Intensive Lowering of LDL Cholesterol Levels With Evolocumab in Autoimmune or Inflammatory Diseases: An Analysis of the FOURIER Trial

BACKGROUND: Patients with an autoimmune or inflammatory disease (AIID) are at increased cardiovascular risk and may benefit more from statin therapy. In the FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor evolocumab lowered low-density lipoprotein cholesterol levels, but not hsCRP (high-sensitivity C-reactive protein) levels, and reduced the risk of cardiovascular events. METHODS: FOURIER was a randomized trial of evolocumab versus placebo in 27 564 patients with stable atherosclerosis who were taking statins. This analysis focused on the effect of evolocumab in patients with or without an AIID, defined as any autoimmune or chronic inflammatory condition. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, unstable angina, or coronary revascularization. RESULTS: At baseline, 889 patients (3.2%) had an AIID, most commonly rheumatoid arthritis (33.7%) or psoriasis (15.6%). Median (interquartile range) low-density lipoprotein cholesterol levels were 90.0 mg/dL (79.5–105.5) and 91.5 mg/dL (79.5–108.5) in patients with or without an AIID, respectively ( P =0.025), and the placebo-adjusted percent reduction with evolocumab was consistent (60.2% versus 59.0%; P =0.57). Baseline hsCRP was higher in patients with an AIID (median 2.1 versus 1.7 mg/L; P <0.001) and did not significantly change with evolocumab in either group. Compared with placebo, evolocumab reduced the rate of the primary end point by 14% in patients without an AIID (hazard ratio, 0.86 [95% CI, 0.80–0.93]) and by 42% in patients with an AIID (hazard ratio, 0.58 [95% CI, 0.38–0.89]; P interaction =0.066). Likewise, evolocumab reduced the key secondary end point of cardiovascular death, myocardial infarction, or stroke by 19% in patients without an AIID (hazard ratio, 0.81 [95% CI, 0.74–0.89]) and 58% in those with an AIID (hazard ratio, 0.42 [95% CI, 0.24–0.74]; P interaction =0.022). CONCLUSIONS: Intensive lowering of low-density lipoprotein cholesterol levels with evolocumab may lead to greater relative reduction in cardiovascular events in patients with an AIID. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01764633.