Beta-blockers In Heart Failure Research Articles

The effect of sustained-release CARvedilol in patients with hypErtension and heart failure with preserved ejection fraction: a study protocol for a pilot randomized controlled trial (CARE-preserved HF).

Although beta-blockers improve clinical outcomes in heart failure with reduced ejection fraction, the benefit of beta-blockers in heart failure with preserved ejection fraction (HFpEF) is uncertain. Global longitudinal strain (GLS) is a robust predictor of heart failure outcomes, and recent studies have shown that beta-blockers are associated with improved survival in those with low GLS (GLS <14%) but not in those with GLS ≥14% among patients with LVEF ≥40%. Therefore, the objective of this trial is to evaluate the effect of sustained-release carvedilol (carvedilol-SR) on the outcome [N-terminal pro-B-natriuretic peptide (NT-proBNP) concentration] in patients with hypertension and HFpEF and will assess the differential effects of these drugs on the outcome, according to the GLS categories. This prospective randomized double-blind multicenter trial (CARE-preserved HF) will include 100 patients with HFpEF from three tertiary hospitals in South Korea. Patients with HFpEF and hypertension aged ≥20 years who have evidence of functional and structural heart disease on echocardiography and elevated natriuretic peptide will be enrolled. Eligible participants will be randomized 1:1 to either the carvedilol-SR group (n = 50) or the placebo group (n = 50). Patients in the carvedilol-SR group will receive 8, 16, 32, or 64 mg carvedilol-SR once daily for 6 months, and the dose of carvedilol will be up-titrated at the discretion of the treating physicians. The primary efficacy outcome was the time-averaged proportional change in N-terminal pro-B-natriuretic peptide concentration from baseline to months 3 and 6. We will also evaluate the differential effects of carvedilol-SR on primary outcomes according to GLS, using a cut-off of 14% or the median value. This randomized controlled trial will investigate the efficacy and safety of carvedilol-SR in patients with HFpEF and hypertension. ClinicalTrial.gov, identifier NCT05553314.

Genetic polymorphisms in ADRB1, ADRB2 and CYP2D6 genes and response to beta-blockers in patients with acute coronary syndrome

Betablockers (BBs) are prescribed for ischaemia in patients with acute coronary syndrome (ACS). In Spain, bisoprolol and carvedilol are the most prescribed BBs, but patients often had to discontinue them due to adverse effects. Single nucleotide polymorphisms (SNPs) in ADRB1, ADRB2 and CYP2D6 genes have strong evidence of pharmacogenetic association with BBs in heart failure or hypertension, but the evidence in ACS is limited. Therefore, our study focuses on investigating how these genes influence the response to BBs in ACS patients. We analysed the association between SNPs in ADRB1 Gly389Arg (rs1801253) and Ser49Gly (rs1801252), ADRB2 Gly16Arg (rs1042713) and Glu27Gln (rs1042714), and CYP2D* 6 (*2– rs1080985, *4- rs3892097, *10 – rs1065852) and the occurrence of bradycardia/hypotension events during one year of follow-up. We performed an observational study and included 285 ACS-PCI-stent patients. A first analysis including patients treated with bisoprolol and a second analysis including patients treated with other BBs were performed. We found that the presence of the G allele (Glu) of the ADRB2 gene (rs1042714; Glu27Gln) conferred a protective effect against hypotension-induced by BBs; OR (CI 95%) = 0,14 (0,03−0,60), p < 0.01. The ADRB2 (rs1042713; Gly16Arg) GG genotype could also prevent hypotensive events; OR (CI 95%) = 0.49 (0.28–0.88), p = 0015. SNPs in ADRB1 and CYP2D6 * 2, CYP2D6 * 4 weren´t associated with primary events. The effect of CYP2D6 * 10 does not seem to be relevant for the response to BBs. According to our findings, SNPs in ADRB2 (rs1042713, rs1042714) could potentially affect the response and tolerance to BBs in ACS-patients. Further studies are necessary to clarify the impact of ADRB2 polymorphisms.

