Concomitant Use Of Beta-blockers Research Articles

Clinical and pharmacological factors influencing serum clozapine and norclozapine levels.

Clozapine (CLO) is a very effective antipsychotic, whose use is associated with dose-dependent risk of complications. Due to high interindividual variability in CLO metabolism, there is a need to identify factors affecting the blood concentrations of CLO and its active metabolite, norclozapine (NCLO). A total of 446 blood samples (collected from 233 women and 213 men, aged from 18 to 77 years) were included in this study and analyzed for CLO and NCLO concentrations. The patients were treated at a psychiatric hospital in Warsaw in the years 2016-2021. Serum CLO and NCLO concentrations were determined with high-performance liquid chromatography coupled to UV. The following factors were shown to increase serum CLO and NCLO levels: higher CLO dose (p < 0.001), female sex (p < 0.001), nonsmoker status (p < 0.001), the use of more than two additional psychotropic drugs (only in the case of CLO; p = 0.046), concomitant use of beta-blockers (for CLO p = 0.049; for NCLO p < 0.001), and older age (for CLO p < 0.001; for NCLO p = 0.011). Despite the use of CLO at daily doses within the recommended range (200-450mg), the evaluated serum CLO and NCLO levels were within the therapeutic ranges in only 37% and 75% of cases, respectively, with 5.6% of cases exceeding the CLO toxicity threshold. The use of CLO at recommended doses does not guarantee achieving therapeutic concentrations of CLO or NCLO. Women and nonsmokers were at the highest risk of having toxic CLO levels.

The effect of concomitant beta-blocker use on survival in patients with metastatic renal cell carcinoma treated with a vascular endothelial growth factor receptor inhibitors in the first line.

Vascular endothelial growth factor (VEGF) inhibition is one of the cornerstones of treatment in the treatment of metastatic renal cell carcinoma (mRCC). Since RCC is a disease of advanced age and hypertension as a side effect of VEGF receptor inhibitors, beta-blocker use is common in these patients. We aimed to compare the treatment efficacy and survival results in case of concomitant use of these two drugs due to the inhibition of VEGF in beta-blockers. A total of 121 patients with a diagnosis of mRCC who used sunitinib or pazopanib in first-line therapy were included in the study. These patients were divided into two groups as those using concomitant beta-blockers and those not using them. The median overall survival (mOS) of the patient using sunitinib or pazopanib and concomitant beta-blocker was 47 (95% CI 29.0-65.0) months, and the mOS of those not using concomitant beta-blocker was 18 (95% CI 8.9-27.1) months (p < 0.001). The median progression-free survival (mPFS) of the patients using sunitinib or pazopanib and concomitant beta-blocker was 20.4 (95% CI 4.5-40.1) months, and the mPFS of those not using it was 11.4 (95% CI 5.9-16.9) months (p = 0.042). Concomitant beta-blocker use was found to be a good prognostic factor for OS in the multivariate analysis (p = 0.029). In the multivariate analysis, concomitant beta-blocker use had a trend towards statistical significance for PFS (p = 0.062). Concomitant use of betablockers with sunitinib or pazopanib is associated with longer overall survial and progression free survival.

In-Hospital Management and Long-term Clinical Outcomes and Adherence in Patients With Acute Decompensated Heart Failure: Primary Results of the First Brazilian Registry of Heart Failure (BREATHE)

