Published in this week’s issue of the New England Journal of Medicine, the IMPROVE-IT Study highlights the cardiac benefits of the ezetimibe and simvastatin combination.
The study attempted to compare the benefits of a simvastatin-only treatment as compared to a treatment with Vytorin (ezetimibe and simvastatin combined). More than 18,000 participants were involved in the study, all having suffered from acute coronary syndromes.
Researchers concluded that in the case of the ezetimibe and simvastatin combination, LDL cholesterol levels (known as bad cholesterol) dropped significantly lower than in the case of simvastatin-only treatment. Additionally, the patients in the Vytorin group experienced better cardiovascular outcomes.
The randomized trial was conducted by Dr. Christopher P. Cannon (from Birmingham and Women’s Hospital in Boston) and his colleagues. The 18,144 patients involved had all been admitted to the hospital because of an acute coronary syndrome in the previous 10 days.
Researchers followed-up with the patients for a period of six years and investigated relevant cardiovascular events such as unstable angina (requiring hospitalization), nonfatal stroke, coronary revascularization, nonfatal myocardial infarction or cardiovascular death.
The results significantly favored the ezetimibe and simvastatin combination. Time-weighted average LDL levels (low-density lipoprotein) were 53.7 in the combination group respectively 69.5 mg/dL in the simvastatin-only group. Additionally, cardiovascular event rates were also smaller in the Vytorin group as compared to the simvastatin-placebo group.
A noteworthy detail was the fact that hepatic adverse effects, cancer rates, gallbladder issues and prespecified muscle rates were similar in both groups, showing that there were virtually no downsides to adding ezetimibe to statin therapy, while the benefits were clear.
Of course, such a massive study begs the question: should the AHA’s current guidelines be amended to an interval of 50 to 55 mg/dL target as the IMPROVE-IT study achieved in its intervention group?
Opinions vary among clinicians, especially since the AHA’s guidelines state that high-risk patients should always be offered more aggressive treatment options to ensure an adequate response to statins.
One point of criticism, for instance, was the choice of statin treatment. Instead of comparing two groups under submaximal statin therapy and a placebo or ezetimibe, the authors should have focused on maximal statin therapy with or without the ezetimibe. The American Heart Association’s current guidelines recommend maximal statin dosages so modest doses of statins aren’t really in question.
Other specialists looked at the fact that lowering LDL-Cholesterol alone was enough to prevent cardiovascular events efficiently. Is the patient going to experience meaningful benefits due to a different titration? IMPROVE-IT failed to set a specific goal and only set out to compare dose-to-dose results.
As such, statins still remain a first-line therapy option for most patients.
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