OSLER

From Wiki Journal Club
Jump to: navigation, search
Sabatine MS, et al. "Efficacy and safety of evolocumab in reducing lipids and cardiovascular events". The New England Journal of Medicine. 2015. 372(16):1500-1509.
PubMed

Clinical Question

Is evolocumab safe and effective to decrease LDL and cardiovascular events in patients who were enrolled in phase 2 and phase 3 trials of evolocumab (familial heterozygous hypercholesterolemia, intolerant to statins, high LDL-C) in the longterm?

Bottom Line

Evolocumab is effective in decreasing LDL-C on top of standard therapies and decreases cardiovascular events in an exploratory analysis.

Larger trials with cardiovascular events as primary outcome is needed to confirm the benefit on cardiovascular events.

Major Points

Phase 2 and phase 3 trials of evolocumab have suggested an decrease in LDL-C with evolocumab.

The OSLER trials confirm this decrease in LDL-C and shows that evolocumab has an adequate safety profile. The exploratory analysis also shows that evolocumab decreases cardiovascular events with a NNT of 90 during 1 year(death, non fatal MI, unstable angina requiring hospitalization, coronary resvascularisation, ischemic stroke, TIA, and heart failure requiring hospitazliation).

However, neurocognitive events were also non-statistically increased in the evolocumab group.

Guidelines

Design

  • Multicenter, unblinded, parallel-group, randomized, controlled trial
  • N=4,465
    • Evolocumab + standard (n=2,976)
    • Standard (n=1,489)
  • Median follow-up: 11.1 months
  • Primary outcome: adverse events

Population

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Interventions

Outcomes

Primary Outcomes

Secondary Outcomes

Subgroup Analysis

Adverse Events

Criticisms

Funding

Industry funded

Further Reading