Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients.

BACKGROUND: Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects ("statin-intolerant" patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo. The primary end point was a four-component composite of major adverse cardiovascular events, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. RESULTS: A total of 13,970 patients underwent randomization; 6992 were assigned to the bempedoic acid group and 6978 to the placebo group. The median duration of follow-up was 40.6 months. The mean LDL cholesterol level at baseline was 139.0 mg per deciliter in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter; the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid. The incidence of a primary end-point event was significantly lower with bempedoic acid than with placebo (819 patients [11.7%] vs. 927 [13.3%]; hazard ratio, 0.87; 95% confidence interval [CI], 0.79 to 0.96; P = 0.004), as were the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (575 [8.2%] vs. 663 [9.5%]; hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P = 0.006); fatal or nonfatal myocardial infarction (261 [3.7%] vs. 334 [4.8%]; hazard ratio, 0.77; 95% CI, 0.66 to 0.91; P = 0.002); and coronary revascularization (435 [6.2%] vs. 529 [7.6%]; hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = 0.001). Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause. The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels. CONCLUSIONS: Among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization). (Funded by Esperion Therapeutics; CLEAR Outcomes ClinicalTrials.gov number, NCT02993406.).

Efficacy and safety of Actovegin in the treatment of intermittent claudication: results of an international, multicenter, placebo-controlled, randomized, phase IIIb clinical trial (APOLLO).

BACKGROUND: This study aimed to assess the efficacy and safety of Actovegin for the treatment of patients with Fontaine stage IIB peripheral arterial disease (PAD). METHODS: The study included 366 patients with Fontaine stage IIB PAD from 19 centers (Russia, Georgia, Kazakhstan). Placebo or Actovegin (1200 mg daily [QD]) were administered intravenously for two weeks, followed by a 10-week course of oral administration (placebo or Actovegin 1200 mg QD). The primary efficacy outcome was percentage change in the initial claudication distance (ICD) by week 12. Secondary outcomes included percent and absolute changes in ICD, absolute claudication distance (ACD) and changes in Quality of Life (QoL) assessed by the SF-36 Mental Health Score. RESULTS: The increase in ICD after 12 weeks of Actovegin treatment was 29.19% (LS mean [Actovegin vs. placebo]; 95% CI: 9.35-49.02; P=0.0041). The percentage increase in ICD at 24 weeks was 35.51% (LS mean; 95% CI: 10.96-60.05; P=0.0047), which correspond to an increase in absolute ICD of 41.22 m (LS mean; 95% CI: 16.77-65.66; P=0.0010). The percentage increase in ACD after 24 weeks was 36.47% compared with the baseline (LS mean; 95% CI: 10.07-62.88; P=0.0069), which corresponded to an absolute increase in ACD of 50.92 m (LS mean; 95% CI: 18.35-83.49; P=0.0023). A statistically significant improvement in QoL with Actovegin compared with placebo was demonstrated within 24 weeks (LS mean 2.28; 95% CI: 0.88-3.68; P=0.0015). Actovegin demonstrated an acceptable safety and tolerability profile with minor differences from placebo. CONCLUSIONS: The results of this 12-week course of Actovegin demonstrated its superiority over placebo in the increase in ICD and ACD at weeks 2, 12 and 24 from the start of treatment. Actovegin has an acceptable safety and tolerability profile.