The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial: Rationale and Design

Ogihara, Toshio; Matsuzaki, Masunori; Matsuoka, Hiroaki; Shimamoto, Kazuaki; Shimada, Kazuyuki; Rakugi, Hiromi; Umemoto, Seiji; Kamiya, Akira; Suzuki, Norihiro; Kumagai, Hiroo; Ohashi, Yasuo; Takishita, Shuichi; Abe, Keishi; Saruta, Takao

doi:10.1291/hypres.28.331

Cited by 54 publications

(37 citation statements)

References 30 publications

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“…6,7 The rationale and design, trial management, and the main results of the COPE trial have already been reported. 6,7 In brief, participants with a sitting systolic BP of X140 mm Hg or a diastolic BP of X90 mm Hg, or both if untreated, or whatever the treatment, were men and women aged 40-85 years who did not achieve the target BP (o140/90 mm Hg) with a sitting position at clinic with monotherapy of benidipine 4 mg per day in the run-in phase (4-8 weeks). These patients were randomly assigned to receive benidipine combined with an ARB, a b-blocker or a thiazide.…”

Section: Study Design Setting and Participantsmentioning

confidence: 99%

“…[1][2][3] Benidipine is a potent and long-acting dihydropyridine calciumchannel blocker (CCB), which inhibits not only L-type and N-type calcium channels but also T-type calcium channels, and regulates the constriction and dilation of renal efferent arterioles. 5 The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial is a prospective, randomized, open-label, blinded-endpoint (PROBE) study to determine the optimal combination of CCB benidipine-based therapy for hypertension, 6,7 and the main results have demonstrated that the percentage of subjects achieving the target BP and the incidence of primary composite cardiovascular end points were similar among benidipine-thiazide diuretic (thiazide), benidipine-angiotensin-receptor blocker (ARB) and benidipine-b-blocker subgroups. However, second analyses suggested that benidipine combined with a b-blocker appeared to be less beneficial in reducing the risk of stroke compared with the benidipine-thiazide combination, and was associated with an increased incidence of new-onset diabetes compared with the benidipine-ARB combination.…”

Section: Introductionmentioning

confidence: 99%

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Combination therapy for hypertension in the elderly: a sub-analysis of the Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial

et al. 2012

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The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial demonstrated that the calcium-channel blocker benidipine-based combination therapies with an angiotensin-receptor blocker (ARB), a b-blocker, or a thiazide diuretic (thiazide) were similarly effective in preventing cardiovascular events and achieving the target blood pressure (BP; o140/ 90 mm Hg). We further evaluated the efficacy and safety of these combination therapies in older (X65 years) and younger (o65 years) hypertensive patients. In this sub-analysis of the COPE trial 3293 patients (1533X65 years old and 1760 o65 years old) were randomly assigned to receive benidipine-based therapy with an ARB, a b-blocker or a thiazide. In each group, the average BP did not differ among the three treatment groups. The incidence of the primary cardiovascular composite end point in the older group was higher than in the younger group (12.7 vs. 8.3 per 1000 person-years, P¼0.023). The primary composite cardiovascular end point, achievement (%) of target BP, and cardiovascular hard composite end points were similar among the three treatment groups. However, the hazard ratios and 95% confidence intervals in older patients were 2.74 (1.08-6.96; b-blocker vs. thiazide, P¼0.022) for fatal and non-fatal stroke, and 2.47 (1.03-5.91; b-blocker vs. ARB, P¼0.043) for newonset diabetes. Thus, benidipine combined with an ARB, a b-blocker, or a thiazide was similarly effective in preventing cardiovascular events and achieving the target BP in both older and younger hypertensive patients. Further studies will be necessary to evaluate the usefulness of benidipine combined with a b-blocker in terms of the incidence of stroke and new-onset diabetes in older patients.

