Lack of impact of adjunctive lipid-modifying therapy in the CLEAR Outcomes trial.

BACKGROUND

Bempedoic acid is a prodrug that reduces circulating low-density lipoprotein (LDL) cholesterol levels by inhibiting the liver enzyme adenosine triphosphate-citrate lyase. Treatment of statin intolerant patients with bempedoic acid was associated with a significantly reduced risk of the primary composite endpoint (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization) in the CLEAR (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen) Outcomes Trial.

OBJECTIVE

To evaluate impact of additional lipid modifying therapy (LMT) on the primary composite endpoint of the CLEAR Outcomes Trial.

RESULTS

Utilization of adjunctive LMT was observed in 1749 (12.5%) enrolled patients. The most common adjunctive LMTs reported were statins (4.0% vs 6.5%), ezetimibe (2.7% vs 5.5%), and proprotein convertase subtilisin/kexin type 9 inhibitors (2.8% vs 4.4%) in the bempedoic acid and placebo groups, respectively. The majority of first MACE-4 events (92.9% of events in bempedoic acid and 90.9% of events in placebo) preceded the initiation of adjunctive LMT. When censored at the time of initiating adjunctive LMT, primary event reduction was observed in favor of bempedoic acid compared to placebo (hazard ratio [HR]: 0.86 [95% CI, 0.77-0.94]) which was similar to the reduction noted with bempedoic acid in the overall trial (HR of 0.87 [95% CI, 0.79-0.96], P = .004).

CONCLUSIONS

The utilization of additional LMT following randomization had no impact on the observed results of the CLEAR Outcomes trial.