Critically Appraised Topic-Therapy Topic:
Use of diuretic therapy for the prevention of heart failure in the elderly
withisolated systolic hypertension.
Sept. 5, 1997
A 68 year old white male with no past medical history had repeated elevated systolic blood
pressure measurements. He does not want to take medications and inquires about the benefit of
Clinical Bottom Lines:
1. Treatment of isolated systolic hypertension with a diuretic based regimen prevented the
development of symptomatic heart failure (p<.001), reduced cardiac mortality and nonfatal
hospitalized heart failure (p<.002) and decreased cardiovascular mortality and nonfatal hospitalized
heart failure (p<.002).
2. Therapy with the stepped cable regimen ( step 1: chlorthalidone 12.5-25 mg; step 2: atenolol
25-50 mg) was beneficial in higher risked groups: men (RR 1.69), increasing age (RR 2.38 age >
80 years old), and a higher baseline systolic blood pressure (RR 1.72 SBP> 180 mm Hg).
3. With a previous history or ECG evidence of myocardial infarction (n=492), the treatment group
had a relative risk reduction of preventing symptomatic heart failure,81%, cardiac mortality and
nonfatal hospitalized heart failure, 59%, and cardiovascular mortality and nonfatal hospitalized heart
A multicentered, controlled clinical trial of 4736 patients with isolated systolic hypertension(SBP>
160 mm Hg) and age greater than 60 years randomized to a diuretic based stepped care regimen:
Step 1: chlorthalidone 12.5-25 mg; Step 2: atenolol 25-50 mg (reserpine if contraindicated) versus
|Fatal/Nonfatal HF||55 (2.3%)||105 (4.4%)||49%||2.1%||48||<.001|
|Fatal/Hopitalized Nonfatal HF||45 (1.9%)||79 (3.3%)||43%||1.4%||71||.002|
|Cardiac death/Hospitalized HF||113 (4.8%)||162 (6.8%)||31%||2.0%||50||.002|
|CV death/Hospitalized HF||123 (5.2%)||174 (7.3%)||30%||2.1%||47||.002|
Comparison of history and/or ECG evidence of myocardial
infarction versus none:
|Previous MI n=492||No MI n=4185|
|Events||RR (95% CI)||RRR||NNT||p||RR (95%
|Fatal/Nonfatal HF||.19(.06-.53)||81%||15||.002||.61 (.42-.88)||39%||65||.008|
|Fatal/Hopitalized Nonfatal HF||.24 (.08-.72)||76%||20||.01||.67(.44-1.02)||33%||101||.06|
|Cardiac death/Hospitalized HF||.41 (.20-.82)||59%||48||.01||.68 (.51-.91)||32%||65||.008|
|CV death/Hospitalized HF||.38 (.19-.76)||62%||17||.007||.70 (.53-.91)||30%||63||.008|
1. A well conducted clinical trial with a large number of patients of which 90% of the treatment
group remained on antihypertensive medication at follow-up, 4.5 years.
2. There were not good objective measures used by the coding panel to determine the degree of
heart failure both at baseline and at follow-up.
3. The diuretic-based stepped care treatment regimen is applicable in a specified patient population
and more study is needed to extrapolate the results to other patient populations.
4. Although side effects were not addressed, chlorthalidone is well tolerated and inexpensive in the
5. The cost of preventing fatal and nonfatal HF combined with chlorthalidone 25 mg after 4.5 years
of therapy, $15,941; one hospitalization for nonfatal HF and/or cardiac death, $16,273; preventing
one hospitalization for nonfatal HF and/or cardiovascular death, $15,634.
Kostis et al. Prevention of Heart Failure by Antihypertensive Drug Treatment in Older PersonsWith
Isolated Systolic Hypertension. JAMA July 16, 1997; 278:212-216.