IN A LARGE-scale analysis of 8,180 patients with atherosclerotic cardiovascular disease (ASCVD), an alternative strategy for lowering low-density lipoprotein (LDL) cholesterol demonstrated similar long-term efficacy to high-intensity statins, but with improved safety profiles. The alternative approach led to lower LDL levels and reduced risks of new-onset diabetes and treatment intolerance.
Statins are the cornerstone of therapy for ASCVD, but their high intensity often leads to side effects, necessitating alternative approaches to LDL cholesterol lowering. This systematic review and individual patient data meta-analysis evaluated two strategies: high-intensity statin therapy and an alternative approach combining moderate-intensity statins with ezetimibe or a treat-to-target strategy. The primary endpoint was a composite of all-cause death, myocardial infarction, stroke, and coronary revascularisation, measured over a three-year period.
Data were gathered from two trials—RACING and LODESTAR—sourcing individual patient data from 8180 participants (average age 64.5 years, 73.3% male). Results showed that the rates of the primary outcome were nearly identical between the groups (7.5% for the alternative strategy vs. 7.7% for high-intensity statins; hazard ratio 0.98, P = 0.82). However, patients on the alternative strategy had significantly lower LDL cholesterol levels (64.8 mg/dL vs. 68.5 mg/dL, P < 0.001). Moreover, those on the alternative strategy had fewer cases of new-onset diabetes (10.2% vs. 11.9%, P = 0.047), fewer requiring antidiabetic medication (6.5% vs. 8.2%, P = 0.02), and less therapy intolerance (4.0% vs. 6.7%, P < 0.001).
The findings suggest that alternative LDL cholesterol-lowering strategies can be considered a viable treatment option for ASCVD patients, as they provide similar cardiovascular protection as high-intensity statins while reducing adverse effects such as new-onset diabetes and treatment intolerance. Clinically, this opens the door to more personalised and patient-friendly treatment plans, particularly for those who experience side effects with statins. Future studies should continue to explore the long-term safety and efficacy of such alternative strategies, especially in diverse patient populations.
Reference
Lee Y et al. Alternative LDL Cholesterol–lowering strategy vs high-intensity statins in atherosclerotic cardiovascular disease: a systematic review and individual patient data meta-analysis. JAMA Cardiol. 2024;DOI:10.1001/jamacardio.2024.3911.
