trandolapril and Obesity

The management of obese hypertensive subjects may require the administration of anti-obesity and antihypertensive drugs. Sibutramine use has raised concerns regarding a potential increase in subjects' blood pressure and heart rate. The primary end-points of this study were an evaluation of the effect of sibutramine together with a verapamil sustained release/trandolapril combination tablet versus verapamil sustained release/trandolapril alone on the blood pressure and heart rate in obese hypertensive patients.. Patients received a low-fat low-calorie diet and were randomly allocated to open-label verapamil sustained release/trandolapril 180/2 mg (n = 26) or sibutramine 10 mg together with verapamil sustained release/trandolapril 180/2 mg (n = 28) daily for 6 months.. Significant reductions in the subjects' systolic blood pressure and diastolic blood pressure were observed in both groups (p < 0.01 versus baseline). At 6 months a greater fall in blood pressure was observed in the sibutramine/verapamil sustained release/trandolapril group compared with the verapamil sustained release/trandolapril group (systolic blood pressure 21.9 +/- 8.1 versus 15.9 +/- 12.3 mmHg and diastolic blood pressure 15.7 +/- 8.1 versus 9.1 +/- 9.9 mmHg) but this was only significant (p = 0.03) for diastolic blood pressure. The subjects' heart rate did not change significantly in any group. No significant sibutramine-associated attenuation of blood pressure reduction was observed during the study. The sibutramine/verapamil sustained release/trandolapril treatment resulted in significantly greater improvement in the subjects' anthropometric variables, homeostasis model assessment and lipid profiles compared with verapamil sustained release/trandolapril administration. The subjects' small dense low-density lipoprotein cholesterol, high-sensitivity C-reactive protein and visfatin plasma levels were only measured in the sibutramine/verapamil sustained release/trandolapril group (all decreased by p < 0.05 versus baseline).. The sibutramine/verapamil sustained release/trandolapril combination in obese hypertensive patients significantly reduced their blood pressure and improved their anthropometric and metabolic variables without affecting the heart rate.

Topics: Adult; Antihypertensive Agents; Appetite Depressants; Blood Pressure; Body Weights and Measures; C-Reactive Protein; Cyclobutanes; Delayed-Action Preparations; Diet; Drug Combinations; Drug Therapy, Combination; Female; Heart Rate; Humans; Hypertension; Indoles; Lipids; Male; Nicotinamide Phosphoribosyltransferase; Obesity; Verapamil

Current guidelines for the treatment of hypertension do not provide specific recommendations for obese hypertensive patients. To identify an optimal treatment regimen for obese hypertensive patients, we studied the interactions between a drug-based weight loss approach by sibutramine and different antihypertensive drug regimens.. This was a prospective, 16-week double-blind placebo-controlled randomized multicenter study in 171 obese hypertensive patients. After a 2-week run-in period, patients receiving 1 of the 3 antihypertensive combination therapies (felodipine 5 mg/ramipril 5 mg [n=57], verapamil 180 mg/trandolapril 2 mg [n=55], or metoprolol succinate 95 mg/hydrochlorothiazide 12.5 mg [metoprolol/hydrochlorothiazide; n=59]) were assigned randomly to sibutramine (15 mg) or placebo. Sibutramine treatment resulted in a significantly greater decrease in body weight, body mass index, and waist circumference and a significant increase in diastolic blood pressure during 24-hour blood pressure monitoring compared with placebo treatment. Sibutramine-induced weight loss and reduction of visceral obesity were markedly attenuated in the metoprolol/hydrochlorothiazide group compared with the other groups. Consistently, improvement in glucose tolerance and hypertriglyceridemia by sibutramine was abrogated in the cohort treated with metoprolol/hydrochlorothiazide compared with the other groups.. The present study demonstrates for the first time that an antihypertensive combination therapy regimen with angiotensin-converting enzyme inhibitors and calcium channel blockers is more advantageous than a beta-blocker/diuretic-based regimen in supporting the weight-reducing actions and concomitant metabolic changes induced by sibutramine in obese hypertensive patients. These data may help to develop future comprehensive treatment strategies and guidelines for this high-risk patient population.

