Effect of perindopril on cerebral and renal perfusion in stroke patients with carotid disease.
OBJECTIVE
The purpose of this study was to investigate the effect of the angiotensin-converting enzyme inhibitor perindopril on mean arterial blood pressure (MABP), cerebral blood flow (CBF), and glomerular filtration rate in hypertensive stroke patients with moderate to severe internal carotid artery (ICA) disease or ICA occlusion.


METHODS
Twenty-four nonacute ischemic stroke patients who had MABP readings >100 mm Hg and moderate to severe ICA stenosis or occlusion were randomized to receive perindopril 4 mg daily or placebo for 14 days. MABP, ICA flow, and both middle cerebral artery (MCA) velocity and resistance index were measured before dose, at 5 time points over the subsequent 24 hours, and finally at 2 weeks. Brain hexamethyl propylene amine oxide single photon emission computed tomography scans were performed before drug administration and at time of peak drug effect (6 to 8 hours) after the first dose. Glomerular filtration rate was measured with (51)Cr EDTA before medication and at 14 days.


RESULTS
A placebo-corrected BP fall of 17/10 mm Hg was seen (P:=0.017), which was maximal at 5.5 hours. No significant change in ICA flow or MCA velocity was seen between groups. No significant change in hemispheric CBF was seen. The mean change from baseline in the treated group was -0.79 mL. 100 g(-1). min(-1) (95% confidence interval [CI], 1.65 to -3.23); mean change in the placebo group was -1.9 mL. 100 g(-1). min(-1) (95%CI, 3.02 to -6.92). Peri-infarct CBF was similarly unaffected. One of the treated patients developed transient acute renal impairment and was withdrawn from the study on day 4.


CONCLUSIONS
Perindopril lowers BP without lowering CBF in hypertensive stroke patients with moderate to severe ICA stenosis or occlusion; monitoring of this patient population for the complications of renal artery stenosis should be considered.
Walters
M R
MR
University Department of Medicine and Therapeutics, University of Glasgow, Glasgow, Scotland, UK. m.walters@clinmed.gla.ac.uk
Bolster
A
A
Dyker
A G
AG
Lees
K R
KR
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects; D002340:Carotid Artery Diseases / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000008:administration & dosage* / Q000009:adverse effects; D012079:Renal Circulation / Q000187:drug effects*; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D020913:Perindopril