trandolapril and Diabetic-Angiopathies

Hypertensive diabetes individuals are at higher risk for cardiovascular events and progression to end stage renal disease. Several well conducted clinical trials indicate that aggressive treatment of hypertension in individual with diabetes reduces these complications. Combinations of two or more antihypertensive drugs are frequently required to reach the target blood pressure and to improve the cardiovascular and renal outcomes in these patients. There are physiological and clinical rationales for renin-angiotensin system blockade in hypertensive diabetics. Trandolapril/verapamil sustained released (SR) is a fixed-dose combination of trandolapril and a sustained release formulation of verapamil and indicated in treatment of hypertension in patients who require more than one drug to reach target blood pressure. The antihypertensive efficacy of trandolapril/verapamil SR has been evaluated extensively in large trials. In the INVEST trial, a verapamil SR-based treatment strategy that included trandolapril in most patients was effective in reducing the primary outcome in hypertensive patients with coronary artery disease. The new onset of diabetes was also significantly lower in the verapamil SR/trandolapril treatment group in comparison with those on the atenolol/hydroclorothiazide treatment group. The BErgamo NEphrologic Diabetes Complications Trial (BENEDICT) documented that in hypertensive diabetes and normoalbuminuria, trandolapril plus verapamil or trandolapril alone delayed the onset of microalbuminuria independent of their blood pressure-reducing effect. Thus, trandolapril/verapamil is an effective option for treatment of hypertensive diabetes patients requiring more than one agent to achieve target blood pressure.

Topics: Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diabetic Angiopathies; Drug Therapy, Combination; Humans; Hypertension; Indoles; Treatment Outcome; Verapamil

Diabetes is a strong and independent risk factor for the development of heart failure, and once heart failure occurs, patients with diabetes have a much poorer prognosis than do those without diabetes. This difference has been explained by the existence of a distinct diabetic cardiomyopathy characterized by morphologic and structural changes to the myocardium and coronary vasculature. Despite diabetic cardiomyopathy, the pharmacologic treatment of heart failure in diabetic patients is similar to that in patients without diabetes, and in general, the clinical response of diabetic patients to drug therapies for heart failure is similar, if not superior, to that of nondiabetic patients. Subgroup analyses from large clinical studies have shown that angiotensin-converting enzyme inhibitors not only reduce mortality in diabetic patients with heart failure, but also reduce the incidence of heart failure in at-risk diabetic patients. B-Blockers remain underused in the diabetic population despite overwhelming evidence of their efficacy in treating heart failure in patients with diabetes.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diabetic Angiopathies; Heart Failure; Humans; Indoles; Losartan; Risk Factors

Angiotensin-converting enzyme (ACE) inhibitors are increasingly used as first-line therapy for hypertension in type 2 diabetes mellitus and are widely believed to improve insulin sensitivity (M). However, the evidence for the latter effect does not stand close scrutiny. We have assessed the effect of the ACE inhibitor trandolapril on M in 16 patients (mean +/- SD age, 58 +/- 10.6 yr) with mild-to-moderate essential hypertension (initial blood pressure, 173 +/- 14.5/93 +/- 8.0 mm Hg), obesity (body mass index, 30 +/- 5.4 kg/m2), and impaired glucose intolerance (n = 4) or type 2 diabetes (n = 12) in a double-blind, placebo-controlled crossover design. All patients underwent three 3-h euglycemic hyperinsulinemic clamp studies (soluble insulin, 1.5 mU/kg x min) after a 2-week placebo run-in and at the end of two 4-week periods of treatment with 2 mg trandolapril or placebo (2-week washout). M (mean +/- SD) did not change with trandolapril: placebo (run-in), 5.2 +/- 1.98 mg/kg x min; placebo, 5.3 +/- 1.70 mg/kg x min; trandolapril, 5.1 +/- 1.65 mg/kg x min; P = 0.58; 95% confidence intervals, -0.74, 0.43 (trandolapril vs. placebo); 95% power to exclude an 8% increase in M. In conclusion, trandolapril had no clinically relevant effect on M in patients with hypertension and type 2 diabetes. Previous reports of improved M during ACE inhibitor treatment may be attributable to suboptimal study design and/or use of surrogate measures of M.

Topics: Adult; Aged; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Blood Pressure; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Female; Glucose; Glucose Clamp Technique; Heart Rate; Humans; Hyperinsulinism; Hypertension; Indoles; Insulin; Male; Middle Aged; Peptidyl-Dipeptidase A; Placebos; Renin

