Vasoactive drugs for acute stroke.
BACKGROUND
It is unclear whether blood pressure should be managed after acute stroke and if so whether it is best to reduce or increase blood pressure.


OBJECTIVE
The objective of this review was to assess the effect of lowering or elevating blood pressure in people with acute stroke, and the effect of different vasoactive drugs on blood pressure in acute stroke.


METHODS
We searched the Cochrane Library (1999 Issue 1) using the CDSR and the CCTR databases, MEDLINE (from 1966), EMBASE (from 1980), BIDS ISI (Science Citation Index from 1981), and existing review articles. We contacted researchers in the field and pharmaceutical companies.


METHODS
Randomised trials of interventions that would be expected, on pharmacological grounds, to alter blood pressure in patients within two weeks of the onset of acute ischaemic or haemorrhagic stroke.


METHODS
Two reviewers independently applied the trial inclusion criteria, assessed trial quality, and extracted the data.


RESULTS
Sixty five trials were identified involving in excess of 11,500 patients; a further 5 trials are ongoing. Data were obtained for 32 trials (5,368 patients). Significant imbalances in baseline blood pressure were present across trials of intravenous calcium channel blockers and prostacyclin. Major imbalances in baseline blood pressure between treatment and control groups have made the interpretation of these results difficult. Intravenous calcium channel blockers (CCBs) and oral CCBs significantly lowered late blood pressure as compared to controls. (systolic/diastolic BP): iv CCBs -8.2/-6.7 mm Hg (95% CI -12.6 to -3.8)/ (95% CI -9.2 to -4.3); oral CCBs -3.2/-2.1 mm Hg (95% CI -5.0 to -1.3)/ (95% CI -3.0 to -1.0). Beta blockers significantly lowered late diastolic blood pressure but not significantly late systolic blood pressure; -5.0/-4.5 mm Hg (95% CI -10.2 to 0.4)/(95% CI -7.8 to -1.15). Angiotensin converting enzyme inhibitors and prostacyclin non-significantly reduced late BP as compared to the controls by -5.4/-3.0 mm Hg (95% CI -16.5 to 5.8)/(95% CI -11.1 to 5.0) and -7.4/-3.9 mmHg (95% CI -15.6 to 0.2)/(95% CI -8.1 to 0.4) respectively. Magnesium, naftidrofuryl and piracetam had no significant effect on blood pressure. Oral CCBs and beta blockers each significantly reduced late heart rate (beats per minute (bpm)): CCBs -2.8 bpm (95%CI -3.9 to -1.7); beta blockers -9.3 bpm (95% CI -12.0 to -6.6). Prostacyclin significantly increased late heart rate by +5.6 bpm (95% CI 0.8 to 10.4). None of the drug classes significantly altered outcome apart from beta blockers and streptokinase which increased early case fatality (odds ratio 1.77, 95%CI, 1.05 to 3.00) and 2.27 (95% CI 1.4 to 3.67).


CONCLUSIONS
There is not enough evidence reliably to evaluate the effect of altering blood pressure on outcome after acute stroke. CCBs, beta blockers, and probably ACE-inhibitors, prostacyclin and nitric oxide, each lowered BP during the acute phase of stroke. In contrast, magnesium, naftidrofuryl and piracetam had little or no effect on BP.
Division of Stroke Medicine, University of Nottingham, City Hospital Campus, Hucknall Road, Nottingham, Nottinghamshire, UK, NG5 1PB. philip.bath@nottingham.ac.uk
D000284:Administration, Oral; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D011464:Epoprostenol / Q000627:therapeutic use; D006801:Humans; D007275:Injections, Intravenous; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D014665:Vasodilator Agents / Q000627:therapeutic use
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D011464:Epoprostenol