From this database, 139,743 patients with CRC were identified, with 97,604 (69.8%) having been treated for disease originating from the colon and 42,139 (30.2%) from the rectum.
The median age of the patients at the time of presentation was 68 years; at 5 years after diagnosis, 70 years; and at 10 years, 74 years. The 5-year overall survival was 59.1%, and it was during that 5 years that 95% of cancer-specific deaths occurred.
During the first 5 years, the major cause of death was CRC, accounting for nearly two-thirds of the mortality (n = 38,992, 65.4%). This was followed by cardiovascular disease (n = 7,140, 12.0%), second primary cancer (n = 3,775, 6.3%), neurologic disease (n = 2,329, 3.9%), and pulmonary disease (n = 2,307, 3.9%).
The most common second primary malignancies affecting CRC survivors were lung and hematologic cancers, followed by pancreatic and liver cancers.
Overall, in long-term survivors, cardiovascular disease was the major cause of death (n = 2,163, 24.0%) although nearly as many deaths were due to CRC (2,094, 23.2%). This was followed by neurologic disease (n = 1,174, 13.0%), secondary primary cancer (n = 1,146, 12.7%), and pulmonary disease (n = 765, 8.5%).
There was no funding source disclosed in the abstract. Dr. Lewis had no disclosures.
SEATTLE – Improvements in diagnosis and treatment have lengthened the survival time of patients with colorectal cancer, but the majority of deaths from CRC occur within the first 5 years.
According to new findings presented at the annual Society of Surgical Oncology Cancer Symposium, CRC as a cause of death is surpassed by cardiovascular disease (CVD) and second primary cancers as time goes on.
Dr. Lewis explained that CRC as a cause of death begins to plateau over time and other causes become more important.
“As time goes on, colorectal cancer becomes less prominent, and by year 8, cardiovascular death surpasses it. By year 10, colorectal cancer is surpassed by second cancers and neurologic diseases.”
Information about long-term health problems in long-term colorectal cancer survivors is limited. To address this, Dr. Lewis and his colleagues sought to understand the trends and causes of death over time.
They analyzed causes of death in CRC patients who have survived 5 years and longer using the California Cancer Registry (2000-2011) that is linked to inpatient records. From this database, 139,743 patients with CRC were identified, with 97,604 (69.8%) having been treated for disease originating from the colon and 42,139 (30.2%) from the rectum.
The median age of the patients at the time of presentation was 68 years; at 5 years after diagnosis, 70 years; and at 10 years, 74 years. The 5-year overall survival was 59.1%, and it was during that 5 years that 95% of cancer-specific deaths occurred.
During the first 5 years, the major cause of death was CRC, accounting for nearly two-thirds of the mortality (n = 38,992, 65.4%). This was followed by cardiovascular disease (n = 7,140, 12.0%), second primary cancer (n = 3,775, 6.3%), neurologic disease (n = 2,329, 3.9%), and pulmonary disease (n = 2,307, 3.9%).
The most common second primary malignancies affecting CRC survivors were lung and hematologic cancers, followed by pancreatic and liver cancers.
Overall, in long-term survivors, cardiovascular disease was the major cause of death (n = 2,163, 24.0%) although nearly as many deaths were due to CRC (2,094, 23.2%). This was followed by neurologic disease (n = 1,174, 13.0%), secondary primary cancer (n = 1,146, 12.7%), and pulmonary disease (n = 765, 8.5%).
There was no funding source disclosed in the abstract. Dr. Lewis had no disclosures.
AT SSO 2017
Key clinical point: Long-term colorectal cancer survivors generally will die from other causes.
Major finding: By year 8, cardiovascular disease surpasses colorectal cancer in survivors, as the leading cause of death.
Data source: Large cancer registry with almost 140,000 colorectal cancer patients.
Disclosures: There was no funding source disclosed in the abstract. Dr. Lewis had no disclosures.
Drugs demonstrate similar safety profile in ACS trial
WASHINGTON, DC—Results of a phase 2 trial suggest rivaroxaban and aspirin have similar safety profiles in patients with acute coronary syndrome (ACS) who are also taking a P2Y12 inhibitor.
Researchers found that, overall, the risk of bleeding was similar whether patients received aspirin or rivaroxaban.
There was no significant difference between the groups when the researchers used TIMI, GUSTO, or BARC bleeding definitions.
However, patients who received rivaroxaban did have a significantly increased risk of bleeding according to the ISTH major bleeding definition.
There was no significant difference between the treatment groups when it came to the study’s efficacy endpoints, although the researchers said the study was not adequately powered to assess efficacy.
These results were presented at the American College of Cardiology’s 66th Annual Scientific Session and published simultaneously in The Lancet.
The study, known as GEMINI-ACS-1, was funded by Janssen Research & Development and Bayer AG.
In this trial, researchers compared rivaroxaban (given at 2.5 mg twice daily) and aspirin (at 100 mg once daily) in patients with ACS who were also receiving clopidogrel or ticagrelor for the secondary prevention of cardiovascular events.
The trial included 3037 adults with unstable angina, non-ST segment elevation myocardial infarction, or ST segment elevation myocardial infarction. Patients had positive cardiac biomarkers and either ischemic electrocardiographic changes or an atherosclerotic culprit lesion identified during angiography.
Within 10 days of hospital admission for ACS, the patients were randomized to receive aspirin (n=1518) or rivaroxaban (n=1519). Patients also received clopidogrel (n=1333) or ticagrelor (n=1704) based on investigator preference.
Patients received a minimum of 180 days of study treatment. The median treatment duration was 291 days.
Safety
The study’s primary endpoint was TIMI clinically significant bleeding not related to coronary artery bypass grafting (CABG) up to day 390.
This type of bleeding occurred in 5.3% of patients in the rivaroxaban group and 4.9% of patients in the aspirin group. The hazard ratio (HR) was 1.09 (P=0.5840).
The researchers also assessed other types of bleeding and used other bleeding definitions. The HRs for these endpoints (with aspirin as the reference) were as follows.
- TIMI major bleeding, HR=1.25 (P=0.6341)
- TIMI non-CABG major bleeding, HR=1.25 (P=0.6341)
- TIMI minor bleeding, HR=2.25 (P=0.1664)
- TIMI bleeding requiring medical attention, HR=1.01 (P=0.9581)
- TIMI insignificant bleeding, HR=0.84 (P=0.5504)
- GUSTO life-threatening or severe bleeding, HR=1.50 (P=0.6571)
- GUSTO life-threatening, severe, or moderate bleeding, HR=1.58 (P=0.3395)
- GUSTO life-threatening, severe, moderate, or mild bleeding, HR=1.04 (P=0.7869)
- BARC 3a and higher bleeding, HR=1.70 (P=0.1263)
- BARC 3b and higher bleeding, HR=1.38 (P=0.4882)
- ISTH major bleeding, HR=1.83 (P=0.0420)
Efficacy
Researchers also examined several exploratory efficacy endpoints. For the composite efficacy endpoint (which included cardiovascular death, myocardial infarction, stroke, and stent thrombosis), the 2 treatment groups had similar rates.
Five percent of patients in the rivaroxaban group and 4.7% of patients in the aspirin group experienced one of these cardiovascular events. The HR was 1.06 (P=0.7316).
There was no significant difference between the treatment arms for the individual components of the efficacy endpoint or for all-cause death.
The HRs were 1.12 (P=0.7401) for cardiovascular death, 1.15 (P=0.4872) for myocardial infarction, 0.58 (P=0.2506) for stroke, 1.37 (P=0.4917) for definite stent thrombosis, and 0.95 (P=0.8771) for all-cause death. 
WASHINGTON, DC—Results of a phase 2 trial suggest rivaroxaban and aspirin have similar safety profiles in patients with acute coronary syndrome (ACS) who are also taking a P2Y12 inhibitor.
Researchers found that, overall, the risk of bleeding was similar whether patients received aspirin or rivaroxaban.
There was no significant difference between the groups when the researchers used TIMI, GUSTO, or BARC bleeding definitions.
However, patients who received rivaroxaban did have a significantly increased risk of bleeding according to the ISTH major bleeding definition.
There was no significant difference between the treatment groups when it came to the study’s efficacy endpoints, although the researchers said the study was not adequately powered to assess efficacy.
These results were presented at the American College of Cardiology’s 66th Annual Scientific Session and published simultaneously in The Lancet.
The study, known as GEMINI-ACS-1, was funded by Janssen Research & Development and Bayer AG.
In this trial, researchers compared rivaroxaban (given at 2.5 mg twice daily) and aspirin (at 100 mg once daily) in patients with ACS who were also receiving clopidogrel or ticagrelor for the secondary prevention of cardiovascular events.
The trial included 3037 adults with unstable angina, non-ST segment elevation myocardial infarction, or ST segment elevation myocardial infarction. Patients had positive cardiac biomarkers and either ischemic electrocardiographic changes or an atherosclerotic culprit lesion identified during angiography.
Within 10 days of hospital admission for ACS, the patients were randomized to receive aspirin (n=1518) or rivaroxaban (n=1519). Patients also received clopidogrel (n=1333) or ticagrelor (n=1704) based on investigator preference.
Patients received a minimum of 180 days of study treatment. The median treatment duration was 291 days.
