Efficacy and safety of atenolol, enalapril, and isradipine in elderly hypertensive women.

PURPOSE: This trial was designed to evaluate the efficacy and safety of three different classes of antihypertensive agents in elderly women. PATIENTS AND METHODS: The trial had three phases: 4 to 8 weeks of placebo, 6 weeks of titration, and 16 weeks of maintenance. White women between 60 and 80 years old with sitting diastolic blood pressures (DBPs) from 95 through 114 mm Hg treated with placebo were evaluated by history, physical examination, laboratory studies, and quality-of-life interview. After double-blind randomization with low-dose atenolol, enalapril, or isradipine, the dose was increased stepwise and hydrochlorothiazide added as needed to achieve goal DBP (less than 90 mm Hg and greater than 10 mm Hg below baseline). During maintenance, patients not at goal were "stepped up," and patients with uncontrolled DBP at maximum dosage were removed from the study. The pretreatment (baseline) blood pressure of the 315 randomized participants averaged 161/100 mm Hg; 92% had been treated previously for hypertension, 15% had diabetes mellitus, 11% smoked, and 38% consumed alcohol. RESULTS: For 245 patients completing the trial, the average decrease in blood pressure during treatment was 18.2/15.6 mm Hg. Antihypertensive efficacy was similar for the monotherapy drug regimens, with 84%, 71%, and 80% of patients receiving atenolol, enalapril, and isradipine, respectively, achieving DBP goal. Of the 70 patients who did not complete the trial, 42 left because of symptoms and 19 because of uncontrolled DBP. No important, unexpected drug-induced changes in symptoms or blood chemistries were noted. Symptom frequency differed little among the three dosage levels, becoming maximal by the second visit at the same dosage level. CONCLUSION: All three drugs lowered DBP comparably, and none produced alarming effects. Thirteen percent of patients left the study because of symptoms.

Dose-response evaluation of oral labetalol in patients presenting to the emergency department with accelerated hypertension.

STUDY OBJECTIVE: Dose-response evaluation of oral labetalol (100, 200, or 300 mg) on heart rate and systemic blood pressure in emergency department patients with hypertensive urgency (diastolic blood pressure, 110 to 140 mm Hg, and no end-organ evidence of hypertensive emergency). METHODS: This acute-treatment, dose-ranging study used a randomized, double-blind, parallel design. Patients with supine diastolic blood pressure of 110 to 140 mm Hg after 30 minutes of bedrest received an oral dose of labetalol. Supine blood pressure and heart rate were measured manually and recorded hourly for four hours after dose. Diastolic blood pressure of 100 mm Hg or less or a 30-mm Hg reduction in diastolic blood pressure was considered a treatment success. RESULTS: Two hundred fifty-five patients were evaluated for inclusion, and 36 patients (19 women and 17 men; mean age, 44 years; age range, 23 to 67 years) were studied. The most frequent reason for exclusion was a spontaneous decrease in diastolic blood pressure to less than 110 mm Hg (31%) with bedrest. There were 12 patients in each treatment group. Compared with baseline, the 100-mg dose significantly (P less than .05) reduced heart rate at three and four hours after dose, and the 300-mg dose significantly (P less than .05) reduced heart rate at one, two, and three hours after dose; the 200-mg dose did not significantly affect heart rate. All doses produced a significant decrease in systolic and diastolic blood pressures at one, two, three, and four hours after dose compared with baseline. There were no statistically significant differences between treatment groups with regard to systolic or diastolic blood pressure or heart rate at baseline or one, two, three, or four hours after dose. At two hours after dose, diastolic blood pressure control was observed in 75%, 58%, and 67% of patients receiving 100, 200, and 300 mg, respectively (P = .903). At four hours after dose, diastolic blood pressure control was observed in 50%, 64%, and 67% of patients receiving 100, 200, and 300 mg, respectively (P = .755). A comparison of treatment success rates between the two time periods showed a waning of response with the 100-mg dose of labetalol at hour 4 compared with hour 2 (P less than .05). No adverse effects were observed. CONCLUSION: Labetalol provides safe and effective treatment for hypertensive urgencies when administered orally in doses of 100 to 300 mg.

Comparison of labetalol versus enalapril as monotherapy in elderly patients with hypertension: results of 24-hour ambulatory blood pressure monitoring.