Serotonin antidepressants and atrial fibrillation burden from cardiac implantable electronic devices.

Depression and anxiety show a bidirectional relationship with atrial fibrillation (AF). Antidepressant use is associated with a reduction in the incidence of AF. However, no studies have examined the relationship between antidepressant use and AF burden (time in AF). This retrospective cohort study examined cardiac implantable device-detected AF episodes and their relationship with antidepressant use, among other treatment factors. Consecutive patients from the Western Health Cardiology Department attending pacemaker checks between 2015 and 2021 were included. Patients with permanent AF were excluded, yielding 285 patients with no or paroxysmal AF, with a total of 772 patient encounters. Generalized estimating equations were used to model two processes: binary AF (present/absent) and the number of days in AF for patients with AF. Each yearly increase with age was associated with an increase in the odds of developing AF (OR 1.03 [1.00-1.05], p = .027). Male gender conferred a reduction in AF incidence (OR 0.30 [0.13-0.68], p = .004). Digoxin use was associated with incident AF (OR 4.43 [1.07-18.4], p = .04). Sotalol and heart-failure beta blocker use were associated with a decrease in AF burden (IRR 0.30 [0.12-0.78], p = .013 and 0.33 [0.14-0.81], p = .015). Selective serotonin reuptake inhibitor antidepressant use was associated with reduced AF burden (IRR 0.27 [0.09-0.81], p = .019), as was selective serotonin/noradrenaline reuptake inhibitor use (IRR 0.07 [0.03-0.15], p < .001). Older age, female gender and digoxin are associated with a higher odds of developing incident AF. Sotalol, heart failure beta blockers and serotonin-based antidepressants are associated with reduced AF burden. Further prospective study into the effects of antidepressants on atrial arrhythmias is warranted.

Role of hospitalists in Japan for heart failure in the elderly: single center retrospective cohort study

ABSTRACT Objective In Japan, the benefits of hospitalist physician-led care after heart failure have not been sufficiently demonstrated. We evaluated quality of care by the general internal medicine hospitalist (GIM-H) system for patients after acute heart failure and compared it with care by cardiologists. Methods This retrospective cohort study enrolled adult patients from within a two-year period who were admitted to our institution for heart failure. Primary outcome measures were medico-economic indicators: length of hospital stay and medical costs. Secondary outcomes included readmission within 30 days of discharge, death within 30 days of admission, rate of prescription of ACEI/ARB and beta-blockers for heart failure with reduced left ventricular ejection fraction, and the percentage of patients receiving bespoke written treatment plans after discharge. This was thought to represent quality of heart failure-specific care. Outcomes between the groups were compared by adjusting for background factors using a propensity score. Results We enrolled 404 patients, and 81 were assigned to each group after matching (mean age: 86 years, female: 64.2%, mean left ventricular ejection fraction: 53.2%). The GIM-H-treated group had a significantly shorter hospital stay (13.7 days vs. 21.8 days, P < 0.001), a significantly lower total medical cost (618,805 JPY vs. 867,857 JPY, P < 0.05) but a higher medical cost per day (48,010 JPY vs 42,813 JPY, P < 0.05) than the cardiologist-treated group. Other indicators were not significantly different. Conclusions : GIM-H physicians in Japan are suggested to be useful and effective in care of patients with heart failure. The hospitalist system may positively impact the health economic outcomes of such patients.

Physician Perspectives on the Use of Beta Blockers in Heart Failure With Preserved Ejection Fraction