Heart failure (HF), a common cause of hospitalization, is associated with poor short-term clinical outcomes. Little is known about the long-term prognoses of patients with HF in Latin America. BREATHE was the first nationwide prospective observational study in Brazil that included patients hospitalized due to acute heart failure (HF). Patients were included during 2 time periods: February 2011-December 2012 and June 2016-July 2018 In-hospital management, 12-month clinical outcomes and adherence to evidence-based therapies were evaluated. A total of 3013 patients were enrolled at 71 centers in Brazil. At hospital admission, 83.8% had clear signs of pulmonary congestion. The main cause of decompensation was poor adherence to HF medications (27.8%). Among patients with reduced ejection fraction, concomitant use of beta-blockers, renin-angiotensin-aldosterone inhibitors and spironolactone decreased from 44.5% at hospital discharge to 35.2% at 3 months. The cumulative incidence of mortality at 12 months was 27.7%, with 24.3% readmission at 90 days and 44.4% at 12 months. In this large national prospective registry of patients hospitalized with acute HF, rates of mortality and readmission were higher than those reported globally. Poor adherence to evidence-based therapies was common at hospital discharge and at 12 months of follow-up.

Could the concomitant use of beta blockers with bevacizumab improve survival in metastatic colon cancer?

Drug-drug interactions are sometimes neglected in oncology practice. Due to drug pharmacokinetic and pharmacodynamic interactions, clinically increased or decreased drug effects and increased or decreased adverse effects may occur. Considering that the concomitant use of these two drugs that affect vascular endothelial growth factor receptor (VEGFR) may cause pharmacological potentiation or additive interaction, we aimed to evaluate the survival outcomes of concomitant use of bevacizumab and beta blockers in patients with metastatic colorectal cancer (mCRC). In total, 181 patients with mCRC administered with bevacizumab plus cytotoxic chemotherapy regimen in a first-line setting were divided into two groups: concomitant beta-blocker user and nonuser. The median overall survival (mOS) was 35.9 (95% CI: 27.9-43.9) months in the beta-blocker-using group and 29.6 (95% CI: 27.9-43.9) months in the beta-blocker-non-using group (p = 0.054). The median progression-free survival (mPFS) was 16.1 (95% CI: 12.4-19.9) months in the beta-blocker-using group and 12.8 (95% CI: 10.6-15.0) months in the beta-blocker-non-using group (p = 0.006). The multivariate analysis revealed that beta-blocker use was an independent predictor of mPFS (HR: 0.66, 95% CI: 0.46-0.93, p = 0.018) and mOS (HR: 0.57, 95% CI: 0.36-0.91, p = 0.02). This study demonstrated that concomitant usage of beta blockers improved both survival outcomes, irrespective of the kind of beta blocker.

Long-term use of renin-angiotensin-system inhibitors after acute myocardial infarction is not associated with survival benefits: Analysis of data from the Korean acute myocardial infarction registry-national institutes of health registry.

IntroductionRenin-angiotensin-system inhibitors (RASi) have shown survival benefits after acute myocardial infarction (MI), but the role of routine long-term use of RASi remains unclear. Thereby, we explored the therapeutic effects of RASi medication at 1-year follow-up from acute MI.MethodsUsing the nationwide Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) registry, we included and analyzed 10,822 subjects. Patients were stratified into those taking RASi at 1-year follow-up (n = 7,696) and those not taking RASi at 1-year follow-up (n = 3,126). Patients were followed up for 2-years from the 1-year follow-up; 2-year all-cause mortality and cardiac mortality were analyzed as primary and secondary outcomes, respectively.ResultsThe use of RASi at 1-year follow-up was not associated with decreased all-cause mortality (log-rank P = 0.195) or cardiac mortality (log-rank P = 0.337). In multivariate analyses, RASi medication at 1-year follow-up did not reduce all-cause mortality (P = 0.758) or cardiac mortality (P = 0.923), while RASi medication at discharge substantially reduced 1-year all-cause and cardiac mortality. Treatment with either an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker at 1-year follow-up did not show survival benefits from 1-year follow-up, respectively. The use of RASi at 1-year follow-up did not show a prognostic interaction between previous history of chronic kidney disease, post-MI acute heart failure, concomitant use of beta-blockers at 1-year follow-up, or 1-year LVEF.ConclusionAcute MI patients taking RASi at 1-year follow-up were not associated with improved 2-year all-cause mortality or cardiac mortality from the 1-year follow-up. This study provides valuable information regarding tailored medication strategy after acute MI.Clinical trial registration[www.ClinicalTrials.gov], identifier [KCT0000863].

