Open-Label Study of Long-Term Evaluation Against LDL Cholesterol | Clinical Trial - OSLER

Description:

The goal of the trial was to assess the longer-term safety and efficacy of evolocumab, a PCSK9 inhibitor, in addition to standard therapy, compared with standard therapy alone.

Contribution to the Literature: The OSLER study suggests that evolocumab in addition to standard medical therapy results in greater LDL-C reduction and a reduction in 1-year composite cardiovascular outcomes compared with standard medical therapy alone.

Study Design

Video 1

Patients from five phase 2 trials and seven phase 3 trials were invited to participate in the OSLER extension program. These patients were randomized in a 2:1 fashion to either evolocumab (n = 2,976) or standard of care (n = 1,489). Evolocumab was administered as open-label, subcutaneous injections dosed either 140 mg q 2 weeks or 420 mg q month.

Patient population:

  • Total number of enrollees: 4,465
  • Duration of follow-up: 11.1 months
  • Mean patient age: 58 years
  • Percentage female: 49%
  • Percentage diabetics: 13%
  • Metabolic syndrome: 34%
  • known coronary artery disease: 20%; known cardiovascular disease/peripheral arterial disease: 9%
  • Any statin therapy: 70% (high intensity: 27%)

Principal Findings:

The primary composite outcome of death, myocardial infarction, unstable angina, coronary revascularization, stroke, transient ischemic attack, and chronic heart failure hospitalization at 1 year were 0.95% vs. 2.18% (p = 0.003).

Secondary outcomes:

  • Absolute reduction in low-density lipoprotein cholesterol (LDL-C) over 48 weeks in evolocumab vs. standard of care alone: 73 mg/dl (~61%), p < 0.001
  • LDL-C <70 mg/dl at 12 weeks: 73.6% vs. 3.8%, p < 0.0001
  • Change in high-density lipoprotein cholesterol (HDL-C) from baseline: 8.7% vs. 1.7%, p < 0.001
  • 1-year all-cause mortality: 0.14% vs. 0.41%, p = 0.33
  • Coronary events: 0.75% vs. 1.3%, p > 0.05
  • Cerebrovascular accident: 0.14% vs. 0.47%, p > 0.05
  • No adverse events directly related to degree of LDL-C lowering

Interpretation:

The results of this trial indicate that evolocumab significantly reduces LDL-C compared with standard of care, with a significant reduction in composite cardiovascular events at 1 year in a mixed group of patients with hyperlipidemia. Although this was not a dedicated cardiovascular outcomes trial with evolocumab, the clinical safety and efficacy noted in this extension study are encouraging. Other trials with this and other PCSK9 inhibitors are ongoing. Longer-term safety and efficacy data are also awaited, especially for neurocognitive effects.

References:

Sabatine MS, Giugliano RP, Wiviott SD, et al., on behalf of the Open-Label Study of Long-Term Evaluation Against LDL Cholesterol (OSLER) Investigators. Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events. N Engl J Med 2015;Mar 15:[Epub ahead of print].

Presented by Dr. Marc S. Sabatine at ACC.15, San Diego, CA, March 15, 2015.

Clinical Topics: Dyslipidemia, Prevention, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins

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


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