β-blockers are commonly used in heart failure with preserved ejection fraction (HFpEF), even in the absence of a compelling indication and despite the potential to cause harm. Identifying reasons for β-blocker prescription in HFpEF could permit the development of strategies to reduce unnecessary use and potentially improve medication prescribing patterns in this vulnerable population. We administered an online survey regarding β-blocker prescribing behavior to physicians trained in internal medicine or geriatrics (noncardiology physicians) and to cardiologists at 2 large academic medical centers. The survey assessed the reasons for β-blocker initiation, agreement regarding initiation and/or continuation of β-blockers by another clinician, and deprescribing behavior. The response rate was 28.2% (n=231). Among respondents, 68.2% reported initiating β-blockers in patients with HFpEF. The most common reason for initiating a β-blocker was for treatment of an atrial arrhythmia. Notably, 23.7% of physicians reported initiating a β-blocker without an evidence-based indication. When a β-blocker was considered not necessary, 40.1% of physicians reported they were rarely or never willing to deprescribe. The most common reason for not deprescribing a β-blocker when the physician felt that a β-blocker was unnecessary was the concern about interfering with another physicians' treatment plan (76.6%). In conclusion, a significant proportion of noncardiology physicians and cardiologists report prescribing β-blockers to patients with HFpEF, even when evidence-based indications are absent, and rarely deprescribe β-blockers in these scenarios.

Implications of Under-Reporting Medication Side Effects: Beta-Blockers in Heart Failure as a Case Example.

Perceiving medication side effects but not reporting them to a clinician is common. Patterns of "under-reporting" and their implications are not well described. We aimed to address this gap by examining patterns of under-reporting perceived side effects of beta-blockers among patients with heart failure. In 2016, a survey that evaluated medication-taking behavior was administered to 1114 participants (46.5% response rate) from The Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort with prior adjudicated heart failure hospitalization or a heart failure Medicare claim. We examined the results of survey respondents who reported taking a beta-blocker to understand patterns of under-reporting perceived beta-blocker side effects. We defined an under-reporter as a participant who perceived experiencing a side effect from their beta-blocker but did not share it with their clinician (according to survey responses). We conducted a multivariable logistic regression analysis to identify determinants of being an under-reporter. Co-variates included age, sex, race, income, level of education, geographical location, and pill burden. We also examined whether under-reporters differed in self-reported medication adherence and willingness to take additional medication to prevent a future healthcare encounter compared to participants who reported perceived side effects to their clinicians and those who did not experience side effects. Among 310 respondents, 28% (n = 87) were under-reporters. Black race (odds ratio 2.11, confidence interval 1.21-3.67) and education less than college (odds ratio 2.00, confidence interval 1.09-3.67) were associated with being an under-reporter. Self-reported medication adherence was similar between groups (under-reporters: 46.3%; those who reported perceived side effects: 49.4%; those who did not experience side effects: 45.0%); under-reporters were more frequently unwilling to take additional medication to prevent a doctor's visit (18.9% vs 12.1% vs 10.8%), emergency room visit (21.6% vs 13.3% vs 9.9%), and hospitalization (17.6% vs 10.8% vs 9.0%) compared with the other groups. We conclude that under-reporting perceived side effects of beta-blockers among adults with heart failure is common, is associated with Black race and low education, and may contribute to patient willingness to take additional medication to prevent future medical encounters.

Evaluating Guideline Directed Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction Post-coronary Artery Bypass Grafting

Background: Limited evidence regarding the use of guideline directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) undergoing coronary artery bypass grafting (CABG) is available. Objective: The purpose of this study was to characterize prescription of HFrEF GDMT use before and after CABG. Methods: A retrospective analysis of adult patients with an ejection fraction ≤40% undergoing CABG was performed. The primary objective was to evaluate patients receiving HFrEF GDMT, defined as a heart failure beta-blocker (HFBB) and a renin-angiotensin inhibitor preoperatively and postoperatively. Secondary outcomes included dosing, percent of patients on each individual therapy, mineralocorticoid receptor antagonist (MRA) use, and the combination thereof. The follow up period was 1 year. Results: Thirty-eight patients met criteria for inclusion. Prior to CABG, 52.6% of patients were receiving HFrEF GDMT. The prescribing rate of HFrEF GDMT was not significantly higher at any point within 1 year postoperatively (P = .299). The rate of renin-angiotensin inhibitors, HFBB, and aldosterone antagonists use significantly increased from 13.2% preoperatively to 36.8% at 1 year after CABG (P = .022). Doses of individual therapies were not significantly different across all time points preoperatively and postoperatively. Conclusion: HFrEF GDMT use and doses of individual therapies after CABG were not maximized. Collaborative efforts between cardiac surgeons, heart failure cardiologists, and pharmacists could be used to optimize HFrEF GDMT use and dose titration.

