Editorial Comment—Persisting Dilemma: To Treat or Not to Treat Blood Pressure in Acute Ischemic Stroke
Treatment of blood pressure in acute stroke is controversial, whether attempts are made to reduce or to increase blood pressure. Few clinical studies are available to guide clinicians. A Cochrane review1 on deliberately altering blood pressure within 2 weeks of stroke onset found 5 small trials, involving 218 patients randomized to nimodipine, nicardipine, captopril, clonidine, glyceryl trinitrate, or perindopril versus placebo or control treatment. The limited number of data made it impossible to assess the relationship between blood pressure and clinical outcome.
Ahmed et al2 made a post hoc analysis on the effect of intravenous nimodipine in acute ischemic stroke within 24 hours. They found that a reduction of diastolic blood pressure of about 15 mm Hg was associated with poor outcome, whereas a spontaneous fall in the placebo group of about 8 mm Hg was associated with a better outcome.
In this issue of Stroke, Castillo et al found that a fall in systolic blood pressure of more than 20 mm Hg was associated with neurological deterioration and poor outcome. This was an observational study in 258 acute stroke patients, of whom many had their blood pressure lowered. Antihypertensive treatment was started already in the emergency department by other doctors than those involved in the study. The blood pressure–lowering treatment was given according to international guidelines, which, however, are based on reasoning rather than on evidence. Antihypertensive drugs were given to 38.7% of patients with early neurological deterioration versus 16.9% in those without deterioration, P<0.05. In patients with poor outcome, antihypertensive drugs were given to 30.1% versus 9.5% in patients with good outcome, P<0.05.
The findings seem to agree with those of Ahmed et al,2 while they are at variance with those of Chamorro et al,3 who found that a 20% to 30% drop in mean arterial blood pressure on day 2 after stroke onset almost tripled the odds of full recovery with no indication of adverse effect of hypotensive agents.
In an observational study of 759 patients with acute ischemic stroke, Christensen et al4 found that a spontaneous fall in blood pressure within the first 4 hours after admission was associated with good outcome. A partial explanation of the divergent results might be that a spontaneous fall in blood pressure is a benign change in contrast to an induced fall in blood pressure. This notion is supported by a Cochrane review5 on the effect of calcium antagonists for acute ischemic stroke, in which intravenous administration of calcium antagonists was associated with poor outcome compared to placebo.
Further, Castillo et al found a U-shaped association between blood pressure and outcome with a systolic blood pressure of 180 mm Hg being the optimal. A U-shape was also found in the International Stroke Trial (IST),6 but here the optimal blood pressure was around 150 mm Hg. The IST being so much larger is likely to yield the more robust data. However, analysis of the GAIN International Trial7 in 1455 patients with acute ischemic stroke did not find a U-shape of the relation between blood pressure and outcome. Neither was a 30% decrease in mean arterial pressure from baseline associated with outcome. If the U-shape relation is real, it may reflect cardiac failure being more important in those with low systolic blood pressure and an adverse effect on brain edema in those with very high blood pressure.
In agreement with most guidelines, antihypertensive treatment in acute stroke should probably be restricted to those in the high range of systolic blood pressure. Due to the tendency for the blood pressure to fall spontaneously within the first hours after admission, antihypertensive treatment might be delayed for 8 to 12 hours, if earlier treatment is not required as for instance in patients suitable for thrombolysis. Presumably, antihypertensive treatment needs to be tailored individually. It is unlikely that there will be one treatment for all.
There is an urgent need for a sufficiently large randomized clinical trial on antihypertensive treatment in acute stroke in order to solve the dilemma.8
Blood pressure in acute stroke collaboration (BASC). Interventions for deliberately altering blood pressure in acute stroke. The Cochrane Library, Issue 3, 2003. Oxford: Update Software; 2003.
Ahmed N, Näsman P, Wahlgren NG. Effect of intravenous nimodipine on blood pressure and outcome after acute stroke. Stroke. 2000, 131: 1250–1255.
Chamorro A, Vila N, Ascaso C, Elices E, Schonewille W, Blanc R. Blood pressure and functional recovery in acute ischemic stroke. Stroke. 1998; 29: 1850–1853.
Horn J, Limburg M. Calcium antagonists for acute ischemic stroke (Cochrane Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software; 2003.
Leonardi-Bee J, Bath PMW, Philips SJ, Sandercock PAG, for the IST Collaborative Group. Blood pressure and clinical outcomes in the international stroke trial. Stroke. 2002; 33: 1315–1320.
Aslanyan S, Fazekas F, Weir CJ, Horner S, Lees KR. For the GAIN International Steering Committee and Investigators. Effect of blood pressure during the acute period of ischemic stroke on stroke outcome: a tertiary analysis of the GAIN International Trial. Stroke. 2003; 34: 2420–2425.
Bath PM. Efficacy of Nitric Oxide in Stroke (ENOS) Trial. Stroke. 2001; 32: 2450–2451.Abstract.