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

ABSTRACT: Platelets play an important role in cardiovascular disease, and ?-blockers are often prescribed for cardiovascular disease prevention. ?-Blockers may directly affect platelet aggregation, because ?-adrenergic receptors are present on platelets. There is uncertainty about the existence and magnitude of an effect of ?-blockers on platelet aggregation. The aim of this study was to perform a systematic review and meta-analysis of the effect of ?-blockers on platelet aggregation.MEDLINE and EMBASE were searched until April 2014. Two reviewers independently performed data extraction and risk of bias assessment. Type of ?-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.We retrieved 31 studies (28 clinical trials and three observational studies). ?-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 ?-blockers decreased platelet aggregation more than selective nonlipophilic ?-blockers.Clinically used ?-blockers significantly reduce platelet aggregation. Nonselective lipophilic ?-blockers seem to reduce platelet aggregation more effectively than selective nonlipophilic ?-blockers. These findings may help to explain why some ?-blockers are more effective than others in preventing cardiovascular disease.

SUBMITTER: Bonten TN

PROVIDER: S-EPMC4243868 | biostudies-other | 2014 Nov

REPOSITORIES: biostudies-other

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

Bonten Tobias N TN Plaizier Chiara E I CE Snoep Jaap-Jan D JJ Stijnen Theo T Dekkers Olaf M OM van der Bom Johanna G JG

British journal of clinical pharmacology 20141101 5

<h4>Aims</h4>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.<h4>Meth ...[more]

PMID: 24730697

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Project description:Objective To investigate the efficacy and safety of alpha blockers in the treatment of patients with ureteric stones.Design Systematic review and meta-analysis.Data sources Cochrane Central Register of Controlled Trials, Web of Science, Embase, LILACS, and Medline databases and scientific meeting abstracts to July 2016.Review methods Randomized controlled trials of alpha blockers compared with placebo or control for treatment of ureteric stones were eligible. : Two team members independently extracted data from each included study. The primary outcome was the proportion of patients who passed their stone. Secondary outcomes were the time to passage; the number of pain episodes; and the proportions of patients who underwent surgery, required admission to hospital, and experienced an adverse event. Pooled risk ratios and 95% confidence intervals were calculated for the primary outcome with profile likelihood random effects models. Cochrane Collaboration's tool for assessing risk of bias and the GRADE approach were used to evaluate the quality of evidence and summarize conclusions.Results 55 randomized controlled trials were included. There was moderate quality evidence that alpha blockers facilitate passage of ureteric stones (risk ratio 1.49, 95% confidence interval 1.39 to 1.61). Based on a priori subgroup analysis, there seemed to be no benefit to treatment with alpha blocker among patients with smaller ureteric stones (1.19, 1.00 to 1.48). Patients with larger stones treated with an alpha blocker, however, had a 57% higher risk of stone passage compared with controls (1.57, 1.17 to 2.27). The effect of alpha blockers was independent of stone location (1.48 (1.05 to 2.10) for upper or middle stones; 1.49 (1.38 to 1.63) for lower stones). Compared with controls, patients who received alpha blockers had significantly shorter times to stone passage (mean difference -3.79 days, -4.45 to -3.14; moderate quality evidence), fewer episodes of pain (-0.74 episodes, -1.28 to -0.21; low quality evidence), lower risks of surgical intervention (risk ratio 0.44, 0.37 to 0.52; moderate quality evidence), and lower risks of admission to hospital (0.37, 0.22 to 0.64; moderate quality evidence). The risk of a serious adverse event was similar between treatment and control groups (1.49, 0.24 to 9.35; low quality evidence).Conclusions Alpha blockers seem efficacious in the treatment of patients with ureteric stones who are amenable to conservative management. The greatest benefit might be among those with larger stones. These results support current guideline recommendations advocating a role for alpha blockers in patients with ureteric stones.Systematic review registration PROSPERO registration No CRD42015024169.

