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Annals of Medicine and Surgery (2012) Jun 2024Recent studies have tried to establish an association between the use of alpha-1-adrenergic receptor antagonists (A1ARAs) used in benign prostatic hyperplasia (BPH) and...
BACKGROUND
Recent studies have tried to establish an association between the use of alpha-1-adrenergic receptor antagonists (A1ARAs) used in benign prostatic hyperplasia (BPH) and the risk of PD. The objective of the study is to compare the risk of Parkinson's disease (PD) between terazosin/alfuzosin/doxazosin (TZ/AZ/DZ) users and tamsulosin users.
METHODS
PubMed, Google Scholar, and Embase were systematically searched from inception to April 2023. Observational studies comparing the risk of PD among patients using different types of A1ARAs were included in the meta-analysis. The primary outcome was the hazard ratio (HR) with a 95% CI for the risk of occurrence of PD among A1ARAs users of two different classes.
RESULTS
This study was based on a total of 678 433 BPH patients, out of which 287 080 patients belonged to the TZ/AZ/DZ cohort and 391 353 patients belonged to the tamsulosin cohort. The pooled incidence of PD was higher in tamsulosin users (1.28%, 95% CI: 1.04-1.55%) than in TZ/AZ/DZ drug users (1.11%, 95% CI: 0.83-1.42%). The risk of occurrence of PD was significantly lower in patients taking TZ/AZ/DZ than tamsulosin (= 610,363, HR = 0.82, 95% CI = 0.71-0.94, = 0.01; I = 87.4%).
CONCLUSION
This meta-analysis demonstrated that patients with BPH who take TZ/AZ/DZ have a lower risk for developing PD than those who take tamsulosin.
PubMed: 38846867
DOI: 10.1097/MS9.0000000000002117 -
Archivio Italiano Di Urologia,... Jun 2022Alpha-adrenoreceptor antagonists or alpha-blockers are used in the treatment of hypertension, in the therapy of benign prostatic hyperplasia and in medical expulsive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alpha-adrenoreceptor antagonists or alpha-blockers are used in the treatment of hypertension, in the therapy of benign prostatic hyperplasia and in medical expulsive treatment of ureteral stones. These agents may affect the sexual function, with differences between drugs within the same class, depending on their selectivity for receptor subtypes. The aim of this review was to analyze the effects of alpha-blockers on sexual function.
MATERIALS AND METHODS
We conducted a systematic review and meta-analysis by searching PubMed, EMBASE and other databases for randomized controlled trials (RCTs) reporting sexual adverse effects in patients treated with alpha-blockers. Odds ratios for sexual dysfunction were calculated using random effects Mantel-Haenszel statistics.
RESULTS
Out of 608 records retrieved, 75 eligible RCTs were included in the meta-analysis. Compared with placebo, alphablockers were associated with increased odds of ejaculatory disorders both in patients with lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH) (OR: 7.53, 95% CI: 3.77-15.02, Z = 5.73, p < 0.00001, I2 = 55%) and in patients with ureteral stones (OR: 2.88, 95% CI: 1.50-5.44, Z = 3.19, p < 0.001, I2 = 31%). Uroselective alpha-blockers showed higher odds of ejaculatory disorders. Conversely, nonselective alpha-blockers were not associated with higher odds of ejaculatory dysfunction. Silodosin was associated with increased odds of ejaculatory dysfunction compared with tamsulosin (OR: 3.52, 95% CI: 2.18-5.68, 15 series, 1512 participants, Z = 5.15, p < 0.00001, I2 = 0%). Naftopidil and alfuzosin showed lower odds of ejaculatory dysfunction compared to uroselective alpha-blockers.No statistically significant differences in the odds of erectile dysfunction were observed when alpha-blockers were compared to placebo.
