Effects of antihypertensive treatment after acute stroke in the Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial.
Robinson TG., Potter JF., Ford GA., Bulpitt CJ., Chernova J., Jagger C., James MA., Knight J., Markus HS., Mistri AK., Poulter NR., COSSACS Investigators None.
BACKGROUND: Up to 50% of patients with acute stroke are taking antihypertensive drugs on hospital admission. However, whether such treatment should be continued during the immediate post-stroke period is unclear. We therefore aimed to assess the efficacy and safety of continuing or stopping pre-existing antihypertensive drugs in patients who had recently had a stroke. METHODS: The Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS) was a UK multicentre, prospective, randomised, open, blinded-endpoint trial. Patients were recruited at 49 UK National Institute for Health Research Stroke Research Network centres from January 1, 2003, to March 31, 2009. Patients aged over 18 years who were taking antihypertensive drugs were enrolled within 48 h of stroke and the last dose of antihypertensive drug. Patients were randomly assigned (1:1) by secure internet central randomisation to either continue or stop pre-existing antihypertensive drugs for 2 weeks. Patients and clinicians who randomly assigned patients were unmasked to group allocation. Clinicians who assessed 2-week outcomes and 6-month outcomes were masked to group allocation. The primary endpoint was death or dependency at 2 weeks, with dependency defined as a modified Rankin scale score greater than 3 points. Analysis was by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Register, number ISRCTN89712435. FINDINGS: 763 patients were assigned to continue (n=379) or stop (n=384) pre-existing antihypertensive drugs. 72 of 379 patients in the continue group and 82 of 384 patients in the stop group reached the primary endpoint (relative risk 0.86, 95% CI 0.65-1.14; p=0.3). The difference in systolic blood pressure at 2 weeks between the continue group and the stop group was 13 mm Hg (95% CI 10-17) and the difference in diastolic blood pressure was 8 mm Hg (6-10; difference between groups p<0.0001). No substantial differences were observed between groups in rates of serious adverse events, 6-month mortality, or major cardiovascular events. INTERPRETATION: Continuation of antihypertensive drugs did not reduce 2-week death or dependency, cardiovascular event rate, or mortality at 6 months. Lower blood pressure levels in those who continued antihypertensive treatment after acute mild stroke were not associated with an increase in adverse events. These neutral results might be because COSSACS was underpowered owing to early termination of the trial, and support the continuation of ongoing research trials. FUNDING: The Health Foundation and The Stroke Association.