Beta-blockers and Ambulatory Inotropic Therapy

Continuous infusion of ambulatory inotropic therapy (AIT) is increasingly used in patients with end-stage heart failure (HF). There is a paucity of data concerning the concomitant use of beta-blockers (BB) in these patients. We retrospectively reviewed all patients discharged from our institution on AIT. The cohort was stratified into 2 groups based on BB use. The 2 groups were compared for differences in hospitalizations due to HF, ventricular arrhythmias and ICD therapies (shock or antitachycardia pacing). Between 2010 and 2017, 349 patients were discharged on AIT (95% on milrinone); 74% were males with a mean age of 61 ± 14 years. BB were used in 195 (56%) patients, whereas 154 (44%) did not receive these medications. Patients in the BB group had longer duration of AIT support compared to those in the non-BB group (141 [1-2114] vs 68 [1-690] days). After adjusting for differences in baseline characteristics and indication for AIT, patients in the BB group had significantly lower rates of hospitalizations due to HF (hazard ratio [HR] 0.61 (0.43-0.86); P = 0.005), ventricular arrhythmias (HR 0.34 [0.15-0.74]; P = 0.007) and ICD therapies (HR 0.24 [0.07-0.79]; P = 0.02). In patients with end-stage HF on AIT, the use of BB with inotropes was associated with fewer hospitalizations due to HF and fewer ventricular arrhythmias.

Digoxin use in contemporary heart failure with reduced ejection fraction: an analysis from the Swedish Heart Failure Registry.

Digoxin is included in some heart failure (HF) guidelines but controversy persists about the true role for and impact of treatment with this drug, particularly in the absence of atrial fibrillation (AF). The aim of this study was to assess the association between clinical characteristics and digoxin use and between digoxin use and mortality/morbidity in a large, contemporary cohort of patients with HF with reduced ejection fraction (HFrEF) stratified by history of AF. Patients with HFrEF (EF<40%) enrolled in the Swedish HF registry between 2005 and 2018 were analysed. The independent association between digoxin use and patient characteristics was assessed by logistic regression, and between digoxin use and outcomes [composite of all-cause mortality or HF hospitalization (HFH), all-cause mortality, and HFH] by Cox regressions in a 1:1 propensity score matched population. Digoxin use was analysed at baseline and as a time-dependent variable. Of 42 456 patients with HFrEF, 16% received digoxin, 29% in the AF group and 2.8% in the non-AF group. The main independent predictors of use were advanced HF, higher heart rate, history of AF, preserved renal function, and concomitant use of beta blockers. Digoxin use was associated with lower risk of all-cause death/HFH [hazard ratio (HR): 0.95; 95% confidence interval (CI): 0.91-0.99] in AF, but with higher risk in non-AF (HR: 1.24; 95% CI: 1.09-1.43). Consistent results were observed when digoxin use was analysed as a time-dependent variable. The great majority of digoxin users had a history of AF. Digoxin use was associated with lower mortality/morbidity in patients with AF, but with higher mortality/morbidity in patients without AF.

The use of angiotensin receptor blockers is associated with greater recovery of cardiac function than angiotensin-converting-enzyme inhibitors among patients with dilated cardiomyopathy