Topics: Adrenergic alpha-Antagonists; Humans; Lower Urinary Tract Symptoms; Male; Prostatic Hyperplasia; Randomized Controlled Trials as Topic
PubMed: 35775356
DOI: 10.4081/aiua.2022.2.252 -
Hellenic Journal of Cardiology : HJC =... 2022The real-world implementation of heart failure (HF) guidelines remains unclear. Our present systematic review and meta-analysis aimed to examine the rate of HF patients... (Meta-Analysis)
Meta-Analysis Review
The real-world implementation of heart failure (HF) guidelines remains unclear. Our present systematic review and meta-analysis aimed to examine the rate of HF patients receiving guideline-directed treatment to identify the proportion of under-treatment patients and those who are treated with optimal doses, to evaluate the correlation of under-treatment patients' characteristics with the prescribed therapy, and finally, to evaluate the combined effect of the above on incidental mortality and rehospitalization. We conducted a systematic review of the literature indexed in Medline. We screened 1224 papers and excluded 1166 as they did not meet the inclusion criteria. Of the remaining 58 papers, which were evaluated by studying the full text, 11 papers that referred to 45866 patients were finally studied in this work. Angiotensin-Converting-Enzyme Inhibitor (ACEI) and Angiotensin II-Receptor Blocker (ARB) use was estimated to be 80.9% (95% CI: 73.9%, 86.4%), β-blockers' use was 78% (95% CI: 70.4%, 84.1%), Mineralocorticoid Receptor Antagonists' use was 47.4% (95% Cl 41.6%, 53.4%), and cardiac resynchronization therapy's use was 5.8% (95% Cl 3.4%, 9.6%). Meta-regression analysis showed that prescription of more than the half of target dose of ACEI/ARBs was found to be associated with reduced all-cause mortality (Z = -3.61, P = 0.0003), while the relationship with β-blockers was borderline (Z = -1.56, P = 0.11). A satisfactory adherence to the prescription of guideline-recommended treatment in patients with HF was observed. However, the under titration of the life-saving HF drugs need to be improved as only ultimate adherence to guideline-directed treatments may lead to the reduction of HF burden.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Stroke Volume
PubMed: 35508296
DOI: 10.1016/j.hjc.2022.04.006 -
ESC Heart Failure Oct 2022Due to concerns regarding neurohormonal activation and fluid retention, adrenergic alpha-1 receptor antagonists (A1Bs) are generally avoided in the setting of heart... (Meta-Analysis)
Meta-Analysis
Due to concerns regarding neurohormonal activation and fluid retention, adrenergic alpha-1 receptor antagonists (A1Bs) are generally avoided in the setting of heart disease, namely, symptomatic heart failure (HF) with reduced ejection fraction (HFrEF). However, this contraindication is mainly supported by ancient studies, having recently been challenged by newer ones. We aim to perform a comprehensive meta-analysis aimed at ascertaining the extent to which A1Bs might influence cardiovascular (CV) outcomes. We systematically searched PubMed, Cochrane Central Register of Controlled Trials and Web of Science for both prospective and retrospective studies, published until 1 December 2020, addressing the impact of A1Bs on both clinical outcomes-namely, acute heart failure (AHF), acute coronary syndrome (ACS), CV and all-cause mortality-and on CV surrogate measures, specifically left ventricular ejection fraction (LVEF) and exercise tolerance, by means of exercise duration. Both randomized controlled trials (RCTs) and studies including only HF patients were further investigated separately. Study-specific odds ratios (ORs) and mean differences (MDs) were pooled using traditional meta-analytic techniques, under a random-effects model. A record was registered in PROSPERO database, with the code number CRD42020181804. Fifteen RCTs, three non-randomized prospective and two retrospective studies, encompassing 32 851, 19 287, and 71 600 patients, respectively, were deemed eligible; 62 256 patients were allocated to A1B, on the basis of multiple