Beta-blockers for hypertension.

BACKGROUND: Beta-blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties. They have shown long-term beneficial effects on mortality and cardiovascular disease (CVD) when used in people with heart failure or acute myocardial infarction. Beta-blockers were thought to have similar beneficial effects when used as first-line therapy for hypertension. However, the benefit of beta-blockers as first-line therapy for hypertension without compelling indications is controversial. This review is an update of a Cochrane Review initially published in 2007 and updated in 2012. OBJECTIVES: To assess the effects of beta-blockers on morbidity and mortality endpoints in adults with hypertension. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to June 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 6), MEDLINE (from 1946), Embase (from 1974), and ClinicalTrials.gov. We checked reference lists of relevant reviews, and reference lists of studies potentially eligible for inclusion in this review, and also searched the the World Health Organization International Clinical Trials Registry Platform on 06 July 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) of at least one year of 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, resolving discrepancies by consensus. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and conducted fixed-effect or random-effects meta-analyses, as appropriate. We also used GRADE to assess the certainty of the evidence. GRADE classifies the certainty of evidence as high (if we are confident that the true effect lies close to that of the estimate of effect), moderate (if the true effect is likely to be close to the estimate of effect), low (if the true effect may be substantially different from the estimate of effect), and very low (if we are very uncertain about the estimate of effect). MAIN RESULTS: Thirteen RCTs met inclusion criteria. They compared beta-blockers to placebo (4 RCTs, 23,613 participants), diuretics (5 RCTs, 18,241 participants), calcium-channel blockers (CCBs: 4 RCTs, 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 RCTs, 10,828 participants). These RCTs were conducted between the 1970s and 2000s and most of them had a high risk of bias resulting from limitations in study design, conduct, and data analysis. There were 40,245 participants taking beta-blockers, three-quarters of them taking atenolol. We found no outcome trials involving the newer vasodilating beta-blockers (e.g. nebivolol).There was no difference in all-cause mortality between beta-blockers and placebo (RR 0.99, 95% CI 0.88 to 1.11), diuretics or RAS inhibitors, but it was higher for beta-blockers compared to CCBs (RR 1.07, 95% CI 1.00 to 1.14). The evidence on mortality was of moderate-certainty for all comparisons.Total CVD was lower for beta-blockers compared to placebo (RR 0.88, 95% CI 0.79 to 0.97; low-certainty evidence), a reflection of the decrease in stroke (RR 0.80, 95% CI 0.66 to 0.96; low-certainty evidence) since there was no difference in coronary heart disease (CHD: RR 0.93, 95% CI 0.81 to 1.07; moderate-certainty evidence). The effect of beta-blockers on CVD was worse than that of CCBs (RR 1.18, 95% CI 1.08 to 1.29; moderate-certainty evidence), but was not different from that of diuretics (moderate-certainty) or RAS inhibitors (low-certainty). In addition, there was an increase in stroke in beta-blockers compared to CCBs (RR 1.24, 95% CI 1.11 to 1.40; moderate-certainty evidence) and RAS inhibitors (RR 1.30, 95% CI 1.11 to 1.53; moderate-certainty evidence). However, there was little or no difference in CHD between beta-blockers and diuretics (low-certainty evidence), CCBs (moderate-certainty evidence) or RAS inhibitors (low-certainty evidence). In the single trial involving participants aged 65 years and older, atenolol was associated with an increased CHD incidence compared to diuretics (RR 1.63, 95% CI 1.15 to 2.32). Participants taking beta-blockers were more likely to discontinue treatment due to adverse events than participants taking RAS inhibitors (RR 1.41, 95% CI 1.29 to 1.54; moderate-certainty evidence), but there was little or no difference with placebo, diuretics or CCBs (low-certainty evidence). AUTHORS' CONCLUSIONS: Most outcome RCTs on beta-blockers as initial therapy for hypertension have high risk of bias. Atenolol was the beta-blocker most used. Current evidence suggests that initiating treatment of hypertension with beta-blockers leads to modest CVD reductions and little or no effects on mortality. These beta-blocker effects are inferior to those of other antihypertensive drugs. Further research should be of high quality and should explore whether there are differences between different subtypes of beta-blockers or whether beta-blockers have differential effects on younger and older people.

A combined strategies intervention on the World Health Organization prescribing indicators: A quasi-randomised trial.

BACKGROUND: Irrational medicine use is a global problem that may potentiate antimicrobial resistance. AIM: This study aims to assess prescribing practices and the effect of a prescription audit and feedback coupled with small-group education intervention on prescribing indicators. SETTING: The study was conducted in public-sector healthcare facilities in Eswatini. METHODS: A cluster quasi-randomised controlled study was conducted from 2016 to 2019 using the World Health Organization/ International Network for Rational Use of Drugs (WHO/INRUD) prescribing indicators at baseline, post-intervention and post-follow-up. A 6-month unblinded intervention was tested in 32 healthcare facilities, randomly allocated to intervention (16) and control (16) arms. Prescribing practices were assessed post-intervention, and 6 months after the intervention, through an audit of 100 randomly selected prescriptions from each facility. Comparisons of WHO or INRUD prescribing indicators were conducted using the intention-to-treat analysis at the two times. RESULTS: At baseline, in both arms, rational prescribing standards were met by the number of medicines per prescription and the use of injections. Antibiotic use was above 50% in both arms. After adjustment for baseline antibiotics use, region and level of care, there were no significant differences in all prescribing indicators between the two arms, post-intervention and at 6 months follow-up. CONCLUSION: In a lower middle-income setting with a high prevalence of irrational prescribing practices, a prescription audit, feedback and small-group education intervention had no benefits in improving rational prescribing.Contribution: Multifaceted strategies, strengthening of pharmacy and therapeutics committees, and holistic monitoring of medicine use are recommended to promote rational medicine use.

