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ODYSSEY OUTCOMES: Alirocumab reduces CV event risk for polyvascular disease, CABG
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Alirocumab reduced the risk for major adverse CV events and death in patients with recent ACS and polyvascular disease and in those with CABG after an ACS event, according to two analyses of the ODYSSEY OUTCOMES trial published in the Journal of the American College of Cardiology.
As Healio previously reported, the ODYSSEY OUTCOMES trial found that reducing LDL to very low levels with the PCSK9 inhibitor alirocumab (Praluent, Sanofi Aventis) lowered risk for major adverse CV events and all-cause mortality in patients with ACS on statin therapy.
Polyvascular disease, ACS
J. Wouter Jukema , MD, PhD, FESC, FACC, chairman in the department of cardiology at Leiden University Medical Center in the Netherlands, categorized 18,924 patients from the ODYSSEY OUTCOMES trial as having monovascular disease (n = 17,370), polyvascular disease in two vascular beds (n = 1,405) or polyvascular disease in three vascular beds (n = 149).
The primary major adverse CV event endpoint was a composite of nonfatal MI, CHD death, unstable angina requiring hospitalization or fatal or nonfatal ischemic stroke. Patients were followed up for a median of 2.8 years.
Of the patients assigned placebo, the incidence of major adverse CV events was 10% in those with one diseased vascular bed, 22.2% in patients with two diseased vascular beds and 39.7% in those with three diseased vascular beds. The absolute risk reduction in patients assigned alirocumab was 1.4% for patients with one diseased vascular bed (95% CI, 0.6-2.3), 1.9% for those with two diseased vascular beds (95% CI, –2.4 to 6.2) and 13% for patients with three diseased vascular beds (95% CI, –2 to 28; P for interaction = .0006).
Incidence of death in patients assigned placebo was 3.5% for patients with one diseased vascular bed, 10% for those with two diseased vascular beds and 21.8% for patients with three diseased vascular beds. The absolute risk reduction in patients assigned alirocumab was 0.4% for those with one diseased vascular bed (95% CI, –0.1 to 1), 1.3% for patients with two diseased vascular beds (95% CI, –1.8 to 4.3) and 16.2% for those with three diseased vascular beds (95% CI, 5.5-26.8; P for interaction = .002).
“The large absolute benefit of PCSK9 inhibition with alirocumab, when added to high-intensity statin therapy, is a potential benefit for this group of patients,” Jukema and colleagues wrote. “However, further studies are needed to guide the selection of patients with ACS for treatment with a PCSK9 inhibitor in the context of other established and evolving therapies in atherosclerosis so that efficacy and efficiency are optimized.”
Treatment after CABG
Shaun Goodman, MD, MSc, staff cardiologist and associate head in the division of cardiology at St. Michael’s Hospital at the University of Toronto, professor and Heart and Stroke Foundation of Ontario (Polo) Chair in the department of medicine at the University of Toronto and co-director of the Canadian VIGOUR Center at the University of Alberta in Canada, and colleagues categorized patients as no CABG (n = 16,896; median age, 58 years; 26% women), CABG after index ACS but before randomization (n = 1,025; median age, 60 years; 21% women) or CABG performed before the index ACS (n = 1,003; median age, 63 years; 20% women).
The primary endpoint was a composite of CHD death, fatal or nonfatal ischemic stroke, nonfatal MI or unstable angina requiring hospitalization.
The HR for major adverse CV events was 0.86 for the no CABG group (95% CI, 0.78-0.95), 0.85 for the index CABG group (95% CI, 0.54-1.35) and 0.77 for the prior CABG group (95% CI, 0.61-0.98). For death, the HR for patients who did not have CABG was 0.88 (95% CI, 0.75-1.03), 0.85 for those with index CABG (95% CI, 0.46-1.59) and 0.67 for patients with prior CABG (95% CI, 0.44-1.01). These results were consistent with the overall trial results for major adverse CV events (HR = 0.85; 95% CI, 0.78-0.93) and death (HR = 0.85; 95% CI, 0.73-0.98).
Absolute risk reductions for major adverse CV events varied among those who did not undergo CABG (1.3%; 95%, 0.5-2.2), patients with index CABG (0.9%; 95%, –2.3 to 4) and those with prior CABG (6.4%; 95% CI, 0.9-12). This was also seen for the absolute risk reductions for death in the no CABG (0.4%; 95% CI, –0.1 to 1), index CABG (0.5%; 95% CI, –1.9 to 2.9) and prior CABG groups (3.6%; 95% CI, 0-7.2).
“The current analysis reinforces the concept that the benefits from effective secondary prevention therapies in atherosclerosis are greatest among those at high residual atherothrombotic risk,” Goodman and colleagues wrote.
“A reasonable first step in the approach to patient care is for physicians to be less complacent and apply, with enthusiasm, secondary prevention guidelines in post CABG and polyvascular disease patients, to strive to eliminate smoking and enforce lifestyle modifications with known benefits in ASCVD,” Jacques Genest, MD, senior scientist at the Centre for Translational Biology and professor in the department of medicine at McGill University in Montreal, and colleagues wrote in a related editorial. “The studies by Goodman, et al and Jukema, et al show once again that patients at the highest risk derive the most benefit from aggressive LDL-C lowering. The significant reduction in mortality association with a low LDL-C on alirocumab can no longer be ignored.” – by Darlene Dobkowski
References:
Genest J, et al. J Am Coll Cardiol. 2019;doi:10.1016/j.jacc.2019.07.016.
Goodman SG, et al. J Am Coll Cardiol. 2019;doi:10.1016/j.jacc.2019.07.015.
Jukema JW, et al. J Am Coll Cardiol. 2019;doi:10.1016/j.jacc.2019.03.013.
Disclosures: The study was funded by Sanofi and Regeneron. Jukema reports he received research support from Amgen, Astellas, AstraZeneca, Daiichi-Sankyo, Eli Lilly, Merch-Schering-Plough, Pfizer, Roche and Sanofi. Goodman reports he received research grants from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Daiichi-Sankyo, Eli Lilly, Luitpold Pharmaceuticals, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, Servier and Tenax Therapeutics; has received honoraria from Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Fenix Group International, Ferring Pharmaceuticals, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi and Servier; and served as a consultant or on the advisory board for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Pfizer, Sanofi, Servier and Tenax Therapeutics. Genest reports he co-chairs HF Canada; received support from Aegerion, Amgen, Pfizer, Sanofi and Valeant for HF Canada; received honoraria from Amgen, Merck Novartis and Sanofi; and collaborated on clinical trials with Amgen, Eli Lilly, Novartis and Sanofi. Please see the studies and editorial for all other authors’ relevant financial disclosures.