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The Cochrane Database of Systematic... Jul 2023Different first-line drug classes for patients with hypertension are often assumed to have similar effectiveness with respect to reducing mortality and morbidity... (Review)
Review
BACKGROUND
Different first-line drug classes for patients with hypertension are often assumed to have similar effectiveness with respect to reducing mortality and morbidity outcomes, and lowering blood pressure. First-line low-dose thiazide diuretics have been previously shown to have the best mortality and morbidity evidence when compared with placebo or no treatment. Head-to-head comparisons of thiazides with other blood pressure-lowering drug classes would demonstrate whether there are important differences.
OBJECTIVES
To compare the effects of first-line diuretic drugs with other individual first-line classes of antihypertensive drugs on mortality, morbidity, and withdrawals due to adverse effects in patients with hypertension. Secondary objectives included assessments of the need for added drugs, drug switching, and blood pressure-lowering.
SEARCH METHODS
Cochrane Hypertension's Information Specialist searched the Cochrane Hypertension Specialized Register, CENTRAL, MEDLINE, Embase, and trials registers to March 2021. We also checked references and contacted study authors to identify additional studies. A top-up search of the Specialized Register was carried out in June 2022.
SELECTION CRITERIA
Randomized active comparator trials of at least one year's duration were included. Trials had a clearly defined intervention arm of a first-line diuretic (thiazide, thiazide-like, or loop diuretic) compared to another first-line drug class: beta-blockers, calcium channel blockers, alpha adrenergic blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, direct renin inhibitors, or other antihypertensive drug classes. Studies had to include clearly defined mortality and morbidity outcomes (serious adverse events, total cardiovascular events, stroke, coronary heart disease (CHD), congestive heart failure, and withdrawals due to adverse effects).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
We included 20 trials with 26 comparator arms randomizing over 90,000 participants. The findings are relevant to first-line use of drug classes in older male and female hypertensive patients (aged 50 to 75) with multiple co-morbidities, including type 2 diabetes. First-line thiazide and thiazide-like diuretics were compared with beta-blockers (six trials), calcium channel blockers (eight trials), ACE inhibitors (five trials), and alpha-adrenergic blockers (three trials); other comparators included angiotensin II receptor blockers, aliskiren (a direct renin inhibitor), and clonidine (a centrally acting drug). Only three studies reported data for total serious adverse events: two studies compared diuretics with calcium channel blockers and one with a direct renin inhibitor. Compared to first-line beta-blockers, first-line thiazides probably result in little to no difference in total mortality (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.84 to 1.10; 5 trials, 18,241 participants; moderate-certainty), probably reduce total cardiovascular events (5.4% versus 4.8%; RR 0.88, 95% CI 0.78 to 1.00; 4 trials, 18,135 participants; absolute risk reduction (ARR) 0.6%, moderate-certainty), may result in little to no difference in stroke (RR 0.85, 95% CI 0.66 to 1.09; 4 trials, 18,135 participants; low-certainty), CHD (RR 0.91, 95% CI 0.78 to 1.07; 4 trials, 18,135 participants; low-certainty), or heart failure (RR 0.69, 95% CI 0.40 to 1.19; 1 trial, 6569 participants; low-certainty), and probably reduce withdrawals due to adverse effects (10.1% versus 7.9%; RR 0.78, 95% CI 0.71 to 0.85; 5 trials, 18,501 