Project description:BackgroundPreclinical and retrospective studies suggest that beta-blockers are active against breast cancer. We carried out a systematic review and meta-analysis to assess the impact of beta-blockers on the outcomes of patients with early-stage breast cancer.MethodsA systematic literature search was performed to identify studies comparing outcomes of patients with early-stage breast cancer according to beta-blocker use (yes versus no). The primary endpoint was recurrence-free survival (RFS), defined as the occurrence of breast cancer recurrence or death. Secondary objectives were pathologic complete response (pCR), breast cancer recurrence, breast cancer-specific mortality and overall survival (OS). Hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were extracted from each study and a pooled analysis with the random-effect model was conducted. The Higgins' I-squared test was used to quantify heterogeneity. Egger's test was applied to assess publication bias. All P values were two-sided and considered significant if ≤0.05.ResultsOverall, 13 studies were included as follows: RFS (6), pCR (2), breast cancer recurrence (6), breast cancer-specific mortality (7) and OS (5). The use of beta-blockers was associated with a significant RFS improvement in the overall population (N = 21 570; HR 0.73; 95% CI, 0.56-0.96; P = 0.025) and in patients with triple-negative disease (N = 1212; HR 0.53; 95% CI, 0.35-0.81; P = 0.003). No significant differences in terms of pCR (N = 1554; OR 0.77; 95% CI, 0.44-1.36; P = 0.371), breast cancer recurrence (N = 37 957; OR 0.66; 95% CI, 0.42-1.03; P = 0.065), breast cancer-specific mortality (N = 64 830; HR 0.77; 95% CI, 0.56-1.08; P = 0.130) or OS (N = 103 065; HR 1.03; 95% CI, 0.87-1.23; P = 0.692) were observed according to beta-blocker use.DiscussionIn this meta-analysis, beta-blocker use was associated with a longer RFS in patients with early-stage breast cancer, with a more pronounced effect observed in those with triple-negative disease. Beta-blockers arise as an interesting option to be explored in prospective studies for patients with early-stage breast cancer.

Project description:AimPeripheral vasoconstriction has long been described as a vascular adverse effect of ?-adrenoceptor blockers. Whether ?-adrenoceptor blockers should be avoided in patients with peripheral vascular disease depends on pharmacological properties (e.g. preferential binding to ?1 -adrenoreceptors or intrinsic sympathomimetic activity). However, this has not been confirmed in experimental studies. We performed a network meta-analysis in order to assess the comparative risk of peripheral vasoconstriction of different ?-adrenoceptor blockers.MethodWe searched for randomized controlled trials (RCTs) including ?-adrenoceptor blockers that were published in core clinical journals in the Pubmed database. All RCTs reporting peripheral vasoconstriction as an adverse effect of ?-adrenoceptor blockers and controls were included. Sensitivity analyses were conducted including possibly confounding covariates (latitude, properties of the ?-adrenoceptor blockers, e.g. intrinsic sympathomimetic activity, vasodilation, drug indication, drug doses). The protocol and the detailed search strategy are available online (PROSPERO registry CRD42014014374).ResultsAmong 2238 records screened, 38 studies including 57?026 patients were selected. Overall, peripheral vasoconstriction was reported in 7% of patients with ?-adrenoceptor blockers and 4.6% in the control groups (P < 0.001), with heterogeneity among drugs. Atenolol and propranolol had a significantly higher risk than placebo, whereas pindolol, acebutolol and oxprenolol had not.ConclusionOur results suggest that ?-adrenoceptor blockers have variable propensity to enhance peripheral vasoconstriction and that it is not related to preferential binding to ?1 -adrenoceptors. These findings challenge FDA and European recommendations regarding precautions and contra-indications of use of ?-adrenoceptor blockers and suggest that ?-adrenoceptor blockers with intrinsic sympathomimetic activity could be safely used in patients with peripheral vascular disease.

Dataset Information

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

Publications

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

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