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Effects of an Antihypertensive Combination in Japanese Hypertensive Outpatients Based on the Long-acting Calcium Channel Blocker Benidipine on Vascular and Renal Events: A Sub-analysis of the COPE Trial

[ Vol. 16 , Issue. 3 ]


Seiji Umemoto*, Toshio Ogihara, Masunori Matsuzaki, Hiromi Rakugi, Kazuyuki Shimada, Koichi Hayashi, Hirofumi Makino, Yasuo Ohashi, Takao Saruta and The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial Group   Pages 238 - 245 ( 8 )


Background: In the trial known as COPE (Combination Therapy of Hypertension to Prevent Cardiovascular Events), three benidipine (a Calcium Channel Blocker; CCB) regimens were compared. Hypertensive Japanese outpatients aged 40–85 years (n=3,293) who did not achieve the target blood pressure of <140/90 mmHg with benidipine 4 mg/day were treated with the diuretic thiazide (n=1,094) or a β-blocker (n=1,089) or an additional Angiotensin Receptor Blocker (ARB; n=1,110). A significantly higher incidence of hard cardiovascular composite endpoints and of fatal or non-fatal strokes was observed in the benidipine-β-blocker group compared to the benidipine-thiazide group.

Objective and Methods: We further evaluated the treatment effects of the three benidipine-based regimens on vascular and renal events in a sub-analysis of the COPE patients.

Results: A total of 10 vascular events (0.8 per 1,000 person-years) including one aortic dissection (0.1 per 1,000 person-years) and nine cases of peripheral artery disease (0.8 per 1,000 person-years) were documented, as was a total of seven renal events (0.6 per 1,000 person-years). No significant differences in vascular and renal events were revealed among the three treatment groups: vascular events, p=0.92; renal events, p=0.16, log-rank test.

Conclusion: Blood pressure-lowering therapy with benidipine combined with an ARB, β-blocker, or thiazide was similarly effective in the prevention of vascular and renal events in hypertensive outpatients, although there are not enough events to compare the difference in the three treatment groups.


Antihypertensive therapy, calcium channel blocker, combination therapy, vascular event, renal event, randomized clinical trial.


Center for Integrated Medical Research, Hiroshima University Hospital, Hiroshima, Morinomiya University of Medical Sciences, Osaka, Yamaguchi University, Ube, Yamaguchi, Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Shin-oyama City Hospital, Oyama, Tochigi, Department of General Medicine, Tokyo Dental College, Ichikawa General Hospital Ichikawa Chiba, Okayama University, Okayama, Department of Integrated Science and Engineering for Sustainable Society, Faculty of Science and Engineering, Chuo University, Bunkyo-ku, Tokyo, Keio University, Shinjuku-ku, Tokyo

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