Perspective on the Role of Four Beta-blockers in Heart Failure.

The current recommendations of the American College of Cardiology/ American Heart Association and a previous Bayesian analysis clearly show a mortality benefit with the use of β- blockers in chronic HF, especially for bisoprolol, carvedilol, and sustained-release metoprolol succinate. The main objective was to report the evidence on the use of the afore-mentioned β-blockers in subjects with heart failure and to characterize the stages of heart failure in response to the four different β-blockers. Furthermore, it shed light on the patient's satisfaction and improved quality of life using the afore-mentioned β-blockers in subjects with heart failure. The current perspective presented the clinical outcomes, including hospitalization, morbidity, mortality, patient's satisfaction, and quality of life, of four beta (β)-blockers, namely bisoprolol, carvedilol, metoprolol succinate, and nebivolol in different stages of heart failure. The use of these three agents should be recommended for all stable subjects with current or previous symptoms of heart failure and heart failure with reduced ejection fraction unless there is any contraindication. The fore-mentioned β-blockers (bisoprolol, carvedilol, and metoprolol succinate) can be initiated early, even in stable and symptom-free (at rest) subjects with heart failure. β-blockers in heart failure should be commenced at small doses and then titrated upward as tolerated to achieve the desired clinical effects on heart rate and symptom control. Cardiologists should weigh the benefit-risk in subjects with heart failure and other coexisting cardiovascular problems such as atrial fibrillation and diabetes.

Perceived risk profile and treatment optimization in heart failure: an analysis from BIOlogy Study to TAilored Treatment in chronic heart failure.

BackgroundAchieving target doses of angiotensin‐converting‐enzyme inhibitor/angiotensin‐receptor blockers (ACEi/ARB) and beta‐blockers in heart failure with reduced ejection fraction (HFrEF) is often underperformed. In BIOlogy Study to TAilored Treatment in chronic heart failure (BIOSTAT‐CHF) study, many patients were not up‐titrated for which no clear reason was reported. Therefore, we hypothesized that perceived‐risk profile might influence treatment optimization.MethodsWe studied 2100 patients with HFrEF (LVEF≤40%) to compare the clinical characteristics and adverse events associated with treatment up‐titration (after a 3‐month titration protocol) between; a) patients not reaching target doses for unclear reason; b) patients not reaching target doses due to symptoms and/or side effects; c) patients reaching target doses.ResultsFor ACEi/ARB, (a), (b) and (c) was observed in 51.3%, 25.9% and 22.7% of patients, respectively. For beta‐blockers, (a), (b) and (c) was observed in 67.5%, 20.2% and 12.3% of patients, respectively. By multinomial logistic regression analysis for ACEi/ARB, patients in group (a) and (b) had lower blood pressure and poorer renal function, and patients in group (a) were older and had lower ejection fraction. For beta‐blockers, patients in group (a) and (b) had more severe congestion and lower heart rate. At 9 months, adverse events (i.e., hypotension, bradycardia, renal impairment, and hyperkalemia) occurred similarly among the three groups.ConclusionsPatients in whom clinicians did not give a reason why up‐titration was missed were older and had more co‐morbidities. Patients in whom up‐titration was achieved did not have excess adverse events. However, from these observational findings, the pattern of subsequent adverse events among patients in whom up‐titration was missed cannot be determined.

