-
The American Journal of Cardiology Mar 2014Despite the use of traditional antianginal medications (i.e., β blockers, calcium channel blockers, and nitrates) and revascularization therapies, symptoms of chronic... (Meta-Analysis)
Meta-Analysis Review
Despite the use of traditional antianginal medications (i.e., β blockers, calcium channel blockers, and nitrates) and revascularization therapies, symptoms of chronic stable angina pectoris (CSAP) persist in ≥25% of patients. The objective of this systematic review was to synthesize the available evidence from randomized controlled trials (RCTs) of ranolazine for the treatment of CSAP. We systematically searched the Cochrane Register of Controlled Trials, EMBASE, and MEDLINE through July 2013 for RCTs comparing ranolazine with placebo or antianginal medications administered as part of usual care for the management of CSAP. End points of interest included exercise stress test performance (duration, time to angina, and time to ST-segment depression), frequency of angina attacks/week, nitroglycerin use/week, and quality of life. We identified 7 RCTs (n = 3,317) of patients with CSAP due to coronary artery disease. Comparators included placebo, amlodipine, and atenolol. All but 1 trial showed a statistically significant improvement in all 3 exercise stress test parameters with ranolazine compared with placebo. Ranolazine also reduced angina frequency and nitroglycerin use compared with placebo. These findings were consistent whether or not patients were also prescribed traditional antianginal pharmacotherapy. In conclusion, ranolazine reduces anginal symptoms among patients with symptomatic CSAP despite their use of traditional antianginal medications.
Topics: Acetanilides; Angina, Stable; Chronic Disease; Enzyme Inhibitors; Humans; Piperazines; Randomized Controlled Trials as Topic; Ranolazine; Treatment Outcome
PubMed: 24462341
DOI: 10.1016/j.amjcard.2013.11.070 -
The Cochrane Database of Systematic... Dec 2013Peripheral arterial disease (PAD) causes considerable morbidity and mortality. Hypertension is a risk factor for PAD. Treatment for hypertension must be compatible with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial disease (PAD) causes considerable morbidity and mortality. Hypertension is a risk factor for PAD. Treatment for hypertension must be compatible with the symptoms of PAD. Controversy regarding the effects of beta-adrenoreceptor blockade for hypertension in patients with PAD has led many physicians to stop prescribing beta-adrenoreceptor blockers. Little is known about the effects of other classes of anti-hypertensive drugs in the presence of PAD. This is the second update of a Cochrane review first published in 2003.
OBJECTIVES
To determine the effects of anti-hypertensive drugs in patients with both raised blood pressure and symptomatic PAD in terms of the rate of cardiovascular events and death, symptoms of claudication and critical leg ischaemia, and progression of atherosclerotic PAD as measured by ankle brachial index (ABI) changes and the need for revascularisation (reconstructive surgery or angioplasty) or amputation.
SEARCH METHODS
For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Cochrane Peripheral Vascular Diseases Group Specialised Register (last searched March 2013) and CENTRAL (2013, Issue 2).
SELECTION CRITERIA
Randomised controlled trials (RCTs) of at least one anti-hypertensive treatment against placebo or two anti-hypertensive medications against each other, with interventions lasting at least one month. Trials had to include patients with symptomatic PAD.
DATA COLLECTION AND ANALYSIS
Data were extracted by one author (DAL) and checked by the other (GYHL). Potentially eligible studies were excluded when the results presentation prevented adequate extraction of data and enquiries to authors did not yield raw data.
