The Consensus Statement includes two parts, the Consensus Statement itself, and the Recommendation to the European Stroke Organisation (ESO) on revision of ESO Guidelines. Please note that the final text of the Guidelines, is decided by ESO and that the recommendation in this document may not be the final guidelines version. As soon as the guidelines are confirmed, they will appear on this website as well as on the ESO website www.eso-stroke.org

A. Karolinska Stroke Update Consensus Statement

Blood pressure management in the acute phase of stroke

The following Consensus Statement was adopted by the 7th Karolinska Stroke Update meeting on November 18, 2008.

The consensus statement was proposed by the chairman of the session, Professor Jacques De Keyser, Brussels, the co-chair Professor László Csiba, Debrecen, and the session secretary Dr Magnus Thorén, Stockholm, together with the speakers of the session. The statement was then finally approved by the participants of the meeting, after listening to the different presentations.
The speakers in this session were Professor Philip Bath, Nottingham, and Dr Niaz Ahmed. Stockholm.

Controversies to discuss at the 2008 consensus session:

• In acute ischemic stroke: should previous antihypertensive drugs be continued or stopped temporarily?
• If antihypertensive drugs are required in acute ischemic stroke, which type(s) of drugs should be used?
• Does early treatment with antihypertensive drugs improve outcome post-ischemic stroke?
• Should we lower blood pressure more aggressively in hemorrhagic stroke?

Background

Blood pressure management in the early phase of stroke (within 7 days) is still a debated issue. Both high blood pressure and low blood pressure in acute ischemic stroke are independent prognostic factors for poor outcome [1]. It remains unclear whether blood pressure in acute ischemic stroke should be modified, and if so, what would be the optimal range.

Discussion

In acute ischemic stroke: should previous antihypertensive drugs be continued or stopped temporarily?

High blood pressure in acute ischemic stroke may improve cerebral blood flow and outcome, as suggested by animal experiments and small proof-of-concept studies in patients [2]. In many centers it is common practice either to continue or to stop antihypertensive drugs temporarily.

Many questions are still unanswered about the safety and potential benefits of this method.

Two RCTs investigate the effects on outcome of stopping versus continuing previous antihypertensive treatment: the Continue Or Stop post-Stroke Antihypertensives Collaborative Study (COSSACS, 2900 patients)[3[, and Efficacy of Nitric Oxide in Stroke (ENOS, 2500 patients) trial [4]. Until these results are available, it is under the judgement of the treating physician whether to continue or stop antihypertensive drugs in the patient with acute ischemic stroke. Result from SITS study and PRoFESS trial presented during the meeting will add new knowledge on this issue.

If antihypertensive drugs are required in acute ischemic stroke, which type(s) of drugs should be used?

ESO guidelines suggest that cautious blood pressure lowering is recommended in patients with extremely high blood pressures (>220/120 mmHg) on repeated measurements, or with other severe medical problems, including severe cardiac failure, aortic dissection or hypertensive encephalopathy. Previous studies suggest that there is potential for differential benefit or harm between classes of antihypertensive medication used during the acute phase of ischemic stroke. Dysphagia is common is acute stroke, and in these cases oral medication may be difficult to administer.

The use of sublingual nifedipine can result in an abrupt decrease in blood pressure [5]. In the BEST Study (302 patients), treatment with atenolol or propranolol was associated with a trend to increased death. However, patients that had been taking beta-blockers at the time of their stroke had better outcome [6]. A meta-analysis on the use of calcium antagonists showed no overall effect on death or dependency [7, 8]. However, in one study (INWEST, 295 patients), intravenous nimodipine was significantly associated with a poor outcome [9].
 
Labetalol, urapidil, nitroglycerin (glyceryl trinitrate), and captopril are commonly used in hypertensive emergencies [10], but there are no completed large RCTs supporting their use in acute stroke.

Does early treatment with antihypertensive drugs improve outcome post-ischemic stroke?

Analyses of IST (18000 patients) confirmed that in the first two days after stroke the majority of patients have a high blood pressure and that this is associated with poor outcome and a higher risk of recurrence within 14 days, especially if the SBP >200 mmHg [1]

The angiotensin receptor type 1 blocker candesartan was used in the ACCESS study, including 339 hypertensive patients (BP>200 systolic and/or >110 diastolic pressure) within 30 hours (median) after stroke. Although no effect on death or disability (primary outcome) was seen, the number of deaths and vascular events at 1 year were significantly fewer among candesartan-treated patients (Grade C evidence).

