Fixed-dose Combination Therapy for Hypertension Atenolol + chlorthalidone ...

2449 patients with mild, moderate or severe hypertension participated in this 4-week postsurveillance study. Arterial hypertension was treated with atenolol (100mg) + chlorthalidone (25mg) tablets; 72.9% of patients received 1 tablet daily throughout the study; 3.9% started on Y2 tablet and then increased to 1 tablet daily; 21 .3% received V2 tablet daily, or started on 1 tablet but had the dosage reduced to Y2 tablet daily; and 1.9% had a different dose to the above.

After 4 weeks' treatment, systolic and diastolic blood pressure had decreased markedly by a mean of 16.7% and 17.7%, respectively. The mean diastolic blood pressure decreased to < 90mm Hg in all age groups. Further, the reduction in blood pressure and heart rate over the 4-week period revealed a similar pattern for patients < 60 years and patients> 60 years. 83.5% of all cases showed excellent or good activity of the medication as determined by the investigators. The remaining 16.5% of cases included patients with fair or poor results or those who discontinued therapy because of adverse reactions. These results were comparable for patients < 60 years and> 60 years of age. 216 adverse reactions were recorded. 92/2449 (3.8%) patients discontinued medication because of side effects. 31 cases of bradycardia were reported and occurred significantly (p > 0.01) more often in patients> 60 years (19 cases); otherwise the incidence of side effects could not be related to age or sex. A wide range of side effects was observed; according to investigators, side effects were mainly nervous, cardiovascular and general body (e.g. asthenia, malaise) disorders (25.5, 26.4 and 27.3% of cases, respectively).

The 4-week study reveals that atenolol + chlorthalidone is efficacious and produces a low incidence of side effects. The results compare well with other studies and in general patients appeared to respond in a similar manner regardless of age. Emanue/i, A. et al. : Journal of International Medicine 12: 314 (No 5, 1984)

... and hydrochlorothiazide + amiloride + timolol are effective 604 general practice patients with mild to moderate hypertension entered a 12-week trial designed to

compare once- and twice-daily doses of 'Moducren', a fixed ratio combination of hydrochlorothiazide (25mg), amiloride (2.5mg) and timolol (10mg). The 335 patients already receiving antihypertensive therapy discontinued their treatment for 2 weeks before the trial began. Patients were randomly allocated to receive 'Moducren' either 1 tablet once daily or Y2 tablet bid, which was doubled if necessary after 2 weeks to achieve a sitting diastolic BP < 91 mm Hg.

After 2 weeks, systolic and diastolic BP decreased by 22/12mm Hg in both groups. When all patients were included in the analysis, 81 % of the once-daily and 82% of the twice-daily group responded (a decrease in diastolic BP of 10mm Hg or a diastolic BP < 90mm Hg at the final visit). When the withdrawals were included, the corresponding values were 90 and 88%, respectively. After 12 weeks, 78% of once-daily and 74% of twice-daily patients had a diastolic BP controlled at ::::; 90mm Hg. 57% of the once-daily patients with controlled BP and 56% of the corresponding twice-daily group, were taking the equivalent of 1 tablet 'Moducren'/day. 54 patients withdrew during the trial, 46 because of adverse effects. The most frequently reported side effects were central nervous system related effects (9% of patients at 12 weeks), followed by cardiovascular/respiratory (4%). The number of patients reporting side effects decreased during the trial from 34% to 9% of once-daily and 7% of twice-daily patients. 87% of patients and 85% of doctors thought the treatment suitable.

Thus, the combination treatment 'Moducren' was shown to have good initial control of BP, be acceptable to the patient, and require only a simple dosage regimen. It was concluded therefore, that either on a once­or twice-daily basis, it is a suitable antihypertensive therapy for patients with mild to moderate hypertension. Young. J.H. et al.: Pharmatherapeutica 4: 64 (No 1. 1984)

8 INPHARMA® 24 Nov 1984 0156-2703/84/1124-0008/0$01.00/0 © ADIS Press