Antihypertensive Efficacy and Safe Use of Once-Daily Sustained-Release Diltiazem in the Elderly: A Comparison with Captopril

The efficacy and safety of sustained-release diltiazem, 200 – 300 mg once daily was compared with that of captopril, 12.5 – 25 mg twice-daily, in 100 elderly patients (65 – 85 years old) with mild to moderate essential hypertension (supine diastolic blood pressure 95 – 115 mmHg). All patients received placebo for 2 weeks, followed by an 8-week double-blind period, and were randomized to either diltiazem ( n = 50) or captopril ( n = 50). Their blood pressure was measured at trough level at week 4 immediately before dosing, i.e. 24 h post diltiazem dose or 12 h post captopril dose. Also at week 4, in non-responders, diltiazem was increased from 200 to 300 mg once daily and captopril from 12.5 to 25 mg twice daily to achieve a target supine diastolic blood pressure reduction of at least 10 mmHg or a diastolic blood pressure below 90 mmHg. Supine diastolic blood pressure, at week 8, was significantly ( P < 0.001) reduced from 102 ± 1 to 90 ± 1 mmHg with diltiazem and from 103 ± 1 to 89 ± 1 mmHg with captopril, bringing this parameter within normal limits for both groups. Supine systolic blood pressure was also significantly ( P < 0.001) reduced. Target blood pressure was achieved in 68% of patients taking diltiazem and in 70% taking captopril. Distribution of adverse events was comparable in both groups; no significant changes in laboratory or electrocardiographic parameters occurred. Two serious events were reported with captopril: one sudden death and one cerebrovascular stroke. Sustained-release diltiazem once a day is a convenient, well tolerated, first line treatment for hypertension in the elderly, for whom the possibility of using two dose levels allows a close regimen adjustment, 200 mg being recommended as a starting dose.

Efficacy of Low-Dose Captopril Given Twice Daily to Patients with Essential Hypertension Uncontrolled by a Beta Blocker plus Thiazide Diuretic

Thirty-two patients with moderate to severe essential hypertension whose supine diastolic blood pressure (SDBP) was ⩾95 mm Hg following 2 weeks' treatment with the optimal dosage of beta blocker-diuretic combination were randomly assigned to the addition of either Captopril 25 mg or 50 mg b.i.d. After 6 weeks' treatment, if patients were not normalized (SDBP <95 mm Hg), the dose of Captopril was doubled for a further 6 weeks. The addition of Captopril led to a significant fall in standing and supine diastolic and systolic blood pressure at the end of the sixth and twelfth week of treatment. There was no difference in the change in blood pressure between the two groups. At the end of the study SDBP was normalized in 66% of patients and a further 12·5% had their SDBP reduced by >10%. Captopril 25 or 50 mg administered twice daily proved to be a very effective antihypertensive agent when added to a beta blocker-diuretic combination in patients resistant to optimal doses of these drugs.

Results of a National Therapeutic Trial Conducted in 10 000 Hypertensive Patients by 2000 General Practitioners

1. 10 294 hypertensive patients were treated and followed by 2200 general practitioners under the supervision of 130 cardiologists and nephrologists. 2. The treatment groups, randomly allocated, were designated to use three distinct antihypertensive drugs, administered alone, and combined two-by-two. 3. Some 75% of patients had a supine diastolic blood pressure of less than 95 mmHg after 4 months treatment. 4. A total of 12% of patients had dropped out by 4 months from entry; no clear relationship was established between side effects and drop out.

Prazosin and Hydrallazine in the Treatment of Hypertension

1. Two vasodilators, prazosin and hydrallazine, have been compared in three double-blind cross-over studies designed to test their effect when used in combination with a β-adrenoceptor-blocking agent and a thiazide. 2. Single doses of 3 mg of prazosin or 75 mg of hydrallazine were administered to patients whose blood pressures remained uncontrolled on a thiazide and a β-adrenoceptor-blocking agent. Both agents produced significant falls in systolic and diastolic blood pressure apparent at 1 h. The effects of prazosin persisted for 6–7 h and those of hydrallazine for 4–6 h. Tachycardia was more marked and more prolonged after hydrallazine and continued after the blood pressure had risen to base-line levels or above. 3. In 6 week and 12 week double-blind cross-over studies, mean falls in blood pressure were similar with prazosin and hydrallazine. Similar falls in the supine diastolic blood pressure were achieved with 1 mg of prazosin and 20 mg of hydrallazine, but for a given fall in supine diastolic blood pressure, prazosin produced a significantly lower standing diastolic blood pressure. 4. Severe side effects were more pronounced after hydrallazine, which necessitated withdrawal of seven patients, whereas only one patient on prazosin withdrew from the trial because of side effects.