dihydropyridines and Hypotension--Orthostatic

The purpose of this study was to compare the combination treatments of manidipine/delapril and olmesartan/hydrochlorothiazide (HCTZ) in elderly diabetic hypertensives. After a 4-week placebo period, 158 hypertensive patients with type 2 diabetes (age range: 66 to 74 years) were randomized to receive combination treatment of 10 mg manidipine plus 30 mg delapril or 20 mg olmesartan plus 12.5 mg HCTZ for 48 weeks in a prospective, parallel arm trial. After 12 weeks, manidipine or HCTZ was doubled in nonresponders (systolic blood pressure [SBP] > or =130 mmHg and/or diastolic blood pressure [DBP] > or =80 mmHg). Patients were checked at the end of the placebo period and every 12 weeks thereafter. At each visit, lying, sitting and standing BP as well as fasting glycemia, glycosylated hemoglobin (HbA1c), electrolytes, uric acid, total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG) were evaluated. Both combinations reduced sitting SBP (-27.7 and -28.3 mmHg, respectively; both p<0.001) and DBP (-15.1 and -14.8 mmHg, respectively; both p<0.01) with no difference between the two treatments. Standing DBP was more markedly reduced by olmesartan/HCTZ (-19.5 mmHg; p<0.001) than by manidipine/delapril (-14.7 mmHg; p<0.05 vs. olmesartan/HCTZ). No changes in metabolic parameters were observed with manidipine/delapril, whereas an increase in HbA1c (+0.7%; p<0.05), uric acid (+0.4 mg/dL; p<0.05) and TG (+41.3 mg/dL; p<0.05), and a decrease in serum potassium (-0.3 mmol/L; p<0.05) and HDL-C (-3.4 mg/dL; p<0.05) were found in the olmesartan/HCTZ group. In conclusion, both combinations were similarly effective in reducing BP in elderly hypertensive diabetic patients. However, manidipine/delapril offered some advantages in terms of the less-pronounced BP orthostatic changes and absence of metabolic adverse effects.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Diabetes Complications; Diabetes Mellitus, Type 2; Dihydropyridines; Diuretics; Drug Combinations; Endpoint Determination; Female; Humans; Hydrochlorothiazide; Hypertension; Hypotension, Orthostatic; Imidazoles; Indans; Male; Nitrobenzenes; Piperazines; Posture; Prospective Studies; Tetrazoles

The aim of this study was to compare the influences of antianginal drugs such as mononitrate, beta-blocker and calcium channel blocker on cardiovascular responsiveness to orthostasis.. The responses to passive orthostasis (tilt provocation at 60 degrees for 3 min) were measured in normotensive healthy volunteers with whole-body impedance cardiography and finger blood-pressure monitoring after a single moderate oral dose of isosorbide-5-mononitrate (CAS 16051-77-7, 10 mg), the beta1-blocker bisoprolol fumarate (CAS 104344-23-2, 5 mg), the dihydropyridine calcium channel blocker nisoldipine (CAS 63675-72-9, 5 mg), and placebo in a randomised, double-blind fashion.. In supine position, none of the drugs altered pre-tilt arterial pressure or heart rate (HR) when compared to placebo. Nisoldipine decreased systemic vascular resistance index (SVRI) when compared to either placebo or bisoprolol, and increased the cardiac index (CI) when compared to placebo. During the passive orthostasis, the mononitrate decreased SVRI when compared to placebo or bisoprolol. The mononitrate increased HR and pulse wave velocity (PWV) when compared to the other study groups, and decreased the stroke index when compared to placebo. In the bisoprolol group, the tilt responses of diastolic arterial pressure, HR, CI, left cardiac work index, and PWV decreased significantly compared to those in the placebo group. Nisoldipine did not alter the responses to orthostasis when compared to placebo. When compared to the mononitrate, both nisoldipine and bisoprolol decreased CI response to orthostasis.. The mononitrate adversely affects the cardiovascular responsiveness to orthostasis. The beta-blocker reduces the responses and thus probably oxygen demand during orthostasis. The dihydropyridine calcium blocker seems to influence the responsiveness less than the mononitrate or beta-blocker.

Topics: Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Adult; Calcium Channel Blockers; Dihydropyridines; Double-Blind Method; Female; Hemodynamics; Humans; Hypotension, Orthostatic; Isosorbide Dinitrate; Male; Nisoldipine; Nitric Oxide Donors; Supine Position; Tilt-Table Test