title: Effects of blood pressure lowering in patients with acute ischemic stroke and carotid artery stenosis.
abstract: BACKGROUND
  The Scandinavian Candesartan Acute Stroke Trial (SCAST) showed no beneficial clinical effects of blood pressure lowering with the angiotensin receptor blocker candesartan in the acute phase of stroke. In the present analysis we wanted to see if the effects of blood pressure lowering are harmful in the subgroup of patients with carotid artery stenosis.
  
  
  METHODS
  SCAST was a randomized- and placebo-controlled, double-masked trial of 2029 patients with acute stroke and high systolic blood pressure (≥ 140 mmHg). Of 1733 patients with ischemic stroke 993 underwent carotid artery imaging, and the degree of stenosis was categorized as no/insignificant (0-49%, n = 806), moderate (50-69%, n = 97) or severe (≥ 70%, n = 90). The trial's two co-primary effect variables were the composite end-point of vascular death, stroke or myocardial infarction, and functional outcome at six-months, according to the modified Rankin Scale.
  
  
  RESULTS
  Among patients with moderate or severe carotid artery stenosis the vascular end-point occurred in 9 of 87 patients (10.3%) treated with candesartan and in 17 of 100 controls (17.0%), and there was no evidence of a different risk in patients with severe stenosis (adjusted hazard ratio 0.74, 95% confidence interval 0.28-1.96, P = 0.54). For functional outcome there was also no clear difference, although in patients with severe stenosis the risk of a poor outcome was somewhat higher than in any of the other groups (adjusted odds ratio 2.24, 95% confidence interval 0.71-7.09, P = 0.16). Progressive stroke also occurred more often in patients with carotid artery stenosis treated with candesartan (10 of 87 patients (11.5%) vs. 4 of 100 patients (4.0%)), with a trend towards an increased risk with increasing severity of stenosis (P-value for linear trend = 0.04).
  
  
  CONCLUSIONS
  There is no clear evidence that the effect of candesartan is qualitatively different in patients with carotid artery stenosis, but there are signals that patients with severe stenosis are at particularly high risk of stroke progression and poor functional outcome.
authors.affiliation: Dept of Neurology, Oslo University Hospital, Oslo, Norway.
authors.forename: Mirza
authors.initials: M
authors.lastname: Jusufovic
authors.forename: Else Charlotte
authors.initials: EC
authors.lastname: Sandset
authors.forename: Philip M W
authors.initials: PM
authors.lastname: Bath
authors.forename: Björn W
authors.initials: BW
authors.lastname: Karlson
authors.forename: Eivind
authors.initials: E
authors.lastname: Berge
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000150:complications; D016893:Carotid Stenosis / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012537:Scandinavian and Nordic Countries; D020521:Stroke / Q000150:complications* / Q000209:etiology; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan
keywords: acute stroke; blood pressure; candesartan; carotid stenosis; cerebral autoregulation