Safety
The study’s primary endpoint was TIMI clinically significant bleeding not related to coronary artery bypass grafting (CABG) up to day 390.
This type of bleeding occurred in 5.3% of patients in the rivaroxaban group and 4.9% of patients in the aspirin group. The hazard ratio (HR) was 1.09 (P=0.5840).
The researchers also assessed other types of bleeding and used other bleeding definitions. The HRs for these endpoints (with aspirin as the reference) were as follows.
- TIMI major bleeding, HR=1.25 (P=0.6341)
- TIMI non-CABG major bleeding, HR=1.25 (P=0.6341)
- TIMI minor bleeding, HR=2.25 (P=0.1664)
- TIMI bleeding requiring medical attention, HR=1.01 (P=0.9581)
- TIMI insignificant bleeding, HR=0.84 (P=0.5504)
- GUSTO life-threatening or severe bleeding, HR=1.50 (P=0.6571)
- GUSTO life-threatening, severe, or moderate bleeding, HR=1.58 (P=0.3395)
- GUSTO life-threatening, severe, moderate, or mild bleeding, HR=1.04 (P=0.7869)
- BARC 3a and higher bleeding, HR=1.70 (P=0.1263)
- BARC 3b and higher bleeding, HR=1.38 (P=0.4882)
- ISTH major bleeding, HR=1.83 (P=0.0420)
Efficacy
Researchers also examined several exploratory efficacy endpoints. For the composite efficacy endpoint (which included cardiovascular death, myocardial infarction, stroke, and stent thrombosis), the 2 treatment groups had similar rates.
Five percent of patients in the rivaroxaban group and 4.7% of patients in the aspirin group experienced one of these cardiovascular events. The HR was 1.06 (P=0.7316).
There was no significant difference between the treatment arms for the individual components of the efficacy endpoint or for all-cause death.
The HRs were 1.12 (P=0.7401) for cardiovascular death, 1.15 (P=0.4872) for myocardial infarction, 0.58 (P=0.2506) for stroke, 1.37 (P=0.4917) for definite stent thrombosis, and 0.95 (P=0.8771) for all-cause death.
WASHINGTON, DC—Results of a phase 2 trial suggest rivaroxaban and aspirin have similar safety profiles in patients with acute coronary syndrome (ACS) who are also taking a P2Y12 inhibitor.
Researchers found that, overall, the risk of bleeding was similar whether patients received aspirin or rivaroxaban.
There was no significant difference between the groups when the researchers used TIMI, GUSTO, or BARC bleeding definitions.
However, patients who received rivaroxaban did have a significantly increased risk of bleeding according to the ISTH major bleeding definition.
There was no significant difference between the treatment groups when it came to the study’s efficacy endpoints, although the researchers said the study was not adequately powered to assess efficacy.
These results were presented at the American College of Cardiology’s 66th Annual Scientific Session and published simultaneously in The Lancet.
The study, known as GEMINI-ACS-1, was funded by Janssen Research & Development and Bayer AG.
In this trial, researchers compared rivaroxaban (given at 2.5 mg twice daily) and aspirin (at 100 mg once daily) in patients with ACS who were also receiving clopidogrel or ticagrelor for the secondary prevention of cardiovascular events.
The trial included 3037 adults with unstable angina, non-ST segment elevation myocardial infarction, or ST segment elevation myocardial infarction. Patients had positive cardiac biomarkers and either ischemic electrocardiographic changes or an atherosclerotic culprit lesion identified during angiography.
Within 10 days of hospital admission for ACS, the patients were randomized to receive aspirin (n=1518) or rivaroxaban (n=1519). Patients also received clopidogrel (n=1333) or ticagrelor (n=1704) based on investigator preference.
Patients received a minimum of 180 days of study treatment. The median treatment duration was 291 days.
Safety
The study’s primary endpoint was TIMI clinically significant bleeding not related to coronary artery bypass grafting (CABG) up to day 390.
This type of bleeding occurred in 5.3% of patients in the rivaroxaban group and 4.9% of patients in the aspirin group. The hazard ratio (HR) was 1.09 (P=0.5840).
The researchers also assessed other types of bleeding and used other bleeding definitions. The HRs for these endpoints (with aspirin as the reference) were as follows.
- TIMI major bleeding, HR=1.25 (P=0.6341)
- TIMI non-CABG major bleeding, HR=1.25 (P=0.6341)
- TIMI minor bleeding, HR=2.25 (P=0.1664)
- TIMI bleeding requiring medical attention, HR=1.01 (P=0.9581)
- TIMI insignificant bleeding, HR=0.84 (P=0.5504)
- GUSTO life-threatening or severe bleeding, HR=1.50 (P=0.6571)
- GUSTO life-threatening, severe, or moderate bleeding, HR=1.58 (P=0.3395)
- GUSTO life-threatening, severe, moderate, or mild bleeding, HR=1.04 (P=0.7869)
- BARC 3a and higher bleeding, HR=1.70 (P=0.1263)
- BARC 3b and higher bleeding, HR=1.38 (P=0.4882)
- ISTH major bleeding, HR=1.83 (P=0.0420)
Efficacy
Researchers also examined several exploratory efficacy endpoints. For the composite efficacy endpoint (which included cardiovascular death, myocardial infarction, stroke, and stent thrombosis), the 2 treatment groups had similar rates.
Five percent of patients in the rivaroxaban group and 4.7% of patients in the aspirin group experienced one of these cardiovascular events. The HR was 1.06 (P=0.7316).
There was no significant difference between the treatment arms for the individual components of the efficacy endpoint or for all-cause death.
The HRs were 1.12 (P=0.7401) for cardiovascular death, 1.15 (P=0.4872) for myocardial infarction, 0.58 (P=0.2506) for stroke, 1.37 (P=0.4917) for definite stent thrombosis, and 0.95 (P=0.8771) for all-cause death.
PE patients rarely receive CDT or ST, study shows
WASHINGTON, DC—New research suggests US patients with pulmonary embolism (PE) rarely receive catheter-directed thrombolysis (CDT) or systemic thrombolysis (ST).
Investigators analyzed data from more than 100,000 patients who were hospitalized for PE and found that roughly 2% received CDT or ST.
These findings were presented at the American College of Cardiology’s 66th Annual Scientific Session (abstract 904-12).
“For years, ST and CDT have been available for use in patients with PE,” said study investigator Srinath Adusumalli, MD, of the University of Pennsylvania in Philadelphia.
“However, there has been little research done to understand how these therapies are being utilized in the real world. Our initial data suggest that, in fact, both ST and CDT are used infrequently to treat PE, including in young, critically ill patients who may experience the highest clinical benefit from those therapies.”
Dr Adusumalli and his colleagues performed a retrospective study in which they collected data from the OptumInsight national commercial insurance claims database.
The team identified 100,744 patients who had been hospitalized with PE during a 10-year period (2004-2014). About 2% of these patients (2.2%, n=2175) received either CDT (n=761) or ST (n=1414).
During the period studied, the number of PE hospitalizations increased by 306% (P<0.001), while the number of patients treated with CDT increased by 197% (P=0.001) and the number treated with ST increased by 514% (P<0.001).
The investigators said these findings are clinically useful and could impact decisions about patient care, but more research is needed.
“This study is the first in a 2-step research plan,” noted Bram Geller, MD, of the University of Pennsylvania.
“[O]ur next phase will be to actually evaluate the safety and clinical effectiveness of CDT versus ST by exploring patient outcomes in the OptumInsight commercial insurance claims database.”
WASHINGTON, DC—New research suggests US patients with pulmonary embolism (PE) rarely receive catheter-directed thrombolysis (CDT) or systemic thrombolysis (ST).
Investigators analyzed data from more than 100,000 patients who were hospitalized for PE and found that roughly 2% received CDT or ST.
These findings were presented at the American College of Cardiology’s 66th Annual Scientific Session (abstract 904-12).
“For years, ST and CDT have been available for use in patients with PE,” said study investigator Srinath Adusumalli, MD, of the University of Pennsylvania in Philadelphia.
“However, there has been little research done to understand how these therapies are being utilized in the real world. Our initial data suggest that, in fact, both ST and CDT are used infrequently to treat PE, including in young, critically ill patients who may experience the highest clinical benefit from those therapies.”
Dr Adusumalli and his colleagues performed a retrospective study in which they collected data from the OptumInsight national commercial insurance claims database.
The team identified 100,744 patients who had been hospitalized with PE during a 10-year period (2004-2014). About 2% of these patients (2.2%, n=2175) received either CDT (n=761) or ST (n=1414).
During the period studied, the number of PE hospitalizations increased by 306% (P<0.001), while the number of patients treated with CDT increased by 197% (P=0.001) and the number treated with ST increased by 514% (P<0.001).
The investigators said these findings are clinically useful and could impact decisions about patient care, but more research is needed.
“This study is the first in a 2-step research plan,” noted Bram Geller, MD, of the University of Pennsylvania.
“[O]ur next phase will be to actually evaluate the safety and clinical effectiveness of CDT versus ST by exploring patient outcomes in the OptumInsight commercial insurance claims database.”
WASHINGTON, DC—New research suggests US patients with pulmonary embolism (PE) rarely receive catheter-directed thrombolysis (CDT) or systemic thrombolysis (ST).