MAIN RESULTS
Eight RCTs were included with a total of 3610 PAD patients. Four studies compared a recognised class of anti-hypertensive treatment with placebo and four studies compared two anti-hypertensive treatments with each other. Studies were not pooled due to the variation of the comparisons and the outcomes presented. Overall the quality of the available evidence was unclear, primarily as a result of a lack of detail in the study reports on the randomisation and blinding procedures and incomplete outcome data. Two studies compared angiotensin converting enzyme (ACE) inhibitors against placebo. In one study there was a significant reduction in the number of cardiovascular events in patients receiving ramipril (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.91; n = 1725). In the second trial using perindopril (n = 52) there was a marginal increase in claudication distance but no change in ABI and a reduction in maximum walking distance. A trial comparing the calcium antagonist verapamil versus placebo in patients undergoing angioplasty (n = 96) suggested that verapamil reduced restenosis (per cent diameter stenosis (± SD) 48.0% ± 11.5 versus 69.6% ± 12.2; P < 0.01), although this was not reflected in the maintenance of a high ABI (0.76 ± 0.10 versus 0.72 ± 0.08 for verapamil versus placebo). Another study (n = 80) demonstrated no significant difference in arterial intima-media thickness (IMT) in men receiving the thiazide diuretic hydrochlorothiazide (HCTZ) compared to those receiving the alpha-adrenoreceptor blocker doxazosin (-0.12 ± 0.14 mm and -0.08 ± 0.13 mm, respectively; P = 0.66). A study (n = 36) comparing telmisartan to placebo found a significant improvement in maximum walking distance at 12 months with telmisartan (median (interquartile range (IQR)) 191 m (157 to 226) versus 103 m (76 to 164); P < 0.001) but no differences in ABI (median (IQR) 0.60 (0.60 to 0.77) versus 0.52 (0.48 to 0.67)) or arterial IMT (median (IQR) 0.08 cm (0.07 to 0.09) versus 0.09 cm (0.08 to 0.10)). Two studies compared the beta-adrenoreceptor blocker nebivolol with either the thiazide diuretic HCTZ or with metoprolol. Both studies found no significant differences in intermittent or absolute claudication distance, ABI, or all-cause mortality between the anti-hypertensives. A subgroup analysis of PAD patients (n = 2699) in a study which compared a calcium antagonist-based strategy (verapamil slow release (SR) ± trandolapril) to a beta-adrenoreceptor blocker-based strategy (atenolol ± hydrochlorothiazide) found no significant differences in the composite endpoints of death, non-fatal myocardial infarction or non-fatal stroke with or without revascularisation (OR 0.90, 95% CI 0.76 to 1.07 and OR 0.96, 95% CI 0.82 to 1.13, respectively).
AUTHORS' CONCLUSIONS
Evidence on the use of various anti-hypertensive drugs in people with PAD is poor so that it is unknown whether significant benefits or risks accrue. However, lack of data specifically examining outcomes in PAD patients should not detract from the overwhelming evidence on the benefit of treating hypertension and lowering blood pressure.
Topics: Antihypertensive Agents; Female; Humans; Hypertension; Intermittent Claudication; Male; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic
PubMed: 24307487
DOI: 10.1002/14651858.CD003075.pub3 -
The Cochrane Database of Systematic... Sep 2013Beta (β) blockers are indicated for use in coronary artery disease (CAD). However, optimal therapy for people with CAD accompanied by intermittent claudication has been... (Review)
Review
BACKGROUND
Beta (β) blockers are indicated for use in coronary artery disease (CAD). However, optimal therapy for people with CAD accompanied by intermittent claudication has been controversial because of the presumed peripheral haemodynamic consequences of beta blockers, leading to worsening symptoms of intermittent claudication. This is an update of a review first published in 2008.
OBJECTIVES
To quantify the potential harmful effects of beta blockers on maximum walking distance, claudication distance, calf blood flow, calf vascular resistance and skin temperature when used in patients with peripheral arterial disease (PAD).
SEARCH METHODS
For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched March 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2013, Issue 2).
SELECTION CRITERIA
Randomised controlled trials (RCTs) evaluating the role of both selective (β1) and non-selective (β1 and β2) beta blockers compared with placebo. We excluded trials that compared different types of beta blockers.
DATA COLLECTION AND ANALYSIS
Primary outcome measures were claudication distance in metres, time to claudication in minutes and maximum walking distance in metres and minutes (as assessed by treadmill).Secondary outcome measures included calf blood flow (mL/100 mL/min), calf vascular resistance and skin temperature (ºC).
