Stroke prevention in patients without coronary heart disease: A link with antihypertensive treatment effect on angiotensin and sympathetic systems ?

Abstract

HOPE trial has shown that in patients with a high prevalence of coronary heart disease (CHD = 80 %) an angiotensin converting enzyme inhibitor (ACEI) decreases the risk of stroke beyond what is expected from the BP-reduction. The objective of this study is to see whether suppression of the renin-angiotensin and/or sympathetic systems (RA/SS) by antihypertensive drugs also gives such a protection in primary or secondary stroke prevention trials in which patients have a low initial prevalence (<30 %) of CHD. All the large randomized primary prevention trials in mild hypertension published since 1985 as well as the 2 recent large secondary stroke prevention trials (PATS and PROGRESS) were reviewed. The BP-independent stroke risk change was calculated by substracting, from the stroke risk change observed in the trial, the risk change expected from the BP change. This latter was calculated from the log-linear relation between stroke risk and diastolic BP established by MacMahon in cohort studies of individuals without initial cardiovascular complications and from the relation established by Rodgers et al in the patients of the UKTIA trial showing that 10 mmHg SBP decrease is expected to reduce the stroke recurrence risk by 28 %. The trials were then classified as giving RA/SS-stimulation if diuretics or calcium antagonists were compared to placebo, betablockers or ACEI (which decrease angiotensin II formation) or to alpha 1 blockers (which are neutral). When the reverse comparison was made the trial was considered as RASS-suppressing. Trials comparing associations of 2 drugs with opposite effect on RASS to placebo or to similar associations were considered as having a neutral effect on RASS. In hypertension primary prevention trials, median of DBP-independent stroke risk change was significantly higher in trials with RASS-suppression (+18%;p=0.006) or with neutral effect on RASS (+10%;p=0.02) than in trials with RASS stimulation (−16 %). In secondary stroke prevention trials the SBP-independent stroke risk change was significantly higher with perindopril alone (+9 %; p=0.01), or with the combination perindopril + indapamide (−9 %; p<0.05) than with indapamide alone (−15 %). In patients without high prevalence of CHD, stroke prevention is worse when RASS are not activated by the antihypertensive treatment.