Abstract Background We previously showed that angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) were associated with heart failure with recovered ejection fraction (HFrecEF) in patients with dilated cardiomyopathy (DCM). However, the different effects of these drugs on cardiac reverse remodeling have not been fully elucidated. The aim of this study was to assess comparative effectiveness of ACEi versus ARB on recovery of left ventricular ejection fraction (LVEF) among patients with DCM. Methods We analyzed the clinical personal records of DCM, a national database of Japanese Ministry of Health, Labour and Welfare, from 2003 to 2014. Patients with LVEF &amp;lt;40% and on either ACEi or ARB were included. Eligible patients were divided into two groups according to the use of ACEi or ARB. A one-to-one propensity case-matched analysis was used. A propensity score was estimated by fitting a logistic-regression model which adjusted for age, sex, duration of HF, NYHA functional class (I-II vs. III-IV), systolic blood pressure, diastolic blood pressure, heart rate, atrial fibrillation, pacing, left bundle branch block, LVEF, hypertension, diabetes mellitus, hyperuricemia, chronic kidney disease, B-type natriuretic peptide (BNP), beta-blockers, mineralocorticoid receptor antagonists, loop diuretics, thiazides, digitalis, amiodarone, and oral inotropes. The primary outcome was defined as LVEF ≥40% at 3 years of follow-up. Results Out of 4,618 eligible patients, 2,238 patients received ACEi and 2,380 patients received ARB. Propensity score matching yielded 1,341 pairs. Mean age was 56.0 years and 2,041 (76.1%) was male. Mean LVEF was 27.6%, and median duration of HF was 1 year. The primary outcome was observed more frequently in ARB group than in ACEi group (59.8% vs. 54.1%; odds ratio [OR] 1.26; 95% confidence interval [CI] 1.08–1.47; P=0.003). The change in LVEF from baseline to 3 years of follow-up was greater in ARB group than in ACEi group (15.8±0.4 vs. 14.0±0.4%, P=0.002). In the ACEi group, 946 patients (70.6%) continued to receive ACEi at 3 years of follow-up, while 1,088 patients (81.3%) continued to receive ARB in the ARB group. Per-protocol analysis consistently showed that ARB increased the prevalence of HFrecEF (62.0% vs. 54.0%; OR 1.39; 95% CI 1.17–1.66; P&amp;lt;0.001). Subgroup analysis showed that ARB increased frequency of HFrecEF regardless systolic blood pressure, heart rate, LVEF, chronic kidney disease, and concomitant use of beta-blockers and mineralocorticoid receptor antagonists. Conclusions The use of ARB was associated with HFrecEF more frequently than ACEi among patients with DCM and reduced LVEF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Health Sciences Research Grants from the Japanese Ministry of Health, Labour and Welfare (Comprehensive Research on Cardiovascular Diseases)Japan Agency for Medical Research and Development (AMED) grant

Concomitant beta-blocker use is associated with a reduced rate of remission in patients with rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs: a post hoc multicohort analysis.

Background:Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with increased risk of cardiovascular disease (CVD). Treatment for CVD may involve pharmacological agents that antagonise beta adrenergic receptors. These receptors may play an important role in immunology, and the effects of beta-blockers (BB) in RA is unknown. The aim of this study was to investigate the association between BB use and remission in patients with RA initiating tocilizumab +/− conventional synthetic (cs-) DMARD therapy.Methods:Data was pooled from five randomised trials investigating tocilizumab and/or csDMARD treatment in RA (primarily methotrexate). The association between BB use and remission according to the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) was assessed by Cox proportional hazard analysis. Sensitivity analysis in patients with pre-existing CVD and an exploratory analysis of the impact of other CVD drugs were conducted.Results:Data were available from 5502 participants, 594 (10.8%) of whom were using systemic BB. BB use was associated with less frequent SDAI remission in the total [adjusted hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.57–0.87, p = 0.001] and CVD cohort [adjusted HR 0.72 (0.57–0.90, p = 0.005)]. The association was consistent between trials (interaction p = 0.44) and treatment arms (interaction p = 0.06). No significant association between remission and β1-receptor selectivity was identified (p = 0.16), and the association was independent from other cardiovascular drug use. Similar associations between BB use and CDAI remission were observed.Conclusion:In a large, pooled cohort of RA patients initiating csDMARDs and/or tocilizumab, BB use was independently associated with less frequent remission.

