New CLEAR Outcomes data: Bempedoic acid cuts risk for recurrent CV events
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Key takeaways:
- New data show bempedoic acid reduced the total burden of CV events in high-risk patients.
- The benefits of bempedoic acid were greater for those who experienced recurrent CV events.
A prespecified analysis of the CLEAR Outcomes trial shows that the benefits of bempedoic acid extend to patients with recurrent CV events, including a total reduction in MI risk of 31% vs. placebo.
As Healio previously reported, data from the CLEAR Outcomes trial demonstrated bempedoic acid (Nexletol, Esperion Therapeutics) reduced risk for major CV events by 13% compared with placebo, including a 23% lower risk for MI, among adults with a history of CVD or at high risk deemed statin intolerant. In a new analysis, researchers assessed the impact of bempedoic acid on the total incidence of major adverse CV events.
“Traditional trials have used a time-to-first-event analysis to compare the effect of a new intervention with standard of care,” Stephen J. Nicholls, MBBS, PhD, director of the Victorian Heart Hospital and Institute and professor of cardiology at Monash University in Melbourne, Australia, and colleagues wrote. “An alternative approach investigates the effects of interventions on the total number of clinical events that occur during a clinical trial. As cardiovascular outcomes trials typically recruit high-risk patients, many individuals experience more than one clinical event during follow-up. This provides the opportunity to understand whether apparent benefits on first events extend to subsequent events in patients at high cardiovascular risk.”
Assessing total CV events
Nicholls and colleagues analyzed data from 13,970 adults with or at high risk for CVD with hypercholesterolemia and documented statin intolerance. The mean age of participants was 66 years; 51.8% were men and 69.9% had prior atherosclerotic CVD; baseline LDL was 139 mg/dL. Researchers randomly assigned patients to 180 mg oral bempedoic acid once daily (n = 6,992) or placebo (n = 6,978) and followed the cohort for a median of 40.6 months. Mean baseline LDL was 139 mg/dL. The primary endpoint was time to first event for a composite of CV death, nonfatal MI, nonfatal stroke or coronary revascularization. The key secondary endpoint was time to first event for CV death, nonfatal MI or nonfatal stroke. For this prespecified analysis, researchers compared the total number of CV events in the treatment groups.
The findings were published in JAMA Cardiology.
During the study, there were 1,746 primary events and 915 additional secondary MACE events. Of patients experiencing more than one MACE event, 437 had two events, 114 had three events and 61 experienced at least four clinical events.
Assessing the total incidence of CV events, treatment with bempedoic acid was associated with a 20% risk reduction for the composite of four MACE events (HR = 0.8; 95% CI, 0.72-0.89; P < .001), as well as a 17% reduction in risk for the composite of three MACE events (HR = 0.83; 95% CI, 0.73-0.93; P = .002), a 31% reduction in risk for MI (HR = 0.69; 95% CI, 0.58-0.83; P < .001) and a 22% reduction in risk for coronary revascularization (HR = 0.78; 95% CI, 0.68-0.89; P < .001).
The researchers noted there was a lower HR for patients who received bempedoic acid who experienced an increasing number of CV events, underscoring the benefits of lowering LDL for those at high CV risk.
Benefits across CV risk strata
“Approximately half of the clinical events projected to be prevented by treating 1,000 patients with bempedoic acid for 5 years represent a reduction in coronary revascularization, whereas the other half reflects a reduction in cardiovascular death, MI and stroke,” the researchers wrote. “The previously reported safety findings of the CLEAR Outcomes study demonstrated that treatment with bempedoic acid was generally well tolerated, with small increases in the incidence of gout and cholelithiasis and small elevations in liver enzymes and creatinine level. These findings have implications for integration of bempedoic acid into treatment algorithms for the prevention and treatment of cardiovascular disease.”
In June, data reported by Healio also showed bempedoic acid reduced risk for MACE by 30% compared with placebo for primary prevention patients, including those with diabetes. CLEAR Outcomes was unique for its inclusion criteria: only participants who signed a statin intolerance confirmation form, stating they were unable to tolerate statins even though they would reduce the person’s risk for MI, stroke or death.
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