The efficacy of low dose metoprolol CR/ZOK in mild hypertension and in elderly patients with mild to moderate hypertension.

In two separate but similarly designed placebo-controlled studies, the efficacy of metoprolol CR/ZOK 50 mg once daily was evaluated in 64 patients (mean age 53 years) with mild hypertension (Study I) and in 34 elderly patients (mean age 68 years) with mild to moderate hypertension (Study II). Both studies were of randomized, double-blind, parallel-group design, the entry criteria for diastolic blood pressure being greater than or equal to 90 less than 105 mm Hg in Study I and greater than or equal to 95 less than 110 mm Hg in Study II. Study I: The impact of metoprolol CR/ZOK 50 mg once daily for 4 weeks compared with placebo 24 hours post dosing was to produce a significant reduction in supine (P = .0001), and standing (P less than .0001) systolic blood pressures and the standing diastolic pressure (P = .035). The supine diastolic pressure was lower after metoprolol CR/ZOK but not significantly so. Study II: Metoprolol CR/ZOK 50 mg daily given to elderly hypertensives when compared with placebo 24 hours post dosing produced a significant fall in supine (P = .022) and standing (P = .022) diastolic pressure. Systolic pressure and heart rate were not significantly reduced. One patient in Study II had a nonfatal myocardial infarct whilst receiving placebo. There were no other serious adverse effects in either study and no patients were withdrawn from the trial because of drug related unwanted events. The studies indicate that 50 mg metoprolol CR/ZOK may be an effective antihypertensive agent which may prove useful in the treatment of mild to moderate hypertension, particularly in the elderly.

Efficacy and tolerability of a new controlled-release formulation of metoprolol: a comparison with conventional metoprolol tablets in mild to moderate hypertension.

In a double-blind study with parallel groups 195 hypertensive patients were randomly allocated to treatment with either conventional tablets of metoprolol, 100 mg once daily, or a new controlled-release (CR) formulation of metoprolol, 100 mg once daily. The dose was doubled if the patient's diastolic blood pressure remained greater than or equal to 95 mmHg after six weeks on 100 mg, whereas well-controlled patients continued on 100 mg once daily for a further six-week period. In the metoprolol tablet group the 200 mg dose was administered in the form of Durules. There was a significant reduction from the placebo baseline in systolic and diastolic blood pressure and heart rate at 24 h after both six weeks and 12 weeks of active treatment; no significant difference in the mean reduction from baseline between the two groups was demonstrated. However, significantly more patients responded to treatment with metoprolol CR when compared with those patients taking metoprolol tablets. After six weeks of active treatment 61% of the metoprolol CR group and 56% of the conventional metoprolol tablet group had a diastolic blood pressure less than 95 mmHg. After another six weeks the corresponding figures were 83% and 69% respectively. Between week 6 and 12, 36% of patients in the metoprolol CR group and 42% of patients in the conventional metoprolol tablet group were receiving a 200 mg dose. All formulations of metoprolol were well-tolerated. Fewer subjective symptoms were reported during active treatment than during the placebo phase. There were no differences between the groups with regard to changes in laboratory variables from baseline, changes in all combined symptoms, or changes in any one symptom.

Serum potassium and body weight during treatment with two fixed combinations of beta-blockers and diuretics in hypertensive patients: a controlled study.

Two fixed combinations of beta-blockers and diuretics, penbutolol plus furosemide and pindolol plus clopamide, were compared with respect to efficacy, safety, and tolerability in hypertensive out-patients. The two preparations were equally effective in reducing blood pressure when given as a single daily dose. Doubling the dosage for those patients who responded poorly did not improve therapeutic response. The group treated with pindolol-clopamide had a significant increase in mean body weight and a substantial decrease in serum potassium concentrations. No direct relationship between these findings could be demonstrated, but the loss of potassium would be an important consideration when treating patients who are particularly vulnerable to the consequences of hypokalemia.

A comparison of a combination of penbutolol and frusemide with the two compounds individually in the treatment of hypertension.

Forty-one patients completed a randomized, double-blind, between-group comparison of a combination of penbutolol and frusemide, with penbutolol alone, and frusemide alone in the management of mild to moderate essential hypertension. The results suggest that the combination caused a superior reduction in systolic and diastolic pressure compared with penbutolol and a superior reduction in systolic blood pressure compared with frusemide.

A comparative study of atenolol and penbutolol in hypertensive patients.

In a randomized controlled, double-blind clinical trial with 45 patients with moderate hypertension atenolol 100 mg and penbutolol 40 mg were equally effective in lowering the blood pressure. During the 6 weeks of treatment there was no change in body weight and serious side-effects were not observed, but bradycardia occurred more frequently with atenolol than with penbutolol. Withdrawal of medication during the final week of the study did not cause any adverse reaction.

The effect of pretreatment with cimetidine on the bioavailability and disposition of atenolol and metoprolol.

1 Plasma levels of atenolol and metoprolol and their effects on exercise heart rate have been studied after oral administration of single doses of 100 mg of the two drugs in ordinary tablets alone and during concomittant cimetidine medication of 1 g per day. 2 Cimetidine caused no significant changes in the bioavailability of any of the two beta-adrenoceptor blockers and the rate of elimination of metoprolol was unaffected by the histamine H2-receptor blocker. A slight but significant increase in the elimination half-life from 6.5 +/- 0.6 to 7.9 +/- 0.6 (P less than 0.05) was noted for atenolol after pretreatment with cimetidine. The beta-adrenoceptor blocking effect was about the same for the used doses of atenolol and metoprolol and it was not changed during cimetidine therapy.

Once-daily penbutolol or atenolol can replace combination therapy in essential hypertension.

Antihypertensive therapy was stopped in twenty-one patients with moderate hypertension. Almost all of them had been on combination therapy, usually propranolol or metoprolol with chlorthalidone, for more than a year. After a placebo 'wash-out' period of 4 weeks patients were randomly allocated in a controlled trial to a fixed daily dose of either 100 mg atenolol or 40 mg penbutolol for 6 weeks. Single-agent therapy at these doses successfully controlled the blood pressure in nineteen of the twenty-one patients, including six previously inadequately controlled on a combination. Although no conclusions can be drawn about the long-term benefits, in the patient population under study either penbutolol or atenolol given at a standard dose should provide good initial blood pressure control in most patients with mild to moderate hypertension.

Use of fixed doses of beta blocking drugs in the treatment of hypertension. Randomised study of atenolol and penbutolol.

Atenolol 100 mg and penbutolol 40 mg given once a day were both effective in controlling moderate hypertension, as judged by a randomised controlled, double-blind trial in 45 patients treated for six weeks. Both drugs significantly reduced the resting supine and erect blood pressures. No serious adverse effects could be attributed to either drug. Bradycardia occurred more frequently with atenolol than with penbutolol. Penbutolol, which possesses intrinsic sympathomimetic activity, may be useful in the treatment of patients in whom some other beta-blocker has failed to bring about adequate control of the blood pressure, despite marked bradycardia.