MAIN RESULTS
We included six RCTs that fulfilled the above criteria, with a total of 119 participants. The beta blockers studied were atenolol, propranolol, pindolol and metoprolol. All trials were of poor quality with the drugs administered over a short time (10 days to two months). None of the primary outcomes were reported by more than one study. Similarly, secondary outcome measures, with the exception of vascular resistance (as reported by three studies), were reported, each by only one study. Pooling of such results was deemed inappropriate. None of the trials showed a statistically significant worsening effect of beta blockers on time to claudication, claudication distance and maximal walking distance as measured on a treadmill, nor on calf blood flow, calf vascular resistance and skin temperature, when compared with placebo. No reports described adverse events associated with the beta blockers studied.
AUTHORS' CONCLUSIONS
Currently, no evidence suggests that beta blockers adversely affect walking distance, calf blood flow, calf vascular resistance and skin temperature in people with intermittent claudication. However, because of the lack of large published trials, beta blockers should be used with caution, if clinically indicated.
Topics: Adrenergic beta-Antagonists; Atenolol; Humans; Intermittent Claudication; Metoprolol; Peripheral Vascular Diseases; Pindolol; Propranolol; Randomized Controlled Trials as Topic; Regional Blood Flow; Walking
PubMed: 24027118
DOI: 10.1002/14651858.CD005508.pub3 -
The Cochrane Database of Systematic... May 2013Stroke affects 15 million people per year worldwide. Despite recent developments in acute stroke treatment, prevention remains very important. Stroke has a high rate of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Stroke affects 15 million people per year worldwide. Despite recent developments in acute stroke treatment, prevention remains very important. Stroke has a high rate of recurrence; therefore secondary prevention is also important. Many clinical approaches to control risk factors have been proposed. One of these approaches is the prescription of beta-blockers that have effects beyond the reduction of blood pressure, which can reduce the recurrence of stroke.
OBJECTIVES
To evaluate the efficacy of beta-blockers for preventing stroke recurrence and for reducing death and major vascular events in people with a previous stroke or transient ischaemic attack (TIA), and to determine their safety, particularly with regard to the development of diabetes mellitus.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (December 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR) (The Cochrane Library 2011, Issue 12), the Database of Abstracts of Reviews of Effects (DARE) (December 2011), MEDLINE (1966 to December 2011), EMBASE (1980 to December 2011), and Latin American and Caribbean Health Sciences Literature (LILACS) (1982 to December 2011). We also searched ongoing trials registers and reference lists.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that included participants with previous stroke or TIA due to arterial thrombosis or embolism.The intervention was any beta-blocker versus control, or beta-blocker plus other treatment versus other treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the trials identified, appraised quality, and extracted data.
MAIN RESULTS
We included two RCTs involving 2193 participants in the review. Both studies randomised participants to either beta-blocker (atenolol 5 mg) or placebo. No statistical differences were noted among the groups in risks of fatal and non-fatal stroke (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.75 to 1.17). For all other outcomes analysed (death from all causes, cardiac death, non-fatal myocardial infarction, major vascular events), we observed no significant differences between the groups.
AUTHORS' CONCLUSIONS
To date, no available evidence supports the routine use of beta-blockers for secondary prevention after stroke or TIA. More studies with larger samples are needed.
Topics: Adrenergic beta-1 Receptor Antagonists; Atenolol; Cause of Death; Humans; Ischemic Attack, Transient; Myocardial Infarction; Secondary Prevention; Stroke
PubMed: 23728669
DOI: 10.1002/14651858.CD007890.pub2 -
Journal of General Internal Medicine Sep 2013Systematic review of preventive pharmacologic treatments for community-dwelling adults with episodic migraine. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Systematic review of preventive pharmacologic treatments for community-dwelling adults with episodic migraine.
DATA SOURCES
Electronic databases through May 20, 2012.
ELIGIBILITY CRITERIA
English-language randomized controlled trials (RCTs) of preventive drugs compared to placebo or active treatments examining rates of ≥50 % reduction in monthly migraine frequency or improvement in quality of life.
