Ezetimibe/simvastatin combination therapy lowers recurrent CV events more than simvastatin alone

Reduction in Total (First and Recurrent) Cardiovascular Events with Ezetimibe/Simvastatin compared with Simvastatin Alone post ACS in the IMPROVE-IT Trial

News - Mar. 18, 2015

Presented at the ACC Scientific Session 2015 by: Sabina Murphy (Brigham and Women's Hospital, Boston, MA, USA)


When enrolled in a trial, subjects who experience a non-fatal event continue to be followed during the trial and may experience additional events. Analysis of acute coronary syndrome (ACS) trials often use survival analysis methods that only consider the first event a patient experiences, not subsequent events. All events are, however, important to patients and clinicians.
The IMPROVE-IT trial evaluated whether ezetimibe (10 mg) added to simvastatin (40 mg) would provide a clinical benefit compared with simvastatin (40 mg) therapy alone. Previously presented data have shown that ezetimibe/simvastatin combination therapy significantly lowered the primary endpoint of first event of cardiovascular disease, unstable angina, coronary revascularisation and cerebrovascular accident as compared with simvastatin monotherapy (32.7 vs. 34.7% 7-year event rate, HR: 0.936, P=0.016).
This analysis tested the hypothesis that ezetimibe/simvastatin combination therapy also reduces total events (first [n=5314] + recurrent [n=4231]), as compared with simvastatin alone during the median 6-year follow-up after an ACS in IMPROVE-IT.

Main results

  • Fewer total primary endpoint events were seen with combination therapy as compared with simvastatin alone (4562 vs 4983, RR: 0.91, P=0.007).
    An RR for additional events of 0.88 (95%CI:0.79-0.98) was observed (251 fewer events).
  • A secondary endpoint of CHD death, myocardial infarction (MI) and urgent revascularisation events showed a difference of 367 fewer events with ezetimibe/simvastatin, yielding a total events RR of 0.85 (P=0.002) as opposed to an HR for first event of 0.912 (P=0.016).
    An RR for additional events of 0.79 (95%CI:0.69-0.91) was observed (251 fewer events).
  • The reduction in total number of events with ezetimibe/simvastatin combination therapy seemed particularly driven by a lower number of revascularisations, non-fatal stroke and non-fatal MIs.
  • A Wei, Lin, Weissfeld Model for primary endpoint sensitivity analysis confirmed that ezetimibe/simvastatin therapy is associated with lower risks for first and total events.


Lipid-lowering combination therapy with ezetimibe added to simvastatin reduces the number of total primary endpoint events as compared with simvastatin therapy alone, specifically driven by fewer MIs, strokes and urgent revascularisations. These findings support the benefit of continuation of intensive combination lipid-lowering therapy after a CV event.

- Our reports of the ACC Scientific Session are based on the information provided at the congress -

Facebook Comments


We’re glad to see you’re enjoying PACE-CME…
but how about a more personalized experience?

Register for free