It Takes Two to Tango When Lowering Lipids After Percutaneous Coronary Intervention

Volume 29, Issue 3

Patients with established atherosclerotic cardiovascular disease (ASCVD) have a very high risk of disease progression and recurrence of major adverse cardiovascular events (MACE) remains unacceptably common. Strategies for reducing residual rates of MACE revolve around high-intensity statin therapy, which can be further augmented by the addition of ezetimibe and PCSK9 inhibitors. 

The use of ancillary lipid-lowering agents as a statin-sparing strategy in patients with established ASCVD has not been extensively studied. The RACING trial in a broad cohort of patients with very high-risk features for ASCVD found that a strategy of combining rosuvastatin 10 mg daily with ezetimibe 10 mg daily did not reduce rates of MACE when compared to rosuvastatin 20 mg daily as monotherapy. These findings were confirmed in the subgroup of patients with diabetes. Of note, combination therapy was more effective at lowering LDL than monotherapy, and fewer patients discontinued therapy in the combination group. 

In this week’s issue of Talking Therapeutics, we explore the findings from another subgroup analysis from the RACING Trial.

Finally, a Win for Combination Therapy

A new subgroup analysis from the RACING trial in over 70,000 patients undergoing percutaneous coronary intervention (PCI) was recently published. Unlike the prior analysis from this trial, in PCI patients combination lipid-lowering therapy was associated with a lower occurrence of the primary endpoint of cardiovascular death, myocardial infarction, coronary artery revascularization, hospitalization for heart failure treatment, or nonfatal stroke (11.6% vs 15.2% HR: 0.75; 95% CI: 0.70-0.79; P < 0.001). Similar to prior analysis, combination lipid-lowering therapy was associated with fewer discontinuations due to side effects. Importantly, combination therapy had a lower occurrence of new-onset diabetes requiring medication. 

Maybe a Bold New Strategy

I was honestly a little surprised by the design of this study, given that high-intensity statins are so effective at reducing rates of recurrent MACE in patients with established ASCVD. It seemed like a bold strategy to reduce statin potency in favor of combination with ezetimibe. 

These data are provocative, given that combination therapy with ezetimibe and a lower potency statin was able to both reduce rates of MACE and reduce the risk of key statin-related side effects. These results are preliminary as they came from a subgroup study that included a fairly homogenous patient population from South Korea. However, future studies should definitely investigate this hypothesis further to see if these benefits hold true in a more heterogenous patient population.