Does early treatment with antihypertensive drugs improve outcome post-ischemic stroke?

The EUSI recommendation in 2003 was that routine blood pressure lowering is not required, except for extremely elevated values (>180/105 mmHg) confirmed by repeated measurements.

About 1/3 of patients with intracerebral hemorrhage demonstrate hematoma expansion in the first few hours after onset [9] More aggressively blood pressure reduction may lower the rate of hematoma expansion. Blood pressure reduction < 140 mm Hg was the goal of a RCT “Intensive blood pressure reduction in acute cerebral hemorrhage trial” (INTERACT, 404 patients)[10]. The target blood pressure of 140 mm Hg was well tolerated and reduced hematoma expansion, although non-significantly, and there was no measurable effect on functional outcome. This question is being further investigated in the large INTERACT 2 RCT (3000 patients).

Conclusion

Acute ischemic stroke

1. It is recommended that blood pressures of 185/110 mmHg or higher is lowered before thrombolysis. Blood pressure should be maintained below this level during and immediately after thrombolysis (Class IV, GCP)
2. Routine blood pressure lowering is not recommended following acute stroke (Class IV, GCP)
3. Cautious blood pressure lowering is recommended in patients with extremely high blood pressures (>220/120 mmHg) on repeated measurements, with severe cardiac failure, aortic dissection or hypertensive encephalopathy (Class IV, GCP)
4. It is recommended that abrupt blood pressure lowering be avoided (Class II, Level C)
5. It is recommended that low blood pressure secondary to hypovolemia or associated with neurological deterioration in acute stroke should be treated with volume expanders (Class IV,GCP)

Haemorrhagic stroke

Routine blood pressure lowering is not recommended, except for extremely elevated values (>180/105 mmHg) confirmed by repeated measurements.

In conclusion, there is not sufficient evidence to make new ESO recommendations on these issues at this point.

References:

1.      Leonardi-Bee J, Bath PM, Phillips SJ, Sandercock PA. Blood pressure and clinical outcomes in the International Stroke Trial. Stroke 2002; 33, 1315-1320.

2.      Mistri AK, Robinson TG, Potter JF. Pressor therapy in acute ischemic stroke: systematic review. Stroke 2006; 37, 1565-1571.

3.      COSSACS (Continue or Stop post-Stroke Antihypertensives Collaborative Study): rationale and design. J Hypertens 2005; 23, 455-458.

4.      Glyceryl trinitrate vs. control, and continuing vs. stopping temporarily prior antihypertensive therapy, in acute stroke: rationale and design of the Efficacy of Nitric Oxide in Stroke (ENOS) trial (ISRCTN99414122). Int J Stroke 2006; 1, 245-249.

5.     Grossman E, Messerli FH, Grodzicki T, Kowey P. Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergencies? JAMA 1996; 276, 1328-1331.

7.      Horn J, Limburg M. Calcium Antagonists for Ischemic Stroke. Stroke 2001; 32, 570-576.

8.     Horn J, Limburg M. Calcium antagonists for acute ischemic stroke. Cochrane Database of Systematic Reviews 2000, Issue 1. Art. No.: CD001928. DOI: 10.1002/14651858.CD001928

9.     Ahmed N, Nasman P, Wahlgren NG: Effect of intravenous nimodipine on blood pressure and outcome after acute stroke. Stroke 2000:31:1250-55.

10.      Klijn CJ, Hankey GJ. Management of acute ischaemic stroke: new guidelines from the American Stroke Association and European Stroke Initiative. Lancet Neurol 2003; 2, 698-701.

11.      Davis SM, Broderick J, Hennerici M et al. Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology 2006; 66, 1175-1181.

12.    Anderson CS, Huang Y, Wang JG et al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol 2008; 7, 391-399.

B. Recommendation by Karolinska Stroke Update participants to ESO Guidelines Committee to revise ESO guidelines:

No changes of the current ESO guidelines were suggested.