High blood pressure. Causes, symptoms, treatments

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2017-04-09

This randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy and safety of single daily dose diltiazem extended-release (XR) and indapamide, given alone and combined, in 255 male and 170 female patients with mild to moderate hypertension. Blood pressure was assessed both manually in the office and by 24-hour ambulatory blood pressure monitoring (ABPM) techniques. Between-treatment efficacy comparisons were based on ABPM plots and changes from baseline in supine systolic (SuSBP) and diastolic (SuDBP) blood pressure after 6 weeks of double-blind treatment. Periodic 12-lead electrocardiograms (ECG), clinical laboratory tests, and physical examinations were used to assess safety. Both diltiazem XR 180, 240, and 360 mg and indapamide 2.5 mg monotherapy reduced ambulatory blood pressure to a greater extent than placebo. The ABPM data demonstrate that 2.5 mg indapamide produces an additional reduction in diastolic blood pressure when combined with fixed doses of diltiazem XR (120, 180, and 240 mg). The reduction was consistent over the entire 24-hour recording period for all combinations. Compared with monotherapy groups, higher therapeutic response rates (SuDBP < or = 90 mm Hg or Delta SuDBP > or = 10 mm Hg decrease from baseline) were also observed with combination therapy. Office blood pressure data qualitatively and quantitatively supported the observations made from the ABPM data. There were no unexpected adverse events or side-effect trends and no dose-response or clinically significant laboratory, ECG, or physical examination adverse effects. The combination therapy regimens were well tolerated with safety profiles comparable with those of the individual therapies.

A low dose (1.25 mg) of indapamide (Lozol, Rhône-Poulenc Rorer Pharmaceuticals, Collegeville, PA) was evaluated in 222 elderly patients (> or = 50 years) with mild to moderate essential hypertension in a multicenter, randomized, double-blind, parallel-group clinical trial. A 4-week single-blind placebo washout period was followed by an 8-week double-blind treatment period. Patients were randomized to receive indapamide 1.25 mg/day or to receive placebo. The primary efficacy variable was the mean change in sitting diastolic blood pressure from baseline to week 8. Eighty-one patients in the indapamide group (73%) and 87 patients in the placebo group (78%) completed the 8 weeks of double-blind therapy. Therapy with 1.25 mg of indapamide produced greater reductions compared with placebo in sitting diastolic blood pressure after 8 weeks of therapy, with statistical significance (P < or = 0.0015) seen after only 2 weeks of therapy and continuing throughout the 8 weeks. All secondary efficacy measures (sitting systolic blood pressure, standing systolic and diastolic blood pressures, and > or = 10 mm Hg decrease or final value of < or = 90 mm Hg in sitting diastolic blood pressure) also showed superior (P < or = 0.0014) improvement in the indapamide group compared with placebo after 8 weeks of double-blind treatment. During the 8-week double-blind treatment period, incidence rates for all adverse events and for drug-related adverse events were similar between the two treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertension and obesity are closely related. Obese patients tend to have increased intravascular volume and cardiac output and decreased total peripheral vascular resistance and plasma renin activity. Lean patients with essential hypertension usually have increased total peripheral resistance. Left ventricular adaptation in obesity consists of eccentric left ventricular hypertrophy (LVH), regardless of the level of arterial pressure. Obesity and hypertension occurring together place a dual burden on the left ventricle and are associated with systolic and diastolic dysfunction, lipid abnormalities, insulin resistance, and a propensity for frequent, complex ventricular arrhythmias. Congestive heart failure and sudden death are common sequelae of obesity-hypertension and LVH. Treatment should include vigorous efforts at weight reduction and sodium restriction. Diuretics are ideal agents from a hemodynamic standpoint but often do not improve the total risk profile, with the possible exception of indapamide (Lozol). Calcium blockers may be ideal agents because of their favorable effects on both hemodynamics and total cardiovascular risk profile.

Indapamide (Lozol) is a new diuretic and antihypertensive agent. The drug appears to have a unique mechanism of action, combining diuretic effects with a direct vascular action, presumably secondary to calcium channel blockade. Available studies indicate that indapamide is comparable to hydrochlorothiazide, chlorothiazide, furosemide, and other diuretic agents in the management of hypertension and edema. The drug produces toxicity similar to that of the thiazide and loop diuretics; however, it does not appear to increase cholesterol levels. Although it is claimed that indapamide produces no effect on glucose levels, hyperglycemia has been reported. Indapamide is safe and effective for treatment of hypertension in mild to severe renal impairment, but advantages over furosemide are questionable. Indapamide is a unique diuretic, but does not appear to offer advantages over other available agents.