Effect of β-blockers on platelet aggregation: a systematic review and meta-analysis

Abstract

Aims: Platelets play an important role in cardiovascular disease, and β-blockers are often prescribed for cardiovascular disease prevention. β-Blockers may directly affect platelet aggregation, because β-adrenergic receptors are present on platelets. There is uncertainty about the existence and magnitude of an effect of β-blockers on platelet aggregation. The aim of this study was to perform a systematic review and meta-analysis of the effect of β-blockers on platelet aggregation.

Methods: MEDLINE and EMBASE were searched until April 2014. Two reviewers independently performed data extraction and risk of bias assessment. Type of β-blocker, population, treatment duration and platelet aggregation were extracted. Standardized mean differences were calculated for each study and pooled in a random-effects meta-analysis.

Results: We retrieved 31 studies (28 clinical trials and three observational studies). β-Blockers decreased platelet aggregation (standardized mean difference -0.54, 95% confidence interval -0.85 to -0.24, P < 0.0001). This corresponds to a reduction of 13% (95% confidence interval 8-17%). Nonselective lipophilic β-blockers decreased platelet aggregation more than selective nonlipophilic β-blockers.

Conclusions: Clinically used β-blockers significantly reduce platelet aggregation. Nonselective lipophilic β-blockers seem to reduce platelet aggregation more effectively than selective nonlipophilic β-blockers. These findings may help to explain why some β-blockers are more effective than others in preventing cardiovascular disease.

Keywords: meta-analysis; platelet aggregation; β-blockers.

Figure 1

Flow chart of study selection. *Conditions affecting platelet aggregation: physical or psychological stress, acute cardiovascular disease or pregnancy. †In vitro was defined as studies in which β-blockers were added after blood drawing. ‡No outcome measures and/or no measure of variability (SE or SD), t statistic or exact P value reported

Figure 2

Effect of β-blockers on platelet aggregation by agonists. Forest plot of standardized mean differences (SMD) of the effects of β-blockers on platelet aggregation by different agonists. Abbreviations are as follows, ADP, adenosine diphosphate; CI, confidence interval. *Median (interquartile range) concentrations of the used agonists. Thrombin was used only for measurement of threshold concentration platelet aggregation

Figure 3

Overall effect over β-blockers on platelet aggregation. Forest plot of standardized mean differences (SMD) of the effects of β-blockers on platelet aggregation. The black diamonds represent the effect estimate (SMD), where a negative SMD represents a decrease of platelet aggregation. The size of the grey squares around the effect estimates corresponds to the weight of the study in the meta-analysis. Horizontal lines represent corresponding 95% confidence intervals (CI). The estimate and CI of the pooled effect is indicated by the diamond

Figure 4

Subgroup analyses. Forest plot of standardized mean differences (SMD) of the effects of subgroups β-blockers on platelet aggregation. The effect estimates and CI of each subgroup are indicated by the diamonds. Subgroups are as follows: selective (metoprolol and atenolol); nonselective (propranolol, labetalol, timolol and carvedilol); lipophilic (propranolol, labetalol, timolol, metoprolol and carvedilol); nonlipophilic (atenolol); healthy subjects; diseased subjects (hypertension, coronary artery disease, diabetes or previous myocardial infarction); short-term treatment (<1 week); and long-term treatment (>1 week)

Figure 5

Funnel plot of all included studies. Two studies with extreme effects are the studies of Campbell [26] (1981; SMD −8) and Frishman [25] (1978; SMD −6.5)