The Angiotensin-Receptor Blocker Candesartan for Treatment of Acute Stroke (SCAST): A Randomised, Placebo-Controlled, Double-Blind Trial

Study Questions:

What is the effect of careful blood pressure lowering treatment with the angiotensin-receptor blocker candesartan in patients with acute stroke and raised blood pressure?

Methods:

Participants in this randomized, placebo-controlled, double-blind trial were recruited from 146 centers in nine north European countries. Patients older than 18 years with acute stroke (ischemic or hemorrhagic) and systolic blood pressure of 140 mm Hg or higher were included within 30 hours of symptom onset. Patients were randomly allocated to candesartan or placebo (1:1) for 7 days, with doses increasing from 4 mg on day 1 to 16 mg on days 3-7. Randomization was stratified by center, with blocks of six packs of candesartan or placebo. Patients and investigators were masked to treatment allocation. There were two co-primary effect variables: the composite endpoint of vascular death, myocardial infarction, or stroke during the first 6 months; and functional outcome at 6 months, as measured by the modified Rankin Scale. Analyses were by intention to treat.

Results:

A total of 2,029 patients were randomly allocated to treatment groups (1,017 candesartan, 1,012 placebo), and data for status at 6 months were available for 2,004 patients (99%; 1,000 candesartan, 1,004 placebo). During the 7-day treatment period, blood pressures were significantly lower in patients allocated candesartan than in those on placebo (mean 147/82 mm Hg [standard deviation 23/14] in the candesartan group on day 7 vs. 152/84 mm Hg [22/14] in the placebo group; p < 0.0001). During 6 months’ follow-up, the risk of the composite vascular endpoint did not differ between treatment groups (candesartan, 120 events vs. placebo, 111 events; adjusted hazard ratio, 1.09; 95% confidence interval [CI], 0.84-1.41; p = 0.52). Analysis of functional outcome suggested a higher risk of poor outcome in the candesartan group (adjusted common odds ratio, 1.17; 95% CI, 1.00-1.38; p = 0.048 [not significant at p ≤ 0.025 level]). The observed effects were similar for all prespecified secondary endpoints (including death from any cause, vascular death, ischemic stroke, hemorrhagic stroke, myocardial infarction, stroke progression, symptomatic hypotension, and renal failure) and outcomes (Scandinavian Stroke Scale score at 7 days and Barthel index at 6 months), and there was no evidence of a differential effect in any of the prespecified subgroups. During follow-up, nine (1%) patients on candesartan and five (<1%) on placebo had symptomatic hypotension, and renal failure was reported for 18 (2%) patients taking candesartan and 13 (1%) allocated placebo.

Conclusions:

The authors concluded that careful blood pressure lowering treatment with candesartan is not beneficial in patients with acute stroke and raised blood pressure.

Perspective:

This study did not demonstrate any evidence of a beneficial effect of careful blood pressure lowering treatment with an angiotensin-receptor blocker in patients with acute stroke and elevated blood pressure. Instead, treatment with candesartan was associated with a nonsignificant increased risk for adverse outcomes. Future trials may help to clarify whether this finding is generalizable to all patients and all antihypertensives, or whether there are subgroups of patients or different approaches to blood pressure management that may be beneficial. Until additional data are available, there does not appear to be any role for routine blood pressure lowering treatment in the acute phase of stroke.

Clinical Topics: Novel Agents

Keywords: Myocardial Infarction, Stroke, Follow-Up Studies, Benzimidazoles, Angiotensin II Type 1 Receptor Blockers, Blood Pressure, Europe, Tetrazoles


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