Frequency of use and Indications for Beta-Blockers in Heart Failure with Preserved Ejection Fraction

Aim To evaluate trends in beta-blocker prescribing and incidence of possible reasons for beta-blocker administration, including arterial hypertension (AH), atrial fibrillation (AF), ischemic heart disease (IHD), and myocardial infarction, in participants of clinical studies enrolling patients with chronic heart failure with preserved ejection fraction (CHF-PEF).Material and methods A systematic literature search was performed in the PubMed and EMBASE databases. The study included RCSs of pharmacological therapies for patients with CHF-PEF conducted from 1993 through 2019. Studies of beta-blocker efficacy or those including a specific population (CHF-PEF+IHD or CHF-PEF+AH, etc.) were excluded from the analysis. Baseline characteristics of patients, incidence rate of beta-blocker prescribing, and prevalence of AH, AF, IHD, and MI were recorded. Trends in prevalence of concomitant diseases and the proportion of patients using beta-blockers by the year of enrollment to the study were analyzed with the Mann-Kendall test.Results 14 RCSs of 718 selected publications completely met the inclusion and exclusion criteria. Beta-blocker prescribing significantly increased between 1993 and 2019 (tau=0.51; p=0.014) and reached 80 % in recent studies. Furthermore, prevalence of IHD, MI, AH, and AF did not significantly change among the RCS participants (p&gt;0.05 for all). However, while for AH and AF, a tendency toward an increasing prevalence (tau=0.4; p=0.055 and tau=0.043; p=0.063, respectively) could be considered and became statistically significant for AF when the ALDO-DHF study was excluded from the analysis (tau=0.5; p=0.042), the MI prevalence tended to decrease (tau= -0.73; p=0.06).Conclusion Beta-blocker prescribing to patients upon inclusion into RCSs for CHF-PEF has significantly increased for the recent 20 years while the incidence of formal reasons for beta-blocker administration (AF, AH, MI, IHD) did not significantly change.

The impact of right ventricular dysfunction on the effectiveness of beta-blockers in heart failure with preserved ejection fraction

BackgroundWhether beta-blockers improve the clinical outcomes for heart failure with preserved ejection fraction (HFpEF) characterized by variable cardiac pathophysiology remains controversial. This study aimed to clarify cardiac dysfunction affecting the effectiveness of beta-blockers in patients with HFpEF. MethodsFour hundred and nine patients with HFpEF were enrolled retrospectively, and echocardiography and jugular venous pulse were examined to evaluate their cardiac function. The left ventricular (LV) ejection fraction, mean mitral e′, mean mitral E/e′ ratio, right ventricular (RV) systolic pressure, tricuspid annular plane systolic excursion, and jugular venous pulse waveform were used as indicators of LV contractility, LV relaxation ability, LV filling pressure, RV afterload, RV contractility, and RV diastolic function, respectively. The dominant ‘Y’ descent of the jugular venous waveform was detected as an established hemodynamic sign of a less-distensible right ventricle. ResultsTwo hundred and thirteen patients with HFpEF received beta-blockers. During a mean follow-up period of 33±20 months, 92 patients had cardiovascular events of HFpEF. A less-distensible right ventricle and RV systolic pressure were independent risk factors for cardiovascular events of HFpEF (p=0.016 and p=0.002, respectively). The administration of beta-blockers was not an independent factor, but patients with HFpEF and a distensible right ventricle who received them had fewer events than those who did not (p=0.017). Patients with HFpEF and lower RV systolic pressure (<33mmHg) who received beta-blockers also had fewer events than those who did not (p=0.028). A less-distensible right ventricle or higher RV systolic pressure (≥33mmHg) prevented the beneficial effects of beta-blockers for HFpEF. ConclusionsBeta-blocker usage was not associated with a reduction in the rate of cardiovascular events of HFpEF, but it may have beneficial effects on HFpEF with preserved RV function. RV function may serve as an indicator to administer beta-blockers to patients with HFpEF.

Betabloqueantes en la insuficiencia cardiaca con fracción de eyección preservada: ¿prescribir o deprescribir?

Betabloqueantes en la insuficiencia cardiaca con fracción de eyección preservada: ¿prescribir o deprescribir?

Beta-blocker target dosing and tolerability in a dedicated heart failure clinic in Johannesburg.