STUDY APPRAISAL AND SYNTHESIS METHODS
We assessed risk of bias and strength of evidence and conducted random effects meta-analyses of absolute risk differences and Bayesian network meta-analysis.
RESULTS
Of 5,244 retrieved references, 215 publications of RCTs provided mostly low-strength evidence because of the risk of bias and imprecision. RCTs examined 59 drugs from 14 drug classes. All approved drugs, including topiramate (9 RCTs), divalproex (3 RCTs), timolol (3 RCTs), and propranolol (4 RCTs); off-label beta blockers metoprolol (4 RCTs), atenolol (1 RCT), nadolol (1 RCT), and acebutolol (1 RCT); angiotensin-converting enzyme inhibitors captopril (1 RCT) and lisinopril (1 RCT); and angiotensin II receptor blocker candesartan (1 RCT), outperformed placebo in reducing monthly migraine frequency by ≥50 % in 200-400 patients per 1,000 treated. Adverse effects leading to treatment discontinuation (68 RCTs) were greater with topiramate, off-label antiepileptics, and antidepressants than with placebo. Limited direct evidence as well as frequentist and exploratory network Bayesian meta-analysis showed no statistically significant differences in benefits between approved drugs. Off-label angiotensin-inhibiting drugs and beta-blockers were most effective and tolerable for episodic migraine prevention.
LIMITATIONS
We did not quantify reporting bias or contact principal investigators regarding unpublished trials.
CONCLUSIONS
Approved drugs prevented episodic migraine frequency by ≥50 % with no statistically significant difference between them. Exploratory network meta-analysis suggested that off-label angiotensin-inhibiting drugs and beta-blockers had favorable benefit-to-harm ratios. Evidence is lacking for long-term effects of drug treatments (i.e., trials of more than 3 months duration), especially for quality of life.
Topics: Adult; Anticonvulsants; Evidence-Based Medicine; Humans; Migraine Disorders; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 23592242
DOI: 10.1007/s11606-013-2433-1 -
BMJ (Clinical Research Ed.) Jan 2013To clarify whether any particular β blocker is superior in patients with heart failure and reduced ejection fraction or whether the benefits of these agents are mainly... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To clarify whether any particular β blocker is superior in patients with heart failure and reduced ejection fraction or whether the benefits of these agents are mainly due to a class effect.
DESIGN
Systematic review and network meta-analysis of efficacy of different β blockers in heart failure.
DATA SOURCES
CINAHL(1982-2011), Cochrane Collaboration Central Register of Controlled Trials (-2011), Embase (1980-2011), Medline/PubMed (1966-2011), and Web of Science (1965-2011).
STUDY SELECTION
Randomized trials comparing β blockers with other β blockers or other treatments.
DATA EXTRACTION
The primary endpoint was all cause death at the longest available follow-up, assessed with odds ratios and Bayesian random effect 95% credible intervals, with independent extraction by observers.
RESULTS
21 trials were included, focusing on atenolol, bisoprolol, bucindolol, carvedilol, metoprolol, and nebivolol. As expected, in the overall analysis, β blockers provided credible mortality benefits in comparison with placebo or standard treatment after a median of 12 months (odds ratio 0.69, 0.56 to 0.80). However, no obvious differences were found when comparing the different β blockers head to head for the risk of death, sudden cardiac death, death due to pump failure, or drug discontinuation. Accordingly, improvements in left ventricular ejection fraction were also similar irrespective of the individual study drug.
CONCLUSION
The benefits of β blockers in patients with heart failure with reduced ejection fraction seem to be mainly due to a class effect, as no statistical evidence from current trials supports the superiority of any single agent over the others.
