Intensive lipid lowering therapy better in elderly after acute coronary syndrome: JAMA

Simvastatin-ezetimibe combo better than simvastatin monotherapy for lipid reduction in older patients aged 75 years or above hospitalized after Acute Coronary Syndrome (ACS), revealed a subanalysis of IMPROVE-IT trial published in JAMA.

Elderly patients are most susceptible to adverse cardiovascular events after being hospitalized with an acute coronary syndrome (ACS). Studies supporting intensive lipid-lowering therapy is limited.

The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) evaluated the effect of higher-intensity treatment to lower lipid levels with ezetimibe combined with simvastatin compared with simvastatin and placebo (henceforth referred to as simvastatin monotherapy) among patients with a stabilized ACS and observed that ezetimibe added to statin therapy incrementally lowered low-density lipoprotein cholesterol (LDL-C) levels and improved CVD outcomes.

IMPROVE-IT enrolled patients with no upper age limit. In this secondary analysis, the authors examined the association of age with the benefit of intensive treatment to lower lipid levels with ezetimibe combined with simvastatin vs simvastatin monotherapy in IMPROVE-IT.

In this prespecified secondary analysis of the global, multicenter, prospective clinical randomized Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), outcomes and risks were compared by age among patients 50 years or older after hospitalization for ACS. Data were collected from October 26, 2005, through July 8, 2010, with the database locked October 21, 2014. Data were analyzed May 29, 2015, through March 13, 2018, using Kaplan-Meier curves and Cox proportional hazards models.

Double-blind randomized assignment to combined simvastatin and ezetimibe or simvastatin and placebo with follow-up for a median of 6 years (interquartile range, 4.3-7.1 years).

Main outcomes taken into account were: The primary composite endpoint consisted of death due to cardiovascular disease, myocardial infarction (MI), stroke, unstable angina requiring hospitalization, and coronary revascularization after 30 days. Individual adverse ischemic and safety endpoints and lipid variables were also analyzed.

Main Findings

• Of 18 144 patients enrolled mean [SD] age, 64.1 [9.8] years), 5173 were 65 to 74 years old, and 2798 were 75 years or older at randomization.


• Treatment with simvastatin-ezetimibe resulted in lower rates of the primary endpoint than simvastatin-placebo, including 0.9% for patients younger than 65 years and 0.8% for patients 65 to 74 years of age (hazard ratio, with the greatest absolute risk reduction of 8.7% for patients 75 years or older.


• The rate of adverse events did not increase with simvastatin-ezetimibe vs simvastatin-placebo among younger or older patients.

"In IMPROVE-IT, patients hospitalized for ACS derived benefit from higher-intensity therapy to lower lipid levels with simvastatin-ezetimibe compared with simvastatin monotherapy, with the greatest absolute risk reduction among patients 75 years or older. Addition of ezetimibe to simvastatin was not associated with any significant increase in safety issues among older patients. These results may have implications for guideline recommendations regarding lowering of lipid levels in the elderly." the authors conclude.

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doi:10.1001/jamacardio.2019.2306