Ezetimibe in addition to a moderate intensity vs a high dose statin in ASCVD patients – the RACING trial
So, this trial might appear a bit boring and maybe not so relevant – but maybe only at first. What might add to the difficulty reading or interpreting it is the non-inferiority design – and we might to a methods primer on that in the future. However, this trial may be the answer for a very important question: what do we do with patients who are intolerant to higher doses of statins – can a statin-sparing regimen be the answer?

This was a randomized controlled trial of a high-intensity statin, rosuvastatin 20mg daily vs a moderate-intensity statin – 10mg of rosuvastatin daily – plus 10mg of ezetimibe or Zetia. The trial recruited 3,780 patients with atherosclerotic cardiovascular disease and followed them for three years. The primary endpoint was the composite of cardiovascular death, major adverse cardiovascular events, or non-fatal stroke, and was reached in 9.9% in the high-intensity statin group vs 9.1% in the combination group.

Our guest is Christopher P. Cannon, M.D.. He is a cardiologist at Brigham and Women’s Hospital in Boston and a professor at Harvard Medical School. He has run major trials of statins and other interventions to prevent major adverse cardiovascular (and cerebrovascular) events, including the IMPROVE-IT study.

Here are Ben's personal take-aways from this fascinating conversation:
1. 10mg rosuvastatin + 10mg ezetimibe is as effective as 20mg of rosuvastatin in preventing MACCE in ASCVD patients
2. ezetimibe is an add-on option when the statin dose has to be lowered, eg in patients
--with statin-related side effects
--at risk for diabetes (eg, "pre-diabetes")
3. lowering LDL is proportional to reducing the MACCE risk
4. ezetimibe is anti-inflammatory

References:
-RACING Study: BK Kim et al.: Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial. Lancet. 2022 Jul 30;400(10349):380-90. https://pubmed.ncbi.nlm.nih.gov/35863...
-IMPROVE-IT: CP Canon et al.: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med . 2015 Jun 18;372(25):2387-97. https://pubmed.ncbi.nlm.nih.gov/26039...
-DI Swerdlow et al.: HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet 2015; 385: 351-61. https://pubmed.ncbi.nlm.nih.gov/25262...
-SU Khan et al.: Association of Lowering Low-Density Lipoprotein Cholesterol With Contemporary Lipid-Lowering Therapies and Risk of Diabetes Mellitus: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2019;8:e011581. https://pubmed.ncbi.nlm.nih.gov/30898...
-MG Silverman et al.: Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions. A Systematic Review and Meta-analysis. JAMA. 2016;316(12):1289-97. https://pubmed.ncbi.nlm.nih.gov/27673...
-PM Ridker et al.: Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017;377(12):1119-1131. https://pubmed.ncbi.nlm.nih.gov/28845...
-Y Ouchi et al.: Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older (EWTOPIA 75): A Randomized, Controlled Trial. Circulation. 2019.140(12):992-1003. https://pubmed.ncbi.nlm.nih.gov/31434...

Subscribe to our YouTube Channel: https://www.youtube.com/@IMJournalClu...
Subscribe to our audio-only podcast: https://linktr.ee/imjournalclub
Subscribe to our mailing list: https://www.getrevue.co/profile/IMJou...