Calcium channel blocker exposure and psoriasis risk: Pharmacovigilance investigation and literature data

Evidence regarding a possible association between psoriatic manifestations and use of calcium channel blockers (CCBs) is sparse. Currently, psoriatic manifestations are not listed in the summary of product characteristics (SmPC) of CCBs. In this context, we aimed to investigate the association between psoriasis and CCB exposure. We reviewed spontaneous reports recorded in the French national pharmacovigilance database (FPVD) between 1985 and 2019. The association between CCB exposure and risk of psoriasis was assessed using the case/non-case method. We also analyzed literature data. Ninety-four reports of psoriatic manifestations after CCB exposure were recorded in the FPVD. Both induction and exacerbation cases were observed. Time to onset was less than 2 years in 64% of reports and outcome was favorable in 71% of reports after CCB discontinuation. These features were concordant with those of literature reports. The reporting odds ratio (ROR) was 2.45 (95% CI 1.99-3.02). Concomitant use of betablockers or angiotensin II receptor blockers did not interact with the association between CCB exposure and psoriasis risk. The ROR for the stratum "use of angiotensin converting enzyme inhibitors" (ACEI) was 2.14 (95% CI 1.29-3.55), while the ROR for the stratum ACEI non-use was 0.12 (95% CI 0.10-0.15). Large-scale epidemiologic studies were focused only on first diagnoses and did not include exacerbations; psoriasis risk was therefore probably underestimated. We found a statistically significant association between CCB exposure and psoriasis risk, which constitutes a safety signal. This risk is a class effect, time to onset is mostly less than 2 years and outcome is favorable after CCB discontinuation. Psoriasis should be mentioned in the SmPCs of all CCBs, and healthcare workers should be aware of this risk. Attention should be paid to patients taking CCB and ACEI concomitantly.

Are ACE Inhibitors and Beta-blockers Dangerous in Patients at Risk for Anaphylaxis?

The objective of this article is to review the available studies regarding angiotensin converting enzyme (ACE) inhibitors and beta-blockers and their effect on patients at risk for anaphylaxis. A literature search was conducted in PUBMED to identify peer-reviewed articles using the following keywords: anaphylaxis, ACE inhibitor, beta-blocker, food allergy, radiocontrast media, venom allergy, skin testing, and immunotherapy. Some studies show an increased risk of anaphylaxis in patients who are taking ACE inhibitors and beta-blockers, whereas others studies do not show an increased risk. For venom immunotherapy, there are more data supporting the concomitant use of beta-blockers and ACE inhibitors in the build-up and maintenance phases. Most of the medical literature is limited to case reports and retrospective data. Prospective controlled trials are needed on this important topic. For those patients at risk of anaphylaxis who lack cardiovascular disease, it is recommended to avoid beta-blockers and possibly ACE inhibitors. However, for those patients with cardiovascular disease, beta-blockers and ACE inhibitors have been shown to increase life expectancy. Consideration should be given for the concomitant use of these medications while patients are receiving venom immunotherapy.