clinical indications: chronic HF itself [14 studies, with 72 558 patients, including seven studies with 850 HFrEF or HF with mildly reduced ejection fraction (HFmrEF) patients], arterial hypertension (four studies, with 44 184 patients) and low urinary tract symptoms (two studies, with 6996 patients). There were 25 998 AHF events, 1325 ACS episodes, 955 CV deaths and 33 567 all-cause deaths. When considering only RCTs, A1Bs were, indeed, found to increase AHF risk (OR 1.78, [1.46, 2.16] 95% CI, P < 0.00001, i 2%), although displaying no significant effect on neither ACS nor CV or all-cause mortality rates (OR 1.02, [0.91, 1.15] 95% CI, i 0%; OR 0.95, [0.47, 1.91] 95% CI, i 17%; OR 1.1, [0.84, 1.43] 95% CI, i 17%, respectively). Besides, when only HF patients were evaluated, A1Bs revealed themselves neutral towards not only ACS, CV, and all-cause mortality events (OR 0.49, [0.1, 2.47] 95% CI, i 0%; OR 0.7, [0.21, 2.31] 95% CI, i 21%; OR 1.09, [0.53, 2.23] 95% CI, i 17%, respectively), but also AHF (OR 1.13, [0.66, 1.92] 95% CI, i 0%). As for HFrEF and HFmrEF, A1Bs were found to exert a similarly inconsequential effect on AHF rates (OR 1.01, [0.5-2.05] 95% CI, i 6%). Likewise, LVEF was not significantly influenced by A1Bs (MD 1.66, [-2.18, 5.50] 95% CI, i 58%). Most strikingly, exercise tolerance was higher in those under this drug class (MD 139.16, [65.52, 212.8] 95% CI, P < 0.001, i 26%). A1Bs do not seem to exert a negative influence on the prognosis of HF-and even of HFrEF-patients, thus contradicting currently held views. These drugs' impact on other major CV outcomes also appear trivial and they may even increment exercise tolerance.
Topics: Humans; Adrenergic alpha-Antagonists; Heart Failure; Hospitalization; Randomized Controlled Trials as Topic; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left
PubMed: 35894772
DOI: 10.1002/ehf2.14012 -
International Journal of Surgery... May 2023Oral medications, onabotulinumtoxinA injections, and transcutaneous tibial nerve stimulation (TTNS) are recommended by the American Urological Association/Society of... (Meta-Analysis)
Meta-Analysis
The effectiveness and safety of oral medications, onabotulinumtoxinA (three doses) and transcutaneous tibial nerve stimulation as non or minimally invasive treatment for the management of neurogenic detrusor overactivity in adults: a systematic review and network meta-analysis.
BACKGROUND
Oral medications, onabotulinumtoxinA injections, and transcutaneous tibial nerve stimulation (TTNS) are recommended by the American Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction guidelines as non or minimally invasive treatments for patients with neurogenic detrusor overactivity (NDO) without treatment hierarchy.
OBJECTIVE
The objective was to compare and rank the effectiveness and safety of oral medications, three doses of onabotulinumtoxinA, and TTNS on improving urodynamic outcomes in patient-reported outcomes and safety outcomes in patients with NDO.
METHODS
The authors searched PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov, from their inception to October 2022 and included randomized controlled studies on the drug, onabotulinumtoxinA, and TTNS for the treatment of patients with NDO. Outcomes included urodynamic parameters, voiding diary, quality of life changes, adverse event rate and postvoid residual.
RESULTS
A total of 26 articles and 2938 patients were included in the statistics. Regarding effectiveness, all interventions except TTNS and α-blockers were statistically different for the placebo group. The urodynamic outcome and patient-reported outcome suggested that onabotulinumtoxinA injection (urodynamic outcome: onabotulinumtoxinA 200 U, the mean surface under the cumulative ranking curve (SUCRA): 87.4; patient-reported outcome: onabotulinumtoxinA 100 U, mean SUCRA: 89.8) was the most effective treatment, and the safety outcome suggested that TTNS (SUCRA: 83.3) was the safest. Cluster analysis found that antimuscarinics and β3-adrenoceptor-agonists possessed good effectiveness and safety.
