Combination Treatment Reduces Ischemic Stroke Risk in Acute Coronary Syndrome

Coronary artery and heart scan
Coronary artery and heart scan
Patients who experience acute coronary syndrome are at greater risk of recurrent ischemic events, including stroke.

Adding ezetimibe to simvastatin therapy reduces the risk for ischemic stroke in stabilized patients with acute coronary syndrome (ACS) and a history of prior stroke, according to findings from the double-blind, placebo-controlled IMPROVE IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) trial published in Circulation.

In IMPROVE-IT, investigators randomly assigned patients with ACS to either placebo/simvastatin or an ezetimibe/simvastatin combination and assessed outcomes at a median follow-up of 6 years. Researchers specifically evaluated efficacy of both treatment groups, providing special attention to those with ACS and a history of stroke.

A total of 18,144 patients were included in this study, of which 641 (3.5%) had a history of ≥1 stroke event prior to entering the trial. The majority of previous strokes were ischemic in nature (82%).

Patients in the ezetimibe/simvastatin treatment group experienced a greater reduction in the first event of stroke compared with the placebo/simvastatin group, but the difference in risk reduction was not considered statistically significant (4.2% vs 4.8%; hazard ratio [HR] 0.86; 95% CI, 0.73-1.00; P =.052).

The addition of ezetimibe to simvastatin resulted in a significantly lower incidence of stroke of any etiology (HR 0.83; 95% CI, 0.70-0.98; P =.029) as well as a lower risk for ischemic stroke (HR 0.76; 95% CI, 0.63-0.91; P =.003) compared with the placebo/simvastatin arm. Prior stroke resulted in a greater risk for stroke recurrence; however, the addition of ezetimibe to simvastatin resulted in an 8.6% and 7.6% absolute risk reduction for stroke of any etiology (10.2% vs 18.8%; number needed to treat [NNT]=12; HR 0.60; 95% CI, 0.38-0.95; P =.030) and ischemic stroke (8.7% vs 16.3%; NNT=13; HR 0.52; 95% CI, 0.31-0.86; P =.011), respectively.

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Because modified Rankin scores were not collected for these patients, the investigators suggest their findings are limited because they are unable to identify differential disability caused by stroke between the 2 treatment groups. In addition, the researchers had no available data on stroke subtypes prior to randomization. Knowing this information may be helpful to further understand the risk for hemorrhagic stroke across the treatment groups.

In conclusion, the investigators believe that adding ezetimibe “to a moderate-high intensity statin regimen for prevention of ischemic stroke in patients with established ischemic heart disease with or without a prior stroke” represents a reasonable and effective clinical approach in ACS.


Bohula EA, Wiviott SD, Giugliano RP, et al. Prevention of stroke with the addition of ezetimibe to statin therapy in patients with acute coronary syndrome in IMPROVE-IT [published online September 30, 2017]. Circulation. doi: 10.1161/CIRCULATIONAHA.117.029095