participants; ARR 2.2%; moderate-certainty). Compared to first-line calcium channel blockers, first-line thiazides probably result in little to no difference in total mortality (RR 1.02, 95% CI 0.96 to 1.08; 7 trials, 35,417 participants; moderate-certainty), may result in little to no difference in serious adverse events (RR 1.09, 95% CI 0.97 to 1.24; 2 trials, 7204 participants; low-certainty), probably reduce total cardiovascular events (14.3% versus 13.3%; RR 0.93, 95% CI 0.89 to 0.98; 6 trials, 35,217 participants; ARR 1.0%; moderate-certainty), probably result in little to no difference in stroke (RR 1.06, 95% CI 0.95 to 1.18; 6 trials, 35,217 participants; moderate-certainty) or CHD (RR 1.00, 95% CI 0.93 to 1.08; 6 trials, 35,217 participants; moderate-certainty), probably reduce heart failure (4.4% versus 3.2%; RR 0.74, 95% CI 0.66 to 0.82; 6 trials, 35,217 participants; ARR 1.2%; moderate-certainty), and may reduce withdrawals due to adverse effects (7.6% versus 6.2%; RR 0.81, 95% CI 0.75 to 0.88; 7 trials, 33,908 participants; ARR 1.4%; low-certainty). Compared to first-line ACE inhibitors, first-line thiazides probably result in little to no difference in total mortality (RR 1.00, 95% CI 0.95 to 1.07; 3 trials, 30,961 participants; moderate-certainty), may result in little to no difference in total cardiovascular events (RR 0.97, 95% CI 0.92 to 1.02; 3 trials, 30,900 participants; low-certainty), probably reduce stroke slightly (4.7% versus 4.1%; RR 0.89, 95% CI 0.80 to 0.99; 3 trials, 30,900 participants; ARR 0.6%; moderate-certainty), probably result in little to no difference in CHD (RR 1.03, 95% CI 0.96 to 1.12; 3 trials, 30,900 participants; moderate-certainty) or heart failure (RR 0.94, 95% CI 0.84 to 1.04; 2 trials, 30,392 participants; moderate-certainty), and probably reduce withdrawals due to adverse effects (3.9% versus 2.9%; RR 0.73, 95% CI 0.64 to 0.84; 3 trials, 25,254 participants; ARR 1.0%; moderate-certainty). Compared to first-line alpha-blockers, first-line thiazides probably result in little to no difference in total mortality (RR 0.98, 95% CI 0.88 to 1.09; 1 trial, 24,316 participants; moderate-certainty), probably reduce total cardiovascular events (12.1% versus 9.0%; RR 0.74, 95% CI 0.69 to 0.80; 2 trials, 24,396 participants; ARR 3.1%; moderate-certainty) and stroke (2.7% versus 2.3%; RR 0.86, 95% CI 0.73 to 1.01; 2 trials, 24,396 participants; ARR 0.4%; moderate-certainty), may result in little to no difference in CHD (RR 0.98, 95% CI 0.86 to 1.11; 2 trials, 24,396 participants; low-certainty), probably reduce heart failure (5.4% versus 2.8%; RR 0.51, 95% CI 0.45 to 0.58; 1 trial, 24,316 participants; ARR 2.6%; moderate-certainty), and may reduce withdrawals due to adverse effects (1.3% versus 0.9%; RR 0.70, 95% CI 0.54 to 0.89; 3 trials, 24,772 participants; ARR 0.4%; low-certainty). For the other drug classes, data were insufficient. No antihypertensive drug class demonstrated any clinically important advantages over first-line thiazides.
AUTHORS' CONCLUSIONS
When used as first-line agents for the treatment of hypertension, thiazides and thiazide-like drugs likely do not change total mortality and likely decrease some morbidity outcomes such as cardiovascular events and withdrawals due to adverse effects, when compared to beta-blockers, calcium channel blockers, ACE inhibitors, and alpha-blockers.
Topics: Aged; Female; Humans; Male; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Coronary Disease; Diabetes Mellitus, Type 2; Diuretics; Heart Failure; Hypertension; Stroke; Thiazides; Middle Aged
PubMed: 37439548
DOI: 10.1002/14651858.CD008161.pub3 -
Kidney Medicine May 2022There is conflicting evidence regarding the type of β-blockers to use in dialysis patients. This systematic review seeks to determine whether highly dialyzable...
