Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome
Gregory G Schwartz1, P Gabriel Steg1, Michael Szarek1
1From the Division of Cardiology, University of Colorado School of Medicine, Aurora (G.G.S.); Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris Diderot University, Sorbonne Paris Cité, FACT (French Alliance for Cardiovascular Trials), and INSERM Unité 1148 (P.G.S.), and Sanofi (C.H., G.L.) - all in Paris; the National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London (P.G.S.); the State University of New York Downstate School of Public Health, Brooklyn (M.S.), and Regeneron Pharmaceuticals, Tarrytown (R.P., W.J.S.) - both in New York; Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston (D.L.B.); the Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham (V.A.B.); Estudios Cardiológicos Latinoamérica, Instituto Cardiovascular de Rosario, Rosario, Argentina (R.D.); Sanofi, Bridgewater, NJ (J.M.E., A.M., J.-F.T.); the Canadian VIGOUR Centre, University of Alberta, Edmonton, and St. Michael's Hospital, University of Toronto, Toronto - both in Canada (S.G.G.); Stanford Center for Clinical Research, Department of Medicine, Stanford University, Stanford, CA (R.A.H., K.W.M.); the Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands (J.W.J.); Duke Clinical Research Institute, Duke University Medical Center (K.Q., M.T.R., P.T.), and the Division of Cardiology, Department of Medicine, Duke University School of Medicine (M.T.R.), Durham, NC; Green Lane Cardiovascular Services, Auckland City Hospital, Auckland, New Zealand (H.D.W.); and the Department of Medicine III, Goethe University, Frankfurt am Main, Germany (A.M.Z.).
Insights
Alirocumab significantly reduced the risk of recurrent cardiovascular events in patients with acute coronary syndrome on statin therapy. This PCSK9 inhibitor offers a vital option for secondary prevention in high-risk individuals.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Patients with acute coronary syndrome (ACS) face a high risk of recurrent ischemic cardiovascular events.
- High-intensity statin therapy is standard, but further risk reduction is often needed.
Purpose of the Study:
- To evaluate the efficacy of alirocumab, a PCSK9 inhibitor, in reducing cardiovascular events post-ACS.
- To assess alirocumab's benefit in patients already on high-intensity statin therapy.
Main Methods:
- A multicenter, randomized, double-blind, placebo-controlled trial (ODYSSEY OUTCOMES) involving 18,924 patients post-ACS.
- Patients received alirocumab (75 mg every 2 weeks) or placebo, with dose adjustment to target LDL cholesterol <50 mg/dL.
- Primary endpoint: composite of coronary heart disease death, MI, ischemic stroke, or unstable angina requiring hospitalization.
Main Results:
- A composite primary endpoint event occurred in 9.5% of the alirocumab group vs. 11.1% in the placebo group (HR 0.85; P<0.001).
- All-cause mortality was also reduced (3.5% vs. 4.1%).
- Adverse events were similar, except for injection-site reactions.
Conclusions:
- Alirocumab significantly reduced the risk of recurrent ischemic cardiovascular events in ACS patients on high-intensity statin therapy.
- The benefit was more pronounced in patients with higher baseline LDL cholesterol.
- Alirocumab represents an effective treatment option for secondary cardiovascular prevention.
Background:
Patients who have had an acute coronary syndrome are at high risk for recurrent ischemic cardiovascular events. We sought to determine whether alirocumab, a human monoclonal antibody to proprotein convertase subtilisin-kexin type 9 (PCSK9), would improve cardiovascular outcomes after an acute coronary syndrome in patients receiving high-intensity statin therapy.
Methods:
We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving 18,924 patients who had an acute coronary syndrome 1 to 12 months earlier, had a low-density lipoprotein (LDL) cholesterol level of at least 70 mg per deciliter (1.8 mmol per liter), a non-high-density lipoprotein cholesterol level of at least 100 mg per deciliter (2.6 mmol per liter), or an apolipoprotein B level of at least 80 mg per deciliter, and were receiving statin therapy at a high-intensity dose or at the maximum tolerated dose. Patients were randomly assigned to receive alirocumab subcutaneously at a dose of 75 mg (9462 patients) or matching placebo (9462 patients) every 2 weeks. The dose of alirocumab was adjusted under blinded conditions to target an LDL cholesterol level of 25 to 50 mg per deciliter (0.6 to 1.3 mmol per liter). The primary end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.
Results:
The median duration of follow-up was 2.8 years. A composite primary end-point event occurred in 903 patients (9.5%) in the alirocumab group and in 1052 patients (11.1%) in the placebo group (hazard ratio, 0.85; 95% confidence interval [CI], 0.78 to 0.93; P<0.001). A total of 334 patients (3.5%) in the alirocumab group and 392 patients (4.1%) in the placebo group died (hazard ratio, 0.85; 95% CI, 0.73 to 0.98). The absolute benefit of alirocumab with respect to the composite primary end point was greater among patients who had a baseline LDL cholesterol level of 100 mg or more per deciliter than among patients who had a lower baseline level. The incidence of adverse events was similar in the two groups, with the exception of local injection-site reactions (3.8% in the alirocumab group vs. 2.1% in the placebo group).
Conclusions:
Among patients who had a previous acute coronary syndrome and who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who received alirocumab than among those who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; ODYSSEY OUTCOMES ClinicalTrials.gov number, NCT01663402 .).
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