Sinus Bradycardia in Habitual Cocaine Users

Common physiological manifestations of cocaine are related to its adrenergic effects, due to inhibition of dopamine and norepinephrine uptake at the postsynaptic terminal. Few studies have documented bradycardia secondary to cocaine use, representing the antithesis of its adrenergic effects. We assessed the prevalence of sinus bradycardia (SB) in habitual cocaine users and postulated a mechanism for this effect. One hundred sixty-two patients with a history of cocaine use were analyzed and compared with age- and gender-matched controls. SB was defined as a rate of <60 beats/min and habitual cocaine use as 2 or more documented uses >30days apart. Propensity score-matching analysis was applied to balance covariates between cocaine users and nonusers and reduce selection bias. Patients with a history of bradycardia, hypothyroidism, or concomitant beta-blocker use were excluded. Mean age of study patients was 44 ± 8years. SB was observed in 43 of 162 (27%) cocaine users and in 9 of 149 (6%) nonusers (p= 0.0001). Propensity score-matching analysis matched 218 patients from both groups. Among matched patients SB was observed in 25 of 109 (23%) cocaine users and in 5 of 109 (5%) nonusers (p= 0.0001). Habitual cocaine use was an independent predictor of SB and associated with a sevenfold increase in the risk of SB (95% CI 2.52 to 19.74, p= 0.0002). In conclusion, habitual cocaine use is a strong predictor of SB and was unrelated to recency of use. A potential mechanism for SB may be related to cocaine-induced desensitization of the beta-adrenergic receptor secondary to continuous exposure. Symptomatic SB was not observed; thus, pacemaker therapy was not indicated.

Elucidating the role of incidental use of beta-blockers in patients with metastatic brain tumors in controlling tumor progression and survivability.

Beta-adrenergic antagonists have demonstrated beneficial effects in tumor progression and survivability in patients with various cancers by inhibiting norepinephrine-induced tumor cell migration. However, little is known about their effects on the outcomes of metastatic brain tumors (MBTs). This study was undertaken to evaluate the effects of beta-blockers, if any, on the outcome of MBTs, and their possible role in controlling tumor progression and survivability. A retrospective cohort analysis of 225 patients identified as having MBTs presenting to our institution from 2001 through 2013 was conducted by reviewing electronic patient records. Patients were categorized into three groups: Group A comprised hypertensives on beta-blockers only (40, 18%), Group B comprised hypertensive patients on antihypertensive medications other than beta-agonists (65, 29%), and Group C comprised normotensives (120, 53%). All outcomes were compared using the data on pre - and post-gamma knife radiosurgery (GKRS) for these groups. One-way analysis of variance (ANOVA) was used to compare the radiological and clinical outcomes in the patient population following beta-blockers usage in Group A versus groups B and C. Cox regression model was used to demonstrate prognostic factors for the outcome in patients having different primaries. Overall survival period was plotted on Kaplan-Meier curves. The log-rank (Mantel-Cox) test was used to analyze the survival difference in the cases. P < 0.05 was considered significant. The mean age of patients was 57.34 ± 10.98 years (range: 30-87 years) and 44% were males. More than half (130/225, 58%) of patients with MBT had their primary tumor source in the lung, 16% in the breast, and 7% each in the kidneys and the rectum. Frontal lobe was the most commonly affected (80, 35.5%). Statistically significant control of tumor growth (P = 0.001), tumor progression (P = 0.0001), and higher survival outcomes (P = 0.015) were observed in Group A as compared to other groups. In comparing the different groups, breast primaries showed the strongest correlation to survival benefit (P = 0.049) from beta-blocker usage as a primary antihypertensive medication. Concomitant use of beta-blockers with conventional therapy may offer potential benefit to hypertensive patients developing MBTs by ameliorating tumor progression and conferring a survival advantage. This effect was most notable in patients with primary tumors originating in the breast. Prospective studies, molecular research, and randomized controlled trials are warranted to further explore this promising effect.

Abstract 17713: A Three year Retrospective Analysis of Adverse Cardiac Outcomes in Heart Failure Patients Using Cocaine on Beta-blockers

