The ACCESS Study

TLDR

Early neurohumoral inhibition with candesartan cilexetil is hypothesized to benefit stroke survivors by modestly lowering blood pressure, though the mechanisms of AT1 receptor blockade on cardiovascular outcomes remain unclear. The ACCESS study aimed to evaluate the safety of modest blood pressure reduction with candesartan cilexetil in early stroke treatment and to estimate the sample size needed for a future phase III efficacy trial. A prospective, double‑blind, placebo‑controlled, randomized, multicenter phase II trial enrolled 500 patients to assess candesartan cilexetil safety. The safety trial was halted early after 342 patients due to endpoint imbalance, yet candesartan cilexetil significantly lowered 12‑month mortality and vascular events (OR 0.475) without increasing hypotension‑related adverse events, indicating it is a safe early antihypertensive option.

Abstract

Background and Purpose— The Acute Candesartan Cilexetil Therapy in Stroke Survivors (ACCESS) study was designed to assess the safety of modest blood pressure reduction by candesartan cilexetil in the early treatment of stroke. The study was also designed to provide an estimate of the number of cases required to perform a larger phase III efficacy study. Methods— Five hundred patients were recruited in a prospective, double-blind, placebo-controlled, randomized, multicenter phase II study. Results— This safety trial was stopped prematurely when 342 patients (339 valid) had been randomized because of an imbalance in end points. Demographic data, cardiovascular risk factors, and blood pressure on admission, on study onset, and within the whole study period were not significantly different between the 2 groups. However, the cumulative 12-month mortality and the number of vascular events differed significantly in favor of the candesartan cilexetil group (odds ratio, 0.475; 95% CI, 0.252 to 0.895). There were no significant differences in concomitant medication and in number or type of side effects. Conclusions— Although the mechanisms by which angiotensin type 1 (AT 1 ) receptor blockade affects cardiovascular morbidity and mortality are still unresolved, the present study shows that early neurohumoral inhibition has similar beneficial effects in cerebral and in myocardial ischemia. The fact that no cardiovascular or cerebrovascular event occurred as a result of hypotension is of significant clinical importance. When there is need for or no contraindication against early antihypertensive therapy, candesartan cilexetil is a safe therapeutic option according to the ACCESS results.