RATIONALE & OBJECTIVE
There is conflicting evidence regarding the type of β-blockers to use in dialysis patients. This systematic review seeks to determine whether highly dialyzable β-blockers are associated with higher rates of cardiovascular events and mortality in hemodialysis patients than poorly dialyzable β-blockers.
STUDY DESIGN
A systematic review of the existing literature was conducted. A meta-analysis was performed using data from the selected studies.
SETTING & STUDY POPULATIONS
Participants were from the United States, Canada, and Taiwan. The mean ages of participants ranged from 55.9-75.7 years.
SELECTION CRITERIA FOR STUDIES
We searched the Ovid MEDLINE database from 1990 to September 2020. Studies without adult hemodialysis participants and without comparisons of at least 2 β-blockers of different dialyzability were excluded.
DATA EXTRACTION
Baseline and adjusted outcome data were extracted from each study.
ANALYTICAL APPROACH
Random-effects models were used to calculate pooled risk ratios using fully adjusted models from individual studies.
RESULTS
Four cohort studies were included. Pooling fully adjusted models, highly dialyzable β-blockers did not influence mortality (HR, 0.94; 95% CI, 0.81-1.08; I = 0.84) compared with poorly dialyzable β-blockers but were associated with a reduction in cardiovascular events (HR, 0.88; 95% CI, 0.83-0.93). There was significant heterogeneity between studies (I = 0.35). Only 1 study reported on adverse events. Intradialytic hypotension was more common in those on carvedilol (a poorly dialyzable β-blocker) compared with those on metoprolol (a highly dialyzable β-blocker; adjusted incidence rate ratio, 1.10; 95% CI, 1.09-1.11).
LIMITATIONS
No randomized controlled trials were identified. Each study used different analytic methods and different definitions for outcomes. Classifications of β-blockers varied. Only 1 study reported on adverse events.
CONCLUSIONS
Pooled data suggest highly dialyzable β-blockers are associated with similar mortality events and fewer cardiovascular events compared with poorly dialyzable β-blockers.
PubMed: 35539430
DOI: 10.1016/j.xkme.2022.100460 -
Arquivos Brasileiros de Cardiologia 2023The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is controversial.
OBJECTIVE
We performed a meta-analysis to assess the effectiveness of these drugs in preventing cardiotoxicity.
METHODS
The meta-analysis included prospective, randomized studies in adults receiving anthracycline chemotherapy and compared the use of RAAS inhibitors or beta-blockers versus placebo with a follow-up of 6 to 18 months. The primary outcome was change in left ventricular ejection fraction (LVEF) during chemotherapy. Secondary outcomes were the incidence of heart failure, all-cause mortality, and changes in end-diastolic measurement. Heterogeneity was assessed by stratification and meta-regression. A significance level of p < 0.05 was adopted.
RESULTS
The search resulted in 17 studies, totaling 1,530 patients. The variation (delta) in LVEF was evaluated in 14 studies. Neurohormonal therapy was associated with a lower delta in pre- versus post-therapy LVEF (weighted mean difference 4.42 [95% confidence interval 2.3 to 6.6]) and higher final LVEF (p < 0.001). Treatment resulted in a lower incidence of heart failure (risk ratio 0.45 [95% confidence interval 0.3 to 0.7]). There was no effect on mortality (p = 0.3). For analysis of LVEF, substantial heterogeneity was documented, which was not explained by the variables explored in the study.
CONCLUSION
The use of RAAS inhibitors and beta-blockers to prevent anthracycline-induced cardiotoxicity was associated with less pronounced reduction in LVEF, higher final LVEF, and lower incidence of heart failure. No changes in mortality were observed. (CRD PROSPERO 42019133615).