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Section: Study Design Setting and Participantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combination therapy for hypertension in the elderly: a sub-analysis of the Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial

et al. 2012

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“…Hypertension is one of the most common cardiovascular diseases, which is a major risk factor for endothelial dysfunction, metabolic syndrome, diabetes, renal dysfunction, congestive heart failure, coronary artery diseases and stroke [1] . Clinically, various antihypertensive drugs such as diuretics, centrally acting adrenergic drugs, vasodilators, calcium channel blockers and angiotensin converting enzyme/receptor blockers have been used to treat hypertension.…”

Section: Introductionmentioning

confidence: 99%

Vasorelaxant and antihypertensive effects of formononetin through endothelium-dependent and -independent mechanisms

Sun

Cao

2011

Acta Pharmacol Sin

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Aim: To investigate the mechanisms underlying the vasorelaxant effect of formononetin, an O-methylated isoflavone, in isolated arteries, and its antihypertensive activity in vivo. Methods: Arterial rings of superior mesenteric arteries, renal arteries, cerebral basilar arteries, coronary arteries and abdominal aortas were prepared from SD rats. Isometric tension of the arterial rings was recorded using a myograph system. Arterial pressure was measured using tail-cuff method in spontaneously hypertensive rats. Results: Formononetin (1-300 μmol/L) elicited relaxation in arteries of the five regions that were pre-contracted by KCl (60 mmol/L), U46619 (1 μmol/L) or phenylephrine (10 μmol/L). The formononetin-induced relaxation was reduced by removal of endothelium or by pretreatment with L-NAME (100 μmol/L). Under conditions of endothelium denudation, formononetin (10, 30, and 100 μmol/L) inhibited the contraction induced by KCl and that induced by CaCl 2 in Ca 2+ -free depolarized medium. In the absence of extracellular Ca 2+ , formononetin (10, 30, and 100 μmol/L) depressed the constriction caused by phenylephrine (10 μmol/L), but did not inhibit the tonic contraction in response to the addition of CaCl 2 (2 mmol/L). The contraction caused by caffeine (30 mmol/L) was not inhibited by formononetin (100 μmol/L). Formononetin (10 and 100 μmol/L) reduced the change rate of Ca 2+ -fluorescence intensity in response to KCl (50 mmol/L). In spontaneously hypertensive rats, formononetin (5, 10, and 20 mg/kg) slowly lowered the systolic, diastolic and mean arterial pressure. Conclusion: Formononetin causes vasodilatation via two pathways: (1) endothelium-independent pathway, probably due to inhibition of voltage-dependent Ca 2+ channels and intracellular Ca 2+ release; and (2) endothelium-dependent pathway by releasing NO. Both the pathways may contribute to its antihypertensive effect.

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“…39 It therefore seems not unreasonable to propose that in the therapeutic targeting of appetite regulation, polypharmacy with a number of therapies might maximize clinical effect while minimizing side effects, mirroring trends in the management of other chronic conditions such as hypertension. 40 Furthermore, as with current medical therapies for obesity, the greatest weight loss is likely to be seen within the context of a multidisciplinary approach incorporating effective lifestyle interventions.…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal satiety signals

2008

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Obesity constitutes a major global healthcare challenge. The morbidity, mortality, and socioeconomic costs of obesity are considerable. No currently available medical therapy delivers substantial, sustainable weight loss. The need to better understand the mechanisms of appetite regulation is therefore clear. Over the last 20 years, peptide hormones released from the gastrointestinal tract in response to nutritional stimuli have come to be recognized as important physiological regulators of appetite. Hormones such as peptide YY, pancreatic polypeptide, glucagon-like peptide-1 and oxyntomodulin are thought to act as postprandial satiety signals. These physiological pathways of appetite control offer a promising basis for anti-obesity therapies. Here, we briefly review the state of current knowledge of these hormones' actions on brain appetite circuits, and prospects for future research and development.

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The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial: Rationale and Design

Cited by 54 publications

References 30 publications

Combination therapy for hypertension in the elderly: a sub-analysis of the Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial

Combination therapy for hypertension in the elderly: a sub-analysis of the Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial

Vasorelaxant and antihypertensive effects of formononetin through endothelium-dependent and -independent mechanisms

Gastrointestinal satiety signals

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