Left ventricular hypertrophy reversal with labetalol and propranolol: a prospective randomized, double-blind study.

Hypertensive patients with left ventricular hypertrophy (LVH) have increased cardiovascular morbidity and mortality. Experimental studies indicate the importance of both the alpha and beta components of the adrenergic nervous system in the development and reversal of LVH. Therefore labetalol (L), a combined alpha and beta blocker, and propranolol (P), a nonselective beta blocker, were evaluated in a randomized, double-blind study of 35 hypertensive patients with echocardiographic evidence of LVH. Following 2 weeks of placebo, L or P was titrated as needed and tolerated to maximum total daily doses of 1600 mg and 640 mg, respectively. A thiazide diuretic was added if necessary for blood pressure control. M-mode echocardiograms were performed at baseline and after 1, 3, 6, and 12 months of blood pressure control. The echocardiograms were read independently by two blinded observers for end-diastolic dimension and wall thicknesses, and left ventricular mass. Fractional shortening, cardiac output, and peripheral vascular resistance were derived using standard formulas. Both drugs reduced blood pressure significantly and comparably. Significant changes in the echocardiographic measurements were observed as early as 1 month and usually persisted throughout the study. Both drugs decreased posterior wall thickness; however, only the decrease in propranolol group achieved statistical significance. Septal wall thickness was reduced by L at 3 and 12 months. End-diastolic dimension increased significantly in the L-treated group at 3, 6, and 12 months of therapy, whereas P had no effect on this measurement.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of betaxolol, a new beta 1-adrenergic antagonist, to propranolol in the treatment of mild to moderate hypertension.

A double-blind, multicenter study compared the safety and efficacy of oral betaxolol 10 to 40 mg once daily (n = 68) with propranolol 40 to 160 mg twice daily (n = 73) in the treatment of mild to moderate essential hypertension. Both agents produced significant (P less than 0.01) and comparable reductions in mean supine systolic and diastolic blood pressures (7/11 mm Hg on betaxolol and 9/10 mm Hg on propranolol). Both betaxolol and propranolol significantly (P less than 0.01) reduced mean supine heart rate by 9 beats per minute. Patients achieved a more significant (P less than 0.01) reduction in blood pressure earlier (weeks 2 and 4 of the titration period) with betaxolol. By the end of treatment there was no significant difference in response between treatment groups. A higher incidence of central nervous system side effects (insomnia, bizarre dreams, depression, hallucinations, dizziness), however, was seen with propranolol than with betaxolol. Overall, the data show that in patients with mild to moderate essential hypertension, betaxolol 10 to 40 mg administered once daily is as effective as and better tolerated than propranolol 40 to 160 mg administered twice daily.

Effect of the calcium channel blocker nitrendipine on left ventricular mass in patients with hypertension.

Reductions in left ventricular (LV) mass have been reported after antihypertensive therapy with certain sympatholytic agents and converting enzyme inhibitors, but little or no improvement has been noted after vasodilator therapy. In this study we evaluated the effect of the calcium channel blocker nitrendipine on echocardiographic LV mass. During a 12-month period, nitrendipine was used as monotherapy in 30 patients and in combination with propranolol or a diuretic in an additional 28 patients. Nitrendipine monotherapy lowered supine blood pressure from 148/97 to 136/83 mm Hg, but LV mass did not change significantly. Supine blood pressure decreased from 155/103 to 134/86 mm Hg in patients receiving combination therapy but, again, changes in LV mass were not significant. These data suggest that nitrendipine is effective in lowering blood pressure, but this is not associated with a significant decrease in LV mass in patients with mild hypertension.

Blood pressure, plasma volume, and catecholamine levels during enalapril therapy in blacks with hypertension.