Topics: Adult; Humans; Renin-Angiotensin System; Stroke Volume; Cardiotoxicity; Ventricular Function, Left; Anthracyclines; Prospective Studies; Adrenergic beta-Antagonists; Antibiotics, Antineoplastic; Heart Failure
PubMed: 37255127
DOI: 10.36660/abc.20220298 -
Annals of Medicine Dec 2022Critical illness may lead to activation of the sympathetic system. The sympathetic stimulation may be further increased by exogenous catecholamines, such as vasopressors... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Critical illness may lead to activation of the sympathetic system. The sympathetic stimulation may be further increased by exogenous catecholamines, such as vasopressors and inotropes. Excessive adrenergic stress has been associated with organ dysfunction and higher mortality. -Blockers may reduce the adrenergic burden, but they may also compromise perfusion to vital organs thus worsening organ dysfunction. To assess the effect of treatment with -blockers in critically ill adults, we conducted a systematic review and meta-analysis of randomized controlled trials.
MATERIALS AND METHODS
We conducted a search from three major databases: Ovid Medline, the Cochrane Central Register for Controlled Trials and Scopus database. Two independent reviewers screened, selected, and assessed the included articles according to prespecified eligibility criteria. We assessed risk of bias of eligible articles according to the Cochrane guidelines. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Sixteen randomized controlled trials comprising 2410 critically ill patients were included in the final review. A meta-analysis of 11 trials including 2103 patients showed a significant reduction in mortality in patients treated with -blockers compared to control (risk ratio 0.65, 95%CI 0.53-0.79; < .0001). There was no significant difference in mean arterial pressure or vasopressor load. Quality of life, biventricular ejection fraction, blood lactate levels, cardiac biomarkers and mitochondrial function could not be included in meta-analysis due to heterogenous reporting of outcomes.
CONCLUSIONS
In this systematic review we found that -blocker treatment reduced mortality in critical illness. Use of -blockers in critical illness thus appears safe after initial hemodynamic stabilization. High-quality RCT's are needed to answer the questions concerning optimal target group of patients, timing of -blocker treatment, choice of -blocker, and choice of physiological and hemodynamic parameters to target during -blocker treatment in critical illness.KEY MESSAGESA potential outcome benefit of -blocker treatment in critical illness exists according to the current review and meta-analysis. Administration of -blockers to resuscitated patients in the ICU seems safe in terms of hemodynamic stability and outcome, even during concomitant vasopressor administration. However, further studies, preferably large RCTs on -blocker treatment in the critically ill are needed to answer the questions concerning timing and choice of -blocker, patient selection, and optimal hemodynamic targets.
Topics: Adrenergic beta-Antagonists; Adult; Critical Illness; Humans; Multiple Organ Failure; Quality of Life; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 35838226
DOI: 10.1080/07853890.2022.2098376 -
The Journal of Trauma and Acute Care... Jun 2021Paroxysmal sympathetic hyperactivity (PSH) and catecholamine surge, which are associated with poor outcome, may be triggered by traumatic brain injury (TBI).β... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Paroxysmal sympathetic hyperactivity (PSH) and catecholamine surge, which are associated with poor outcome, may be triggered by traumatic brain injury (TBI).β Adrenergic receptor blockers (β-blockers), as potential therapeutic agents to prevent paroxysmal sympathetic hyperactivity and catecholamine surge, have been shown to improve survival after TBI. The principal aim of this study was to investigate the effect of β-blockers on outcomes in patients with TBI.
METHODS
For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and Cochrane Library databases from inception to September 25, 2020, for randomized controlled trials, nonrandomized controlled trials, and observational studies reporting the effect of β-blockers on the following outcomes after TBI: mortality, functional measures, and cardiopulmonary adverse effects of β-blockers (e.g., hypotension, bradycardia, and bronchospasm). With use of random-effects model, we calculated pooled estimates, confidence intervals (CIs), and odds ratios (ORs) of all outcomes.