Investigators analyzed data from more than 100,000 patients who were hospitalized for PE and found that roughly 2% received CDT or ST.
These findings were presented at the American College of Cardiology’s 66th Annual Scientific Session (abstract 904-12).
“For years, ST and CDT have been available for use in patients with PE,” said study investigator Srinath Adusumalli, MD, of the University of Pennsylvania in Philadelphia.
“However, there has been little research done to understand how these therapies are being utilized in the real world. Our initial data suggest that, in fact, both ST and CDT are used infrequently to treat PE, including in young, critically ill patients who may experience the highest clinical benefit from those therapies.”
Dr Adusumalli and his colleagues performed a retrospective study in which they collected data from the OptumInsight national commercial insurance claims database.
The team identified 100,744 patients who had been hospitalized with PE during a 10-year period (2004-2014). About 2% of these patients (2.2%, n=2175) received either CDT (n=761) or ST (n=1414).
During the period studied, the number of PE hospitalizations increased by 306% (P<0.001), while the number of patients treated with CDT increased by 197% (P=0.001) and the number treated with ST increased by 514% (P<0.001).
The investigators said these findings are clinically useful and could impact decisions about patient care, but more research is needed.
“This study is the first in a 2-step research plan,” noted Bram Geller, MD, of the University of Pennsylvania.
“[O]ur next phase will be to actually evaluate the safety and clinical effectiveness of CDT versus ST by exploring patient outcomes in the OptumInsight commercial insurance claims database.”
BNP flags high atrial fibrillation prevalence in ESUS stroke
HOUSTON – Following an embolic stroke of undetermined source, a patient’s serum level of brain natriuretic peptide may identify patients at high risk of having covert atrial fibrillation that warrants assessment by prolonged arrhythmia monitoring, based on a post hoc analysis of data collected from 373 patients.
The analysis showed that in older patients with a recent embolic stroke of undetermined source (ESUS) who had a serum brain natriuretic peptide (BNP) level of 100 pg/mL or greater, the prevalence of atrial fibrillation (AF) detected by up to 30 days of Holter monitoring was 33%. In contrast the AF prevalence was 4% among similar ESUS patients with a lower BNP level, Rolf Wachter, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“This evidence is pretty compelling,” commented Hooman Kamel, MD, a neurologist at Weill Cornell Medicine in New York. “We already use other lab tests that have less evidence supporting their use than this, and checking BNP is a simple lab test.”
The results showed that monitoring identified AF in 5% of the control patients and in 14% of those who underwent extended monitoring, a statistically significant difference (Lancet Neurol. 2017 Apr;16[4]:282-90).
Dr. Wachter and his colleagues had baseline BNP measurements for 373 of the patients and analyzed the prevalence of AF based on these levels. The patients averaged 72 years old. Among those with BNP values of at least 100 pg/mL, prolonged arrhythmia monitoring found AF in 33%, while briefer, conventional monitoring found AF in about 4%. This meant that for every three patients receiving prolonged arrhythmia scrutiny in this subgroup, the assessment found one patient with AF. But among patients with a serum BNP of less than 100 pg/mL, prolonged arrhythmia assessment yielded a 10% rate of AF detection, compared with about 4% in the controls, meaning that for every 18 patients screened prolonged Holter monitoring detected one additional case of AF, he reported.
This relationship presumably exists because higher BNP levels identify patients with structural heart abnormalities, a subgroup at increased risk for AF, Dr. Wachter explained. He cautioned that, because this was a post hoc analysis, he would like to see the findings confirmed in prospective studies.
Dr. Wachter has been a speaker on behalf of Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo and has received research support from Boehringer Ingelheim. The FIND-AFRANDOMISED trial received funding from Boehringer Ingelheim.
[email protected]
On Twitter @mitchelzoler
HOUSTON – Following an embolic stroke of undetermined source, a patient’s serum level of brain natriuretic peptide may identify patients at high risk of having covert atrial fibrillation that warrants assessment by prolonged arrhythmia monitoring, based on a post hoc analysis of data collected from 373 patients.
The analysis showed that in older patients with a recent embolic stroke of undetermined source (ESUS) who had a serum brain natriuretic peptide (BNP) level of 100 pg/mL or greater, the prevalence of atrial fibrillation (AF) detected by up to 30 days of Holter monitoring was 33%. In contrast the AF prevalence was 4% among similar ESUS patients with a lower BNP level, Rolf Wachter, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“This evidence is pretty compelling,” commented Hooman Kamel, MD, a neurologist at Weill Cornell Medicine in New York. “We already use other lab tests that have less evidence supporting their use than this, and checking BNP is a simple lab test.”
The results showed that monitoring identified AF in 5% of the control patients and in 14% of those who underwent extended monitoring, a statistically significant difference (Lancet Neurol. 2017 Apr;16[4]:282-90).
Dr. Wachter and his colleagues had baseline BNP measurements for 373 of the patients and analyzed the prevalence of AF based on these levels. The patients averaged 72 years old. Among those with BNP values of at least 100 pg/mL, prolonged arrhythmia monitoring found AF in 33%, while briefer, conventional monitoring found AF in about 4%. This meant that for every three patients receiving prolonged arrhythmia scrutiny in this subgroup, the assessment found one patient with AF. But among patients with a serum BNP of less than 100 pg/mL, prolonged arrhythmia assessment yielded a 10% rate of AF detection, compared with about 4% in the controls, meaning that for every 18 patients screened prolonged Holter monitoring detected one additional case of AF, he reported.
This relationship presumably exists because higher BNP levels identify patients with structural heart abnormalities, a subgroup at increased risk for AF, Dr. Wachter explained. He cautioned that, because this was a post hoc analysis, he would like to see the findings confirmed in prospective studies.
Dr. Wachter has been a speaker on behalf of Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo and has received research support from Boehringer Ingelheim. The FIND-AFRANDOMISED trial received funding from Boehringer Ingelheim.
[email protected]
On Twitter @mitchelzoler
HOUSTON – Following an embolic stroke of undetermined source, a patient’s serum level of brain natriuretic peptide may identify patients at high risk of having covert atrial fibrillation that warrants assessment by prolonged arrhythmia monitoring, based on a post hoc analysis of data collected from 373 patients.
The analysis showed that in older patients with a recent embolic stroke of undetermined source (ESUS) who had a serum brain natriuretic peptide (BNP) level of 100 pg/mL or greater, the prevalence of atrial fibrillation (AF) detected by up to 30 days of Holter monitoring was 33%. In contrast the AF prevalence was 4% among similar ESUS patients with a lower BNP level, Rolf Wachter, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“This evidence is pretty compelling,” commented Hooman Kamel, MD, a neurologist at Weill Cornell Medicine in New York. “We already use other lab tests that have less evidence supporting their use than this, and checking BNP is a simple lab test.”
The results showed that monitoring identified AF in 5% of the control patients and in 14% of those who underwent extended monitoring, a statistically significant difference (Lancet Neurol. 2017 Apr;16[4]:282-90).
Dr. Wachter and his colleagues had baseline BNP measurements for 373 of the patients and analyzed the prevalence of AF based on these levels. The patients averaged 72 years old. Among those with BNP values of at least 100 pg/mL, prolonged arrhythmia monitoring found AF in 33%, while briefer, conventional monitoring found AF in about 4%. This meant that for every three patients receiving prolonged arrhythmia scrutiny in this subgroup, the assessment found one patient with AF. But among patients with a serum BNP of less than 100 pg/mL, prolonged arrhythmia assessment yielded a 10% rate of AF detection, compared with about 4% in the controls, meaning that for every 18 patients screened prolonged Holter monitoring detected one additional case of AF, he reported.
This relationship presumably exists because higher BNP levels identify patients with structural heart abnormalities, a subgroup at increased risk for AF, Dr. Wachter explained. He cautioned that, because this was a post hoc analysis, he would like to see the findings confirmed in prospective studies.
Dr. Wachter has been a speaker on behalf of Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo and has received research support from Boehringer Ingelheim. The FIND-AFRANDOMISED trial received funding from Boehringer Ingelheim.
[email protected]
On Twitter @mitchelzoler
AT THE INTERNATIONAL STROKE CONFERENCE
Key clinical point:
Major finding: Following ESUS, patients with a BNP of 100 pg/mL or greater had a 33% prevalence of AF.
Data source: A post hoc analysis of 373 German patients enrolled in the FIND-AFRANDOMISED trial.
Disclosures: Dr. Wachter has been a speaker on behalf of Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo and has received research support from Boehringer Ingelheim. The FIND-AFRANDOMISED trial received funding from Boehringer Ingelheim.
VIDEO: Evolocumab caused no cognitive issues in FOURIER substudy
WASHINGTON – Don’t give the cognitive effects of evolocumab a second thought, results from a preplanned substudy of the landmark FOURIER study that assessed the impact of this PCSK9 inhibitor on memory or other measures of cognition in a random subgroup of 1,973 patients enrolled in the main study suggest.
Based on these results “I wouldn’t be concerned about adverse cognitive effects” in patients treated with evolocumab (Repatha) or, for the time being, any other PCSK9 inhibitor, said Robert P. Giugliano, MD, in a video interview at the annual meeting of the American College of Cardiology”
Concerns about the cognitive effects of the drugs in this class of lipid-lowering drugs have lingered following suggestions of a possible problem that arose during earlier, much smaller studies of these agents as well as similar concerns that arose about statins that have been perpetuated through misleading posts on the Internet.
