OSLER -1 and -2: PCSK9-Inhibitor Evolocumab Shown to Dramatically Lower LDL

The use of the PCSK9-inhibitor evolocumab plus standard therapy dramatically lowered low-density lipoprotein cholesterol (LDL), according to results from the OSLER-1 AND -2 Trial presented Sunday, March 15 at ACC.15 and simultaneously published in the New England Journal of Medicine.

The trial randomly assigned 4,465 patients who had previously participated in “parent trials” of evolocumab to receive either evolocumab (140 mg every two weeks or 420 mg monthly) plus standard therapy or standard therapy alone. Patients were followed for approximately 11 months with assessment of lipid levels, safety and adjudicated cardiovascular events.

Results of the study found patients receiving evolocumab saw their cholesterol drop 61 percent, from a median of 120 mg per deciliter to 48 milligrams per deciliter. Reductions were sustained through the median 11-month follow-up period. Study investigators also noted evidence of reduction in the rate of cardiovascular events among patients in the evolocumab group. At one year, the rate of cardiovascular events was less (0.95 percent) in the evolocumab group, compared to the standard care group (2.18 percent).

“The reduction in LDL was profound and that may be why we saw a marked reduction in cardiovascular events so quickly,” said Marc Sabatine, MD, MPH, FACC, lead study author. “It suggests that if we can drive a patient’s LDL cholesterol down a large amount to a very low level, we may start to see a benefit sooner than would be expected with a more modest intervention.”

Sabatine also explained that while the initial results of evolocumab are promising, results are limited by the nature of the trial and he and his team will shortly be undertaking a large scale study with expected results by 2017. “We won’t have any definitive answers until this larger trial we are doing is complete, but these data now give us a sense for the potential clinical benefit of these drugs,” he said. “We know from previous research that evolocumab lowers LDL cholesterol, but these data offer support for their potential to reduce major adverse cardiovascular events in our patients.”

Clinical Topics: Dyslipidemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: ACC Annual Scientific Session, Angina, Unstable, Antibodies, Monoclonal, Cholesterol, Follow-Up Studies, Hospitalization, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Proprotein Convertases, Risk, Stroke, Subtilisins

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