Alirocumab yields mortality benefits in acute coronary syndrome

04 Jun 2019
Alirocumab yields mortality benefits in acute coronary syndrome

The addition of alirocumab to intensive statin therapy appears to cut the risk of death following acute coronary syndrome (ACS), especially if treatment is sustained for at least 3 years, if baseline low-density lipoprotein cholesterol (LDL-C) is ≥100 mg/dL or if achieved LDL-C is low, according to data from the ODYSSEY OUTCOMES.

The trial randomized 18,924 patients, who had an ACS 1–12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy, to receive either alirocumab or placebo. Treatment dose was blindly titrated to achieve LDL-C targets (25–50 mg/dL). Outcomes of interest were all-cause death and its components, cardiovascular and noncardiovascular death.

Over a median follow-up of 2.8 years, 334 patients (3.5 percent) in the alirocumab group and 392 (4.1 percent) in the placebo group died (hazard ratio [HR], 0.85, 95 percent CI, 0.73–0.98; p=0.03). This survival advantage with the study drug was attributed to nonsignificantly fewer cardiovascular (2.5 percent vs 2.9 percent; HR, 0.88, 0.74–1.05; p=0.15) and noncardiovascular deaths (1.0 percent vs 1.3 percent; HR, 0.77, 0.59–1.01; p=0.06).

In the group of 8,242 patients who completed ≥3 years of follow-up, alirocumab conferred significant protection against death (HR, 0.78, 0.65–0.94; p=0.01). Of note, patients with nonfatal cardiovascular events were at increased risk of cardiovascular and noncardiovascular deaths (p<0.0001), but treatment with alirocumab led to a lower incidence of total nonfatal cardiovascular events (p<0.001) and might have thus attenuated the number of noncardiovascular deaths.

Posthoc analysis revealed that patients with baseline LDL-C ≥100 mg/dL had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71, 0.56–0.90; p-interaction=0.007) compared with those who had lower LDL-C. The risk of all-cause death decreased in alirocumab-treated patients who achieved LDL-C target (approximately 30 mg/dL) at 4 months of treatment (p-trend=0.017).

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