Topics: Adult; Aged; Antihypertensive Agents; Appetite Depressants; Blood Pressure; Body Weight; Cyclobutanes; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Felodipine; Female; Humans; Hydrochlorothiazide; Hypertension; Indoles; Male; Metoprolol; Middle Aged; Obesity; Prospective Studies; Ramipril; Treatment Outcome; Verapamil

This paper sought to determine if the fixed-dose combination of trandolapril and verapamil is effective in the treatment of hypertensive obese patients resistant to monotherapy. Thirty-six hypertensive obese patients uncontrolled by monotherapy were given the combination of trandolapril-verapamil (2/180 mg) for 12 weeks. Before and after taking the drug, they self-measured their blood pressure. Patients experienced a significant reduction of blood pressure (from 178 +/- 18/100 +/- 12 mm Hg to 135 +/- 14/76 +/- 7 mm Hg, p < 0.001). Eighty percent of patients reached therapeutic goals; one patient suffered from headaches and one had constipation. it was determined that the combination of trandolapril-verapamil is effective and safe for the management of hypertension in obese patients uncontrolled by monotherapy.

Topics: Aged; Antihypertensive Agents; Dose-Response Relationship, Drug; Drug Combinations; Drug Resistance; Female; Humans; Hypertension; Indoles; Male; Mexico; Middle Aged; Obesity; Vasodilator Agents; Verapamil

To evaluate the impact of obesity on mortality in patients with acute myocardial infarction.. This study comprises 6676 consecutive patients with acute myocardial infarction screened for entry into the Danish Trandolapril Cardiac Evaluation (TRACE) study. At baseline, body mass index (BMI) and waist to hip ratio (WHR) were measured. Survival status was determined after 8-10 years.. BMI was used to divide patients into 4 groups: underweight, normal weight, overweight and obese. The normal weight group was used as reference for the other groups. WHR was divided in quartiles and the lowest quartile was used as reference for the three other quartiles. The prevalence of overweight (BMI 25-29.9 kg/m(2)) and obesity (BMI>30 kg/m(2)) were 48% and 13% in males and 31% and 13% in females. Obese patients were younger, less often smokers and more frequently suffered from diabetes and hypertension. In both men and women, there was no association between obesity assessed as BMI and mortality [men: adjusted RR=0.99 (0.85-1.14, p=0.3); women: adjusted RR=0.90 (0.74-1.10, p=0.2)]. Men with WHR in the upper quartile had an increased mortality [adjusted RR=1.21 (1.07-1.37, p<0.01)]. Increasing WHR in women showed a trend of increased mortality, although this was not significant [adjusted RR=1.13 (0.95-1.34, p=0.2)].. In patients with acute myocardial infarction overall obesity as assessed by body mass index is inversely related to mortality. However, abdominal obesity appears to be an independent predictor of all-cause mortality in men and perhaps also in women.

Topics: Adiposity; Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Body Mass Index; Denmark; Double-Blind Method; Female; Humans; Indoles; Intra-Abdominal Fat; Male; Middle Aged; Myocardial Infarction; Obesity; Prevalence; Prognosis; Risk Assessment; Risk Factors; Survival Analysis; Ventricular Dysfunction, Left; Waist-Hip Ratio

