Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

ODYSSEY OUTCOMES Committees and Investigators, Alessandro Salvioni

Research output: Contribution to journalArticle

Abstract

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 .).

Original languageEnglish
Pages (from-to)2097-2107
Number of pages11
JournalThe New England journal of medicine
Volume379
Issue number22
DOIs
Publication statusPublished - Nov 29 2018

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Acute Coronary Syndrome
Placebos
Hydroxymethylglutaryl-CoA Reductase Inhibitors
LDL Cholesterol
alirocumab
Confidence Intervals
Maximum Tolerated Dose
Unstable Angina
Apolipoproteins B
Coronary Disease
Hospitalization
Therapeutics
Stroke
Myocardial Infarction
Monoclonal Antibodies

Keywords

  • Acute Coronary Syndrome/blood
  • Adult
  • Aged
  • Antibodies, Monoclonal/adverse effects
  • Anticholesteremic Agents/adverse effects
  • Cardiovascular Diseases/epidemiology
  • Cholesterol, LDL/blood
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hypercholesterolemia/complications
  • Male
  • Middle Aged
  • Proprotein Convertase 9/antagonists & inhibitors

Cite this

Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. / ODYSSEY OUTCOMES Committees and Investigators ; Salvioni, Alessandro.

In: The New England journal of medicine, Vol. 379, No. 22, 29.11.2018, p. 2097-2107.

Research output: Contribution to journalArticle

ODYSSEY OUTCOMES Committees and Investigators ; Salvioni, Alessandro. / Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. In: The New England journal of medicine. 2018 ; Vol. 379, No. 22. pp. 2097-2107.
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abstract = "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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language = "English",
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TY - JOUR

T1 - Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

AU - ODYSSEY OUTCOMES Committees and Investigators

AU - Schwartz, Gregory G

AU - Steg, P Gabriel

AU - Szarek, Michael

AU - Bhatt, Deepak L

AU - Bittner, Vera A

AU - Diaz, Rafael

AU - Edelberg, Jay M

AU - Goodman, Shaun G

AU - Hanotin, Corinne

AU - Harrington, Robert A

AU - Jukema, J Wouter

AU - Lecorps, Guillaume

AU - Mahaffey, Kenneth W

AU - Moryusef, Angèle

AU - Pordy, Robert

AU - Quintero, Kirby

AU - Roe, Matthew T

AU - Sasiela, William J

AU - Tamby, Jean-François

AU - Tricoci, Pierluigi

AU - White, Harvey D

AU - Salvioni, Alessandro

AU - Zeiher, Andreas M

PY - 2018/11/29

Y1 - 2018/11/29

N2 - 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 .).

AB - 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 .).

KW - Acute Coronary Syndrome/blood

KW - Adult

KW - Aged

KW - Antibodies, Monoclonal/adverse effects

KW - Anticholesteremic Agents/adverse effects

KW - Cardiovascular Diseases/epidemiology

KW - Cholesterol, LDL/blood

KW - Double-Blind Method

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Hypercholesterolemia/complications

KW - Male

KW - Middle Aged

KW - Proprotein Convertase 9/antagonists & inhibitors

U2 - 10.1056/NEJMoa1801174

DO - 10.1056/NEJMoa1801174

M3 - Article

VL - 379

SP - 2097

EP - 2107

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 22

ER -