ACC.23 Updates: New Data on Cholesterol-Lowering Therapies

Volume 25, Issue 2

It’s that time of year, folks! I just returned from the American College of Cardiology 2023 Annual Meeting in sunny New Orleans. As we’ve done in prior iterations of this column, we’ll be covering the most exciting new pieces of science from the meeting in this week’s issue. 

Bempedoic Acid Scores in Patients With Statin Intolerance

Bempedoic acid is an ATP citrate lyase inhibitor that has been shown to effectively lower low-density lipoprotein (LDL) cholesterol. In the CLEAR trial, which was presented at the meeting and published in The New England Journal of Medicine, investigators randomized over 13,000 patients with statin intolerance to receive either bempedoic acid at a dosage of 180 mg daily or placebo. 

After a median of 40 months of follow-up, bempedoic acid reduced rates of fatal or nonfatal myocardial infarction (261 [3.7%] vs 334 [4.8%]; P = .002) and coronary revascularization (435 [6.2%] vs 529 [7.6%]; P = .001). There were no significant differences in rates of all-cause death and death from cardiovascular causes between groups.

Bempedoic acid can raise uric acid levels, and patients randomized to this therapy had higher rates of gout (3.1% vs 2.1%) and cholelithiasis (2.2% vs 1.2%) than the placebo group. Despite these side effects, bempedoic acid appears to be a viable alternative to patients with elevated LDL values and statin intolerance. 

Statin Strategies: High-Intensity Therapy vs Targeted Approach

In sticking with the theme of cholesterol, one of the more interesting papers to come out of the meeting was a trial comparing 2 different approaches to using statins for LDL reduction in patients with established atherosclerotic cardiovascular disease (ASCVD). 

This is a contentious topic that stretches back decades. This dilemma came about in 2004 with the publication of PROVE IT TIMI 22 study, in which patients were randomized to receive high-intensity vs low intensity statin therapy after acute coronary syndromes. Based on the PROVE IT TIMI 22 study, some have argued for the broad application of high-intensity statin therapy regardless of LDL in patients with ASCVD. 

Broad application of high-intensity statin therapy vs a targeted approach (ie, using escalating statin intensity to achieve a specific LDL goal) has not been tested previously. In this new paper, 4400 patients were randomly assigned to receive either targeted therapy or high-intensity treatment with 20-mg rosuvastatin or 40-mg atorvastatin. 

“Among patients with coronary artery disease,” researchers found, “a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization.”

These results are important, as high-intensity statin therapy is associated with more severe side effects compared to moderate-intensity statin therapy. Based on these findings, a stepwise approach to using statins, titrated to a specific goal, seems like a reasonable alternative to broad use of high-intensity statin therapy.