Evolocumab shows particular CV benefit in those with autoimmune disease, inflammation
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Key takeaways:
- CV benefits of PCSK9 inhibition with evolocumab may be stronger in patients with autoimmune or inflammatory disease.
- The treatment effect differences occurred despite similar LDL reduction and no effect on CRP.
Patients with atherosclerosis and elevated LDL plus autoimmune or inflammatory disease may derive particular CV benefit from PCSK9 inhibition with evolocumab, a speaker reported.
The relative CV benefits of evolocumab (Repatha, Amgen) observed in patients with autoimmune or inflammatory disease were stronger compared with those in patients without autoimmune or inflammatory disease, according to a FOURIER substudy presented at the National Lipid Association Scientific Sessions.
“One in every 12 people have an autoimmune disease, and patients with autoimmune or inflammatory diseases are at higher cardiovascular risk due to the effects of chronic systemic inflammation. In prior statin trials, patients with a variety of inflammatory conditions have derived potentially greater relative benefit from statin therapy, perhaps due to the anti-inflammatory effect,” Andre Zimerman, MD, PhD, research fellow in medicine at Brigham and Women’s Hospital and a member of the TIMI Study Group, said during a presentation. “Trials of PCSK9 inhibitors provide us an opportunity to study an alternative lipid-lowering medication without a clear effect on systemic markers of inflammation in patients with autoimmune or inflammatory diseases. For this analysis, using data from the FOURIER trial, we compared the efficacy of evolocumab vs. placebo in patients with and without autoimmune or inflammatory diseases.”
For the FOURIER trial, researchers randomly assigned 27,564 patients with atherosclerotic CVD and LDL of 70 mg/dL or more to subcutaneous evolocumab 140 mg every 2 weeks, 420 mg monthly or placebo. Most patients were also taking a statin and/or ezetimibe.
As Healio previously reported, LDL lowering to a median of 30 mg/dL with evolocumab was associated with reduced risk for CV events.
For the present study, Zimerman and colleagues evaluated the effects of evolocumab on participants in the FOURIER cohort with and without autoimmune disease.
The primary endpoint was a composite of CV death, MI, stroke, unstable angina hospitalization or coronary revascularization.
Overall, 889 participants had an autoimmune or inflammatory disease (mean age, 65 years; 37% women). The most prevalent autoimmune or inflammatory disease in the FOURIER cohort was rheumatoid arthritis (33.7%), followed by psoriasis (15.6%), Hashimoto’s thyroiditis (9.2%), gout (9%), ulcerative colitis (7.6%), Crohn’s disease (3.6%) and Graves’ disease (3.5%).
Participants with autoimmune or inflammatory disease experienced similar LDL reductions with evolocumab compared with those without autoimmune or inflammatory disease (P = .6) and no change in high-sensitivity C-reactive protein.
Evolocumab injections conferred a significantly reduced risk for the primary endpoint among patients with autoimmune or inflammatory disease compared with placebo (HR = 0.58; 95% CI, 0.38-0.89; P = .013) and had a stronger effect than in patients without autoimmune or inflammatory disease (HR = 0.86; 95% CI, 0.5-0.93; P < .001; P for interaction = .066).
Findings were similar when the composite primary endpoint was restricted to CV death, MI and stroke, with an HR of 0.42 in the autoimmune/inflammatory disease group (95% CI, 0.24-0.74; P = .003) and 0.81 in the no autoimmune/inflammatory disease group (95% CI, 0.74-0.89; P < .001; P for interaction = .022).
Moreover, the relative risk for the composite endpoint of CV death, MI or stroke (P for interaction = .022), MI alone (P for interaction = .034) and coronary revascularization (P for interaction = .012) was lower among participants with autoimmune or inflammatory disease compared with those without autoimmune or inflammatory disease.
“Intensive LDL lowering with evolocumab may result in greater relative and absolute reductions in cardiovascular events in patients with autoimmune or inflammatory diseases, despite comparable changes in LDL and no effect on CRP,” Zimerman said during the presentation. “Therefore, more broadly, patients with autoimmune or inflammatory diseases may derive a particular cardiovascular benefit from earlier, more intensive lipid-lowering interventions.”
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Zimerman A, et al. Late breakers. Presented at: National Lipid Association Scientific Sessions; May 30-June 2, 2024; Las Vegas (hybrid meeting).
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