Skip Navigation Bar
 

Results of the NHLBI and NIA clinical trial of the efficacy of antihypertensive treatment for isolated systolic hypertension in those aged 60 years and older

National Heart, Lung, and Blood Institute (NHLBI)
National Institute on Aging (NIA)
June 26, 1991

Abstract:

NIH's National Heart, Lung, and Blood Institute and the National Institute on Aging have announced a treatment that reduces the complications of isolated systolic hypertension. This form of high blood pressure, which affects more than 3 million people aged 60 years and above, can be treated with a stepped-care regimen of low dose chlorthalidone and atenolol with a resultant reduction of stroke (fatal plus non-fatal).

The Systolic Hypertension in the Elderly Program (SHEP) was a 5-year double-blind randomized trial that assessed the ability of antihypertensive drug treatment to reduce risk of nonfatal plus fatal (total) stroke in men and women age 60 and above with isolated systolic hypertension. Persons with average systolic blood pressure 160-219 mm Hg and average diastolic blood pressure 90 mmHg were eligible. SHEP randomized 4,736 people to either active treatment (2,365 persons) or placebo (2,371). The two treatment groups were comparable at baseline. Mean baseline age was 71.6 years; 47.5% were white women, 38.6% white men, 9.3% black women, and 4.6% black men. Mean systolic blood pressure was 170 mmHg: mean diastolic blood pressure, 77 mm Hg. For the active treatment group, a stepped-care regimen was used which included chlorthalidone 12.5 or 25 mg/day, and as needed, addition of atenolol 25 or 50 mg/day or reserpine, 0.05 or 0.10 mg/day. Treatment goal was to reduce systolic blood pressure by at least 20 mm Hg from baseline and to below 160 mm Hg with minimal amounts of study medication. Five-year average systolic blood pressures was 155 mmHg for the placebo group and 143 mm Hg for the active treatment group; diastolic blood pressure values were 72 mmHg and 68 mm Hg respectively. Goal blood pressure was achieved by about 70% of the actively treated group and about 35% of the placebo group during the trial. Average follow-up was 4.5 years. Five-year incidence of total stroke was 5.2/100 for active treatment and 8.2/100 for placebo. The relative risk as computed by proportional hazards regression was 0.64, 95% confidence interval 0.51 to 0.82, p = 0.0003. The results were similar across age and race-sex subgroups. For SHEP secondary end points, rates were again lower for active treatment than placebo, e.g., clinical nonfatal myocardial infarction plus coronary death relative risk was 0.73 (95% confidence interval 0.57 - 0.94); combined major cardiovascular events, relative risk is 0.68 (95% confidence interval 0.58 - 0.79); deaths from all causes, relative risk 0.87 (95% confidence interval 0.73 -1.05). Occurrence of adverse effects was of low order, and findings from behavioral evaluation (including dementia and depression) were similar throughout the trial for the two treatment groups.

Two additional secondary questions were stated at the time of trial planning as subgroup hypotheses. First, would treatment of ISH reduce the frequency of total stroke (fatal and nonfatal) similarly in those receiving and not receiving antihypertensive medication at initial contact? Second, would treatment of ISH reduce the incidence of sudden cardiac death or of coronary plus nonfatal myocardial infarction similarly in those free of baseline ECG abnormalities and in those with such abnormalities? Reduction in stroke incidence for those on and not on medication at initial contact was similar during the trial. The reduction in nonfatal myocardial infarction plus coronary death was greater in those with ECG abnormalities at baseline than in those without such abnormalities. The results for sudden death and for nonfatal myocardial infarction plus coronary death were similar in the two groups.

Conclusion: In persons aged 60 years and over with isolated systolic hypertension antihypertensive stepped-care drug treatment with low dose chlorthalidone as Step 1 medication reduces incidence of total stroke by 36% with 5-year absolute benefit estimated at 30/1,000 participants. Major cardiovascular events are also reduced, with 5-year absolute benefit estimated as 55/1000 participants.

Implications: The SHEP trial conclusively demonstrates that ISH can be effectively and safely treated with a stepped-care regimen including low dose diuretic, chlorthalidone, and low dose beta-blocker, atenolol. These are low cost medications which should be considered as the first choice of treatment for ISH. Other medication regimens have not been tested for efficacy in the treatment of ISH.

