Initial Drug Therapy for Isolated Systolic Hypertension in Elderly Patients According to SHEP Study
The initial recommended drug for isolated systolic hypertension in elderly patients according to the SHEP study is chlorthalidone, a thiazide-type diuretic. 1
Evidence from SHEP Study and Guidelines
The Systolic Hypertension in the Elderly Program (SHEP) demonstrated that chlorthalidone (25-50 mg/day) was effective as first-line therapy for isolated systolic hypertension in elderly patients, with 88% of patients reaching goal blood pressure without requiring a second medication. 1
In the SHEP trial, the treatment regimen began with chlorthalidone as step 1 therapy, with either atenolol or reserpine added as step 2 if needed, resulting in significant reductions in stroke risk. 2, 3
This chlorthalidone-based regimen led to a 36% reduction in stroke incidence (95% CI, 18%-50%) compared to placebo in elderly patients with isolated systolic hypertension. 4
Mechanism of Action and Dosing
The SHEP study found that most patients responded to the lower dose of chlorthalidone (25 mg/day), with similar blood pressure responses across all age, sex, and race subgroups. 1
Treatment with chlorthalidone resulted in an overall mean difference between treatment and placebo groups of 17 mmHg for systolic BP and 6 mmHg for diastolic BP. 1
Benefits on Clinical Outcomes
The SHEP trial demonstrated that treating isolated systolic hypertension with a chlorthalidone-based regimen reduced the incidence of both hemorrhagic and ischemic strokes, including lacunar strokes. 2
Treatment effect was observed within 1 year for hemorrhagic strokes but took until the second year to become apparent for ischemic strokes. 2
Alternative Options
While chlorthalidone was the initial drug used in SHEP, European guidelines note that calcium channel blockers (particularly dihydropyridines) have also shown benefit in trials of isolated systolic hypertension. 4
A comparative study found that fosinopril (an ACE inhibitor) produced identical reductions in systolic blood pressure as chlorthalidone in elderly patients with isolated systolic hypertension, suggesting it could be a suitable alternative. 5
Practical Considerations and Cautions
When using chlorthalidone in elderly patients, monitor for common adverse effects observed in the SHEP study, including decreased serum potassium (0.5 mEq/L lower), increased uric acid (0.9 mg/dL higher), and slightly increased creatinine (0.08 mg/dL higher). 1
Initial doses and subsequent dose titration should be more gradual in elderly patients because of a greater chance of undesirable effects, especially in very old and frail individuals. 4
Blood pressure should always be measured in both sitting and standing positions in elderly patients due to increased risk of postural hypotension. 4
Current Guideline Recommendations
Current guidelines recommend that drug treatment for isolated systolic hypertension in the elderly can be initiated with thiazide diuretics (with chlorthalidone having the strongest evidence from SHEP), calcium antagonists, angiotensin receptor blockers, ACE inhibitors, or beta-blockers. 4
The blood pressure goal for elderly patients with isolated systolic hypertension is generally <140/90 mmHg if tolerated, though many elderly patients may require two or more drugs to achieve this target. 4