Meds Targeting PCSK9 Lower LDL in High-Risk Patients

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Both evolocumab and inclisiran reduced the risk of cardiovascular events and lowered LDL cholesterol levels.
Both evolocumab and inclisiran reduced the risk of cardiovascular events and lowered LDL cholesterol levels.

(HealthDay News) — Evolocumab and inclisiran, medications targeting proprotein convertase subtilisin-kexin type 9 (PCSK9), can benefit patients with atherosclerotic cardiovascular disease by lowering low-density lipoprotein (LDL) cholesterol levels below current targets, according to findings published online in the New England Journal of Medicine. The research was published to coincide with the annual meeting of the American College of Cardiology, held from March 17 to 19 in Washington, DC.

In one study, Marc Sabatine, MD, MPH, chair of cardiovascular medicine at Brigham and Women's Hospital in Boston, and colleagues included 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL or higher who were receiving statin therapy. Participants were randomly assigned to receive evolocumab, a monoclonal antibody that inhibits PCSK9, 140 mg every 2 weeks or 420 mg monthly or placebo.

Sabatine and his team found that inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg/dL and reduced the risk of cardiovascular events, including cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization.

In a second study, Kausik Ray, MD, a cardiologist at Imperial College London, and colleagues found that patients given inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, had dose-dependent reductions in PCSK9 and LDL cholesterol levels. The inclisiran dosage that produced the best results would require a patient to get an initial injection followed by a booster three months later, Ray told HealthDay. They then could wait up to 6 months before needing another injection.

The two clinical trials were funded by the drugs' respective makers — Amgen for evolocumab and the Medicines Company/Alnylam Pharmaceuticals for inclisiran.

References

  1. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 17 March 2017. doi: 10.1056/NEJMoa1615664
  2. Ray KK, Landmesser U, Leiter LA, et al. Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol. N Engl J Med. 17 March 2017. doi: 10.1056/NEJMoa1615758

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