The aim of this study was to evaluate the effect of trandolapril, an angiotensin converting enzyme inhibitor, on blood pressure, forearm blood flow and insulin sensitivity in comparison with nifedipine gastrointestinal therapeutic system.. This is a multicentre, two-way parallel-group, open-label comparative study in 90 overweight hypertensive patients, who were randomly assigned to treatment for 8 weeks with either trandolapril or nifedipine. At baseline and after treatment, all patients underwent an oral glucose tolerance test, an evaluation of their metabolic profiles and a euglycaemic hyperinsulinaemic clamp test. In a subgroup of 18 patients, a forearm study was carried out.. Blood pressure fell by the second week of treatment and remained significantly reduced compared with baseline in both treatment groups. Plasma triglyceride levels were also significantly reduced after trandolapril therapy, but no significant changes occurred in the other metabolic parameters during treatment with either drug. During the euglycaemic hyperinsulinaemic clamp, whole-body glucose use was similar in the two treatment groups at baseline, and a moderate but statistically significant increase in insulin sensitivity was observed after trandolapril treatment (trandolapril: 5.0 +/- 0.2 versus 4.5 +/- 0.2 mg/kg per min; nifedipine: 4.1 +/- 0.3 versus 4.2 +/- 0.3 mg/kg per min; P < 0.05, versus baseline and trandolapril versus nifedipine treatment). Skeletal muscle glucose uptake was significantly higher after trandolapril than after nifedipine therapy (5.0 +/- 0.7 and 3.0 +/- 0.4 mg/min, respectively; P < 0.01). As forearm blood flow was similar in the two treatment groups at baseline and was unchanged after 8 weeks of therapy, skeletal muscle glucose extraction was significantly greater in the ACE inhibitor treated-group than in the nifedipine comparative group (trandolapril: baseline 21 +/- 2, treatment 24 +/- 3 mg/dl; nifedipine: baseline 18 +/- 3, treatment 16 +/- 2 mg/dl; P < 0.05, trandolapril versus nifedipine treatment).. During short-term treatment, ACE inhibition with trandolapril was able to moderately improve insulin sensitivity, in comparison with calcium blockade, and this effect appeared to be independent of the haemodynamic action of the drug.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Flow Velocity; Blood Pressure; Calcium; Calcium Channel Blockers; Female; Follow-Up Studies; Forearm; Glucose; Glucose Tolerance Test; Humans; Hypertension; Indoles; Insulin Resistance; Italy; Male; Middle Aged; Muscle, Skeletal; Nifedipine; Obesity; Peptidyl-Dipeptidase A; Treatment Outcome

An open multicentre study, performed in 340 overweight (body mass index: BMI > or = 25), hypertensive (95 mmHg < or = DBP < 115 mmHg) patients, evaluated the clinical and metabolic safety of trandolapril and confirmed its antihypertensive activity. After a two-week washout period, the patients received trandolapril 2 mg as a single morning dose for 12 weeks. Doubling of the dosage was authorized after the first four weeks when the DBP remained higher than 90 mmHg with a fall in DBP < 10 mmHg. Of the 287 patients who completed the study, 15.1% had to receive a double dose of trndolapril during the second treatment period. After four weeks of treatment, SBP was decreased by 18.6 mmHg, DBP was decreased by 13.4 mmHg and 63.1% of patients were controlled. After three months of treatment, SBP was decreased by 23.3 mmHg, DBP was decreased by 16.8 mmHg and 84.7% of patients were controlled. Subgroup analysis, according to the BMI (BMI > or = or < 30), showed that the fall in blood pressure was identical regardless of the BMI; the proportion of patients treated with a double dose of trandolapril was also independent of the BMI. A second subgroup analysis, according to the waist/hips ratio, did not reveal any difference according to the android or gynoid profile of excess weight. Twelve patients (3.9%) dropped out of the trial because of adverse events, 10 of which were attributable to treatment; 6.5% of patients reported an adverse effect attributable to treatment. Laboratory assays performed before and after three months of treatment demonstrated the very good metabolic safety profile of trandolapril, in view of the slight but significant reduction of total cholesterol, triglycerides and blood glucose. However, an average weight loss of one kilogram was reported. The global safety was considered to be good or excellent by the investigators in 94.8% of cases.

