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Blood pressure-lowering treatment in acute intracerebral haemorrhage

Berge, Eivind

doi: 10.1097/HJH.0000000000000537

Department of Internal Medicine and Cardiology, Oslo University Hospital, Oslo, Norway

Correspondence to Eivind Berge, Department of Internal Medicine and Cardiology, Oslo University Hospital, Oslo, Norway. E-mail:

Acute intracerebral haemorrhage is a devastating disease, and there are few means to affect its natural course. The general principles of effective acute stroke care apply [1], but there are no specific treatments available, except perhaps surgical evacuation of selected haematomas [2]. Haemostatic treatment with factor VIIa inhibitors has shown disappointing results, although trials of other haemostatic agents are ongoing.

It was therefore a long hope coming through when the results of the second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) were presented in 2013 [3]. The study showed that early and intensive blood pressure-lowering treatment during the first 6 h of intracerebral haemorrhage was associated with improved functional outcome 3 months later. The trial just failed to show a statistically significant difference in the primary analysis of the dichotomous modified Rankin scale, but the more sensitive ordinal method gave a statistically significant result. Subsidiary analyses have also shown consistency of results, both for important secondary effect variables (such as quality of life), and in various subgroups of patients [3]. The trial has generally been interpreted as showing a positive effect of treatment, and has had an important influence on guidelines for treatment of high blood pressure in the acute phase of intracerebral haemorrhage [1].

Because INTERACT2 was not clearly positive by its primary analysis, and because it is so far the only large trial of its kind, it is reassuring to see that the results can be supported by other sources of evidence. In this issue of the Journal, authors from the Stroke Acute Management with Urgent Risk Factor Assessment and Improvement – Intracerebral Hemorrhage (SAMURAI-ICH) study have looked at the effects of blood pressure-lowering in a case series of 211 Japanese patients with intracerebral haemorrhage and systolic high blood pressure over 180 mmHg [4]. Patients were treated with intravenous nicardipine within 3 h of stroke onset, and the aim was to achieve a systolic blood pressure between 120 and 160 mmHg and to keep the pressure in that range during the first 24 h [5]. The study was well done and the blood pressure reduction was impressive: the median time to reach the target blood pressure was only 30 min, and the proportion of time with blood pressure within target range was nearly 80%. In the multivariable analysis reported in this issue, there are statistically significant associations between level of relative systolic blood pressure reduction and reduction in the risk of haematoma expansion and neurological deterioration in the acute phase and functional outcome at 3 months. Data on deaths are not reported.

The quality of the evidence from the SAMURAI-ICH study is clearly inferior to that of INTERACT2, by the small sample size (with imprecision of estimates), the selection of Japanese patients only (with questions about generalizability), the observational study design (with potential for observer bias) and the lack of a hard and important end-point such as death. Still, the study is valuable as an opportunity to test the robustness of the findings from INTERACT2, and, importantly, the study supports the INTERACT2 conclusions in all important respects.

The results from INTERACT2 and the SAMURAI-ICH study are applicable to a broad range of patients with intracerebral haemorrhage, and are therefore highly relevant for clinicians who treat patients with this disease. There are, however, unanswered questions, for example, related to the maximal time window for treatment to be effective. Many patients are admitted to hospital later than the first 3–6 h, and it is unknown whether, or to what extent, they will benefit from blood pressure-lowering treatment. Other trials have shown that treatment does no good if started many hours later, say, at around 18 [6] or 26 h [7]. There are also unanswered questions related to the optimal choice of drug and intensity of treatment, but the second Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH II) trial is ongoing [8] and will hopefully be able to confirm the results of INTERACT2 and the SAMURAI-ICH study, and answer some of the remaining questions.

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Conflicts of interest

There are no conflicts of interest.

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