Despite the significant clinical benefits of beta-blockers in heart failure with reduced ejection fraction (HFrEF), prescription for and adherence to these agents is reported to be poor. There are few data on the use and tolerance of beta-blocker therapy in patients with HFrEF in South Africa and it is unknown whether these patients would benefit from further heart rate-lowering therapy. Data from all patients with HFrEF attending the heart failure clinic of Charlotte Maxeke Johannesburg Academic Hospital from January 2000 to December 2014 were retrospectively collected. We first determined the rates of beta-blocker intolerance in this population and then categorised the patients according to their most recent dose of beta-blocker (low, moderate or target dose) in order to identify factors associated with beta-blocker intolerance. Lastly, we used the data to identify patients who would be suitable for further treatment with heart rate-lowering therapy. Five hundred patients, with a median follow up of 58.7 months, were identified during the study period. Black South Africans constituted the majority (66.4%) and most patients had HFrEF due to hypertension (32.8%). At the last recorded clinic visit at the end of the study period, 489 patients (97.8%) were taking a beta-blocker with 59.8% prescribed a beta-blocker at target dose. Consistent with previous data, bradycardia was the commonest cause for failing to reach target beta-blocker dose. Only 61 (12%) patients were on no (n = 11) or low (n = 50) dose of beta-blocker at final clinic visit. As per current guidelines, only 10.6% (n = 53) of this cohort of patients would qualify for further treatment with heart rate-lowering therapy. In a dedicated heart failure clinic in South Africa, beta-blockers were well-tolerated in the treatment of HFrEF. The potential role of specific heart rate-lowering therapy in patients treated adequately with heart failure medication and proper up-titration of beta-blockers is relatively small.

Higher versus lower doses of ACE inhibitors, angiotensin-2 receptor blockers and beta-blockers in heart failure with reduced ejection fraction: Systematic review and meta-analysis.

BackgroundCurrent heart failure (HF) guidelines recommend titrating angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) and beta-blockers (BBs) to target doses used in pivotal placebo-controlled randomized controlled trials (RCTs). Despite a number of RCTs comparing different doses (i.e. higher versus lower doses) of ACEIs, ARBs and BBs, the effects of higher versus lower doses on efficacy and safety remains unclear. For this reason, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of higher versus lower doses of ACEIs, ARBs and BBs in patients with HFrEF.MethodsWe searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) via Ovid from inception to April 25th, 2018 and opentrials.net and clinicaltrials.gov for relevant trials that compared different doses of medications in heart failure. We analyzed trials by drug class (ACEIs, ARBs, and BBs) for efficacy outcomes (all-cause mortality, cardiovascular mortality, all-cause hospitalizations, HF hospitalizations, HF worsening). For safety outcomes, we pooled trials within and across drug classes.ResultsOur meta-analysis consisted of 14 RCTs. Using GRADE criteria, the quality of evidence for ACEIs and ARBs was assessed as generally moderate for efficacy and high for adverse effects, whereas overall quality for BBs was very low to low. Over ~2–4 years higher versus lower doses of ACEIs, ARBs or BBs did not significantly reduce all-cause mortality [ACEIs relative risk (RR) 0.94 (95% confidence interval 0.87–1.02)], ARBs RR 0.96 (0.87–1.04), BBs RR 0.25 (0.06–1.01)] or all cause hospitalizations [ACEIs relative risk (RR) 0.94 (95% confidence interval 0.86–1.02)], ARBs RR 0.98 (0.93–1.04), BBs RR 0.93 (0.39–2.24)]. However, all point estimates favoured higher doses. Higher doses of ARBs significantly reduced hospitalization for HF [RR 0.89 (0.80–0.99)– 2.8% ARR], and higher doses of ACEIs and ARBs significantly reduced HF worsening [RR 0.85 (0.79–0.92)– 5.1% ARR and 0.91 (0.84–0.99)– 3.2% ARR, respectively] compared to lower doses. None of the differences between higher versus lower doses of BBs were significant; however, precision was low. Higher doses of these medications compared to lower doses increased the risk of discontinuation due to adverse events, hypotension, dizziness, and for ACEIs and ARBs, increased hyperkalemia and elevations in serum creatinine. Absolute increase in harms for adverse effects ranged from ~ 3 to 14%.ConclusionsHigher doses of ACEIs and ARBs reduce the risk of HF worsening compared to lower doses, and higher doses of ARBs also reduce the risk of HF hospitalization but the evidence is sparse and imprecise. Higher doses increase the chance of adverse effects compared to lower doses. Evidence for BBs is inconclusive. These results support initially always starting at low doses of ACEIs/ARBs and only titrating the dose up if the patient tolerates dose increases.