The battery of memory and cognition assessments used in EBBINGHAUS, the FOURIER substudy, should lay concerns about brain effects of evolocumab to rest, at least within the context of the median 26 months of treatment that patients in FOURIER received, said Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston and lead investigator of the EBBINGHAUS substudy. Further analysis also showed that, even among patients who achieved LDL cholesterol levels of less than 25 mg/dL, treatment with evolocumab appeared to cause no deterioration of the measured mental functions.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
WASHINGTON – Don’t give the cognitive effects of evolocumab a second thought, results from a preplanned substudy of the landmark FOURIER study that assessed the impact of this PCSK9 inhibitor on memory or other measures of cognition in a random subgroup of 1,973 patients enrolled in the main study suggest.
Based on these results “I wouldn’t be concerned about adverse cognitive effects” in patients treated with evolocumab (Repatha) or, for the time being, any other PCSK9 inhibitor, said Robert P. Giugliano, MD, in a video interview at the annual meeting of the American College of Cardiology”
Concerns about the cognitive effects of the drugs in this class of lipid-lowering drugs have lingered following suggestions of a possible problem that arose during earlier, much smaller studies of these agents as well as similar concerns that arose about statins that have been perpetuated through misleading posts on the Internet.
The battery of memory and cognition assessments used in EBBINGHAUS, the FOURIER substudy, should lay concerns about brain effects of evolocumab to rest, at least within the context of the median 26 months of treatment that patients in FOURIER received, said Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston and lead investigator of the EBBINGHAUS substudy. Further analysis also showed that, even among patients who achieved LDL cholesterol levels of less than 25 mg/dL, treatment with evolocumab appeared to cause no deterioration of the measured mental functions.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
WASHINGTON – Don’t give the cognitive effects of evolocumab a second thought, results from a preplanned substudy of the landmark FOURIER study that assessed the impact of this PCSK9 inhibitor on memory or other measures of cognition in a random subgroup of 1,973 patients enrolled in the main study suggest.
Based on these results “I wouldn’t be concerned about adverse cognitive effects” in patients treated with evolocumab (Repatha) or, for the time being, any other PCSK9 inhibitor, said Robert P. Giugliano, MD, in a video interview at the annual meeting of the American College of Cardiology”
Concerns about the cognitive effects of the drugs in this class of lipid-lowering drugs have lingered following suggestions of a possible problem that arose during earlier, much smaller studies of these agents as well as similar concerns that arose about statins that have been perpetuated through misleading posts on the Internet.
The battery of memory and cognition assessments used in EBBINGHAUS, the FOURIER substudy, should lay concerns about brain effects of evolocumab to rest, at least within the context of the median 26 months of treatment that patients in FOURIER received, said Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston and lead investigator of the EBBINGHAUS substudy. Further analysis also showed that, even among patients who achieved LDL cholesterol levels of less than 25 mg/dL, treatment with evolocumab appeared to cause no deterioration of the measured mental functions.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
AT ACC 2017
Evolocumab strikes gold in FOURIER trial
WASHINGTON – The PCSK9 inhibitor evolocumab reduced the incidence of the composite endpoint of cardiovascular death, MI, or stroke by an additional 20% in patients with established cardiovascular disease who were already on background maximum-tolerated statin therapy in the landmark FOURIER trial, Marc S. Sabatine, MD, reported at the annual meeting of the American College of Cardiology.
FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) was eagerly anticipated as the first dedicated cardiovascular outcomes trial to report results for a proprotein convertase subtilisin/kexin type 9 inhibitor, the novel drug class that achieves previously unattainable LDL lowering.
FOURIER randomized 27,564 patients with preexisting high-risk cardiovascular disease in 49 countries to double-blind therapy with subcutaneous evolocumab (Repatha) at either 140 mg every 2 weeks or 420 mg once monthly or to placebo injections. Participants had a baseline LDL-cholesterol level of 70 mg/dL or above while on statin therapy, which continued throughout the study. Sixty-nine percent of subjects were on high-intensity statin therapy, and the rest were on a moderate-intensity statin.
The median LDL level plunged from 92 mg/dL at baseline to 30 mg/dL in the evolocumab group, a 59% reduction. Moreover, one-quarter of patients on evolocumab achieved an LDL below 20 mg/dL. And this effect remained durable over the median 26 months of study follow-up.
“The LDL reduction achieved with evolocumab was rock steady over time,” observed Dr. Sabatine, professor of medicine at Harvard Medical School, Boston, and chair of the Thrombolysis in Myocardial Infarction Study Group.
The primary study endpoint – a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization – occurred in 11.3% of controls and 9.8% of the evolocumab group, for a significant 15% relative risk reduction. But Dr. Sabatine drew attention to the prespecified and fully powered secondary endpoint of cardiovascular death, MI, or stroke, which he considers more clinically relevant: 7.4% in controls, compared with 5.9% in the evolocumab group, for a 20% reduction in risk.
The cardiovascular benefits of greater lipid lowering grew over time. The evolocumab group’s relative risk reduction in the secondary composite endpoint was 16% in the first 12 months of follow-up and 25% beyond 12 months.
Even more impressively, the relative risk reduction in the stripped-down secondary endpoint of fatal or nonfatal MI or stroke was 19% in the first 12 months and 33%, compared with placebo, beyond 12 months.
The benefit in terms of cardiovascular risk reduction was consistent across baseline LDL subgroups, including those in the lowest baseline quartile, whose average baseline LDL was 74 mg/dL. Thus, the former LDL goal of a target below 70 mg/dL as representing maximum benefit has flown out the window.
“Even lower LDL appears to be even better, now down in this trial to 22 mg/dL,” the cardiologist declared.
There was no significant difference between the two study arms in the cardiovascular mortality rate, although Dr. Sabatine didn’t consider that surprising.
“Over the past decade, none of the trials of more intensive LDL lowering when compared with patients on moderate-intensity LDL-lowering therapy showed a significant reduction in cardiovascular mortality, which thankfully is now less common after acute MI and acute stroke than it had been in the past,” he said.
The number needed to treat (NNT) in order to prevent one additional cardiovascular death, MI, or stroke, based upon the current 3-year follow-up data, is roughly 50, according to Dr. Sabatine. Projecting out to 5 years, based upon the close fit between FOURIER and the data from the Cholesterol Treatment Trialists Collaboration, the NNT at 5 years for evolocumab is about 30, although the true NNT may actually prove to be smaller than that, given the steadily increasing benefit seen through 3 years. The projected 5-year NNT for the composite of coronary revascularization, cardiovascular death, MI, or stroke drops to about 20, he added.
The treatment was safe and well tolerated. The rate of study discontinuation attributable to treatment-related adverse events was low, at about 1.5% in both treatment arms. The rates of neurocognitive adverse events, new-onset diabetes, cataracts, and muscle-related complaints didn’t differ between the evolocumab and placebo groups, either. Of note, no one developed neutralizing antibodies to evolocumab. Long-term follow-up will continue in roughly 6,000 FOURIER participants.
Discussant Pamela B. Morris, MD, said FOURIER contains an important secondary message that mustn’t get lost in the enthusiasm for a safe and effective new drug.
“I’m very struck by the high event rate in this population, even with LDL levels down to 30 mg/dL. I think what that says is that although LDL cholesterol is etiologic and incredibly important, there were multiple other risk factors in this population, and given a 4.2% event rate per year despite achieving a very low LDL, we can’t take our foot off the gas in terms of other risk factors,” said Dr. Morris of the Medical University of South Carolina, Charleston.
Discussant Sidney C. Smith Jr., MD, a member of the 2013 ACC/AHA cholesterol treatment guidelines committee, which did away with LDL lowering to a target level in favor of a risk-based approach which embraced percent reduction in LDL as a therapeutic goal, asked Dr. Sabatine if it’s time for the committee to revisit and perhaps restore the concept of shooting for an LDL target range.
“We labored with that in the 2013 guidelines, as to whether there’s some optimal range for LDL or one can look at percent reduction as an indicator,” noted Dr. Smith, professor of medicine at the University of North Carolina in Chapel Hill.
Dr. Sabatine replied, “Dr. [Eugene] Braunwald has made the analogy that if this was smoking, we wouldn’t want people to just reduce their amount of smoking by 50%, we’d want them to reduce it to zero cigarettes.”
The investigator added, “My own feeling is that the benefit is more closely related to the absolute reduction than the percent reduction in LDL, and like any other risk factor, you want to get it down as low as you can go.”
In a later video interview, Dr. Smith said that the FOURIER data make a strong case – at least in these first years of what will be much-longer-term drug therapy – that a target LDL in the range of 25-35 mg/dL may be optimal in a very-high-risk patient population.
Dr. Sabatine reported receiving grant support and consultant fees from Amgen, which funded the FOURIER trial.
Simultaneous with his presentation at the ACC meeting, the FOURIER results were published online at NEJM.org (doi: 10.1056/NEJMoa1615664).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – The PCSK9 inhibitor evolocumab reduced the incidence of the composite endpoint of cardiovascular death, MI, or stroke by an additional 20% in patients with established cardiovascular disease who were already on background maximum-tolerated statin therapy in the landmark FOURIER trial, Marc S. Sabatine, MD, reported at the annual meeting of the American College of Cardiology.
FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) was eagerly anticipated as the first dedicated cardiovascular outcomes trial to report results for a proprotein convertase subtilisin/kexin type 9 inhibitor, the novel drug class that achieves previously unattainable LDL lowering.
FOURIER randomized 27,564 patients with preexisting high-risk cardiovascular disease in 49 countries to double-blind therapy with subcutaneous evolocumab (Repatha) at either 140 mg every 2 weeks or 420 mg once monthly or to placebo injections. Participants had a baseline LDL-cholesterol level of 70 mg/dL or above while on statin therapy, which continued throughout the study. Sixty-nine percent of subjects were on high-intensity statin therapy, and the rest were on a moderate-intensity statin.
The median LDL level plunged from 92 mg/dL at baseline to 30 mg/dL in the evolocumab group, a 59% reduction. Moreover, one-quarter of patients on evolocumab achieved an LDL below 20 mg/dL. And this effect remained durable over the median 26 months of study follow-up.
“The LDL reduction achieved with evolocumab was rock steady over time,” observed Dr. Sabatine, professor of medicine at Harvard Medical School, Boston, and chair of the Thrombolysis in Myocardial Infarction Study Group.
The primary study endpoint – a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization – occurred in 11.3% of controls and 9.8% of the evolocumab group, for a significant 15% relative risk reduction. But Dr. Sabatine drew attention to the prespecified and fully powered secondary endpoint of cardiovascular death, MI, or stroke, which he considers more clinically relevant: 7.4% in controls, compared with 5.9% in the evolocumab group, for a 20% reduction in risk.
The cardiovascular benefits of greater lipid lowering grew over time. The evolocumab group’s relative risk reduction in the secondary composite endpoint was 16% in the first 12 months of follow-up and 25% beyond 12 months.
Even more impressively, the relative risk reduction in the stripped-down secondary endpoint of fatal or nonfatal MI or stroke was 19% in the first 12 months and 33%, compared with placebo, beyond 12 months.
The benefit in terms of cardiovascular risk reduction was consistent across baseline LDL subgroups, including those in the lowest baseline quartile, whose average baseline LDL was 74 mg/dL. Thus, the former LDL goal of a target below 70 mg/dL as representing maximum benefit has flown out the window.
“Even lower LDL appears to be even better, now down in this trial to 22 mg/dL,” the cardiologist declared.
There was no significant difference between the two study arms in the cardiovascular mortality rate, although Dr. Sabatine didn’t consider that surprising.
“Over the past decade, none of the trials of more intensive LDL lowering when compared with patients on moderate-intensity LDL-lowering therapy showed a significant reduction in cardiovascular mortality, which thankfully is now less common after acute MI and acute stroke than it had been in the past,” he said.
The number needed to treat (NNT) in order to prevent one additional cardiovascular death, MI, or stroke, based upon the current 3-year follow-up data, is roughly 50, according to Dr. Sabatine. Projecting out to 5 years, based upon the close fit between FOURIER and the data from the Cholesterol Treatment Trialists Collaboration, the NNT at 5 years for evolocumab is about 30, although the true NNT may actually prove to be smaller than that, given the steadily increasing benefit seen through 3 years. The projected 5-year NNT for the composite of coronary revascularization, cardiovascular death, MI, or stroke drops to about 20, he added.
The treatment was safe and well tolerated. The rate of study discontinuation attributable to treatment-related adverse events was low, at about 1.5% in both treatment arms. The rates of neurocognitive adverse events, new-onset diabetes, cataracts, and muscle-related complaints didn’t differ between the evolocumab and placebo groups, either. Of note, no one developed neutralizing antibodies to evolocumab. Long-term follow-up will continue in roughly 6,000 FOURIER participants.
Discussant Pamela B. Morris, MD, said FOURIER contains an important secondary message that mustn’t get lost in the enthusiasm for a safe and effective new drug.
“I’m very struck by the high event rate in this population, even with LDL levels down to 30 mg/dL. I think what that says is that although LDL cholesterol is etiologic and incredibly important, there were multiple other risk factors in this population, and given a 4.2% event rate per year despite achieving a very low LDL, we can’t take our foot off the gas in terms of other risk factors,” said Dr. Morris of the Medical University of South Carolina, Charleston.
Discussant Sidney C. Smith Jr., MD, a member of the 2013 ACC/AHA cholesterol treatment guidelines committee, which did away with LDL lowering to a target level in favor of a risk-based approach which embraced percent reduction in LDL as a therapeutic goal, asked Dr. Sabatine if it’s time for the committee to revisit and perhaps restore the concept of shooting for an LDL target range.
“We labored with that in the 2013 guidelines, as to whether there’s some optimal range for LDL or one can look at percent reduction as an indicator,” noted Dr. Smith, professor of medicine at the University of North Carolina in Chapel Hill.
Dr. Sabatine replied, “Dr. [Eugene] Braunwald has made the analogy that if this was smoking, we wouldn’t want people to just reduce their amount of smoking by 50%, we’d want them to reduce it to zero cigarettes.”
The investigator added, “My own feeling is that the benefit is more closely related to the absolute reduction than the percent reduction in LDL, and like any other risk factor, you want to get it down as low as you can go.”
In a later video interview, Dr. Smith said that the FOURIER data make a strong case – at least in these first years of what will be much-longer-term drug therapy – that a target LDL in the range of 25-35 mg/dL may be optimal in a very-high-risk patient population.
Dr. Sabatine reported receiving grant support and consultant fees from Amgen, which funded the FOURIER trial.
Simultaneous with his presentation at the ACC meeting, the FOURIER results were published online at NEJM.org (doi: 10.1056/NEJMoa1615664).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – The PCSK9 inhibitor evolocumab reduced the incidence of the composite endpoint of cardiovascular death, MI, or stroke by an additional 20% in patients with established cardiovascular disease who were already on background maximum-tolerated statin therapy in the landmark FOURIER trial, Marc S. Sabatine, MD, reported at the annual meeting of the American College of Cardiology.
FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) was eagerly anticipated as the first dedicated cardiovascular outcomes trial to report results for a proprotein convertase subtilisin/kexin type 9 inhibitor, the novel drug class that achieves previously unattainable LDL lowering.
FOURIER randomized 27,564 patients with preexisting high-risk cardiovascular disease in 49 countries to double-blind therapy with subcutaneous evolocumab (Repatha) at either 140 mg every 2 weeks or 420 mg once monthly or to placebo injections. Participants had a baseline LDL-cholesterol level of 70 mg/dL or above while on statin therapy, which continued throughout the study. Sixty-nine percent of subjects were on high-intensity statin therapy, and the rest were on a moderate-intensity statin.
The median LDL level plunged from 92 mg/dL at baseline to 30 mg/dL in the evolocumab group, a 59% reduction. Moreover, one-quarter of patients on evolocumab achieved an LDL below 20 mg/dL. And this effect remained durable over the median 26 months of study follow-up.
“The LDL reduction achieved with evolocumab was rock steady over time,” observed Dr. Sabatine, professor of medicine at Harvard Medical School, Boston, and chair of the Thrombolysis in Myocardial Infarction Study Group.
The primary study endpoint – a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization – occurred in 11.3% of controls and 9.8% of the evolocumab group, for a significant 15% relative risk reduction. But Dr. Sabatine drew attention to the prespecified and fully powered secondary endpoint of cardiovascular death, MI, or stroke, which he considers more clinically relevant: 7.4% in controls, compared with 5.9% in the evolocumab group, for a 20% reduction in risk.
The cardiovascular benefits of greater lipid lowering grew over time. The evolocumab group’s relative risk reduction in the secondary composite endpoint was 16% in the first 12 months of follow-up and 25% beyond 12 months.
Even more impressively, the relative risk reduction in the stripped-down secondary endpoint of fatal or nonfatal MI or stroke was 19% in the first 12 months and 33%, compared with placebo, beyond 12 months.
The benefit in terms of cardiovascular risk reduction was consistent across baseline LDL subgroups, including those in the lowest baseline quartile, whose average baseline LDL was 74 mg/dL. Thus, the former LDL goal of a target below 70 mg/dL as representing maximum benefit has flown out the window.
“Even lower LDL appears to be even better, now down in this trial to 22 mg/dL,” the cardiologist declared.
There was no significant difference between the two study arms in the cardiovascular mortality rate, although Dr. Sabatine didn’t consider that surprising.
“Over the past decade, none of the trials of more intensive LDL lowering when compared with patients on moderate-intensity LDL-lowering therapy showed a significant reduction in cardiovascular mortality, which thankfully is now less common after acute MI and acute stroke than it had been in the past,” he said.
The number needed to treat (NNT) in order to prevent one additional cardiovascular death, MI, or stroke, based upon the current 3-year follow-up data, is roughly 50, according to Dr. Sabatine. Projecting out to 5 years, based upon the close fit between FOURIER and the data from the Cholesterol Treatment Trialists Collaboration, the NNT at 5 years for evolocumab is about 30, although the true NNT may actually prove to be smaller than that, given the steadily increasing benefit seen through 3 years. The projected 5-year NNT for the composite of coronary revascularization, cardiovascular death, MI, or stroke drops to about 20, he added.