CONCLUSION
OnabotulinumtoxinA injection is probably the most effective way to treat patients with NDO, with increasing effectiveness but decreasing safety as the dose rises. The effectiveness of α-blockers and TTNS was not statistically different from the placebo group. Antimuscarinics and β3-adrenoceptor-agonists have good effectiveness and safety.
Topics: Humans; Adult; Female; Botulinum Toxins, Type A; Quality of Life; Network Meta-Analysis; Muscarinic Antagonists; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Treatment Outcome; Receptors, Adrenergic; Tibial Nerve
PubMed: 36974676
DOI: 10.1097/JS9.0000000000000338 -
The Cochrane Database of Systematic... May 2016Withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment.
OBJECTIVES
To assess the effectiveness of interventions involving the use of alpha2-adrenergic agonists compared with placebo, reducing doses of methadone, symptomatic medications, or an alpha2-adrenergic agonist regimen different to the experimental intervention, for the management of the acute phase of opioid withdrawal. Outcomes included the withdrawal syndrome experienced, duration of treatment, occurrence of adverse effects, and completion of treatment.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1946 to November week 2, 2015), EMBASE (January 1985 to November week 2, 2015), PsycINFO (1806 to November week 2, 2015), Web of Science, and reference lists of articles.
SELECTION CRITERIA
Randomised controlled trials comparing alpha2-adrenergic agonists (clonidine, lofexidine, guanfacine, tizanidine) with reducing doses of methadone, symptomatic medications or placebo, or comparing different alpha2-adrenergic agonists to modify the signs and symptoms of withdrawal in participants who were opioid dependent.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We included 26 randomised controlled trials involving 1728 participants. Six studies compared an alpha2-adrenergic agonist with placebo, 12 with reducing doses of methadone, four with symptomatic medications, and five compared different alpha2-adrenergic agonists. We assessed 10 studies as having a high risk of bias in at least one of the methodological domains that were considered.We found moderate-quality evidence that alpha2-adrenergic agonists were more effective than placebo in ameliorating withdrawal in terms of the likelihood of severe withdrawal (risk ratio (RR) 0.32, 95% confidence interval (CI) 0.18 to 0.57; 3 studies; 148 participants). We found moderate-quality evidence that completion of treatment was significantly more likely with alpha2-adrenergic agonists compared with placebo (RR 1.95, 95% CI 1.34 to 2.84; 3 studies; 148 participants).Peak withdrawal severity may be greater with alpha2-adrenergic agonists than with reducing doses of methadone, as measured by the likelihood of severe withdrawal (RR 1.18, 95% CI 0.81 to 1.73; 5 studies; 340 participants; low quality), and peak withdrawal score (standardised mean difference (SMD) 0.22, 95% CI -0.02 to 0.46; 2 studies; 263 participants; moderate quality), but these differences were not significant and there is no significant difference in severity when considered over the entire duration of the withdrawal episode (SMD 0.13, 95% CI -0.24 to 0.49; 3 studies; 119 participants; moderate quality). The signs and symptoms of withdrawal occurred and resolved earlier with alpha2-adrenergic agonists. The duration of treatment was significantly longer with reducing doses of methadone (SMD -1.07, 95% CI -1.31 to -0.83; 3 studies; 310 participants; low quality). Hypotensive or other adverse effects were significantly more likely with alpha2-adrenergic agonists (RR 1.92, 95% CI 1.19 to 3.10; 6 studies; 464 participants; low quality), but there was no significant difference in rates of completion of withdrawal treatment (RR 0.85, 95% CI 0.69 to 1.05; 9 studies; 659 participants; low quality).There were insufficient data for quantitative comparison of different alpha2-adrenergic agonists. Available data suggest that lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine.
AUTHORS' CONCLUSIONS
Clonidine and lofexidine are more effective than placebo for the management of withdrawal from heroin or methadone. We detected no significant difference in efficacy between treatment regimens based on clonidine or lofexidine and those based on reducing doses of methadone over a period of around 10 days, but methadone was associated with fewer adverse effects than clonidine, and lofexidine has a better safety profile than clonidine.