The effect of enalapril, an antihypertensive inhibitor of angiotensin-converting enzyme, on plasma catecholamine levels and plasma volume (PV) has not been well established. In a randomized, double-blind study, 29 subjects (28 blacks and one white) received one of the following dosing regimens: hydrochlorothiazide (HCTZ), 25 mg twice a day (group 1; n = 12); enalapril, 10 mg twice a day (group 2; n = 12); or enalapril, 10 mg twice a day, with HCTZ, 25 mg twice a day (group 3; n = 5). Dosages were doubled after 4 wk if diastolic blood pressure was greater than or equal to 90 mm Hg. After 8 wk of therapy, supine blood pressure decreased by 24.1/16.0 mm Hg (systolic/diastolic) in group 1, by 10.8/4.0 mm Hg in group 2, and by 48.0/27.8 mm Hg in group 3. Mean values of supine plasma levels of norepinephrine, epinephrine, and dopamine did not change with therapy. PV fell 7.9% in group 1, 1.3% in group 2, and 5.0% in group 3. There were no correlations between changes in PV and blood pressure, but a decrease in PV correlated with an increase in plasma norepinephrine levels in the group treated with HCTZ alone (r = -0.65) and in all 29 subjects combined (r = -0.45). Enalapril alone was not very effective in lowering blood pressure in these subjects, but the combination of enalapril with HCTZ was very effective. There was no evidence of a direct effect of enalapril on the sympathetic nervous system or on PV.

Time course of regression of left ventricular hypertrophy in treated hypertensive patients.

In a prospective study, 32 hypertensive patients with echocardiographic evidence of left ventricular hypertrophy were treated with methyldopa, hydrochlorothiazide, or methyldopa and hydrochlorothiazide combined. Echocardiograms and electrocardiograms were obtained in each of the 32 patients before treatment, at the point of initial blood pressure control, and then one, three, and six months thereafter; in 27 patients these studies were also obtained after 12 and 18 months. Left ventricular end-diastolic posterior wall thickness decreased in seven patients whose blood pressure was controlled with methyldopa alone (p less than 0.01) and in 17 patients whose blood pressure was controlled with methyldopa and hydrochlorothiazide combined (p less than 0.01); in both groups, the reduction in left ventricular posterior wall thickness at end-diastole was apparent one month after blood pressure control was established (p less than 0.05). In contrast, no significant reduction in left ventricular posterior wall thickness at end-diastole was observed in eight patients who had equivalent control of blood pressure with hydrochlorothiazide alone (p = 0.34). During the 18-month follow-up period, ventricular septal thickness at end-diastole decreased in the group treated with methyldopa and hydrochlorothiazide combined (p = 0.03); whereas, ventricular septal thickness at end-diastole appeared to increase in the group treated with hydrochlorothiazide alone (p less than 0.01). These results suggest that evidence of regression of left ventricular hypertrophy may be detected as early as one month after blood pressure is controlled with methyldopa or methyldopa and hydrochlorothiazide combined; whereas, long-term control of hypertension with hydrochlorothiazide alone was not associated with evidence of regression of left ventricular hypertrophy. Although the patient number are small, these data suggest that there are differences in the long-term effects of diuretics and sympatholytic drugs on left ventricular anatomy, which may, in part, relate to divergent effects on the sympathetic nervous system.

Diuretic potency of combined hydrochlorothiazide and furosemide therapy in patients with azotemia.

The effect of combined hydrochlorothiazide and furosemide therapy was studied in eight hypertensive patients with renal insufficiency who had poor response to either furosemide or hydrochlorothiazide alone. The study was divided into two parts. In part A, five patients had an inadequate response to furosemide in doses of 160 to 240 mg/day followed a strict protocol in order to compare the effect of increased doses of furosemide with combined hydrochlorothiazide-furosemide administration. All had azotemia, presumable from nephrosclerosis, and had serum creatinine concentrations ranging from 2.3 to 4.9 mg/dl. Four of the five patients had inadequate arterial pressure control, and the remaining patients had fluid retention from the administration of minoxidil. In all five patients, plasma volume was either increased or normal, despite long-term treatment with furosemide. Increasing the dose of furosemide to between 320 and 480 mg/day had only a modest additional diuretic effect, and plasma volume and arterial pressure were not significantly changed. Adding hydrochlorothiazide, 25 to 50 mg twice a day, produced a marked diuresis, and a significant reduction in weight, plasma volume and mean arterial pressure (p less than 0.025 for all three patients). In part B, combined hydrochlorothiazide-furosemide therapy was used to treat three additional patients who had an inadequate response to either diuretic alone. The results indicate that combined hydrochlorothiazide-furosemide is a potent diuretic regimen and is effective in many patients wit chronic renal failure who have a poor response to furosemide alone.