The Combination
Therapy of
Hypertension to Prevent Cardiovascular Events (COPE) trial compared the
dihydropyridine T/
L-type calcium channel blocker
benidipine-based
therapies when combined with an
angiotensin receptor blocker (ARB), a β-blocker (BB) or a
thiazide diuretic (TD). The results suggested that
benidipine combined with a BB appeared to be less beneficial in reducing the risk of
stroke compared with the
benidipine-TD combination (hazard ratio (HR): 2.31, P=0.0109). We further evaluated the treatment effects on different
stroke subtypes among the three
benidipine-based regimens. The COPE trial was an investigator-initiated, multicenter study with PROBE design. Patients with
atrial fibrillation or flutter were excluded from the study. All
stroke events were subclassified with the Trial of Org 10,172 in
Acute Stroke Treatment (TOAST) criteria. The total incidence of
stroke was 4.7,
hemorrhagic stroke was 1.6 and
ischemic stroke was 2.5 per 1000 person-years. The incidence of
lacunar stroke was 1.1, large-artery
stroke was 0.6,
cardioembolic stroke was 0.3, unknown ischemic type was 0.6 and
transient ischemic attack was 0.6 per 1000 person-years. Although few differences in
stroke subtypes were observed among the three treatment groups, multi-adjusted HRs for the incidence rates of all types of
stroke, hemorrhagic stroke and
ischemic stroke were significantly higher with the
benidipine-BB regimen than with the
benidipine-TD regimen. The incidence of both hemorrhagic and
ischemic stroke in the
benidipine-ARB regimen was not different compared with the other two treatment regimens. This prespecified sub-analysis suggested that a blood pressure-lowering
therapy with a
benidipine-TD regimen might be beneficial for hypertensive patients to prevent both hemorrhagic and
ischemic stroke.