Topics: Acute Disease; Adrenergic alpha-2 Receptor Agonists; Clonidine; Controlled Clinical Trials as Topic; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome
PubMed: 27140827
DOI: 10.1002/14651858.CD002024.pub5 -
Urologia Internationalis 2023Urolithiasis is one of the most common diseases in the world, and at present, ureteroscopy (URS) is the first choice for its treatment. Although the effect is good,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Urolithiasis is one of the most common diseases in the world, and at present, ureteroscopy (URS) is the first choice for its treatment. Although the effect is good, there is a risk of insertion failure of ureteroscope. Tamsulosin, as an α-receptor blocker, has the function of relaxing ureteral muscles, and can help stones to be discharged from ureteral orifice. In this study, we aimed to determine the effect of preoperative tamsulosin on ureteral navigation, operation, and safety.
METHODS
This study was conducted and reported according to the meta-analysis extension of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The PubMed and Embase databases were searched for studies. Data were extracted according to the PRISMA principles. We collected and combined randomized controlled trial and researches in reviews of preoperative tamsulosin to explore the effect of preoperative tamsulosin on ureteral navigation, operation, and safety. A data synthesis was performed using RevMan 5.4.1 software (Cochrane). Heterogeneity was mainly evaluated with I2 tests. Key metrics include: success rate of ureteral navigation, time of URS, stone-free rate, and postoperative symptoms.
RESULT
We summarized and analyzed 6 studies. We noted a statistically significant improvement in the success rate of ureteral navigation (Mantel-Haenszel [M-H], odds ratio [OR]: 3.78, 95% confidence interval [CI]: [2.34, 6.12], p < 0.01) and stone-free rate (M-H, OR: 2.25, 95% CI: [1.16, 4.36], p = 0.02) with tamsulosin preoperatively. At the same time, we also observed that postoperative fever (M-H, OR: 0.37, 95% CI: [0.16, 0.89], p = 0.03) and postoperative analgesia (M-H, OR: 0.21, 95% CI: [0.05, 0.92], p = 0.04) were also reduced because of preoperative tamsulosin.
CONCLUSION
Preoperative tamsulosin can not only increase the one-time success rate of ureteral navigation and the stone-free rate of URS but also reduce the incidence of postoperative adverse symptoms such as postoperative fever and postoperative pain.
Topics: Humans; Tamsulosin; Ureteral Calculi; Sulfonamides; Treatment Outcome; Ureter; Adrenergic alpha-Antagonists
PubMed: 36812907
DOI: 10.1159/000528889 -
The Cochrane Database of Systematic... Jan 2008Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral oedema, the accumulation of fluid within the brain, is believed to be an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral oedema, the accumulation of fluid within the brain, is believed to be an important contributor to the secondary brain damage that occurs following injury. The release of kinins is thought to be an important factor in the development of cerebral vasogenic oedema and the use of beta-2 receptor antagonists, which prevent the release of these kinins, have been proposed as a potential therapeutic intervention.
OBJECTIVES
The objective was to assess the safety and effectiveness of beta-2 receptor antagonists for TBI.
SEARCH STRATEGY
We searched the Cochrane Injuries Group's specialised register, CENTRAL, MEDLINE, EMBASE, National Research Register, LILACs, Zetoc, Web of Knowledge and Current Controlled Trials. We also searched the internet and checked the reference lists of relevant papers to identify any further studies. The searches were conducted in March 2007.
SELECTION CRITERIA
Randomised controlled trials of beta-2 receptor antagonists versus placebo for TBI.
DATA COLLECTION AND ANALYSIS
Two authors independently screened search results and assessed the full texts of potentially relevant studies for inclusion. Data were extracted and methodological quality was examined. Relative risks (RR) and 95% confidence intervals (CIs) were calculated and data were pooled using a fixed effect model.
