No Long-Term Benefit of Candesartan for Patients with Acute Stroke

Summary

Elevated blood pressure (BP) in the acute phase of stroke has been associated with poor short- and long-term outcomes [Leonard-Bee J et al. Stroke 2002]. The Scandinavian Candesartan Acute Stroke Trial [SCAST; NCT00120003] did not demonstrate a difference at 6 months between BP lowering with candesartan and placebo for 7 days in the acute phase of stroke (HR, 1.09; 95% CI, 0.84 to 1.41; p=0.52) [Sandset EC et al. Lancet 2011]. The aim of this SCAST prespecified secondary analysis was to investigate whether a difference might be observed over longer follow-up.

  • Cerebrovascular Disease
  • Hypertensive Disease
  • Cardiology Clinical Trials
  • Cerebrovascular Disease
  • Hypertensive Disease
  • Cardiology Clinical Trials
  • Cardiology

Among patients with acute stroke, approximately 75% have systolic blood pressure (BP) ≥140 mm Hg [Qureshi AI et al. Am J Emerg Med 2007; Leonard-Bee J et al. Stroke 2002]. Elevated BP in the acute phase of stroke has been associated with poor short- and long-term outcomes [Leonard-Bee J et al. Stroke 2002]. The Phase 2, prospective, randomized Acute Candesartan Cilexetil Therapy in Stroke Survivors study [ACCESS] in 500 patients with stroke found that vascular events and mortality were significantly lowered by candesartan, without a significant difference in adverse event rates [Schrader J et al. Stroke 2003]. However, large clinical trials have yet to demonstrate a beneficial effect of BP lowering in the acute phase of stroke.

The Scandinavian Candesartan Acute Stroke Trial [SCAST; NCT00120003] did not demonstrate a difference at 6 months between BP lowering with candesartan and placebo for 7 days in the acute phase of stroke (HR, 1.09; 95% CI, 0.84 to 1.41; p=0.52) [Sandset EC et al. Lancet 2011]. The aim of this SCAST prespecified secondary analysis, presented by A. G. Hornslien, MD, Oslo University Hospital Ullevaal, Oslo, Norway, was to investigate whether a difference might be observed over longer follow-up.

In total, 2029 patients with acute ischemic or hemorrhagic stroke and systolic BP ≥140 mm Hg were randomly assigned to candesartan versus placebo for 7 days. Of these patients, long-term follow-up data were available in 632 patients who were allocated to candesartan and 624 patients who were allocated to placebo. Follow-up data were collected from national patient, hospital, and death registries in Norway, Sweden, and Denmark. The primary end point was the composite of stroke, myocardial infarction, or vascular death. The secondary end points were recurrent stroke and all-cause death. Time to first event was analyzed by Cox proportional-hazards regression with adjustment for baseline variables (age, stroke type, systolic BP, and Scandinavian Stroke Scale score).

Baseline characteristics were well balanced between the 2 arms. At 3 years, there was no significant difference in the primary end point between the candesartan group (28.2%) and the placebo group (32.5%; adjusted HR, 0.87; 95% CI, 0.71 to 1.07; p=0.19).

There was no significant difference in the recurrent stroke rate between the candesartan group (16.9%) and the placebo group (adjusted HR, 0.83; 95% CI, 0.64 to 1.07; p=0.15) at 3 years. Similarly, no significant difference was observed in the rates of all-cause death in the candesartan group (17.9%) compared with the placebo group (18.8%; adjusted HR, 1.00; 95% CI, 0.77 to 1.30; p=1.00).

In this study, candesartan treatment during the acute phase of stroke in patients with elevated BP had no significant effect on the occurrence of vascular events, recurrent stroke, or death at 3 years. These results are consistent with the 6-month results and support the conclusion that there is no indication for routine BP-lowering treatment with candesartan in the acute phase of stroke.

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