Background: It is an established fact that beta-blockers (BB) improve survival in patients with HFrEF. However cocaine abusers with HFrEF are currently excluded from this life-saving treatment due to concerns with a theoretical risk of unopposed alpha adrenergic receptor-mediated coronary vasospasms and possible myocardial infarctions (MI). Our study seeks to compare heart failure (HF) outcomes in patients on beta blockers with surreptitious cocaine abuse to those not receiving beta blockers. Methods: From our HF registry, we retrospectively identified 132 patients admitted to the hospital for CHF with related complaints like chest pain or shortness of breath between 2006 and 2008 and cocaine positive drug test. We reviewed the concomitant use of BB in relation to the primary composite end points: MI, total ER visits, HF related admissions 2006-2008, ejection fraction (EF), mean BNP and all- cause mortality. Characteristics of patients with and without BB use were compared using chi-square for categorical and t-test for continuous variables. Considering the variance in baseline characteristics between patients, we also adjusted for co-founding factors like age, sex, Body mass index (BMI) and race before evaluating the independent relationship between BB use and the composite primary endpoints listed above. Results: BB were used in 60 patients (45%), no distinction was made between selective BBs or nonselective BBs. The analysis of our cohort data showed no significant difference in the number of MI (p - 0.819), ER visits (p - 0.627), HF- related admissions (p-0.382), mean BNP (p-0.480), EF (p-0.273) in HF patients using cocaine on BB vs those not on BB. Findings were similar after adjusting for cofounding variables - race, sex, BMI and race (OR for having an MI with BB use was 1.185[95% CI 0.277-5.069]). Conclusions: BB treatment of HFrEF with concomitant cocaine abuse may be safer than previously suggested. Prospectively randomized trials will be needed to clarify the safety of beta blockers in cocaine abusing HFrEF patients. Limitations: Our study was limited by the absence of distinction between selective and nonselective BB as alpha-blocking BBs like carvedilol have been proposed as safe since they can moderate the theoretical alpha mediated effects of cocaine.

Increased Mortality Associated With Digoxin in Contemporary Patients With Atrial Fibrillation: Findings From the TREAT-AF Study

BackgroundDespite endorsement of digoxin in clinical practice guidelines, there exist limited data on its safety in atrial fibrillation/flutter (AF). ObjectivesThe goal of this study was to evaluate the association of digoxin with mortality in AF. MethodsUsing complete data of the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) study from the U.S. Department of Veterans Affairs (VA) healthcare system, we identified patients with newly diagnosed, nonvalvular AF seen within 90 days in an outpatient setting between VA fiscal years 2004 and 2008. We used multivariate and propensity-matched Cox proportional hazards to evaluate the association of digoxin use with death. Residual confounding was assessed by sensitivity analysis. ResultsOf 122,465 patients with 353,168 person-years of follow-up (age 72.1 ± 10.3 years, 98.4% male), 28,679 (23.4%) patients received digoxin. Cumulative mortality rates were higher for digoxin-treated patients than for untreated patients (95 vs. 67 per 1,000 person-years; p < 0.001). Digoxin use was independently associated with mortality after multivariate adjustment (hazard ratio [HR]: 1.26, 95% confidence interval [CI]: 1.23 to 1.29, p < 0.001) and propensity matching (HR: 1.21, 95% CI: 1.17 to 1.25, p < 0.001), even after adjustment for drug adherence. The risk of death was not modified by age, sex, heart failure, kidney function, or concomitant use of beta-blockers, amiodarone, or warfarin. ConclusionsDigoxin was associated with increased risk of death in patients with newly diagnosed AF, independent of drug adherence, kidney function, cardiovascular comorbidities, and concomitant therapies. These findings challenge current cardiovascular society recommendations on use of digoxin in AF.

Factors associated with utilization of dipeptidyl-4 inhibitors in patients with type 2 diabetes mellitus: a cross-sectional retrospective study.

Dipeptidyl-4 (DPP-4) inhibitors are oral antidiabetic agents recently introduced to Malaysia. Thus, limited data is available on their utilization patterns and factors associated with their use. This study aims to analyse the utilization patterns of DPP-4 inhibitors, factors that influenced the choice of agent, and the rationale for treatment with DPP-4 inhibitors in patients with type 2 diabetes mellitus. This retrospective study was conducted to address the utilization pattern of DPP-4 inhibitors and factors that influence choice in type 2 diabetes mellitus patients. 299 subjects taking either sitagliptin or vildagliptin from September 2008 to September 2012 were included in the study. Sitagliptin was more frequently prescribed than vildagliptin. Of the patients prescribed DPP-4 inhibitors, 95% received combinations of these and other agents, whereas only 5% were prescribed DPP-4 inhibitors as monotherapy. Factors affecting the utilization of DPP-4 inhibitors included age (P = 0.049) and concomitant use of beta blockers (P = 0.045) and aspirin (P = 0.008). Early identification of factors associated with DPP-4 inhibitors is essential to enhance quality use of the drugs.

