Effects of a benidipine-based combination therapy on the risk of stroke according to stroke subtype: the COPE trial.

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.
AuthorsSeiji Umemoto, Toshio Ogihara, Hiromi Rakugi, Masayasu Matsumoto, Kazuo Kitagawa, Kazuyuki Shimada, Jitsuo Higaki, Sadayoshi Ito, Hiromichi Suzuki, Yasuo Ohashi, Takao Saruta, Masunori Matsuzaki,
JournalHypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 36 Issue 12 Pg. 1088-95 (Dec 2013) ISSN: 1348-4214 [Electronic] England
PMID23985703 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Dihydropyridines
  • Diuretics
  • Vasodilator Agents
  • benidipine
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 1 Receptor Blockers (therapeutic use)
  • Antihypertensive Agents (therapeutic use)
  • Atrial Fibrillation (epidemiology)
  • Atrial Flutter (epidemiology)
  • Blood Pressure (physiology)
  • Brain Ischemia (complications)
  • Dihydropyridines (therapeutic use)
  • Diuretics (therapeutic use)
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Heart Rate (physiology)
  • Humans
  • Hypertension (complications, drug therapy)
  • Intracranial Hemorrhages (complications)
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Risk Factors
  • Stroke (classification, etiology, prevention & control)
  • Survival Analysis
  • Vasodilator Agents (therapeutic use)

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