CLEAR Outcomes trial shows statin-intolerant patients benefit from bempedoic acid
The late-breaking CLEAR Outcomes trial presented at the 2023 American College of Cardiology (ACC) meeting found bempedoic acid can be used in statin-intolerant patients to reduce low-density lipoprotein (LDL) cholesterol levels. This large study also found a low incidence of muscle-related adverse events, which is a common complaint among statin-intolerant patients.[1]
Steven Nissen, MD, chief academic officer of Cleveland Clinic's Heart, Vascular and Thoracic Institute, spoke to Cardiovascular Business about the trial's results and what they could mean for patient care going forward.
Nissen noted that the cholesterol-lowering drug bempedoic acid reduced the combined rate of major adverse cardiovascular events by 13%, meeting its primary endpoint in a large study of patients with high cholesterol who were unable to tolerate statins.
The study enrolled over 14,000 statin-intolerant patients between December 2016 and August 2019 at more than 1,200 sites in 32 countries. To participate, patients and their clinicians were required to acknowledge in writing their awareness of the benefits of statins and confirm the patient was unable to tolerate statin therapy. All participants had LDL levels of 100 mg/dL or higher at baseline and either a previous cardiac event or other risk factors for heart disease. On average, patients were 65 years old, nearly half were women (48%) and about 70% had experienced a previous cardiac event. Participants were randomly assigned to take 180 mg of bempedoic acid or a placebo daily and were followed for over three years.
Nissen said the oral drug is activated in the liver rather than peripheral tissue like muscle, so it eliminated the side effects of muscle aches some patients experience with statins.
"Overall we are very satisfied we established that this drug, bempedoic acid, could be taken by people who could not tolerate statins and could reduce major adverse cardiovascular events with a very good safety profile. The drug was indeed very well tolerated," Nissen said.
The positive results included a mean LDL cholesterol level reduction. The observed reduction was 21.1 percentage points in favor of bempedoic acid compared to placebo. The primary end-point of nonfatal myocardial infarction, nonfatal stroke, coronary revascularization and cardiovascular death was significantly lower with bempedoic acid than with placebo (819 patients [11.7%] vs. 927 [13.3%]).
The study also found that fatal and non-fatal myocardial infarction rates were reduced by 23%. The coronary revascularization rate was also reduced by 19% over the placebo group.
There was no increase in diabetes as has been seen in some statin trials. However, Nissen said, there was a 1% increase in the incidence of gout and gallstones.
Nissen said patients taking the drug in combination with the non-statin LDL-C lower drug ezetimibe were found to have the same LDL-lowering effect as a moderate-intensity statin.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: dfornell@innovatehealthcare.com