LOS ANGELES – Routinely lowering blood pressure in patients with acute ischemic or hemorrhagic stroke results in no apparent long-term benefits.
Patients who received candesartan – an angiotensin receptor blocker – or placebo within the first week after a stroke had virtually the same cardiovascular, clinical, and functional outcomes 6 months later, Dr. Eivind Berge reported at a Feb. 11 press briefing during the International Stroke Conference.
In fact, said Dr. Berge, patients taking the drug experienced slightly – though not significantly – increased rates of poor outcomes. "When we looked at the secondary end points, we found a slight difference in favor of placebo," in most cardiovascular outcomes, he said, with placebo significantly better in the finding of stroke progression within 2 days.
"This was statistically significant with a P value of .04," said Dr. Berge, principal investigator of the Scandinavian Candesartan Acute Stroke Trial (SCAST).
Other trials have examined the effect of different antihypertensives on stroke outcome, but SCAST is the largest to date and the only one that has studied candesartan, said Dr. Berge, who is also an internist at the Oslo University Hospital. The study enrolled 2,029 patients with ischemic or hemorrhagic stroke.
All patients in the SCAST trial had a systolic blood pressure of at least 140 mm Hg within 30 hours of symptom onset. They were randomized to either candesartan (1,017) or placebo (1,012) and treated for 7 days. Patients taking the study drug began treatment at 4 mg and progressed to 16 mg on days 3-7.
The patients’ mean age was 71 years; at baseline, their mean systolic blood pressure was 171 mm Hg, and their mean diastolic pressure was 90 mm Hg. About 85% had suffered an ischemic stroke, while 14% had hemorrhagic strokes; the remaining patients had a transient ischemic attack.
The study had two primary end points: the combination of death or major disability according to the modified Rankin Scale (mRS) by 6 months, and the combination of vascular death, heart attack, or another stroke within 6 months.
Secondary end points were all-cause death, and additional cardiovascular outcomes, including another stroke, heart attack, stroke progression, symptomatic hypotension, renal failure, and symptomatic venous thromboembolism.
Candesartan lowered blood pressure almost immediately, Dr. Berge said. By the end of the treatment period, blood pressures in the active group dropped to a mean of 147/82, compared with 152/84 in the placebo group. "Blood pressure was lowered by a statistically significant amount [compared with placebo] by day 2. From day 4 onward, we saw more modest blood pressure reduction."
But, at 6 months, none of the primary composite end points were significantly different between the two groups. The adjusted analysis showed that the composite vascular end point occurred in 12% of the active group and 11% of the placebo group; the adjusted hazard ratio in both groups was 1.09.
There were similar numbers of patients in each of the seven mRS levels. The most frequent mRS level at 6 months was 1 (290 active and 317 placebo patients). An mRS of 0 was achieved by 175 active patients and 192 placebo patients, while 84 active and 78 placebo patents had died.
Nor were there any statistically significant differences in any of the secondary end points, with the exception of stroke progression within 2 days. This occurred in 6% of the candesartan patients and 4% of the placebo patients (risk ratio 1.47; P = .04).
Dr. Berge said the findings were in accord with 10 previous studies, none of which found a significant advantage to lowering blood pressure in acute stroke. "All of these previous studies were small trials of different blood pressure–lowering agents with 100 or fewer patients," Dr. Berge said. Therefore he says he believes further investigations are still warranted.
"There are two ongoing trials that we hope will clarify whether there are subgroups of patients or different approaches to blood pressure–lowering management where a treatment benefit can be obtained," he said.
The study was published simultaneously to Dr. Berge’s presentation at a press conference in the Feb. 11 issue of the Lancet (doi:10.1016/S0140-6736[11]60104-9).
The study was sponsored by the Southeastern Norway Regional Health Authority and Oslo University. Dr. Berge disclosed that he and some of the other authors had received speaker fees and other remuneration from AstraZeneca and Takeda but that none of these were related to candesartan.