In a clinical trial involving 18,924 patients from 57 countries who had suffered a recent heart attack or threatened heart attack, researchers found that the cholesterol-lowering drug alirocumab reduced by 15% the chance of having additional heart problems or stroke.
Alirocumab is in the class of drugs called PCSK9 antibodies. “It works by increasing receptors on the liver that attract particles of LDL cholesterol from the blood and break them down. The result is that blood levels of LDL or ‘bad’ cholesterol decrease by approximately 50%, even when patients are already taking a statin,” explained Dr Gregory Schwartz, co-author of the study and professor of medicine at the University of Colorado School of Medicine.
The trial looked at patients who were at least 40-years-old, had been hospitalised with a heart attack or threatened heart attack (unstable angina), and had levels of LDL cholesterol of at least 70mg per decilitre despite taking high doses of statins.
Half of the patients received alirocumab by self-injection under the skin every two weeks, and the other half received placebo injections. The patients were followed for an average of nearly three years. During that time, LDL cholesterol levels averaged 40 to 66mg per decilitre in patients given alirocumab, compared with 93 to 103mg per decilitre with placebo. Death from coronary heart disease, another heart attack or episode of unstable angina, or a stroke occurred in 903 patients given alirocumab, compared with 1,052 patients given the placebo, corresponding to a 15% reduction in risk.
“Statins have been the main cholesterol-lowering drugs for heart patients for more than 30 years, and they are very effective,” Schwartz said. “Now we know that we can improve the outcomes after a heart attack by adding alirocumab to statins in selected patients.”
In the trial, alirocumab was safe and generally well-tolerated. The only common side effect with alirocumab was itching, redness, or swelling at the injection site which was usually mild. It occurred in 3.8% of those given alirocumab, compared with 2.1% of patients who received the placebo.
Alirocumab was approved by the US Food and Drug Administration in 2015 as a treatment for high cholesterol, but it has only now been shown to also reduce the risk of heart disease events and stroke.
The study was funded by Sanofi and Regeneron Pharmaceuticals. Schwartz co-chaired the study with Dr Philippe Gabriel Steg, from Hôpital Bichat, Assistance Publique Hôpitaux de Paris in Paris, France.
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.
Gregory G Schwartz, P Gabriel Steg, Michael Szarek, Deepak L Bhatt, Vera A Bittner, Rafael Diaz, Jay M Edelberg, Shaun G Goodman, Corinne Hanotin, Robert A Harrington, J Wouter Jukema, Guillaume Lecorps, Kenneth W Mahaffey, Angèle Moryusef, Robert Pordy, Kirby Quintero, Matthew T Roe, William J Sasiela, Jean-François T