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OSLER: Two studies indicate long-term safety, efficacy of evolocumab for LDL reduction
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SAN DIEGO — Patients treated with the PCSK9 inhibitor evolocumab in addition to standard care experienced a significant reduction to LDL cholesterol and lower risk for CV events, according to combined data from the OSLER-1 and -2 trials presented at the American College of Cardiology Scientific Sessions.
The two open-label trials incorporated a total of 4,465 patients (n = 1,324 for OSLER-1 and n = 3,141 for OSLER-2) who had completed at least one of the prior 12 trials of evolocumab (Amgen). After 12 weeks of treatment, LDL cholesterol decreased from a median of 120 mg/dL at baseline to 48 mg/dL among evolocumab recipients compared with nonrecipients (P < .001). Patients reached LDL cholesterol levels below 100 mg/dL at 12 weeks in 90.2% of the evolocumab group and 26% in the standard therapy group, and had reached levels below 70 mg/dL in 73.6% and 3.8% of cases, respectively (P < .001 for both). The observed reductions in LDL persisted over the course of the study.
Marc S. Sabatine
“The reduction in LDL was profound, and that may be why we saw a marked reduction in cardiovascular events so quickly,” Marc S. Sabatine, MD, MPH, from the TIMI Study Group, division of cardiovascular medicine, Brigham and Women's Hospital and Harvard Medical School, said in a press release.
Participants were randomly assigned 2:1 to receive standard therapy either alone or with subcutaneous evolocumab at a dose of either 140 mg every 2 weeks for 56 weeks (OSLER-1) or 420 mg monthly for 48 weeks (OSLER-2). The primary endpoint was prevalence of adverse events, and the secondary endpoint was a change in percentage to LDL cholesterol. The trial also assessed the incidence of CV events including death, MI, unstable angina or HF requiring hospitalization, revascularization and stroke or transient ischemic attack. Follow-up was conducted over a median of 11.1 months.
The incidence rate of adverse events was 69.2% in the evolocumab group and 64.8% in the standard-therapy group. Events leading to discontinuation of evolocumab occurred in 2.4% of recipients. Neurocognitive events occurred in less than 1% of patients; however, the researchers noted that these events were more common among evolocumab recipients. Risk for neurocognitive events was not influenced by the level of LDL cholesterol achieved during treatment.
Incidence of CV events at 1 year was significantly lower in the evolocumab group compared with standard therapy (2.18% vs. 0.95%; HR = 0.47; 95% CI, 0.28-0.78). This effect was consistent across all evaluated CV event types, as well as across different types of patients.
“There is consistency throughout these results, regardless of whether patients are on a statin or not, or whether they have known vascular disease or not,” he said in a press conference.
According to a press release, a larger, ongoing trial of 27,500 patients will evaluate the effect of evolocumab on CV outcomes, with results expected in 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,” Sabatine said in the release. “We know from previous research that evolocumab lowers LDL cholesterol, but these data offer support for [its] potential to reduce major adverse CV events in our patients.” – by Adam Taliercio and Erik Swain
References:
Sabatine MS, et al. Late-Breaker II Press Conference. Presented at: American College of Cardiology Scientific Sessions: March 14-16, 2015; San Diego.
Sabatine MS, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1500858.
Disclosures: Amgen sponsored and designed both trials, and was responsible for data collection and analysis. Sabatine reports receiving consultant fees and/or honoraria from Amgen, AstraZeneca, Cubist, CVS Caremark, Intarcia, Medscape, Merck, MyoKardia, Vox Media and Zeus Scientific; and conducting research for or receiving research grants from Abbott Laboratories, Amgen, AstraZeneca, Critical Diagnostics, Daiichi-Sankyo, Eisai, Gilead Sciences, GlaxoSmithKline, Intarcia, Merck, Roche Diagnostics, Sanofi and Takeda Pharmaceuticals.