Cardiovascular Diseases and Drug Treatment in Patients with the History of Cerebral Stroke: Data of the Outpatient Registry REGION

Aim. To evaluate the structure of combined cardiovascular diseases, drug treatment and observation of patients with a history of stroke in the framework of prospective outpatient registries. Material and methods. The study was conducted based on 3 outpatient clinics of Ryazan city. Patients with a history of acute cerebrovascular accident (ACVA) of any remoteness (AR) were included into ACVA-AR outpatient registry (n=511). Patients who had visited the outpatient clinics for the first time (FT) after cerebral stroke (n=475) were included into the ACVA-FT outpatient registry. The structure of the cardiovascular diseases (CVD), compliance with the clinical recommendations of the prescribed and received drug therapy were evaluated. The proportion of patients with dispensary observation for CVD, using preferential drug provision was determined. Results. A combination of 2 or more CVDs was found in 84.4% and 82.5% of cases, and severe cardiovascular multimorbidity (3-4 CVDs) – in 69% and 64% of cases, respectively, in ACVA-AR and ACVA-FT registers. Compliance with the clinical guidelines prescribed and received drug therapy was insufficient at the outpatient stage. Necessary prescription of drugs with a proven beneficial effect on the prognosis were observed significantly more frequent in the ACVA-FT registry, compared to the ACVA-AR registry at the enrolling stage of the study (p&lt;0.05): statins for stroke – 50.1% vs 25.2%; statins for coronary heart disease (CHD) – 47.2% vs 27.9%; antiplatelet agents for CHD without atrial fibrillation – 65.6% vs 54.3%; anticoagulants for atrial fibrillation – 17.7% vs 9.3%; beta-blockers for heart failure 43.5% vs 33.1%, respectively. After 2-3 years of the follow-up frequency of prognostically significant prescriptions in patients of the compared registries were not significantly different, except prescriptions for statin therapy (47.6% vs 21.3%, respectively). The prognostically significant prescriptions during the enrolling stage in ACVA-AR and ACVA-FT registries occurred in 44.4% and 54% of the total number of proper prescriptions, and in the long-term follow-up period – in 55% and 57%, respectively; and the dispensary observation coverage was only 35.0% and 31.8%, respectively. According to patient contact only 21-24% of patients used the system of preferential drug provision at the stage of inclusion into the registers, and after 2-3 years of follow-up – 1.5-2 times less (12-14%). Conclusion The results of the study REGION found the presence of cardiovascular multimorbidity in 83% of patients with a history of stroke, insufficient quality of prescribed drug therapy in the out-patient clinic, especially in the ACVA-AR registry. The quality of medical treatment of patients improved within 2-3-year follow-up after the reference visit to out-patient clinic, but not sufficiently. Increase in dispensary observation coverage and optimization of the system of preferential drug provision are also important reserves for improving the quality of treatment of patients with a history of stroke, as well as prevention of cardiovascular complications.