To compare the anti-hypertensive effect of combination therapy versus a single drug regimen schedule (dose-titration or switching to a different drug class) in type 2 diabetic hypertensive patients with inadequate blood pressure (BP) control on monotherapy.. Prospective, randomized, open-fashion, parallel study of two therapeutic strategies during an 8-week period.. Primary care centers in Spain.. A total of 898 men and women with type 2 diabetes mellitus and hypertension, receiving antihypertensive treatment with one single drug and whose BP was > 140 and/or 90 mmHg.. Patients were randomized to a fixed combination therapy (verapamil 180 mg plus trandolapril 2 mg; Knoll AG, Ludwigshafen, Germany) or continued on a single drug regimen, either increasing the dose of the current drug or switching to a different drug class.. Absolute BP reduction in the two groups of treatment, and the percentage of normalized patients (< 140/90 mmHg) in each group.. The diastolic BP (DBP) decrease (5.6 mmHg) was significantly greater in patients treated with combination therapy, compared to patients on monotherapy (2.9 mmHg). The decrease in systolic BP (SBP) was not significantly different (11.1 versus 10.0 mmHg). In addition, a significantly higher number of patients treated with combination therapy (82% versus 74%) reached diastolic BP normalization (< 90 mmHg).. In type 2 hypertensive patients with uncontrolled BP despite anti-hypertensive monotherapy, the change to combination therapy was more effective in attaining DBP control than any monotherapy schedule (either increasing the dose or switching to another different drug class).

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Attitude to Health; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diastole; Drug Therapy, Combination; Female; Humans; Hypertension; Indoles; Male; Middle Aged; Prospective Studies; Verapamil

The aim of this study was to evaluate the action of trandolapril on blood glucose control and microalbuminuria in mild to moderate hypertensive in patients with non-insulin-dependent diabetes. Sixty-seven patients, aged between 33 and 79, were enrolled. After a two week placebo run-in period, treatment with trandolapril as monotherapy was given for 3 months. The dose of trandolapril was adjusted between 1 and 4 mg/day according to antihypertensive response. Patients were assessed clinically and by laboratory investigations each month. Two patients were excluded from efficacy analysis because of major protocol deviations. Mean DBP fell, under the influence of treatment, from 101 +/- 5 mmHg to 82 +/- 7 mmHg (p < 0.0001) and mean SBP from 171 +/- 9 mmHg tp 147 +/- 11 mmHG (p < 0.0001). At three months, 54 patients (84%) had a DBP < or = 90 mmHg. Microalbuminuria decreased significantly (p = 0.03) during treatment. Microalbuminuria returned to normal in 11 of the 13 patients in whom the baseline value was above 21 micrograms/min and increased to above normal in 2 of the 26 patients who had a normal baseline value. Blood glycosylated hemoglobin, fructosamine, glucose and creatinine, and creatinine clearance remained stable. Plasma potassium rose slightly in 7 patients. Six adverse events were reported (4 coughs, 1 peripheral edema, 1 plantar mal perforans). One patient died from pulmonary embolism. In conclusion, trandolapril is an effective antihypertensive agent in hypertensive diabetics. Trandolapril causes a significant decrease in microalbuminuria and does not interfere with blood glucose control in these patients.

Topics: Aged; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Hypertension; Indoles; Male; Middle Aged

Diabetic angiopathy is a serious problem in antidiabetic therapy. We wanted to investigate whether treatment with the endothelin(A) receptor antagonist LU 135252 or with the angiotensin-converting enzyme inhibitor trandolapril might prevent angiopathy in long-term type I diabetes mellitus. Six groups of male Wistar rats were investigated: untreated age-matched control rats, healthy controls treated with trandolapril (0.3 mg/kg), healthy controls treated with LU 135252 (100 mg/kg), untreated diabetic rats, and diabetic rats treated with either trandolapril or LU 135252. Rats were rendered diabetic by injection of streptozotozin. Duration of the disease was 6 months. Thereafter, rats were sacrificed, and hearts, kidneys, and a mesenterial loop were removed. Hearts and kidneys were processed histologically; the mesenterial loop was perfused with saline at constant pressure for investigation of microvessels using microvideoangiometry while treated with either 30 mM KCl, 1 microM acetylcholine, or 1 microM sodium nitroprusside. All diabetic rats developed hyperglycemia without differences among these three groups. Diabetic rats exhibited marked anemia, which was significantly antagonized by both treatments. The heart capillaries/muscle fibers ratio was decreased significantly in diabetic animals, which was prevented fully by both treatments. Renal glomerular diameter was increased in diabetic rats. This was significantly antagonized by LU 135252 but not by trandolapril. Deposition of homogeneous eosinophilic material within the glomeruli was nearly completely prevented by LU 135252. The acetylcholine-induced vasodilation in mesenteric microvessels was significantly attenuated in diabetic rats, which was significantly antagonized by both treatments. We conclude that both angiotensin and endothelin seem to contribute to the development of diabetic angiopathy and that, in addition to angiotensin-converting enzyme inhibition, blockade of endothelin(A) receptors may be an interesting new approach to antiangiopathic therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Glucose; Blood Pressure; Blood Vessels; Body Weight; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Diabetic Nephropathies; Endothelin Receptor Antagonists; Endothelium, Vascular; Erythrocytes; Heart Rate; Indoles; Kidney Function Tests; Male; Muscle, Smooth, Vascular; Myocardium; Phenylpropionates; Pyrimidines; Rats; Rats, Wistar; Receptor, Endothelin A