Topics: Adrenergic beta-Antagonists; Bayes Theorem; Heart Failure; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Stroke Volume; Treatment Outcome
PubMed: 23325883
DOI: 10.1136/bmj.f55 -
The American Journal of Cardiology Mar 2013Because carvedilol is a unique vasodilating β blocker (BB) exerting antioxidant activity and pleiotropic effects, it was theorized that it may confer more potent... (Meta-Analysis)
Meta-Analysis Review
Because carvedilol is a unique vasodilating β blocker (BB) exerting antioxidant activity and pleiotropic effects, it was theorized that it may confer more potent beneficial effects on cardiovascular mortality and morbidity in acute myocardial infarction (AMI) and heart failure (HF) settings. A systematic review and meta-analysis was performed of randomized, controlled, direct-comparison trials that included adults receiving atenolol, bisoprolol, metoprolol, nebivolol, or carvedilol to evaluate the effects of carvedilol compared to other BBs on mortality, cardiovascular events, and hospital readmissions in the setting of AMI or systolic HF. Compared to β(1)-selective BBs used in HF (8 trials, n = 4,563), carvedilol significantly reduced all-cause mortality (risk ratio 0.85, 95% confidence interval 0.78 to 0.93, p = 0.0006). In 3 trials of patients with AMI (n = 644), carvedilol significantly reduced all-cause mortality by 45% (fixed-effects model: risk ratio 0.55, 95% confidence interval 0.32 to 0.94, p = 0.03, random-effects model: risk ratio 0.56, 95% confidence interval 0.26 to 1.12, p = 0.10), with no reduction in non-fatal MI (risk ratio 0.61, 95% confidence interval 0.31 to 1.22, p = 0.16). In conclusion, carvedilol, as compared against atenolol, bisoprolol, metoprolol and nebivolol in randomized direct comparison trials, significantly reduced all-cause mortality in systolic HF patients. Additionally, carvedilol significantly reduced all-cause mortality compared with β(1)-selective BBs in AMI patients using the fixed-effects model but not using the random-effects model.
Topics: Adrenergic beta-1 Receptor Antagonists; Atenolol; Benzopyrans; Bisoprolol; Carbazoles; Carvedilol; Ethanolamines; Global Health; Humans; Metoprolol; Myocardial Infarction; Nebivolol; Platelet Aggregation Inhibitors; Propanolamines; Survival Rate; Treatment Outcome
PubMed: 23290925
DOI: 10.1016/j.amjcard.2012.11.031 -
International Journal of Clinical... Aug 2013Antihypertensive medicines are to known to cause diverse disturbances to electrolyte homeostasis; however, their potential to affect zinc is less well known. The primary... (Review)
Review
BACKGROUND
Antihypertensive medicines are to known to cause diverse disturbances to electrolyte homeostasis; however, their potential to affect zinc is less well known. The primary aim was to explore whether antihypertensive medicines have the potential to affect zinc status.
METHODS
A review of electronic databases was undertaken. Full-length English language articles describing clinical trials involving antihypertensive medicines and reporting on zinc measurements were reviewed.
RESULTS
Eight eligible studies were identified which involved the use of ACE inhibitors, thiazide diuretics, beta blockers, or ARB drugs of which five included a control group Studies used urinary zinc excretion, plasma zinc levels or erythrocyte zinc as key measures of zinc status. Studies reported increased urinary zinc losses for captopril (from 50 mg/day), enalapril (20 mg/day), losartan (50 mg/day), losartan (50 mg/day) together with hydrochlorothiazide (12.5 mg/day), captopril (75 mg/day) together with frusemide (40 mg/day) and stand-alone hydrochlorothiazide (25 mg/day). Serum levels of zinc decreased with captopril (50-150 mg/day), verapamil (240 mg/day), atenolol (50-150 mg/day) and the combination of losartan (50 mg/day) and hydrochlorothiazide (12.5 mg/day), eryrthrocyte levels decreased with use of valsartan (80 mg/day) and in some studies for captopril, but not for metoprolol (100 mg/day), atenolol (50-150 mg/day), verapamil (240 mg/day), doxazosin (4 mg/day) or amlodipine 10 mg/day). Major limitations were that most studies were small and did not report on dietary zinc intake.
