wering therapy (n=11594). Prior to the hospitalization for the qualifying ACS event, 34% of the patients were on statin therapy. At one-year, the average LDL-C for patients continuing on therapy was 53.2 mg/dL (1.4 mmol/L) for the ezetimibe/simvastatin group and 69.9 mg/dL (1.8 mmol/L) for the simvastatin monotherapy group.
The primary endpoint was a composite consisting of cardiovascular death, major coronary events (MCE; defined as non-fatal myocardial infarction, documented unstable angina that required hospitalization, or any coronary revascularization procedure occurring at least 30 days after randomized treatment assignment) and non-fatal stroke. The study demonstrated that treatment with ezetimibe/simvastatin provided incremental benefit in reducing the primary composite endpoint of cardiovascular death, MCE, and non-fatal stroke compared with simvastatin alone (relative risk reduction of 6.4%, p=0.016). The primary endpoint occurred in 2572 of 9067 patients (7-year Kaplan-Meier [KM] rate 32.72%) in the ezetimibe/simvastatin group and 2742 of 9077 patients (7-year KM rate 34.67%) in the simvastatin alone group. (See Figure 1 and Table 5.) This incremental benefit is expected to be similar with coadministration of ezetimibe and atorvastatin. Total mortality was unchanged in this high risk group.
There was an overall benefit for all strokes; however there was a small non-significant increase in hemorrhagic stroke in the ezetimibe-simvastatin group compared with simvastatin alone. The risk of hemorrhagic stroke for ezetimibe coadministered with higher potency statins in long-term outcome studies has not been eva luated.
The treatment effect of ezetimibe/simvastatin was generally consistent with the overall results across many subgroups, including sex, age, race, medical history of diabetes mellitus, baseline lipid levels, prior statin therapy, prior stroke, and hypertension.
Figure 1: Effect of ezetimibe/simvastatin on the Primary Composite Endpoint of Cardiovascular Death, Major Coronary Event, or Non-fatal Stroke
Table 5
Major Cardiovascular Events by Treatment Group in All Randomized Patients in IMPROVE-IT
Outcome
Ezetimibe/Simvastatin
10/40 mg*
(N=9067)
Simvastatin
40 mg†
(N=9077)
Hazard Ratio
(95% CI)
p-value
n
K-M %‡
n
K-M %‡
Primary Composite Efficacy Endpoint
(CV death, Major Coronary Events and non-fatal stroke)
2572
32.72%
2742
34.67%
0.936 (0.887, 0.988)
0.016
Components of Primary Composite Endpoint and Select Efficacy Endpoints (first occurrences of specified event at any time)
Cardiovascular death
537
6.89%
538
6.84%
1.000 (0.887, 1.127)
0.997
Major Coronary Event:
Non-fatal MI
945
12.77%
1083
14.41%
0.871 (0.798, 0.950)
0.002
Unstable angina requiring hospitalization
156
2.06%
148
1.92%
1.059 (0.846, 1.326)
0.618
Coronary revascularization after 30 days
1690
21.84%
1793
23.36%
0.947 (0.886, 1.012)
0.107
Non-fatal stroke
245
3.49%
305
4.24%
0.802 (0.678, 0.949)
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