The treatment was safe and well tolerated. The rate of study discontinuation attributable to treatment-related adverse events was low, at about 1.5% in both treatment arms. The rates of neurocognitive adverse events, new-onset diabetes, cataracts, and muscle-related complaints didn’t differ between the evolocumab and placebo groups, either. Of note, no one developed neutralizing antibodies to evolocumab. Long-term follow-up will continue in roughly 6,000 FOURIER participants.
Discussant Pamela B. Morris, MD, said FOURIER contains an important secondary message that mustn’t get lost in the enthusiasm for a safe and effective new drug.
“I’m very struck by the high event rate in this population, even with LDL levels down to 30 mg/dL. I think what that says is that although LDL cholesterol is etiologic and incredibly important, there were multiple other risk factors in this population, and given a 4.2% event rate per year despite achieving a very low LDL, we can’t take our foot off the gas in terms of other risk factors,” said Dr. Morris of the Medical University of South Carolina, Charleston.
Discussant Sidney C. Smith Jr., MD, a member of the 2013 ACC/AHA cholesterol treatment guidelines committee, which did away with LDL lowering to a target level in favor of a risk-based approach which embraced percent reduction in LDL as a therapeutic goal, asked Dr. Sabatine if it’s time for the committee to revisit and perhaps restore the concept of shooting for an LDL target range.
“We labored with that in the 2013 guidelines, as to whether there’s some optimal range for LDL or one can look at percent reduction as an indicator,” noted Dr. Smith, professor of medicine at the University of North Carolina in Chapel Hill.
Dr. Sabatine replied, “Dr. [Eugene] Braunwald has made the analogy that if this was smoking, we wouldn’t want people to just reduce their amount of smoking by 50%, we’d want them to reduce it to zero cigarettes.”
The investigator added, “My own feeling is that the benefit is more closely related to the absolute reduction than the percent reduction in LDL, and like any other risk factor, you want to get it down as low as you can go.”
In a later video interview, Dr. Smith said that the FOURIER data make a strong case – at least in these first years of what will be much-longer-term drug therapy – that a target LDL in the range of 25-35 mg/dL may be optimal in a very-high-risk patient population.
Dr. Sabatine reported receiving grant support and consultant fees from Amgen, which funded the FOURIER trial.
Simultaneous with his presentation at the ACC meeting, the FOURIER results were published online at NEJM.org (doi: 10.1056/NEJMoa1615664).
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Key clinical point:
Major finding: The projected NNT with evolocumab for 5 years in order to prevent one additional cardiovascular death, MI, or stroke is roughly 30 patients.
Data source: The FOURIER trial was a randomized, double-blind, placebo-controlled trial including more than 27,000 patients with high-risk cardiovascular disease on background statin therapy.
Disclosures: The presenter reported receiving grant support and consultant fees from Amgen, which funded the study.
Calcium scores may assist cardiac screening in African Americans
A new study suggests calcium scores may help physicians as they navigate a wide cardiac screening guideline gap over recommendations about statin therapy in African Americans.
In a study sample of Mississippi residents, researchers found that the 2016 U.S. Preventive Services Task Force guidelines would reject statins for a quarter of the African Americans who’d be deemed statin eligible by the 2013 American College of Cardiology/American Heart Association (ACC/AHA) recommendations.
“ACC/AHA guidelines are more sensitive, but may lead to overtreatment of those who may not be at increased risk of cardiovascular disease,” said study coauthor Aferdita Spahillari, MD, a cardiology fellow at Tufts Medical Center and Beth Israel Deaconess Medical Center, Boston. In contrast, the task force guidelines “are more specific, yet they may miss individuals at higher risk who should be treated with statins,” she said.
Regardless of which screening guidelines are used, Dr. Spahillari said, “calcium scoring may aid decision making in those cases where guideline recommendations may be divergent.”
The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the JAMA Cardiology (doi: 10.1001/jamacardio.2017.0944).
The researchers sought to answer these questions: How do the ACC/AHA and task force guidelines perform at identifying at-risk African Americans? And can calcium scores help refine decisions regarding statins? According to Dr. Spahillari, the latter issue has been studied in whites but not large African American populations.
Insight could help physicians better provide preventive treatment to African Americans, who face a higher risk of cardiac problems compared with whites. In addition, “studies have shown that racial disparities exist in prescription of cardioprotective medications,” Dr. Spahillari said, “and African Americans are prescribed statins less frequently than whites.”
For the new study, researchers tracked 2,812 African American individuals aged 40-75 years (mean age 55 [SD 9.4], 65.3% female, mean body mass index 31.6 kg/m2 [SD 7.0]) in the Jackson, Miss., area. They were examined in 2000-2004, 2005-2008, and 2009-2013 and included if they didn’t show signs of prevalent subclinical and clinical atherosclerotic cardiovascular disease and weren’t on statins at baseline.
If the task force guidelines regarding 10-year risk had been in existence, 1,072 (38.1%) of the participants would have been deemed eligible for treatment. A higher number – 1,404 (49.9%) – would have been eligible under ACC/AHA guidelines (risk difference, 11.8%; 95% CI, 10.5-13.1; P less than .001).
The two sets of guidelines diverged on the eligibility of 13.8% of the total subjects: 361 (12.8%) were deemed eligible for statins by the ACC/AHA guidelines alone. (They account for 25.7% of all the statin-eligible subjects under the ACC/AHA guidelines.)
In contrast, the task force guidelines alone deemed 29 (1%) to be eligible.
Those deemed eligible for statins under both guidelines had a cardiovascular event rate of 9.6 per 1,000 patient-years (95% CI, 7.8-11.8, P = .003) over a median 10-year follow-up. The event rate for those only statin-eligible under the ACC/AHA guidelines had an event rate of 4.1 events per 1,000 patient-years (95% CI, 2.4-6.9; P = .003), which Dr. Spahillari calls “a low to intermediate rate suggesting a decreased sensitivity of the task force recommendations in identifying participants at risk of atherosclerotic cardiovascular disease.”
And what about CAC levels? Task force guidelines identified 404 of 732 (55.2%) African Americans with coronary calcium; ACC/AHA guidelines identified 507 (69.3%).
“Participants eligible for statins under the ACC/AHA guidelines who had CAC were at higher risk than those without CAC,” Dr. Spahillari said. Specifically, among those deemed eligible for statins by the ACC/AHA recommendations, the 10-year event rate per 1,000 person-years was 8.1 (95% CI, 5.9-11.1) in those with CAC and 3.1 (95% CI, 1.6-5.9) in those without CAC (P = .02).
The situation was different under the task force guidelines. CAC didn’t significantly affect the risk in those deemed eligible for statins by the task force guidelines, but it did seem to boost risk in those who weren’t statin eligible, she said.
Among those deemed not statin eligible by the task force guidelines, the event rate per 1,000 person-years was 2.8 in those with CAC (95% CI, 1.5-5.4) and 0.8 in those without (95%, CI 0.3-1.7) (P = .03).
How could CAC levels be useful for physicians? “As the role of CAC measurement is evolving, our findings support that measurement of CAC in an African-American population with an intermediate risk score would be clinically useful,” Dr. Spahillari said.
When ACC/AHA guidelines are used, she said, “the absence of CAC may reduce the number of individuals indicated for treatment with statins by ACC/AHA recommendations and temper concerns for overtreatment.”
What if a physician uses the task force guidelines in this population? “The presence of CAC may push a recommendation for statin treatment in individuals who would otherwise not be indicated for statins,” she said.
The National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities funded the study. One author reported funding from a National Institutes of Health grant. The others had no disclosures.
A new study suggests calcium scores may help physicians as they navigate a wide cardiac screening guideline gap over recommendations about statin therapy in African Americans.
In a study sample of Mississippi residents, researchers found that the 2016 U.S. Preventive Services Task Force guidelines would reject statins for a quarter of the African Americans who’d be deemed statin eligible by the 2013 American College of Cardiology/American Heart Association (ACC/AHA) recommendations.
“ACC/AHA guidelines are more sensitive, but may lead to overtreatment of those who may not be at increased risk of cardiovascular disease,” said study coauthor Aferdita Spahillari, MD, a cardiology fellow at Tufts Medical Center and Beth Israel Deaconess Medical Center, Boston. In contrast, the task force guidelines “are more specific, yet they may miss individuals at higher risk who should be treated with statins,” she said.
Regardless of which screening guidelines are used, Dr. Spahillari said, “calcium scoring may aid decision making in those cases where guideline recommendations may be divergent.”
The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the JAMA Cardiology (doi: 10.1001/jamacardio.2017.0944).
The researchers sought to answer these questions: How do the ACC/AHA and task force guidelines perform at identifying at-risk African Americans? And can calcium scores help refine decisions regarding statins? According to Dr. Spahillari, the latter issue has been studied in whites but not large African American populations.
Insight could help physicians better provide preventive treatment to African Americans, who face a higher risk of cardiac problems compared with whites. In addition, “studies have shown that racial disparities exist in prescription of cardioprotective medications,” Dr. Spahillari said, “and African Americans are prescribed statins less frequently than whites.”
