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Combination therapy with ramipril and candesartan improves blood pressure, endothelial function, insulin resistance and plasma adipocytokine profiles of hypertensive patients to a greater extent than either drug as monotherapy, according to research findings.
Hypertension and coronary heart disease are characterised by endothelial dysfunction, which is frequently associated with diabetes, obesity, the metabolic syndrome and other insulin-resistant states.
Both the angiotensin-converting enzyme (ACE) inhibitor ramipril and the angiotensin II type 1 receptor blocker (ARB) candesartan target the renin-angiotensin system to improve endothelial function in patients with hypertension.
As these drugs have two distinct mechanisms of action, Dr Kwang Kon Koh of Gachon Medical School, Inchon, South Korea, hypothesised that combination therapy might have additive beneficial effects over monotherapy.
To test their hypothesis, the team carried out a randomised double-blind crossover trial in 34 patients with hypertension. Patients were treated with ramipril, candesartan or combination therapy for two months each, with a two-month washout period between each treatment.
Patients showed improved flow-mediated dilation, reduced blood pressure and increased plasma adiponectin levels after each treatment compared with baseline values.
However, combination therapy improved these outcome measures to a greater extent than either ramipril or candesartan alone (p<0.001 and p=0.016 for systolic and diastolic pressure respectively; p<0.001 for flow-mediated dilation; and p=0.048 for adiponectin levels).
Combination therapy also led to a greater reduction in plasma leptin levels compared with monotherapy (p=0.042).
Changes in adiponectin levels correlated with changes in insulin sensitivity following ramipril treatment (r=0.319, p=0.066), candesartan (r=0.607, p<0.001) and combination therapy (r=0.374, p=0.029).
Dr Koh and co-workers conclude in the European Heart Journal: “Combining drugs that target different aspects of the renin angiotensin system may have merit in the treatment of both cardiovascular and metabolic diseases, which are characterised by reciprocal relationships between endothelial dysfunction and insulin resistance.”
Eur Heart J 2007;28:1440-7