Beta-blockers for hypertension.

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.

Beta-blockers for hypertension.

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.

Antiretroviral Therapy-associated Adverse Drug Reactions and their Effects on Virologic Failure- A Retrospective Cohort Study in Nigeria.

BACKGROUND: Adverse drug reactions (ADRs) associated with antiretroviral therapy (ART) can rapidly reverse the gains of ART resulting in poor health outcomes. We need an improved understanding of specific ART-related ADRs that influence virologic outcomes. OBJECTIVE: To investigate the frequency of clinical ADRs and assess their effect on virologic failure in patients on ART. METHOD: We described the prevalence of major clinical ADRs, and the association between specific ADRs and virologic failure in a clinic cohort of HIV-1 infected Nigerians aged ≥18 years, on firstline ART between June 2004 and February 2012. Multivariable logistic regression was run to identify predictors of virologic failure at 24 and 72 weeks of ART. RESULTS: Data of 12,115 patients with a median age of 34 (interquartile range: 29-41) years, and predominantly females (67%) were evaluated. Overall, 957 (7.9%) patients experienced at least one ADR during a median follow-up period of 4 years (interquartile range: 1-7). The three most prevalent ADRs were lipodystrophy (2.6%), anemia (1.9%), and skin rash (0.7%). Virologic failure rate was 36% and 34% at 24 and 72 weeks of ART, respectively. Anemia independently predicted the odds of virologic failure at 72 weeks of ART (adjusted odds ratio, 1.74; 95% CI: 1.2-2.51); adjusted for sex, age, pre-treatment CD4+ cell count, antiretroviral regimen, and medication refill adherence. CONCLUSION: Antiretroviral therapy-associated anemia increases the likelihood of late virologic failure. We recommend routine monitoring of hemoglobin levels and prompt management of anemia in all patients on ART as a strategy to improve virologic success rates.

Prevention of hypertension and diabetes in an urban setting in South Africa: participatory action research with community health workers.

The project aimed to identify factors that contribute to hypertension and diabetes and to design and implement appropriate local interventions to prevent these noncommunicable diseases and promote healthy lifestyles. This was a community-based participatory action research project in which researchers and community health workers (CHWs) were the main participants. The triple A approach to planning interventions was used, that is, the process of assessing the situation, analyzing the findings, and taking action based on this analysis. Both qualitative and quantitative methods were employed. Twenty-two CHWs working in site C, Khayelitsha, a deprived urban area of Cape Town, South Africa, participated in the study. Findings from the situational assessment indicated a lack of knowledge among CHWs and the community about hypertension and diabetes and the risk factors for these non-communicable diseases. Economic constraints and cultural beliefs and practices influenced the community's food choices and participation in physical activity. On the basis of these findings, a training program was proposed that would provide CHWs with the skills to prevent hypertension and diabetes in their community. A program was developed and piloted by the project team. A health club that focuses on promoting healthy lifestyles is currently being piloted. This paper illustrates the unique involvement of CHWs in a successful participatory action research project on the prevention of hypertension and diabetes and promotion of health in a deprived urban setting. The project emphasizes the importance of involving local people in community-based initiatives to promote health and identifies that the primary role of health services is to develop appropriate skills in the local community, monitor activities, and facilitate a link with primary health services.

How strong is the evidence for use of beta-blockers as first-line therapy for hypertension? Systematic review and meta-analysis.

OBJECTIVE: To quantify the effect of first-line antihypertensive treatment with beta-blockers on mortality, morbidity and withdrawal rates, compared with the other main classes of antihypertensive agents. METHODS: We identified eligible trials by searching the Cochrane Controlled Trials Register, Medline, Embase, reference lists of previous reviews, and contacting researchers. We extracted data independently in duplicate and conducted meta-analysis by analysing trial participants in groups to which they were randomized, regardless of subsequent treatment actually received. RESULTS: Thirteen trials with 91,561 participants, meeting inclusion criteria, compared beta-blockers to placebo (four trials; n = 23,613), diuretics (five trials; n = 18,241), calcium-channel blockers (CCBs) (four trials; n = 44,825), and renin-angiotensin system (RAS) inhibitors, namely angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (three trials; n = 10,828). Compared to placebo, beta-blockers reduced the risk of stroke (relative risk 0.80; 95% confidence interval 0.66-0.96) with a marginal fall in total cardiovascular events (0.88, 0.79-0.97), but did not affect all-cause mortality (0.99, 0.88-1.11), coronary heart disease (0.93, 0.81-1.07) or cardiovascular mortality (0.93, 0.80-1.09). The effect on stroke was less than that of CCBs (1.24, 1.11-1.40) and RAS inhibitors (1.30, 1.11-1.53), and that on total cardiovascular events less than that of CCBs (1.18, 1.08-1.29). In addition, patients on beta-blockers were more likely to discontinue treatment than those on diuretics (1.80; 1.33-2.42) or RAS inhibitors (1.41; 1.29-1.54). CONCLUSION: Beta-blockers are inferior to CCBs and to RAS inhibitors for reducing several important hard end points. Compared with diuretics, they had similar outcomes, but were less well tolerated. Hence beta-blockers are generally suboptimal first-line antihypertensive drugs.