Evolocumab atop statins lowers CV-events risk
Intensive LDL-C lowering through the addition of the PCSK9* inhibitor evolocumab to statin therapy significantly reduced the risk of cardiovascular (CV) events in patients with existing atherosclerotic CV disease, according to data from the FOURIER** trial presented at the American College of Cardiology’s 66th Annual Scientific Session (ACC.17) held in Washington, DC, US.
“Evolocumab reduced LDL cholesterol down to 30 mg/dL, [a] really unprecedented low level,” said Dr Marc Sabatine of Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts, US. “We’ve never been able to plumb these depths before. These data strongly suggest that patients benefit from lowering LDL cholesterol well below current targets.”
The double-blind, placebo-controlled, multicentre trial randomized 27,564 patients (mean age 62.5 years, 75 percent male) with a history of CV disease (ischaemic stroke, myocardial infarction [MI], or symptomatic peripheral artery disease) and LDL cholesterol levels of ≥70 mg/dL or non-HDL cholesterol levels of ≥100 mg/dL, who were already on statin therapy, to receive either evolocumab injections (140 mg Q2W or 420 mg QM) or matching placebo. [ACC.17, abstract LB-15607; N Engl J Med 2017;doi:10.1056/NEJMoa1615664]
After a median follow-up of 26 months, the evolocumab arm saw a 15 percent lower risk for the composite primary endpoint of MI, stroke, unstable angina hospitalization, coronary revascularization, and CV death than the placebo arm (9.8 percent vs 11.3 percent, hazard ratio [HR], 0.85; p<0.001).
Furthermore, a 20 percent reduction in the risk for the key secondary endpoint – a composite of MI, stroke, and CV death, was observed with evolocumab (5.9 percent vs 7.4 percent, HR, 0.80; p<0.001), and the benefits were already seen after 1 year.
Also, the benefits were consistent across subgroups, including those on high-intensity statin and those with low LDL cholesterol levels.
“I am impressed with the way you carried out this study. I am less impressed about the absolute results,” said panel discussant Dr Valentin Fuster, who is also the editor-in-chief of the Journal of the American College of Cardiology. “I’m most impressed to see the curves how they were diverging over time … It seems to me that the future is brighter than the present.”
Rates of adverse events (including neurocognitive events and new-onset diabetes) were similar between the evolocumab and placebo arms, except for injection-site reactions, which occurred more commonly in the evolocumab arm (2.1 percent vs 1.6 percent).
The rates of discontinuation were also comparable in both arms and no neutralizing antibodies were developed, according to Sabatine.
“We now have definitive data that by adding evolocumab to a background of statin therapy, we can significantly improve [CV] outcomes and do so safely,” said Sabatine.
Noting the high cost of the drug during a press conference, Fuster said “this is very expensive, and we can’t say everybody will take it now. Instead, we need to be very cautious, and we have to be sure that we identify the right people for treatment.”