CONCLUSION
The available evidence suggests that use of ACE inhibitors and angiotensin 2 receptor antagonists or thiazide diuretics have the potential to reduce zinc levels in hypertensive patients. Additional research using larger participant numbers and accounting for dietary zinc intakes are required.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Food-Drug Interactions; Humans; Hypertension; Risk Factors; Sodium Chloride Symporter Inhibitors; Trace Elements; Zinc
PubMed: 23279674
DOI: 10.1111/ijcp.12040 -
The Cochrane Database of Systematic... Nov 2012This review is an update of the Cochrane Review published in 2007, which assessed the role of beta-blockade as first-line therapy for hypertension. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review is an update of the Cochrane Review published in 2007, which assessed the role of beta-blockade as first-line therapy for hypertension.
OBJECTIVES
To quantify the effectiveness and safety of beta-blockers on morbidity and mortality endpoints in adults with hypertension.
SEARCH METHODS
In December 2011 we searched the Cochrane Central Register of Controlled Trials, Medline, Embase, and reference lists of previous reviews; for eligible studies published since the previous search we conducted in May 2006.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of at least one year duration, which assessed the effects of beta-blockers compared to placebo or other drugs, as first-line therapy for hypertension, on mortality and morbidity in adults.
DATA COLLECTION AND ANALYSIS
We selected studies and extracted data in duplicate. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and combined them using the fixed-effects or random-effects method, as appropriate.
MAIN RESULTS
We included 13 RCTs which compared beta-blockers to placebo (4 trials, N=23,613), diuretics (5 trials, N=18,241), calcium-channel blockers (CCBs: 4 trials, N=44,825), and renin-angiotensin system (RAS) inhibitors (3 trials, N=10,828). Three-quarters of the 40,245 participants on beta-blockers used atenolol. Most studies had a high risk of bias; resulting from various limitations in study design, conduct, and data analysis.Total mortality was not significantly different between beta-blockers and placebo (RR 0.99, 95%CI 0.88 to 1.11; I(2)=0%), diuretics or RAS inhibitors, but was higher for beta-blockers compared to CCBs (RR 1.07, 95%CI 1.00 to 1.14; I(2)=2%). Total cardiovascular disease (CVD) was lower for beta-blockers compared to placebo (RR 0.88, 95%CI 0.79 to 0.97; I(2)=21%). This is primarily a reflection of the significant decrease in stroke (RR 0.80, 95%CI 0.66 to 0.96; I(2)=0%), since there was no significant difference in coronary heart disease (CHD) between beta-blockers and placebo. There was no significant difference in withdrawals from assigned treatment due to adverse events between beta-blockers and placebo (RR 1.12, 95%CI 0.82 to 1.54; I(2)=66%).The effect of beta-blockers on CVD was significantly worse than that of CCBs (RR 1.18, 95%CI 1.08-1.29; I(2)=0%), but was not different from that of diuretics or RAS inhibitors. In addition, there was an increase in stroke in beta-blockers compared to CCBs (RR 1.24, 95%CI 1.11-1.40; I(2)=0%) and RAS inhibitors (RR 1.30, 95%CI 1.11 to 1.53; I(2)=29%). However, CHD was not significantly different between beta-blockers and diuretics, CCBs or RAS inhibitors. Participants on beta-blockers were more likely to discontinue treatment due to adverse events than those on RAS inhibitors (RR 1.41, 95% CI 1.29 to 1.54; I(2)=12%), but there was no significant difference with diuretics or CCBs.
AUTHORS' CONCLUSIONS
Initiating treatment of hypertension with beta-blockers leads to modest reductions in cardiovascular disease and no significant effects on mortality. These effects of beta-blockers are inferior to those of other antihypertensive drugs. The GRADE quality of this evidence is low, implying that the true effect of beta-blockers may be substantially different from the estimate of effects found in this review. Further research should be of high quality and should explore whether there are differences between different sub-types of beta-blockers or whether beta-blockers have differential effects on younger and elderly patients.
Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin Receptor Antagonists; Antihypertensive Agents; Atenolol; Calcium Channel Blockers; Coronary Disease; Diuretics; Heart Arrest; Humans; Hypertension; Middle Aged; Randomized Controlled Trials as Topic; Stroke
PubMed: 23152211
DOI: 10.1002/14651858.CD002003.pub4 -
The Cochrane Database of Systematic... Aug 2012This review is an update of the Cochrane Review published in 2007, which assessed the role of beta-blockade as first-line therapy for hypertension. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review is an update of the Cochrane Review published in 2007, which assessed the role of beta-blockade as first-line therapy for hypertension.
OBJECTIVES
To quantify the effectiveness and safety of beta-blockers on morbidity and mortality endpoints in adults with hypertension.
SEARCH METHODS
In December 2011 we searched the Cochrane Central Register of Controlled Trials, Medline, Embase, and reference lists of previous reviews; for eligible studies published since the previous search we conducted in May 2006.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of at least one year duration, which assessed the effects of beta-blockers compared to placebo or other drugs, as first-line therapy for hypertension, on mortality and morbidity in adults.
DATA COLLECTION AND ANALYSIS
We selected studies and extracted data in duplicate. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and combined them using the fixed-effects or random-effects method, as appropriate.
MAIN RESULTS
We included 13 RCTs which compared beta-blockers to placebo (4 trials, N=23,613), diuretics (5 trials, N=18,241), calcium-channel blockers (CCBs: 4 trials, N=44,825), and renin-angiotensin system (RAS) inhibitors (3 trials, N=10,828). Three-quarters of the 40,245 participants on beta-blockers used atenolol. Most studies had a high risk of bias; resulting from various limitations in study design, conduct, and data analysis.Total mortality was not significantly different between beta-blockers and placebo (RR 0.99, 95%CI 0.88 to 1.11; I(2)=0%), diuretics or RAS inhibitors, but was higher for beta-blockers compared to CCBs (RR 1.07, 95%CI 1.00 to 1.14; I(2)=2%). Total cardiovascular disease (CVD) was lower for beta-blockers compared to placebo (RR 0.88, 95%CI 0.79 to 0.97; I(2)=21%). This is primarily a reflection of the significant decrease in stroke (RR 0.80, 95%CI 0.66 to 0.96; I(2)=0%), since there was no significant difference in coronary heart disease (CHD) between beta-blockers and placebo. There was no significant difference in withdrawals from assigned treatment due to adverse events between beta-blockers and placebo (RR 1.12, 95%CI 0.82 to 1.54; I(2)=66%).The effect of beta-blockers on CVD was significantly worse than that of CCBs (RR 1.18, 95%CI 1.08-1.29; I(2)=0%), but was not different from that of diuretics or RAS inhibitors. In addition, there was an increase in stroke in beta-blockers compared to CCBs (RR 1.24, 95%CI 1.11-1.40; I(2)=0%) and RAS inhibitors (RR 1.30, 95%CI 1.11 to 1.53; I(2)=29%). However, CHD was not significantly different between beta-blockers and diuretics, CCBs or RAS inhibitors. Participants on beta-blockers were more likely to discontinue treatment due to adverse events than those on RAS inhibitors (RR 1.41, 95% CI 1.29 to 1.54; I(2)=12%), but there was no significant difference with diuretics or CCBs.
AUTHORS' CONCLUSIONS
Initiating treatment of hypertension with beta-blockers leads to modest reductions in cardiovascular disease and no significant effects on mortality. These effects of beta-blockers are inferior to those of other antihypertensive drugs. The GRADE quality of this evidence is low, implying that the true effect of beta-blockers may be substantially different from the estimate of effects found in this review. Further research should be of high quality and should explore whether there are differences between different sub-types of beta-blockers or whether beta-blockers have differential effects on younger and elderly patients.
Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin Receptor Antagonists; Antihypertensive Agents; Calcium Channel Blockers; Diuretics; Humans; Hypertension; Middle Aged; Randomized Controlled Trials as Topic; Stroke
PubMed: 22895924
DOI: 10.1002/14651858.CD002003.pub3