Can a Low-Dose Statin Combination Outperform A Moderate Dose Statin Alone and be Safer Too?

Many heart patients require therapy beyond lifestyle to lower LDL-cholesterol (lowering Lipoprotein(a) cholesterol if elevated is another topic not often discussed but also important). The most common approach is a moderate or high dose of a statin medication.

The RACING study compared an approach used at the KAHN CENTER for years, a low dose statin and ezetimibe versus a moderate dose of a statin alone. In this new report, the subset with diabetes were examined and a winner was declared! Which was it?


This study reports on a subgroup analysis of the diabetes mellitus (DM) patients in the larger RACING trial. The primary outcome was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. Patients either got a moderate dose of a statin (rosuvastatin 20 mg) or were randomized to 10 mg rosuvastatin with 10 mg ezetimibe, a non-statin medication. 

Among total patients, 1398 (37.0%) had DM at baseline. The incidence of the primary outcome was 10.0% and 11.3% among patients with DM randomized to ezetimibe/statin combination therapy vs. high-intensity statin monotherapy which was not statistically different (there was no harm using the lower dose combination and there was a slight advantage that might be just chance).

Intolerance-related discontinuation or dose reduction of the study drug was observed in 5.2% and 8.7% of patients in the combination group vs. the single drug group, so there were less side effects with the lower dose approach.

LDL cholesterol levels <70 mg/dL at 1, 2, and 3 years were observed in 81.0%, 83.1%, and 79.9% of patients in the ezetimibe combination therapy group, and 64.1%, 70.2%, and 66.8% of patients in the statin monotherapy group which was statistically and clinically significant favoring the combination.

In the total population, no significant interactions were found between DM status and therapy regarding primary outcome, intolerance-related discontinuation or dose reduction, and the proportion of patients with LDL cholesterol levels <70 mg/dL.


Ezetimibe combination therapy with a lower dose statin advantages observed in the overall RACING trial population were also preserved among patients with DM.

This study supports statin with ezetimibe combination therapy as a suitable alternative to statins alone. The combination lowers the LDL-cholesterol more reliably with less side effects. We will continue to choose this route in patients at the KAHN CENTER. 

Finally, in patients who have inheritied Lipoprotein(a), my observation is that the combination approach yields a lower Lipoprotein(a) too. 


Dr. Joel Kahn

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