Frequency of Tendon Rupture with Bempedoic Acid
Tendon rupture occurs in approximately 1.2% of patients treated with bempedoic acid based on the largest and most recent cardiovascular outcomes trial data, compared to 0.9% with placebo. 1, 2
Quantified Risk Data
The frequency of tendon rupture with bempedoic acid varies by study population and duration:
In the CLEAR Outcomes trial (the largest study with 7,001 patients followed for median 3.4 years): tendon rupture occurred in 1.2% of bempedoic acid patients versus 0.9% of placebo patients 1, 2
In smaller primary hyperlipidemia trials (52-week duration): tendon rupture occurred in 0.5% of bempedoic acid patients versus 0% of placebo patients 3, 1
Broader tendinopathy events (including tendon rupture and injury): occurred in 2% of patients in both bempedoic acid and placebo groups in the cardiovascular outcomes trial 2
Clinical Context and Timing
Tendon rupture with bempedoic acid typically occurs within weeks to months of starting treatment. 1 The most commonly affected tendons include the rotator cuff (shoulder), biceps tendon, and Achilles tendon. 1
High-Risk Patient Populations
The risk of tendon rupture is substantially higher in specific patient subgroups, and bempedoic acid should be used with extreme caution or avoided in these populations:
- Patients over 60 years of age 1
- Those taking corticosteroids concurrently 1
- Those taking fluoroquinolone antibiotics 1
- Patients with renal failure 1
- Patients with previous tendon disorders 1
The 2022 ACC Expert Consensus specifically states that bempedoic acid should be used with caution in patients who have a history of gout or tendon rupture. 3
Comparison to Background Risk
The absolute increase in tendon rupture risk (0.3% difference between bempedoic acid and placebo in CLEAR Outcomes) must be interpreted in context: 2
- Patients with atherosclerotic cardiovascular disease have a baseline TRT prevalence of 3.4% over 12 months, compared to 1.9% in the general population 4
- Use of statins or bempedoic acid was not independently associated with increased TRT risk when controlling for other factors 4
- The most significant risk factors for tendon rupture in ASCVD patients are age 45-64 years (OR 2.19), obesity (OR 1.51), and rheumatoid arthritis (OR 1.47) 4
Critical Management Recommendations
Discontinue bempedoic acid immediately if the patient experiences rupture of a tendon. 1
Consider discontinuing bempedoic acid if the patient experiences joint pain, swelling, or inflammation. 1
Advise patients to rest at the first sign of tendinitis or tendon rupture and to contact their healthcare provider immediately if these symptoms occur. 1
Consider alternative lipid-lowering therapy in patients with a history of tendon disorders or tendon rupture. 1
Common Pitfall
Do not assume the tendon rupture risk with bempedoic acid is comparable to fluoroquinolones—the mechanisms and absolute risk magnitudes differ substantially. While fluoroquinolones increase Achilles tendon rupture risk with an odds ratio of 4.1 (and 43.2 when combined with corticosteroids), bempedoic acid shows a more modest absolute increase of 0.3% over placebo in the largest trial. 5, 2