Topics: Adult; Aged; Ambulatory Care; Antihypertensive Agents; Female; Humans; Hypertension; Indoles; Male; Middle Aged; Obesity; Risk Factors

Women are at greater risk of developing resistant hypertension (RH) than men, yet scarce data exist on RH-associated outcomes in women. We aimed to determine all-cause mortality risk associated with apparent RH (aRH) among women across the spectrum of underlying coronary disease.. We analyzed data from St. James Women Take Heart (WTH; women without coronary disease at baseline), Women's Ischemia Syndrome Evaluation (women with signs/symptoms of ischemia at baseline), and the INternational VErapamil-Trandolapril STudy (INVEST; women with coronary artery disease and hypertension at baseline), totaling 15,108 adult women with no hypertension, non-RH (blood pressure [BP] ≥140/90 mmHg on ≤2 drugs or BP <140/90 mmHg on 1-3 drugs), or aRH (BP ≥140/90 mmHg on ≥3 drugs or anyone on ≥4 drugs) at baseline. The primary outcome was all-cause mortality.. Prevalence of aRH ranged from 0.4% (WTH) to 10.6% (INVEST). Women with aRH, compared to those without, were older, more often black, and more likely to be obese or diabetic. Pooling all cohorts, risk for all-cause death was greater in women with aRH than in women with non-RH (adjusted HR 1.40; 95% CI 1.27-1.55) and women without hypertension (adjusted HR 2.34; 95% CI 1.76-3.11) over a median follow-up of 14.3 years.. aRH prevalence in women varies according to underlying coronary disease, and aRH is associated with a substantial, early, and sustained increased risk of all-cause death. Additional research into early recognition and prevention strategies for RH are needed, especially in black and older women, and those with known cardiovascular risk factors.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Coronary Artery Disease; Drug Resistance; Female; Humans; Hypertension; Indoles; Middle Aged; Myocardial Ischemia; Obesity; Prospective Studies; Risk Factors; Stroke; Treatment Outcome; United States; Verapamil

Topics: Antihypertensive Agents; Calcium Channel Blockers; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diet, Diabetic; Female; Humans; Hypertension; Indoles; Middle Aged; Obesity; Verapamil

We have used an animal model of insulin resistance-the obese Zucker (fa/fa) rat-to test whether oral administration of the non-sulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor, trandolapril, alone or in combination with the Ca2+-channel blocker, verapamil, can induce a beneficial effect on insulin-stimulated glucose transport and metabolism in skeletal muscle. Insulin-stimulated 2-deoxyglucose (2-DG) uptake in the isolated epitrochlearis muscle was less than 50% as great in obese animals compared with lean (Fa/-) controls (P < .05), but was significantly improved in the obese group by both short-term (6 hours, +33%) and long-term (14 days,+70%) oral treatment with trandolapril. Verapamil treatment alone did not alter insulin-stimulated 2-DG uptake in muscle, but simultaneous administration of verapamil and trandolapril resulted in the most pronounced effect on insulin-stimulated 2-DG uptake (+106%). Long-term treatment with trandolapril alone and in combination with verapamil significantly increased muscle glycogen (+26% to 27%), glucose transporter GLUT-4 protein (+27% to 31%), and hexokinase activity (+21% to 49%), and decreased plasma insulin levels (-23% to -29%). Muscle citrate synthase activity was enhanced only when trandolapril and verapamil were administered in combination (+24%). We conclude that the long-acting, non-sulfhydryl-containing ACE inhibitor, trandolapril, alone and in combination with the Ca2+-channel blocker, verapamil, can significantly improve insulin-stimulated glucose transport activity in skeletal muscle of the insulin-resistant obese Zucker rat, and that this improvement is associated with favorable adaptive responses in GLUT-4 protein levels, glycogen storage, and activities of relevant intracellular enzymes of glucose catabolism.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Biological Transport; Calcium Channel Blockers; Female; Glucose; Indoles; Insulin Resistance; Muscle, Skeletal; Obesity; Rats; Rats, Zucker; Verapamil