Bempedoic acid effective in reducing MI risk among statin-intolerant patients with hyperlipidemia

The study found that in patients with hyperlipidemia, bempedoic acid reduced non-fatal myocardial infarction (MI), whereas it failed to show any significant impact on all-cause mortality and stroke.

Bempedoic acid is a drug type that inhibits ATP-citrate lyase, an enzyme involved in cholesterol production.

It has been known that reduction of LDL-C (low-density lipoprotein cholesterol) decreases cardiovascular morbidity and mortality. Bempedoic acid is a promising lipid-modifying agent for patients who are statin intolerant or who cannot reach guidelines recommended LDL-C goals, but there is limited data on its cardiovascular outcomes and safety. Therefore, Thomas Gremmel, Karl Landsteiner Society, St. Pölten, Austria, and colleagues aimed to systematically review RCTs (randomized controlled trials) investigating bempedoic acid versus placebo in patients with hyperlipidemia.

For this purpose, the researchers performed a systematic search on the databases until 20 March 2023. It included all RCTs comparing 180 mg daily bempedoic acid versus placebo in patients with an indication for lipid-lowering therapy.

The primary endpoint of the study was analysed as three-point major adverse cardiovascular events (MACE) comprising non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death. The analysis was conducted using the odds ratio as the outcome measure. A random-effects model was fitted to the data due to the expected heterogeneity across studies.

The authors reported the following findings:

• Out of 258 manuscripts, 10 manuscripts fulfilled the inclusion criteria. In total, these trials included 18,200 patients (9,765 on bempedoic acid, 8,435 on placebo).
• Bempedoic acid significantly reduced MACE compared to placebo (OR 0.84).
• The endpoint reduction was driven by a lower rate of nonfatal MI, whereas bempedoic acid had no significant effect on stroke (OR 0.86) and all-cause mortality (OR 1.19).

The use of drugs to lower lipid levels, particularly statins, has greatly reduced the incidence of cardiovascular disease in the last three decades. However, statins alone may not be sufficient to achieve the desired lowering of LDL-C levels. Unfortunately, some people may be intolerant to statins due to their muscle-related side effects resulting in uncontrolled cholesterol levels.

For these statin-intolerant patients, non-statin drugs such as bempedoic acid come into the picture.

"The main finding of the study that bempedoic acid is effective in reducing non-fatal myocardial infarction holds relevance for this patient population," the researchers wrote.

However, bempedoic acid had no significant effect on stroke and all-cause mortality.

Reference:

David Mutschlechner and others, Cardiovascular events in patients treated with bempedoic acid versus placebo: systematic review and meta-analysis, European Heart Journal - Cardiovascular Pharmacotherapy, 2023;, pvad052, https://doi.org/10.1093/ehjcvp/pvad052