Effets de l'acide eicosapentaénoïque sur la morbi-mortalité cardiovasculaire : l'essai REDUCE-IT

Titre original : 
REDUCE-IT USA: Results from the 3,146 Patients Randomized in the United States.
Titre en français : 
Effets de l'acide eicosapentaénoïque sur la morbi-mortalité cardiovasculaire : l'essai REDUCE-IT
Auteurs : 
Bhatt DL, Miller M, Brinton EA, Jacobson TA, Steg PG, Ketchum SB, Doyle RT, Juliano RA, Jiao L, Granowitz C, Tardif JC, Olshansky B, Chung MK, Gibson CM, Giugliano RP, Budoff MJ, Ballantyne CM; REDUCE-IT Investigators.
Revue : 
Circulation. 2019 Nov 11.

Résumé : 

Background: Some trials have found patients from the United States of America (USA) derive less benefit than patients enrolled outside the USA. This prespecified subgroup analysis of Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial (REDUCE-IT) was conducted to determine the degree of benefit of icosapent ethyl in the USA. 

Methods: REDUCE-IT randomized 8,179 statin-treated patients with qualifying triglycerides ≥135 and <500 mg/dL and low-density lipoprotein (LDL)-cholesterol >40 and ≤100 mg/dL and a history of atherosclerosis or diabetes to icosapent ethyl 4 grams/day or placebo. The primary endpoint was cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary endpoint was cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. A prespecified hierarchy examined individual and composite endpoints. 

Results: A total of 3,146 USA patients (38.5% of the trial) were randomized and followed for a median of 4.9 years; 32.3% were women, 9.7% Hispanic. The primary endpoint occurred in 24.7% of placebo versus 18.2% of icosapent ethyl patients [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.59-0.80, p=0.000001]; the key secondary endpoint occurred in 16.6% versus 12.1% (HR 0.69, 95% CI 0.57-0.83, p=0.00008). All prespecified hierarchy endpoints were meaningfully and significantly reduced, including cardiovascular death (6.7% to 4.7%, HR 0.66, 95% CI 0.49-0.90, p=0.007), myocardial infarction (8.8% to 6.7%, HR 0.72, 95% CI 0.56-0.93, p=0.01), stroke (4.1% to 2.6%, HR 0.63, 95% CI 0.43-0.93, p=0.02), and all-cause mortality (9.8% to 7.2%, HR 0.70, 95% CI 0.55-0.90, p=0.004); for all-cause mortality for the USA versus non-USA patients, pinteraction=0.02. Safety and tolerability findings were consistent with the full study cohort. 

Conclusions: While the non-USA subgroup showed significant reductions in the primary and key secondary endpoints, the USA subgroup demonstrated particularly robust risk reductions across a variety of composite and individual endpoints, including all-cause mortality.