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Effect of Alirocumab on Mortality After Acute Coronary Syndromes.

Publication ,  Journal Article
Steg, PG; Szarek, M; Bhatt, DL; Bittner, VA; Brégeault, M-F; Dalby, AJ; Diaz, R; Edelberg, JM; Goodman, SG; Hanotin, C; Harrington, RA ...
Published in: Circulation
July 9, 2019

BACKGROUND: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. METHODS: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. RESULTS: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths ( P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events ( P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined with achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). CONCLUSIONS: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01663402.

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Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

July 9, 2019

Volume

140

Issue

2

Start / End Page

103 / 112

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Middle Aged
  • Male
  • Injections, Subcutaneous
  • Hypercholesterolemia
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Humans
  • Follow-Up Studies
  • Female
  • Drug Therapy, Combination
 

Citation

APA
Chicago
ICMJE
MLA
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Steg, P. G., Szarek, M., Bhatt, D. L., Bittner, V. A., Brégeault, M.-F., Dalby, A. J., … Schwartz, G. G. (2019). Effect of Alirocumab on Mortality After Acute Coronary Syndromes. Circulation, 140(2), 103–112. https://doi.org/10.1161/CIRCULATIONAHA.118.038840
Steg, Philippe Gabriel, Michael Szarek, Deepak L. Bhatt, Vera A. Bittner, Marie-France Brégeault, Anthony J. Dalby, Rafael Diaz, et al. “Effect of Alirocumab on Mortality After Acute Coronary Syndromes.Circulation 140, no. 2 (July 9, 2019): 103–12. https://doi.org/10.1161/CIRCULATIONAHA.118.038840.
Steg PG, Szarek M, Bhatt DL, Bittner VA, Brégeault M-F, Dalby AJ, et al. Effect of Alirocumab on Mortality After Acute Coronary Syndromes. Circulation. 2019 Jul 9;140(2):103–12.
Steg, Philippe Gabriel, et al. “Effect of Alirocumab on Mortality After Acute Coronary Syndromes.Circulation, vol. 140, no. 2, July 2019, pp. 103–12. Pubmed, doi:10.1161/CIRCULATIONAHA.118.038840.
Steg PG, Szarek M, Bhatt DL, Bittner VA, Brégeault M-F, Dalby AJ, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Lecorps G, Mahaffey KW, Moryusef A, Ostadal P, Parkhomenko A, Pordy R, Roe MT, Tricoci P, Vogel R, White HD, Zeiher AM, Schwartz GG. Effect of Alirocumab on Mortality After Acute Coronary Syndromes. Circulation. 2019 Jul 9;140(2):103–112.

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

July 9, 2019

Volume

140

Issue

2

Start / End Page

103 / 112

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Middle Aged
  • Male
  • Injections, Subcutaneous
  • Hypercholesterolemia
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Humans
  • Follow-Up Studies
  • Female
  • Drug Therapy, Combination