Cardiovascular Outcomes and Efficacy of the PCSK9 Inhibitor Evolocumab in Individuals With Type 1 Diabetes: Insights From the FOURIER Trial.

Abstract

To evaluate the clinical efficacy of intensive LDL cholesterol (LDL-C) lowering in type 1 diabetes mellitus (T1DM). Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) randomized participants with atherosclerotic cardiovascular disease (ASCVD) on statins to evolocumab or placebo (median follow-up 2.2 years). The primary end point (PEP) was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Of 27,564 participants, 10,834 (39.3%) had type 2 diabetes mellitus (T2DM), and 197 (0.7%) had T1DM. In the placebo arm, there was a stepwise increase in the 2.5-year PEP Kaplan-Meier rate from 11.0% to 15.2% to 20.4% in participants with no diabetes, T2DM, and T1DM, respectively (P < 0.0001). Hazard ratios for PEP with evolocumab were 0.87 (95% CI 0.79-0.96), 0.84 (0.75-0.93), and 0.66 (0.32-1.38) in the no diabetes, T2DM, and T1DM groups, and absolute risk reduction was 1.3%, 2.5%, and 7.3%, respectively. Intensive LDL-C lowering may provide substantial clinical benefit in individuals with T1DM and ASCVD. Additional randomized controlled cardiovascular outcomes trials are needed in this population.