Beta-blockers reduce the risk of early death in ischemic stroke

doi:10.1016/j.jns.2006.10.007

Journal of the Neurological Sciences

Volume 252, Issue 1, January 2007, Pages 53-56

https://doi.org/10.1016/j.jns.2006.10.007 Get rights and content

Abstract

Objectives

Beta-blockers reduce mortality in patients after myocardial infarction. Experimental studies suggest that beta-blockers have also neuroprotective properties. The aim of this study was to assess if use of beta-blockers is associated with reduced risk of early death in ischemic stroke patients.

Materials and methods

Retrospective data analysis of 841 consecutive patients with acute ischemic stroke admitted to the stroke unit within 24 h after stroke onset.

Results

10.6% of patients received beta-blockers during hospitalization. Thirty-day case fatality was significantly lower in patients treated with beta-blockers than in those not treated with beta-blockers (6.8% versus 19.0%, P<0.01). After adjustment for other prognostic factors, the use of beta-blockers was associated with reduced risk of early death (relative hazard 0.37, 95% confidence interval 0.16–0.84) independently of age, stroke severity, fasting glucose, total cholesterol level and pneumonia. When patients who died of cardiovascular causes were excluded from the analysis, the use of beta-blocker was no longer significantly associated with risk of death (P = 0.12).

Conclusion

In a retrospective series the use of beta-blockers was associated with reduced risk of early death in patients with ischemic stroke.

Introduction

Many studies have demonstrated the cardioprotective properties of beta-blockers in patients who survived an acute myocardial infarction [1]. Beta-blockers are effective in long-term secondary prevention after myocardial infarction reducing mortality and morbidity [2]. Results of experimental studies suggest that older (propranolol) and newer (carvedilol) beta-blockers could be neuroprotective against glutamate-induced cell death and against focal cerebral ischemia by inhibiting apoptosis and attenuating inflammatory reaction [3], [4], [5], [6], [7].

The aim of our study was to assess if use of beta-blockers in acute phase of ischemic stroke is associated with reduced the risk of early death.

Section snippets

Materials and methods

We analyzed retrospectively our stroke database. Patients to this study were recruited from 841 consecutive patients with ischemic stroke admitted to our stroke unit within 24 h after stroke onset in years 1994–1997. We choose that time period, because in years 1994–1997 we have collected information about beta-blockers use and 30-day case fatality for all patients. For patients who died after discharge from the hospital, the information about 30-day case fatality and cause of death were taken

Results

In years 1994–1997 we hospitalized 841 patients with ischemic stroke admitted to our stroke unit within 24 h after stroke onset. Eight patients had inadequate data for analysis because of immediate death. Thus, complete data were available for 833 patients (mean age: 69.6 ± 12.6; 46.7% men).

Eighty eight from 833 (10.6%) patients received beta-blockers during hospitalization. 94.3% of them were treated with beta-blocker before admission. These patients continued therapy with beta-blockers during

Discussion

We found that therapy with beta-blockers significantly reduced 30-day case fatality in patients with ischemic stroke.

There is no established biological mechanism that explains completely the beneficial effect of beta-blockers during ischemic stroke. The results of our study suggest that beta-blockers decrease the risk of death in stroke patients by reducing number of deaths due to cardiovascular events such as myocardial infarction, heart failure or sudden death. When we excluded from the

References (16)

V. Junker et al.
Stimulation of beta-adrenoceptors activates astrocytes and provides neuroprotection
Eur J Pharmacol
(2002)
J.M. Bamford et al.
Classification and natural history of clinically identifiable subtypes of cerebral infarction
Lancet
(1991)
F. Borrello et al.
Reappraisal of beta-blocker therapy in the acute and chronic post-myocardial infarction period
Rev Cardiovasc Med
(2003)
N. Freemantle et al.
Beta blockade after myocardial infarction: systematic review and meta regression analysis
BMJ
(1999)
M. Standefer et al.
Improved neurological outcome in experimental focal cerebral ischemia treated with propranolol
Neurosurgery
(1986)
P.G. Lysko et al.
Neuroprotective effects of carvedilol, a new antihypertensive agent, in cultured rat cerebellar neurons and in gerbil global brain ischemia
Stroke
(1992)
S.I. Savitz et al.
The novel beta-blocker, carvedilol, provides neuroprotection in transient focal stroke
J Cereb Blood Flow Metab
(2000)
K. Yamagata et al.
Amlodipine and carvedilol prevent cytotoxicity in cortical neurons isolated from stroke-prone spontaneously hypertensive rats
Hypertens Res
(2004)

There are more references available in the full text version of this article.

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View full text

Beta-blockers reduce the risk of early death in ischemic stroke

Abstract

Objectives

Materials and methods

Results

Conclusion

Introduction

Section snippets

Materials and methods

Results

Discussion

Eur J Pharmacol

Lancet

Reappraisal of beta-blocker therapy in the acute and chronic post-myocardial infarction period

Rev Cardiovasc Med

Beta blockade after myocardial infarction: systematic review and meta regression analysis

BMJ

Improved neurological outcome in experimental focal cerebral ischemia treated with propranolol

Neurosurgery

Neuroprotective effects of carvedilol, a new antihypertensive agent, in cultured rat cerebellar neurons and in gerbil global brain ischemia

Stroke

The novel beta-blocker, carvedilol, provides neuroprotection in transient focal stroke

J Cereb Blood Flow Metab

Amlodipine and carvedilol prevent cytotoxicity in cortical neurons isolated from stroke-prone spontaneously hypertensive rats

Hypertens Res