RESULTS
Fifteen studies with 12,721 patients were included. Exposure to β-blockers after TBI was associated with a significant reduction in adjusted in-hospital mortality (OR, 0.39; 95% CI, 0.30-0.51; I2 = 66.3%; p < 0.001). β-Blockers significantly improved the long-term (≥6 months) functional outcome (OR, 1.75; 95% CI, 1.09-2.80; I2 = 0%; p = 0.02). Statistically significant difference was not seen for cardiopulmonary adverse events (OR, 0.91; 95% CI, 0.55-1.50; I2 = 25.9%; p = 0.702).
CONCLUSION
This meta-analysis demonstrated that administration of β-blockers after TBI was safe and effective. Administration of β-blockers may therefore be suggested in the TBI care. However, more high-quality trials are needed to investigate the use of β-blockers in the management of TBI.
LEVEL OF EVIDENCE
Systematic review and meta-analysis, level III.
Topics: Adrenergic beta-Antagonists; Autonomic Nervous System Diseases; Brain Injuries, Traumatic; Hospital Mortality; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33496547
DOI: 10.1097/TA.0000000000003094 -
Neurosurgical Review Apr 2021Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit...
Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was to systematically review the evidence on the effect of beta-blockers on glioma growth. A systematic literature search was performed in the PubMed, Embase, Google Scholar, Web of Science, and Cochrane Central to identify all relevant studies. Preclinical studies concerning the pharmacodynamic effects of beta-blockers on glioma growth and proliferation were included, as well as clinical studies that studied the effect of beta-blockers on patient outcomes according to PRISMA guidelines. Among the 980 citations, 10 preclinical studies and 1 clinical study were included after title/abstract and full-text screening. The following potential mechanisms were identified: reduction of glioma cell proliferation (n = 9), decrease of glioma cell migration (n = 2), increase of drug sensitivity (n = 1), induction of glioma cell death (n = 1). Beta-blockers affect glioma proliferation by inducing a brief reduction of cAMP and a temporary cell cycle arrest in vitro. Contrasting results were observed concerning glioma cell migration. The identified clinical study did not find an association between beta-blockers and survival in glioma patients. Although preclinical studies provide scarce evidence for the use of beta-blockers in glioma, they identified potential pathways for targeting glioma. Future studies are needed to clarify the effect of beta-blockers on clinical endpoints including survival outcomes in glioma patients to scrutinize the value of beta-blockers in glioma care.
Topics: Adrenergic beta-Antagonists; Brain Neoplasms; Cell Death; Cell Proliferation; Clinical Trials as Topic; Drug Evaluation, Preclinical; Glioblastoma; Glioma; Humans; Neovascularization, Pathologic
PubMed: 32172480
DOI: 10.1007/s10143-020-01277-4 -
ESMO Open Apr 2021Preclinical and retrospective studies suggest that beta-blockers are active against breast cancer. We carried out a systematic review and meta-analysis to assess the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preclinical 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.
METHODS
A 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.
RESULTS
Overall, 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.
DISCUSSION
In 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.
Topics: Adrenergic beta-Antagonists; Breast Neoplasms; Female; Humans; Neoplasm Recurrence, Local; Prospective Studies; Retrospective Studies
PubMed: 33639601
DOI: 10.1016/j.esmoop.2021.100066 -
Current Medical Research and Opinion 2015Recent growing evidence suggests that beta-blocker treatment could improve cardiovascular dynamics and possibly the outcome of patients admitted to intensive care with... (Review)
Review
OBJECTIVE
Recent growing evidence suggests that beta-blocker treatment could improve cardiovascular dynamics and possibly the outcome of patients admitted to intensive care with severe sepsis or septic shock.
DESIGN
Systematic review.
DATA SOURCES
MEDLINE and EMBASE healthcare databases.
REVIEW METHODS
To investigate this topic, we conducted a systematic review of the above databases up to 31 May 2015. Due to the clinical novelty of the subject, we also included non-randomized clinical studies. We focused on the impact of beta-blocker treatment on mortality, also investigating its effects on cardiovascular, immune and metabolic function. Evidence from experimental studies was reviewed as well.
