Antihypertensive efficacy and tolerability of different drug regimens in isolated systolic hypertension in the elderly

The pharmacological treatment, mainly based on diuretics, of isolated systolic hypertension (ISH) has recently been shown to reduce the risk of stroke and coronary heart disease in the elderly. The purpose of this study was to compare the antithypertensive effect and tolerability of different drug regimens in elderly subjects with ISH (systolic blood pressure—SBP —≥160 mmHg and diastolic blood pressure — DBP — <90 mmHg). A multicentre, randomized, controlled open trial was planned in the general practice setting. Four widely used treatment schedules were tested: hydrochlorothiazide 25 mg plus amiloride 2·5 mg (H+Am), nifedipine slow release 20 mg (N), atenolol 50 mg (At) and atenolol 25mg plus chlorthalidone 6·25 mg (At+C). After a baseline evaluation, 308 patients (76·3% female, mean age 75·3 ± 7·1 years) were randomized and followed up for 6 months. After 3 months the drug dosage was doubled if the systolic blood pressure goal (SBP<160 mmHg and SBP reduction of at least 20 mmHg) had not been reached Ninety-four subjects (30·5%) presented contraindications to β-blockers. At the 3rd- and 6th-month visits all treatment groups, except At, showed a significant reduction in SBP compared to the control group; DBP showed no significant reduction in any group at any time. At the end of the follow-up the percentage of hypertensives who had reached the BP goal was 14·6% in the control group, 52·9% in H+Am, 54·8% in N, 28·6% in At and 52·2% in At+C. Over two-thirds of the patients on H+Am or N, and about 50% of those on At or At+ C at 6 months were taking the medication at low dose. The rate of therapy discontinuation due to side effects during follow-up was significantly different among the drug regimens tested: 1·9% in the H+Am group compared to 12·5%, 19·2% and 14·8% respectively in N, At and At+C groups (P<0·05 for H+Am vs At). The proportion of subjects who spontaneously reported, mild adverse effects after 3 and 6 months of therapy was not signficantly different in the study groups, even if an excess was observed in the N group at 3 months. In conclusion, these data suggest that. diuretics are a first choice in the treatment of ISH, because of their hypotensive efficacy and acceptability; nifedipine, if well tolerated, is an effective alternative to diuretics; a high proportion of elderly patient with ISH present contraindications to β-blockers, and atenolol has a poor antihypertensive effect.