MAIN RESULTS
Three studies were included, involving 178 participants. All three studies reported the effects of beta-2 receptor antagonists on mortality. The pooled RR for mortality was 0.63 (95% CI 0.36 to 1.10). Two studies measured disability, the RR of death or severe disability with beta-2 receptor antagonists was 0.81 (95% CI 0.59 to 1.09). Two studies measured the effect on intracranial pressure (ICP), although in only one did this finding reach statistical significance. There was no evidence for the presence of heterogeneity.
AUTHORS' CONCLUSIONS
There is no reliable evidence that beta-2 receptor antagonists are effective in reducing mortality or disability after TBI. Further well conducted randomised controlled trials are required.
Topics: Acute Disease; Adrenergic beta-2 Receptor Antagonists; Brain Edema; Brain Injuries; Humans; Intracranial Pressure; Peptides; Quinolines; Randomized Controlled Trials as Topic
PubMed: 18254109
DOI: 10.1002/14651858.CD006686.pub2 -
American Journal of Obstetrics and... Dec 2013The purpose of this study was to evaluate the efficacy and safety of transdermal nitroglycerin as a tocolytic agent in women with preterm labor. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
The purpose of this study was to evaluate the efficacy and safety of transdermal nitroglycerin as a tocolytic agent in women with preterm labor.
STUDY DESIGN
We conducted a systematic review and metaanalysis of randomized controlled trials.
RESULTS
Thirteen studies were included (1302 women) comparing transdermal nitroglycerin vs placebo (2 studies; n = 186); β2-adrenergic receptor agonists (9 studies; n = 1024); nifedipine (1 study; n = 50); and magnesium sulfate (1 study; n = 42). There were no significant differences between transdermal nitroglycerin and placebo for delivery within 48 hours of the initiation of treatment or at <28, <34, or <37 weeks of gestation, adverse neonatal outcomes, and neurodevelopmental status at 24 months of life. Nevertheless, 1 study found a marginally significant reduction in the risk of a composite outcome of major neonatal morbidity and perinatal death (3/74 [4.1%] vs 11/79 [13.9%]; relative risk, 0.29; 95% confidence interval, 0.08-1.00). When compared with β2-adrenergic receptor agonists, transdermal nitroglycerin was associated with a significant reduction in the risk of preterm birth at <34 and <37 weeks of gestation, admission to the neonatal intensive care unit, use of mechanical ventilation, and maternal side effects. There were no significant differences between transdermal nitroglycerin and nifedipine and magnesium sulfate in delivery within 48 hours of treatment and pregnancy prolongation, respectively. Overall, women who received transdermal nitroglycerin had a higher risk of headache.
CONCLUSION
Although transdermal nitroglycerin appears to be more effective than β2-adrenergic receptor agonists, the current evidence does not support its routine use as a tocolytic agent for the treatment of preterm labor. Further double-blind placebo-controlled trials are needed.
Topics: Administration, Cutaneous; Adrenergic beta-2 Receptor Agonists; Female; Humans; Magnesium Sulfate; Nifedipine; Nitroglycerin; Obstetric Labor, Premature; Pregnancy; Tocolytic Agents
PubMed: 23891631
DOI: 10.1016/j.ajog.2013.07.022 -
The Cochrane Database of Systematic... Dec 2015Heart failure is associated with high mortality and hospital readmissions. Beta-adrenergic blocking agents, angiotensin converting enzyme inhibitors (ACEIs), and... (Meta-Analysis)
Meta-Analysis Review
Nurse-led titration of angiotensin converting enzyme inhibitors, beta-adrenergic blocking agents, and angiotensin receptor blockers for people with heart failure with reduced ejection fraction.
BACKGROUND
Heart failure is associated with high mortality and hospital readmissions. Beta-adrenergic blocking agents, angiotensin converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) can improve survival and reduce hospital readmissions and are recommended as first-line therapy in the treatment of heart failure. Evidence has also shown that there is a dose-dependent relationship of these medications with patient outcomes. Despite this evidence, primary care physicians are reluctant to up-titrate these medications. New strategies aimed at facilitating this up-titration are warranted. Nurse-led titration (NLT) is one such strategy.
