Scandinavian Candesartan Acute Stroke Trial - SCAST

Description:

The goal of the trial was to compare treatment with candesartan compared with placebo among patients with acute stroke.

Hypothesis:

The use of candesartan after an acute stroke would improve clinical and functional outcomes.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Stratified
  • Parallel

Patient Populations:

  • Patients at least 18 years of age with acute stroke (within 30 hours) and systolic blood pressure ≥140 mm Hg

    Number of enrollees: 2,029
    Duration of follow-up: 6 months
    Mean patient age: 71 years
    Percentage female: 40%

Exclusions:

  • Contraindication or clear indication for use of an angiotensin-receptor blocker
  • Markedly reduced consciousness
  • Rankin Scale score of 4 or greater
  • Clear indication for antihypertensive treatment during the acute phase of the stroke
  • Limited life span
  • Patient unavailability for follow-up
  • Pregnant or breast-feeding

Primary Endpoints:

  • Vascular death, myocardial infarction, or stroke within 6 months

Secondary Endpoints:

  • Functional outcome at 6 months (as measured by mRS)
  • Vascular death
  • Ischemic stroke
  • Hemorrhagic stroke
  • All stroke
  • Myocardial infarction
  • Stroke progression
  • Neurological status at 7 days (as measured by SSS)
  • Activities of daily living (as measured by Barthel index)

Drug/Procedures Used:

Patients who presented within 30 hours of an acute stroke and had elevated blood pressure were randomized to 7 days of candesartan (uptitrated to 16 mg daily; n = 1,017) versus placebo (n = 1,012).

Principal Findings:

Overall, 2,029 patients were randomized. In the candesartan group versus the placebo group, mean age was 71 years versus 71 years, 40% versus 44% were women, and previous stroke/transient ischemic attack (TIA) was 25% versus 21%, respectively. The proportion of ischemic/hemorrhagic strokes was 85%/14% versus 86%/13%, respectively.

In the candesartan group, mean blood pressure was 171/90 mm Hg at baseline and 147/82 mm Hg at 7 days. In the placebo group, mean blood pressure was 172/91 mm Hg at baseline and 152/84 mm Hg in the placebo group (p < 0.0001 between groups at 7 days).

At 6 months, the primary outcome had occurred in 12% of the candesartan group versus 11% of the placebo group (p = 0.52). Vascular death was 6% versus 6% (p = 0.80), nonfatal myocardial infarction was 1% versus 1%, and nonfatal stroke was 5% versus 4%, respectively. Stroke progression was 6% versus 4% (p = 0.04), respectively. There was a higher risk for poor functional outcome in the candesartan versus placebo group (odds ratio 1.17, p = 0.048).

Interpretation:

Among patients with acute stroke, 7 days of treatment with candesartan lowered blood pressure compared with placebo, although this did not result in clinical benefit. Candesartan did not reduce the incidence of the primary composite outcome of vascular death, myocardial infarction, or stroke within 6 months. Secondary outcomes of stroke progression and poor functional outcome occurred at a slightly higher rate in the candesartan group.

Elevated blood pressure is common in patients with acute stroke; however, due to impaired cerebral autoregulation, it is not known what the optimal blood pressure should be in the acute setting. The ongoing ENOS and INTERACT2 trials will help to further clarify this question. Until then, routine blood pressure lowering in acute stroke does not appear to be warranted.

References:

Sandset EC, Bath PM, Boysen G, et al. The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial. Lancet 2011;377:741-750.

Clinical Topics: Novel Agents

Keywords: Odds Ratio, Myocardial Infarction, Stroke, Follow-Up Studies, Ischemic Attack, Transient, Benzimidazoles, Angiotensin II Type 1 Receptor Blockers, Blood Pressure, Homeostasis, Tetrazoles


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