RESULTS
From the initial search we selected 10 relevant clinical studies. Five prospective studies (two randomized) assessed the hemodynamic effects of the beta1-blocker esmolol. Heart rate decreased significantly in all, but the impact on other parameters differed. The imbalance between prospective studies' size (10 to 144 patients) and the differences in their design disfavor a meta-analysis. One retrospective study showed improved hemodynamics combining metoprolol and milrinone in septic patients, and another retrospective study found no association between beta-blocker administration and mortality. We also found three case series. Twenty-one experimental studies evaluated the hemodynamic, immune and/or metabolic effects of selective and/or non-selective beta-blockers in animal models of sepsis (dogs, mice, pigs, rats, sheep), yielding conflicting results.
CONCLUSIONS
Whilst there is not enough prospective data to conduct a meta-analysis, the available clinical data are promising. We discuss the ability of beta blockade to modulate sepsis-induced alterations at cardiovascular, metabolic, immunologic and coagulation levels.
Topics: Adrenergic beta-Antagonists; Animals; Heart Rate; Hemodynamics; Humans; Metoprolol; Propanolamines; Sepsis; Shock, Septic
PubMed: 26121122
DOI: 10.1185/03007995.2015.1062357 -
British Journal of Clinical Pharmacology Nov 2014Platelets play an important role in cardiovascular disease, and β-blockers are often prescribed for cardiovascular disease prevention. β-Blockers may directly affect... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Adrenergic beta-Antagonists; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Observational Studies as Topic; Platelet Aggregation
PubMed: 24730697
DOI: 10.1111/bcp.12404 -
Respiratory Medicine Aug 2014Empirical results indicate an increased risk for cardiovascular (CV) adverse drug events (ADE) in chronic obstructive pulmonary disease (COPD) patients treated with... (Review)
Review
OBJECTIVE
Empirical results indicate an increased risk for cardiovascular (CV) adverse drug events (ADE) in chronic obstructive pulmonary disease (COPD) patients treated with beta-2-agonists (B2A) and muscarinic antagonists (MA). A systematic review (including a meta-analysis for drug classes with sufficient sample size) was conducted assessing the association between B2A or MA and acute myocardial infarctions (MI) in COPD patients.
METHODS
Comprehensive literature search in electronic databases (MEDLINE, Cochrane database) was performed (January 1, 1946-April 1, 2013). Results were presented by narrative synthesis including a comprehensive quality assessment. In the meta-analysis, a random effects model was used for estimating relative risk estimates for acute MI.
RESULTS
Eight studies (two systematic reviews, two randomized controlled trials, and four observational studies) were comprised. Most studies comparing tiotropium vs. placebo showed a decreased MI risk for tiotropium, whereas for studies with active control arms no clear tendency was revealed. For short-acting B2A, an increased MI risk was shown after first treatment initiation. For all studies, a good quality was found despite some shortcomings in ADE-specific criteria. A meta-analysis could be conducted for tiotropium vs. placebo only, showing a relative risk reduction of MI (0.74 [0.61-0.90]) with no evidence of statistical heterogeneity among the included trials (I(2) = 0%; p = 0.8090).
CONCLUSIONS
An MI-protective effect of tiotropium compared to placebo was found, which might be attributable to an effective COPD treatment leading to a decrease in COPD-related cardiovascular events. Further studies with effective control arms and minimal CV risk are required determining precisely tiotropium's cardiovascular risk.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Cholinergic Antagonists; Epidemiologic Methods; Humans; Muscarinic Antagonists; Myocardial Infarction; Pulmonary Disease, Chronic Obstructive; Risk Factors; Scopolamine Derivatives; Tiotropium Bromide
PubMed: 24950946
DOI: 10.1016/j.rmed.2014.05.014