Bempedoic acid reduced leg complications in artery disease
Among patients with peripheral artery disease, bempedoic acid reduced the relative risk of a first major limb complication by 36% versus placebo.
13,970 participants, placebo-controlled
Limit: Limb events were identified retrospectively from safety reports without supplemental source documentation
Stake: An author takes fees from Daiichi Sankyo, which develops bempedoic acid. Esperion Therapeutics funded the study; authors work for it and hold shares in it.
Edited by Boris Djordjevic · AgingResearch.News
A randomized trial included 1,624 people with peripheral artery disease—narrowed arteries supplying the limbs—who could not tolerate recommended cholesterol-lowering statin treatment. Their average age was 63.9 years; 56.3% were women. Participants received 180 mg bempedoic acid or placebo.
Limb complications affected 5.8% taking bempedoic acid versus 8.3% taking placebo over a median 40 months. These included worsening symptoms requiring blood-flow procedures and severely reduced limb blood supply. Total events, including recurrences, fell 45%. Adverse events affected 85.8% versus 85.2%; serious events affected 32.6% versus 30.3%. Events led 11.0% versus 8.4% to stop treatment. High uric acid occurred in 10.7% versus 5.4%, and gout, a painful joint condition, in 2.9% versus 1.3%. Other rates were 13.4% versus 12.5% for high blood pressure, 7.8% versus 7.0% for joint pain, 6.1% versus 4.9% for nose and throat infections, 5.2% versus 5.3% for muscle pain, and 0.6% versus 0.8% for tendon rupture.
Why it matters
Peripheral artery disease threatens limb health in later life. The authors said the findings support lowering cholesterol to reduce overall vascular risk in people with this condition.
Caveats
This was a post hoc analysis—conducted after the original trial—with limb complications identified through reported adverse events. The trial enrolled statin-intolerant adults aged 18–85, so these results do not establish benefits outside that population.
From the paper
- Participants
The study randomized a total of 13 970 statin-intolerant patients, including 1624 patients with PAD, to either bempedoic acid or placebo.
- Who took part
Briefly, CLEAR Outcomes (NCT02993406) was a randomized, double-blinded, placebo-controlled trial comparing 180 mg bempedoic acid with placebo in patients 18 to 85 years of age with history of or at high risk of cardiovascular diseases who were not able to take recommended statin treatment because of intolerance …
- Duration
At a median of 40.6 months of follow-up in patients randomized to placebo, the rate of ≥1 MALE was 2.2%, with rates of 8.3% and 1.4% in those with and without PAD, respectively.
Results, Risk of MACE and MALE in Patients Taking Placebo With PAD Compared With Those Without PAD
- Result
At 6 months, the difference in the median hsCRP level was −25.9% (95% CI, −31.7 to −20.0) in favor of bempedoic acid.
Results, Impact of Bempedoic Acid in the LDL-C Levels of Patients With PAD
- Absolute difference
In patients with PAD, bempedoic acid reduced the risk of MALE by 36% (5.8% bempedoic acid versus 8.3% placebo; HR, 0.64 [95% CI, 0.44–0.93]; P=0.018; Table and Figure ), translating into an absolute risk reduction of 2.5% at a median of 40 months.
- Harms
A total of 282 patients had MALE over the duration of the trial, with 239 (85%) as adverse events indicating worsening PAD leading to revascularization, 38 (13%) with chronic limb-threatening ischemia, and 25 (9%) with acute limb ischemia (Table S1).
Results, Risk of MACE and MALE in Patients Taking Placebo With PAD Compared With Those Without PAD
- Limitation
Patients enrolled in CLEAR Outcomes were not screened for PAD; therefore, patients with undiagnosed PAD were not included in the prespecified subgroup.
- Total major adverse limb events
Total, including recurrent, MALE were reduced with bempedoic acid (n/100 patient-years; 2.9 with bempedoic acid versus 4.0 with placebo; RR, 0.55 [95% CI, 0.35–0.85]; P=0.007; Table and Figure ).
- Major adverse cardiovascular events or major adverse limb events
The composite of the trial primary outcome and MALE (MACE-4+MALE) was reduced overall with bempedoic acid (HR, 0.87 [95% CI, 0.80–0.95]; P=0.002; Table S3), as was the composite of the key secondary outcome and MALE (MACE-3+MALE: HR, 0.85 [95% CI, 0.77–0.94]; P=0.002; Table S3), with consistent effects in patients with and without PAD but without reaching statistical significance in the PAD subgroup alone (Pinteraction=NS; Figure and Table S3 …
- Total major adverse cardiovascular events or major adverse limb events
When we consider total, including recurrent, events, the composites of MACE-4+MALE and MACE-3+MALE were reduced by bempedoic acid by 19% (RR, 0.81 [95% CI, 0.73–0.89]; P<0.001) and 18% (RR, 0.82 [95% CI, 0.73–0.92]; P<0.001), respectively, with consistent effects, reaching statistical significance in those with and without PAD (Pinteraction=NS; Table S2 …
Quoted word for word from the full text on PubMed Central.
The paper
University of Colorado Anschutz; Monash University
Circulation, Aug 18, 2026, Open access