PURPOSE: This study compared the safety and efficacy of labetalol and enalapril as antihypertensive therapy for elderly patients. PATIENTS AND METHODS: A randomized, open-label, parallel controlled trial was conducted. After completing a 4-week placebo phase, 79 elderly (65 years or older) patients with an average standing diastolic blood pressure (BP) 95 mm Hg or above and 114 mm Hg or less were randomized to receive a 12-week course of either labetalol or enalapril in an open-label design. The patients' BP and heart rate were evaluated biweekly by trained observers unaware of the treatment status, and drug dosage was titrated (up to 400 mg twice a day of labetalol or 40 mg daily of enalapril) to achieve a standing diastolic BP of less than 90 mm Hg and a decrease of 10 mm Hg from baseline. Patients underwent 24-hour ambulatory BP monitoring (ABPM) at the end of the placebo phase and again after 8 weeks of active treatment. RESULTS: The treatment groups were comparable in their reduction of supine diastolic BP, with no significant differences between the two treatments. Labetalol demonstrated a significantly greater reduction (p less than 0.05) in standing diastolic BP at the end of the titration period compared to enalapril, but this difference was not significant by the end of the study period. Based on 24-hour ABPM readings, labetalol reduced mean 24-hour diastolic BP (p less than 0.05) and mean heart rate (p less than 0.05) more than enalapril. The labetalol-treated patients were significantly less often above their diastolic BP goal throughout the 24-hour ABPM period (p less than 0.01). The two treatments were equally well tolerated. CONCLUSIONS: The results indicate that labetalol and enalapril are equally effective in lowering supine diastolic BP in the elderly, but labetalol is more effective in lowering ambulatory BP and heart rate throughout the day.

Comparison of labetalol and hydrochlorothiazide in elderly patients with hypertension using 24-hour ambulatory blood pressure monitoring.

The safety and efficacy of labetalol and hydrochlorothiazide (HCTZ) were compared in a group of 34 patients aged 65 years or older with mild to moderate essential hypertension. After a 4-week placebo run-in period, during which all previous antihypertensive medication was discontinued, patients were randomized to receive either labetalol (100 mg bid) or HCTZ (25 mg bid). The patients' blood pressure and heart rate were evaluated biweekly and drug dosage was titrated (up to 400 mg and 50 mg bid of labetalol and HCTZ, respectively) to achieve a standing diastolic blood pressure less than 90 mm Hg. Patients underwent 24-hour ambulatory blood pressure monitoring at the end of the placebo run-in period and again after the 6-week titration period. Both labetalol and HCTZ significantly (P less than .01) reduced standing systolic (-19.4 vs -27.7 mm Hg) and diastolic (-14.0 vs -15.2 mm Hg) blood pressures following 12 weeks of treatment. Both antihypertensives effectively controlled the 24-hour ambulatory blood pressure, however, the labetalol group experienced a significantly lower rate of rise in diastolic blood pressure (P = .02) and mean arterial pressure (P = .02) during the acceleration period (400-1200) compared to the HCTZ group. HCTZ caused significant decreases in serum potassium (P less than .01) and alkaline phosphatase (P less than .05) and increases in uric acid (P less than .01) and urea nitrogen (P = .07). These results indicate that labetalol may offer some unique advantages over thiazide diuretics that may be particularly important in the treatment of elderly patients with hypertension.

Postmarketing comparison of labetalol and propranolol in hypertensive patients.

A survey was conducted to compare the safety and effectiveness of labetalol and propranolol under routine conditions of clinical use. Patients received either labetalol (n = 805) or propranolol (n = 135) twice daily, according to package insert instructions, for six weeks. Every two weeks the patients were evaluated and weight, heart rate, blood pressure, dose, and adverse symptoms were recorded. Both treatment groups experienced a significant decline in blood pressure at six weeks; blood pressure decreased by 24/15 mmHg in the labetalol patients and by 20/14 mmHg in the propranolol patients. Heart rate decreased significantly in both groups, but the drop in the propranolol group was greater than in the labetalol group. Significantly more propranolol-treated patients reported fatigue (15.2% versus 6.3%), impotence (9.0% versus 3.2%), bad dreams (2.3% versus 0.3%), and cold extremities (2.3% versus 0%). Dizziness was reported more frequently by the labetalol group (9.1% versus 3.8%). Overall, both drugs were safe and effective in treating hypertension, but complaints of beta-blocker-associated side effects were more frequent with propranolol.