For the new study, researchers tracked 2,812 African American individuals aged 40-75 years (mean age 55 [SD 9.4], 65.3% female, mean body mass index 31.6 kg/m2 [SD 7.0]) in the Jackson, Miss., area. They were examined in 2000-2004, 2005-2008, and 2009-2013 and included if they didn’t show signs of prevalent subclinical and clinical atherosclerotic cardiovascular disease and weren’t on statins at baseline.
If the task force guidelines regarding 10-year risk had been in existence, 1,072 (38.1%) of the participants would have been deemed eligible for treatment. A higher number – 1,404 (49.9%) – would have been eligible under ACC/AHA guidelines (risk difference, 11.8%; 95% CI, 10.5-13.1; P less than .001).
The two sets of guidelines diverged on the eligibility of 13.8% of the total subjects: 361 (12.8%) were deemed eligible for statins by the ACC/AHA guidelines alone. (They account for 25.7% of all the statin-eligible subjects under the ACC/AHA guidelines.)
In contrast, the task force guidelines alone deemed 29 (1%) to be eligible.
Those deemed eligible for statins under both guidelines had a cardiovascular event rate of 9.6 per 1,000 patient-years (95% CI, 7.8-11.8, P = .003) over a median 10-year follow-up. The event rate for those only statin-eligible under the ACC/AHA guidelines had an event rate of 4.1 events per 1,000 patient-years (95% CI, 2.4-6.9; P = .003), which Dr. Spahillari calls “a low to intermediate rate suggesting a decreased sensitivity of the task force recommendations in identifying participants at risk of atherosclerotic cardiovascular disease.”
And what about CAC levels? Task force guidelines identified 404 of 732 (55.2%) African Americans with coronary calcium; ACC/AHA guidelines identified 507 (69.3%).
“Participants eligible for statins under the ACC/AHA guidelines who had CAC were at higher risk than those without CAC,” Dr. Spahillari said. Specifically, among those deemed eligible for statins by the ACC/AHA recommendations, the 10-year event rate per 1,000 person-years was 8.1 (95% CI, 5.9-11.1) in those with CAC and 3.1 (95% CI, 1.6-5.9) in those without CAC (P = .02).
The situation was different under the task force guidelines. CAC didn’t significantly affect the risk in those deemed eligible for statins by the task force guidelines, but it did seem to boost risk in those who weren’t statin eligible, she said.
Among those deemed not statin eligible by the task force guidelines, the event rate per 1,000 person-years was 2.8 in those with CAC (95% CI, 1.5-5.4) and 0.8 in those without (95%, CI 0.3-1.7) (P = .03).
How could CAC levels be useful for physicians? “As the role of CAC measurement is evolving, our findings support that measurement of CAC in an African-American population with an intermediate risk score would be clinically useful,” Dr. Spahillari said.
When ACC/AHA guidelines are used, she said, “the absence of CAC may reduce the number of individuals indicated for treatment with statins by ACC/AHA recommendations and temper concerns for overtreatment.”
What if a physician uses the task force guidelines in this population? “The presence of CAC may push a recommendation for statin treatment in individuals who would otherwise not be indicated for statins,” she said.
The National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities funded the study. One author reported funding from a National Institutes of Health grant. The others had no disclosures.
A new study suggests calcium scores may help physicians as they navigate a wide cardiac screening guideline gap over recommendations about statin therapy in African Americans.
In a study sample of Mississippi residents, researchers found that the 2016 U.S. Preventive Services Task Force guidelines would reject statins for a quarter of the African Americans who’d be deemed statin eligible by the 2013 American College of Cardiology/American Heart Association (ACC/AHA) recommendations.
“ACC/AHA guidelines are more sensitive, but may lead to overtreatment of those who may not be at increased risk of cardiovascular disease,” said study coauthor Aferdita Spahillari, MD, a cardiology fellow at Tufts Medical Center and Beth Israel Deaconess Medical Center, Boston. In contrast, the task force guidelines “are more specific, yet they may miss individuals at higher risk who should be treated with statins,” she said.
Regardless of which screening guidelines are used, Dr. Spahillari said, “calcium scoring may aid decision making in those cases where guideline recommendations may be divergent.”
The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the JAMA Cardiology (doi: 10.1001/jamacardio.2017.0944).
The researchers sought to answer these questions: How do the ACC/AHA and task force guidelines perform at identifying at-risk African Americans? And can calcium scores help refine decisions regarding statins? According to Dr. Spahillari, the latter issue has been studied in whites but not large African American populations.
Insight could help physicians better provide preventive treatment to African Americans, who face a higher risk of cardiac problems compared with whites. In addition, “studies have shown that racial disparities exist in prescription of cardioprotective medications,” Dr. Spahillari said, “and African Americans are prescribed statins less frequently than whites.”
For the new study, researchers tracked 2,812 African American individuals aged 40-75 years (mean age 55 [SD 9.4], 65.3% female, mean body mass index 31.6 kg/m2 [SD 7.0]) in the Jackson, Miss., area. They were examined in 2000-2004, 2005-2008, and 2009-2013 and included if they didn’t show signs of prevalent subclinical and clinical atherosclerotic cardiovascular disease and weren’t on statins at baseline.
If the task force guidelines regarding 10-year risk had been in existence, 1,072 (38.1%) of the participants would have been deemed eligible for treatment. A higher number – 1,404 (49.9%) – would have been eligible under ACC/AHA guidelines (risk difference, 11.8%; 95% CI, 10.5-13.1; P less than .001).
The two sets of guidelines diverged on the eligibility of 13.8% of the total subjects: 361 (12.8%) were deemed eligible for statins by the ACC/AHA guidelines alone. (They account for 25.7% of all the statin-eligible subjects under the ACC/AHA guidelines.)
In contrast, the task force guidelines alone deemed 29 (1%) to be eligible.
Those deemed eligible for statins under both guidelines had a cardiovascular event rate of 9.6 per 1,000 patient-years (95% CI, 7.8-11.8, P = .003) over a median 10-year follow-up. The event rate for those only statin-eligible under the ACC/AHA guidelines had an event rate of 4.1 events per 1,000 patient-years (95% CI, 2.4-6.9; P = .003), which Dr. Spahillari calls “a low to intermediate rate suggesting a decreased sensitivity of the task force recommendations in identifying participants at risk of atherosclerotic cardiovascular disease.”
And what about CAC levels? Task force guidelines identified 404 of 732 (55.2%) African Americans with coronary calcium; ACC/AHA guidelines identified 507 (69.3%).
“Participants eligible for statins under the ACC/AHA guidelines who had CAC were at higher risk than those without CAC,” Dr. Spahillari said. Specifically, among those deemed eligible for statins by the ACC/AHA recommendations, the 10-year event rate per 1,000 person-years was 8.1 (95% CI, 5.9-11.1) in those with CAC and 3.1 (95% CI, 1.6-5.9) in those without CAC (P = .02).
The situation was different under the task force guidelines. CAC didn’t significantly affect the risk in those deemed eligible for statins by the task force guidelines, but it did seem to boost risk in those who weren’t statin eligible, she said.
Among those deemed not statin eligible by the task force guidelines, the event rate per 1,000 person-years was 2.8 in those with CAC (95% CI, 1.5-5.4) and 0.8 in those without (95%, CI 0.3-1.7) (P = .03).
How could CAC levels be useful for physicians? “As the role of CAC measurement is evolving, our findings support that measurement of CAC in an African-American population with an intermediate risk score would be clinically useful,” Dr. Spahillari said.
When ACC/AHA guidelines are used, she said, “the absence of CAC may reduce the number of individuals indicated for treatment with statins by ACC/AHA recommendations and temper concerns for overtreatment.”
What if a physician uses the task force guidelines in this population? “The presence of CAC may push a recommendation for statin treatment in individuals who would otherwise not be indicated for statins,” she said.
The National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities funded the study. One author reported funding from a National Institutes of Health grant. The others had no disclosures.
FROM ACC 17
Key clinical point: Cardiac screening guidelines diverge on statin-eligible African Americans, but calcium levels can provide treatment insight.
Major finding: U.S. Preventive Services Task Force guidelines did not recommend statins in 25.7% of 1,404 African Americans who were deemed statin eligible by American College of Cardiology/American Heart Association guidelines.
Data source: Prospective, community-based study of 2,812 African American subjects in Mississippi – aged 40-75 years, mean age 55, 65.3% female, mean body mass index 31.6 kg/m2 – tracked for median of 10 years; 1,743 underwent computed tomography.
Disclosures: The National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities funded the study. One author reported funding from a National Institutes of Health grant. The others had no disclosures.
Trial supports FFR-guided complete revascularization during PCI for STEMI
WASHINGTON – Using fractional flow reserve (FFR) to revascularize noninfarct coronary arteries during percutaneous coronary intervention (PCI) significantly reduced the subsequent 1-year risk of major adverse cardiovascular events among patients with ST-segment myocardial infarction and multivessel disease, according to the results of a randomized, multicenter trial.
Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (hazard ratio, 0.35; 95% confidence interval, 0.22-0.55; P less than .001), Pieter C. Smits, MD, PhD, reported during a late-breaker session at the annual meeting of the American College of Cardiology.
Importantly, coronary angiography overestimated the physiological significance of noninfart lesions in the study, the researchers wrote. About half of noninfarct lesions that were considered significant on angiography had FFR values above 0.80, meaning that they were not physiologically significant.
