benazepril and Obesity

In previous clinical trials in high-risk hypertensive patients, paradoxically higher cardiovascular event rates have been reported in patients of normal weight compared with obese individuals. As a prespecified analysis of the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, we aimed to investigate whether the type of hypertension treatment affects patients' cardiovascular outcomes according to their body size.. On the basis of body-mass index (BMI), we divided the full ACCOMPLISH cohort into obese (BMI ≥30, n=5709), overweight (≥25 to <30, n=4157), or normal weight (<25, n=1616) categories. The ACCOMPLISH cohort had already been randomised to treatment with single-pill combinations of either benazepril and hydrochlorothiazide or benazepril and amlodipine. We compared event rates (adjusted for age, sex, diabetes, previous cardiovascular events, stroke, or chronic kidney disease) for the primary endpoint of cardiovascular death or non-fatal myocardial infarction or stroke. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00170950.. In patients allocated benazepril and hydrochlorothiazide, the primary endpoint (per 1000 patient-years) was 30·7 in normal weight, 21·9 in overweight, and 18·2 in obese patients (overall p=0·0034). However, in those allocated benazepril and amlodipine, the primary endpoint did not differ between the three BMI groups (18·2, 16·9, and 16·5, respectively; overall p=0·9721). In obese individuals, primary event rates were similar with both benazepril and hydrochlorothiazide and benazepril and amlodipine, but rates were significantly lower with benazepril and amlodipine in overweight patients (hazard ratio 0·76, 95% CI 0·59-0·94; p=0·0369) and those of normal weight (0·57, 0·39-0·84; p=0·0037).. Hypertension in normal weight and obese patients might be mediated by different mechanisms. Thiazide-based treatment gives less cardiovascular protection in normal weight than obese patients, but amlodipine-based therapy is equally effective across BMI subgroups and thus offers superior cardiovascular protection in non-obese hypertension.. Novartis Pharmaceuticals.

Topics: Aged; Amlodipine; Antihypertensive Agents; Benzazepines; Body Mass Index; Body Size; Body Weight; Cardiovascular Diseases; Double-Blind Method; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Obesity

In this study, we evaluated whether a combination of an angiotensin-converting enzyme (ACE) inhibitor, benazepril (B), with an angiotensin type I receptor antagonist (AT1RA), irbesartan (I), is as effective or more than drugs as monotherapy in controlling renal damage in obese Zucker rats (OZR), a model of metabolic syndrome.. During six months, G1 (OZR receiving no treatment); G2 (OZR with B 10 mg/kg/day); G3 (OZR with I 50mg/kg/day); and G4 (OZR with B 5mg/kg/day + I 25 mg/kg/day). Kidneys were processed for light microscopy (LM) and immunohistochemistry, including antibodies against interstitial alpha-smooth-muscle-actin (alpha-SMA), plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-beta(1)(TGF-beta 1), and collagen (COL) I, III, and IV.. All treated groups presented similar reduction in blood pressure compared with untreated OZR. However, animals from G4 (B + I) showed better control on proteinuria together with a higher creatinine clearance. Additionally, G4 showed a significant (P < 0.05) lower kidney weight; smaller glomerular area; lower glomerulosclerosis score; lower percentage of tubular atrophy, interstitial fibrosis, and interstitial alpha-SMA; lower tubular PAI-1 score; lower percentage of COL I, III, and IV in renal interstitium; and lower wall/lumen ratio in renal vessels, when compared with the other groups. OZR treated with B and/or I showed a better outcome (P < 0.01) in the carbohydrate and lipid metabolism in comparison with untreated OZR.. These results suggest that combined therapy using B and I is more effective than therapy with either drug at monotherapy for controlling renal damage in this animal model. In addition, data presented here reaffirm the benefit of interacting against renin-angiotensin-system (RAS) in the metabolic syndrome.

Topics: Actins; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Biphenyl Compounds; Collagen; Drug Therapy, Combination; Irbesartan; Kidney; Male; Metabolic Syndrome; Obesity; Organ Size; Plasminogen Activator Inhibitor 1; Rats; Rats, Zucker; Tetrazoles; Transforming Growth Factor beta; Transforming Growth Factor beta1