Why I Use 2 Drug Combination Therapy at Low Doses for Cholesterol Lowering

High doses of cholesterol lowering statin medications are strongly recommended in patients at very high risk (VHR) of atherosclerotic cardiovascular disease (ASCVD). However, concerns about statin-associated adverse effects result in underuse of this strategy in practice.

At the Kahn Center, for years we have selected low dose combination therapy in patients with ASCVD or at high risk as shown on heart CT scanning. Now more data is presented that the low dose combination approach is a great option. 


This was a post hoc analysis of the Randomized Comparison of Efficacy and Safety of Lipid Lowering With Statin Monotherapy vs Statin/Ezetimibe Combination for High-Risk Cardiovascular Disease (RACING) open-label, multicenter, randomized clinical trial. The study was conducted from February 2017 to December 2018 at 26 centers in Korea. Study participants included patients with documented ASCVD. Data were analyzed from April to June 2022.


Patients were randomly assigned to moderate-intensity statin with ezetimibe (rosuvastatin, 10 mg, with ezetimibe, 10 mg) or high-intensity statin monotherapy (rosuvastatin, 20 mg). Patients at VHR for ASCVD were defined according to the 2018 American Heart Association/American College of Cardiology guidelines.


The primary end point was the 3-year outcome of cardiovascular death, coronary or peripheral revascularization, hospitalization of cardiovascular events, or nonfatal stroke.


A total of 3780 patients were categorized as VHR. There was no significant difference in the primary end point between those who received combination therapy versus high-intensity statin monotherapy among patients with VHR disease (11.2% vs 11.7%) and non-VHR disease (7.7% vs 8.7%).

The median low-density lipoprotein cholesterol (LDL-C) level was significantly lower in the combination therapy group than in the high-intensity statin group (VHR, 1 year: 57 mg/dL vs 65 mg/dL; non-VHR, 1 year: 58 mg/dL vs 68 mg/dL). 

Discontinuation or dose reduction of the lipid-lowering drug due to intolerance occurred less frequently in the combination therapy group (VHR, 4.6% vs 7.7% and non-VHR, 5.0% vs 8.7%).


Results suggest that the outcomes of ezetimibe combination observed in the RACING trial were consistent among patients at VHR of ASCVD with lower LDL-C and lower discontinuation rates.

At the Kahn Center, we will continue to emphasize low dose combination cholesterol lowering therapies for those that need very low LDL-C levels for heart disease reversal programs.

Dr. Joel Kahn

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