Some 50% of patients with acute ST-segment elevation myocardial infarction (STEMI) have severe stenotic lesions of noninfarct coronary arteries. These lesions often are managed conservatively, but two recent randomized trials have challenged this approach, tying preventive stent placement to lower rates of subsequent adverse events. However, both studies based the decision to use stents on angiographic appearance, not symptoms or ischemia, even though angiography can fail to accurately estimate the functional severity of a lesion, the investigators wrote. For stable patients, using FFR to guide revascularization instead can prevent adverse events compared with angiography or conservative management, they added.
To more rigorously compare FFR-guided revascularization of noninfarct coronary arteries with infarct-only treatment, the researchers randomly assigned 885 adults with acute STEMI and multivessel disease to one of these two approaches during primary PCI. A total of 295 patients underwent FFR-guided complete revascularization, and 590 underwent infarct-only treatment plus FFR evaluation of noninfarct-artery lesions.
Compared with infarct-only treatment, complete revascularization was associated with lower, but statistically similar, rates of mortality (1.7% vs. 1.4%; HR, 0.80; 95% CI, 0.25-2.6; P = .7), nonfatal myocardial infarction (4.7% vs. 2.4%; HR, 0.5; 95% CI, 0.2-1.1; P = .1), and cerebrovascular events (0.7% vs. 0%). The study lacked power to detect differences in rates of these uncommon events, the researchers noted.
In the infarct-only treatment group, stable or unstable angina accounted for most repeat revascularizations, about 80% of which were clinically indicated based on the study protocol, according to the researchers. Performing FFR-guided revascularization during primary PCI prevents sequential catheterizations and can potentially save costs by reducing predischarge stress tests, they commented. In their study, 12% of patients in the infarct-only group underwent stress tests, compared with 7% of those who underwent FFR-guided revascularization (P = .03).
Two patients experienced a serious adverse event related to FFR, the investigators noted. In one case, the FFR wire caused a dissection in the noninfarcted right coronary artery. The artery subsequently infarcted and the patient died in the hospital. Another patient developed an occlusion of the noninfarcted left anterior descending coronary artery. The patient developed ST-segment elevation and recurrent chest pain, but underwent successful PCI of the artery. There were no other adverse events except for brief episodes of atrioventricular conduction delay and episodes of moderate hypotension, they wrote.
This was an open-label study, and it is possible that patients and physicians in the infarct-only group were biased toward subsequent revascularizations because they knew the angiography results, the researchers also noted.
Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grants support and personal fees from both entities outside the submitted work.
WASHINGTON – Using fractional flow reserve (FFR) to revascularize noninfarct coronary arteries during percutaneous coronary intervention (PCI) significantly reduced the subsequent 1-year risk of major adverse cardiovascular events among patients with ST-segment myocardial infarction and multivessel disease, according to the results of a randomized, multicenter trial.
Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (hazard ratio, 0.35; 95% confidence interval, 0.22-0.55; P less than .001), Pieter C. Smits, MD, PhD, reported during a late-breaker session at the annual meeting of the American College of Cardiology.
Importantly, coronary angiography overestimated the physiological significance of noninfart lesions in the study, the researchers wrote. About half of noninfarct lesions that were considered significant on angiography had FFR values above 0.80, meaning that they were not physiologically significant.
Some 50% of patients with acute ST-segment elevation myocardial infarction (STEMI) have severe stenotic lesions of noninfarct coronary arteries. These lesions often are managed conservatively, but two recent randomized trials have challenged this approach, tying preventive stent placement to lower rates of subsequent adverse events. However, both studies based the decision to use stents on angiographic appearance, not symptoms or ischemia, even though angiography can fail to accurately estimate the functional severity of a lesion, the investigators wrote. For stable patients, using FFR to guide revascularization instead can prevent adverse events compared with angiography or conservative management, they added.
To more rigorously compare FFR-guided revascularization of noninfarct coronary arteries with infarct-only treatment, the researchers randomly assigned 885 adults with acute STEMI and multivessel disease to one of these two approaches during primary PCI. A total of 295 patients underwent FFR-guided complete revascularization, and 590 underwent infarct-only treatment plus FFR evaluation of noninfarct-artery lesions.
Compared with infarct-only treatment, complete revascularization was associated with lower, but statistically similar, rates of mortality (1.7% vs. 1.4%; HR, 0.80; 95% CI, 0.25-2.6; P = .7), nonfatal myocardial infarction (4.7% vs. 2.4%; HR, 0.5; 95% CI, 0.2-1.1; P = .1), and cerebrovascular events (0.7% vs. 0%). The study lacked power to detect differences in rates of these uncommon events, the researchers noted.
In the infarct-only treatment group, stable or unstable angina accounted for most repeat revascularizations, about 80% of which were clinically indicated based on the study protocol, according to the researchers. Performing FFR-guided revascularization during primary PCI prevents sequential catheterizations and can potentially save costs by reducing predischarge stress tests, they commented. In their study, 12% of patients in the infarct-only group underwent stress tests, compared with 7% of those who underwent FFR-guided revascularization (P = .03).
Two patients experienced a serious adverse event related to FFR, the investigators noted. In one case, the FFR wire caused a dissection in the noninfarcted right coronary artery. The artery subsequently infarcted and the patient died in the hospital. Another patient developed an occlusion of the noninfarcted left anterior descending coronary artery. The patient developed ST-segment elevation and recurrent chest pain, but underwent successful PCI of the artery. There were no other adverse events except for brief episodes of atrioventricular conduction delay and episodes of moderate hypotension, they wrote.
This was an open-label study, and it is possible that patients and physicians in the infarct-only group were biased toward subsequent revascularizations because they knew the angiography results, the researchers also noted.
Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grants support and personal fees from both entities outside the submitted work.
WASHINGTON – Using fractional flow reserve (FFR) to revascularize noninfarct coronary arteries during percutaneous coronary intervention (PCI) significantly reduced the subsequent 1-year risk of major adverse cardiovascular events among patients with ST-segment myocardial infarction and multivessel disease, according to the results of a randomized, multicenter trial.
Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (hazard ratio, 0.35; 95% confidence interval, 0.22-0.55; P less than .001), Pieter C. Smits, MD, PhD, reported during a late-breaker session at the annual meeting of the American College of Cardiology.
Importantly, coronary angiography overestimated the physiological significance of noninfart lesions in the study, the researchers wrote. About half of noninfarct lesions that were considered significant on angiography had FFR values above 0.80, meaning that they were not physiologically significant.
Some 50% of patients with acute ST-segment elevation myocardial infarction (STEMI) have severe stenotic lesions of noninfarct coronary arteries. These lesions often are managed conservatively, but two recent randomized trials have challenged this approach, tying preventive stent placement to lower rates of subsequent adverse events. However, both studies based the decision to use stents on angiographic appearance, not symptoms or ischemia, even though angiography can fail to accurately estimate the functional severity of a lesion, the investigators wrote. For stable patients, using FFR to guide revascularization instead can prevent adverse events compared with angiography or conservative management, they added.
To more rigorously compare FFR-guided revascularization of noninfarct coronary arteries with infarct-only treatment, the researchers randomly assigned 885 adults with acute STEMI and multivessel disease to one of these two approaches during primary PCI. A total of 295 patients underwent FFR-guided complete revascularization, and 590 underwent infarct-only treatment plus FFR evaluation of noninfarct-artery lesions.
Compared with infarct-only treatment, complete revascularization was associated with lower, but statistically similar, rates of mortality (1.7% vs. 1.4%; HR, 0.80; 95% CI, 0.25-2.6; P = .7), nonfatal myocardial infarction (4.7% vs. 2.4%; HR, 0.5; 95% CI, 0.2-1.1; P = .1), and cerebrovascular events (0.7% vs. 0%). The study lacked power to detect differences in rates of these uncommon events, the researchers noted.
In the infarct-only treatment group, stable or unstable angina accounted for most repeat revascularizations, about 80% of which were clinically indicated based on the study protocol, according to the researchers. Performing FFR-guided revascularization during primary PCI prevents sequential catheterizations and can potentially save costs by reducing predischarge stress tests, they commented. In their study, 12% of patients in the infarct-only group underwent stress tests, compared with 7% of those who underwent FFR-guided revascularization (P = .03).
Two patients experienced a serious adverse event related to FFR, the investigators noted. In one case, the FFR wire caused a dissection in the noninfarcted right coronary artery. The artery subsequently infarcted and the patient died in the hospital. Another patient developed an occlusion of the noninfarcted left anterior descending coronary artery. The patient developed ST-segment elevation and recurrent chest pain, but underwent successful PCI of the artery. There were no other adverse events except for brief episodes of atrioventricular conduction delay and episodes of moderate hypotension, they wrote.
This was an open-label study, and it is possible that patients and physicians in the infarct-only group were biased toward subsequent revascularizations because they knew the angiography results, the researchers also noted.
Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grants support and personal fees from both entities outside the submitted work.
FROM ACC 17
Key clinical point:
Major finding: Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (HR, 0.35; 95% CI, 0.22-0.55; P less than .001).
Data source: A prospective, multicenter, open-label clinical trial of 885 adults with acute STEMI and multivessel disease.
Disclosures: Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grant support and personal fees from both entities outside the submitted work.