The full article describing the final results of SHEP appears in the June 26, 1991 issue of the JAMA 265;3255-3264.

Full Text:

NIH's National Heart, Lung, and Blood Institute and the National Institute on Aging have announced a treatment that reduces the complications of isolated systolic hypertension. This form of high blood pressure, which affects more than 3 million people aged 60 years and above, can be treated with a stepped-care regimen of low dose chlorthalidone and atenolol with a resultant reduction of stroke (fatal plus non-fatal).

The Systolic Hypertension in the Elderly Program (SHEP) was a 5-year double-blind randomized trial that assessed the ability of antihypertensive drug treatment to reduce risk of nonfatal plus fatal (total) stroke in men and women age 60 and above with isolated systolic hypertension. Persons with average systolic blood pressure 160-219 mm Hg and average diastolic blood pressure 90 mmHg were eligible. SHEP randomized 4,736 people to either active treatment (2,365 persons) or placebo (2,371). The two treatment groups were comparable at baseline. Mean baseline age was 71.6 years; 47.5% were white women, 38.6% white men, 9.3% black women, and 4.6% black men. Mean systolic blood pressure was 170 mmHg: mean diastolic blood pressure, 77 mm Hg. For the active treatment group, a stepped-care regimen was used which included chlorthalidone 12.5 or 25 mg/day, and as needed, addition of atenolol 25 or 50 mg/day or reserpine, 0.05 or 0.10 mg/day. Treatment goal was to reduce systolic blood pressure by at least 20 mm Hg from baseline and to below 160 mm Hg with minimal amounts of study medication. Five-year average systolic blood pressures was 155 mmHg for the placebo group and 143 mm Hg for the active treatment group; diastolic blood pressure values were 72 mmHg and 68 mm Hg respectively. Goal blood pressure was achieved by about 70% of the actively treated group and about 35% of the placebo group during the trial. Average follow-up was 4.5 years. Five-year incidence of total stroke was 5.2/100 for active treatment and 8.2/100 for placebo. The relative risk as computed by proportional hazards regression was 0.64, 95% confidence interval 0.51 to 0.82, p = 0.0003. The results were similar across age and race-sex subgroups. For SHEP secondary end points, rates were again lower for active treatment than placebo, e.g., clinical nonfatal myocardial infarction plus coronary death relative risk was 0.73 (95% confidence interval 0.57 - 0.94); combined major cardiovascular events, relative risk is 0.68 (95% confidence interval 0.58 - 0.79); deaths from all causes, relative risk 0.87 (95% confidence interval 0.73 -1.05). Occurrence of adverse effects was of low order, and findings from behavioral evaluation (including dementia and depression) were similar throughout the trial for the two treatment groups.

Two additional secondary questions were stated at the time of trial planning as subgroup hypotheses. First, would treatment of ISH reduce the frequency of total stroke (fatal and nonfatal) similarly in those receiving and not receiving antihypertensive medication at initial contact? Second, would treatment of ISH reduce the incidence of sudden cardiac death or of coronary plus nonfatal myocardial infarction similarly in those free of baseline ECG abnormalities and in those with such abnormalities? Reduction in stroke incidence for those on and not on medication at initial contact was similar during the trial. The reduction in nonfatal myocardial infarction plus coronary death was greater in those with ECG abnormalities at baseline than in those without such abnormalities. The results for sudden death and for nonfatal myocardial infarction plus coronary death were similar in the two groups.

Conclusion: In persons aged 60 years and over with isolated systolic hypertension antihypertensive stepped-care drug treatment with low dose chlorthalidone as Step 1 medication reduces incidence of total stroke by 36% with 5-year absolute benefit estimated at 30/1,000 participants. Major cardiovascular events are also reduced, with 5-year absolute benefit estimated as 55/1000 participants.

Implications: The SHEP trial conclusively demonstrates that ISH can be effectively and safely treated with a stepped-care regimen including low dose diuretic, chlorthalidone, and low dose beta-blocker, atenolol. These are low cost medications which should be considered as the first choice of treatment for ISH. Other medication regimens have not been tested for efficacy in the treatment of ISH.

The full article describing the final results of SHEP appears in JAMA 1991 Jun 26;265:3255-64.