OBJECTIVES
To assess the effects of NLT of beta-adrenergic blocking agents, ACEIs, and ARBs in patients with heart failure with reduced ejection fraction (HFrEF) in terms of safety and patient outcomes.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials in the Cochrane Library (CENTRAL Issue 11 of 12, 19/12/2014), MEDLINE OVID (1946 to November week 3 2014), and EMBASE Classic and EMBASE OVID (1947 to 2014 week 50). We also searched reference lists of relevant primary studies, systematic reviews, clinical trial registries, and unpublished theses sources. We used no language restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing NLT of beta-adrenergic blocking agents, ACEIs, and/or ARBs comparing the optimisation of these medications by a nurse to optimisation by another health professional in patients with HFrEF.
DATA COLLECTION AND ANALYSIS
Two review authors (AD & JC) independently assessed studies for eligibility and risk of bias. We contacted primary authors if we required additional information. We examined quality of evidence using the GRADE rating tool for RCTs. We analysed extracted data by risk ratio (RR) with 95% confidence interval (CI) for dichotomous data to measure effect sizes of intervention group compared with usual-care group. Meta-analyses used the fixed-effect Mantel-Haenszel method. We assessed heterogeneity between studies by Chi(2) and I(2).
MAIN RESULTS
We included seven studies (1684 participants) in the review. One study enrolled participants from a residential care facility, and the other six studies from primary care and outpatient clinics. All-cause hospital admission data was available in four studies (556 participants). Participants in the NLT group experienced a lower rate of all-cause hospital admissions (RR 0.80, 95% CI 0.72 to 0.88, high-quality evidence) and fewer hospital admissions related to heart failure (RR 0.51, 95% CI 0.36 to 0.72, moderate-quality evidence) compared to the usual-care group. Six studies (902 participants) examined all-cause mortality. All-cause mortality was also lower in the NLT group (RR 0.66, 95% CI 0.48 to 0.92, moderate-quality evidence) compared to usual care. Approximately 27 deaths could be avoided for every 1000 people receiving NLT of beta-adrenergic blocking agents, ACEIs, and ARBs. Only three studies (370 participants) reported outcomes on all-cause and heart failure-related event-free survival. Participants in the NLT group were more likely to remain event free compared to participants in the usual-care group (RR 0.60, 95% CI 0.46 to 0.77, moderate-quality evidence). Five studies (966 participants) reported on the number of participants reaching target dose of beta-adrenergic blocking agents. This was also higher in the NLT group compared to usual care (RR 1.99, 95% CI 1.61 to 2.47, low-quality evidence). However, there was a substantial degree of heterogeneity in this pooled analysis. We rated the risk of bias in these studies as high mainly due to a lack of clarity regarding incomplete outcome data, lack of reporting on adverse events associated with the intervention, and the inability to blind participants and personnel. Participants in the NLT group reached maximal dose of beta-adrenergic blocking agents in half the time compared with participants in usual care. Two studies reported on adverse events; one of these studies stated there were no adverse events, and the other study found one adverse event but did not specify the type or severity of the adverse event.
AUTHORS' CONCLUSIONS
Participants in the NLT group experienced fewer hospital admissions for any cause and an increase in survival and number of participants reaching target dose within a shorter time period. However, the quality of evidence regarding the proportion of participants reaching target dose was low and should be interpreted with caution. We found high-quality evidence supporting NLT as one strategy that may improve the optimisation of beta-adrenergic blocking agents resulting in a reduction in hospital admissions. Despite evidence of a dose-dependent relationship of beta-adrenergic blocking agents, ACEIs, and ARBs with improving outcomes in patients with HFrEF, the translation of this evidence into clinical practice is poor. NLT is one strategy that facilitates the implementation of this evidence into practice.
Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Dose-Response Relationship, Drug; Drug Monitoring; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Practice Patterns, Nurses'; Randomized Controlled Trials as Topic; Stroke Volume; Time Factors
PubMed: 26689943
DOI: 10.1002/14651858.CD009889.pub2