Accuracy of Side Effect Reporting in Australian Prescribing Information

The beneficial effects observed in patients taking inert substances placebo effects are well known. Less recognised are the adverse effects from these inert substances - the nocebo effect. Patients, perceptions strongly influence nocebo effects; thus to distinguish true adverse effects from nocebo effects requires blinding [[1]Planès S. Villier C. Mallaret M. The nocebo effect of drugs.Pharmacology Research & Perspectives. 2016; 4Google Scholar]. Although beta-blockers have proven efficacy in heart failure, use may be limited by concerns about side effect. Side effect information in Australian prescribing information may overestimate the true rate of side effects and limit usage of these life-preserving heart failure medications. We compared the adverse effects listed in a systematic review of randomised control trials of beta-blockers with the adverse effects listed in reference texts: The Australian Medicines Handbook Online and MIMS Online [2Barron A.J. Zaman N. Cole G.D. Wensel R. Okonko D.O. Francis D.P. Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control: recommendations for patient information.International journal of cardiology. 2013; 168: 3572-3579Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar, 3Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd; 2019. January. Available from http://amhonline.net.au.Google Scholar, 4Metoprolol. In. MIMS Online. St Leonards, Australia; MIMS Australia. Available from http://www.mimsonline.com.au.Google Scholar]. 25 of 33 adverse effects listed in the systematic review were listed in AMH or MIMS. Of all listed adverse effects the rates were comparable for 10/25. Adverse effects were overestimated in 15/25 cases. Twelve adverse effects listed as common in reference texts were actually less common in the active treatment arm of randomised control trials. This study demonstrates that Australian reference texts overestimate the true rate of adverse effects attributable to beta-blockers and misinform patients and clinicians. As recognised by Barron et al. [[2]Barron A.J. Zaman N. Cole G.D. Wensel R. Okonko D.O. Francis D.P. Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control: recommendations for patient information.International journal of cardiology. 2013; 168: 3572-3579Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar] overestimating these adverse effects may lead to clinicians and patients ceasing beneficial medications. Reviewing how information on adverse effects is published in Australian prescribing references may improve treatment of many conditions and reduce discontinuation of proven therapies.

A comprehensive review of chronic heart failure pharmacotherapy treatment approaches in African Americans.

Background:Our aim was to review the published literature evaluating treatment approaches for chronic heart failure (HF), notably as it relates to African American patients.Method:We undertook a comprehensive database search (1986–2017) of PubMed, EMBASE, and Ovid/MEDLINE utilizing terms ‘African American’, ‘black’, ‘chronic heart failure’, ‘heart failure’, ‘medication’, ‘chronic therapy’, and ‘clinical trials’. Additional notable studies were obtained from ClinicalTrials.gov. Studies published in English that examine treatment modalities of chronic HF in African American and non-African American patients were included.Results:Examples of current gaps worthy of investigation include whether to maximize thiazides and calcium-channel blockers prior to adding renin–angiotensin system (RAS) inhibitors or beta blockers in HF with preserved ejection fraction; whether hydralazine/isosorbide dinitrate (ISDN) should be initiated during earlier HF stages; whether to prioritize hydralazine/ISDN over other agents such as RAS inhibitors; varying response of African Americans to different agents within drug classes; and the role of mineralocorticoid receptor antagonists.Conclusion:Further studies are needed in order for consensus guidelines to clarify how best to treat this population.

Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic

Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated.Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p > .05) and the most common side effect was hypotension.Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications.

Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials.

Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF ≥ 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 ≥ 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF ≥ 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF ≥50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis. Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.

Clinical Tolerability of Generic vs. Brand Beta Blockers in Heart Failure with Reduced Left Ventricular Ejection Fraction: A Retrospective Cohort from Heart Failure Clinic

Background: Beta blockers have been shown to decrease mortality and morbidity in Heart Failure Reduced Ejection Fraction (HFrEF) patients. However, the side effects are also dose-related leading to the underdosing. Cost constraint may be one of limitations of appropriate beta blocker used which can be improved with generic drug. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportions of patients received at least 50% target dose of beta blocker between generic and brand beta blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients receiving generic and brand beta blocker respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, NYHA class, LVEF, rate of receiving ACEI, ARB or spironolactone. Patients receiving brand beta blocker had less resting heart rate at baseline (74.9 and 84.2 bpm, p=0.001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 vs. 44.5% and 48.0 vs. 55.0%, p>0.05 respectively). Rate of side effects was not different between groups (32.3 vs. 29.5%, p>0.05) and most common side effect was hypotension. Conclusion: This study demonstrated that beta blocker tolerability was comparable between brands and generic. Generic or brand beta blockers should be prescribed to HFrEF patients without contraindication.