Effect of Beta Blockers (Metoprolol or Propranolol) on Effect of Simvastatin in Lowering C-Reactive Protein in Acute Myocardial Infarction

Recent data indicated that statin therapy may fail to reduce the incidence of coronary events in patients concomitantly using beta blockers. The aim of the present study was to examine whether the concomitant use of beta blockers would modify the anti-inflammatory action of statins. Changes in C-reactive protein (CRP) between days 1 and 5 after myocardial infarction were evaluated in 189 patients treated with simvastatin alone (S), beta blockers alone (B; propranolol or metoprolol), S + B, or neither of these 2 medications (N) in a prospective observational cohort. At baseline, median CRP was lower in the S group (0.40 mg/dl, interquartile range 0.1 to 0.6) than the other groups (B: 0.6 mg/dl, interquartile range 0.4 to 1.6; S + B: 0.5 mg/dl, interquartile range 0.3 to 1.2; and N: 0.6 mg/dl, interquartile range 0.2 to 1.5). By day 5, median CRP was 1.3 mg/dl (interquartile range 0.7 to 2.6), 4.3 (interquartile range 1.6 to 8.8), 4.6 (interquartile range 2.8 to 9.5), and 4.4 (interquartile range 1.9 to 9.9) for the S, B, S + B, and N groups, respectively. After adjusting for log(e) baseline CRP, the difference in log(e) CRP between days 1 and 5 was significantly lower in the S group compared with the B (-0.74 +/- 0.23 [SE], p = 0.001) or S + B group (-0.99 +/- 0.20 [SE], p <0.0001). The significance remained after adjustment for age, gender, and baseline CRP. There was no significant difference in change in CRP between the SB and B groups. In conclusion, the present study confirmed the anti-inflammatory action of statins and showed that concomitant use of beta blockers may significantly attenuate this effect.

Statin use and recurrence of atrial fibrillation after successful cardioversion

Statins have important pleiotropic effects and have been shown to reduce vascular inflammation and the incidence of atrial fibrillation (AF) after cardiac surgery. The role of statins in patients with existing AF is poorly understood. We examined the effect of statins on recurrence of AF in patients after successful cardioversion. Statin use and documented recurrence of AF after successful cardioversion were evaluated in 625 patients with new onset AF who were followed prospectively in the Canadian Registry of Atrial Fibrillation. Logistic regression was used to model the effect of statin use on the recurrence of AF at 1 year while adjusting for potential confounders including concurrent medications. In a predominantly male population (62%) with median age 63 years, 12.3% were on statins at baseline. Overall, 32.5% had documented recurrence of AF at 1 year; 23.4% in patients on statins compared to 33.8% in those not on statins (P = .07). After adjustment for baseline differences and concomitant beta-blocker use, statin use was associated with a 74% reduction in AF recurrence, but only in statin users on beta-blockers (OR 0.26, 95% CI 0.10-0.66); statin users not on beta-blockers (OR 1.07, 95% CI 0.44-2.58). In an observational study of patients with new onset AF, statin use was associated with a significant 74% reduction in the odds of recurrent AF, but only in patients also taking beta-blockers. Importantly, statin without concomitant beta-blocker use was not associated with any changes in AF recurrence.

Genetic determinants of plasma HDL-cholesterol levels in familial hypercholesterolemia

The objective of this study was to determine the extent to which common genetic variants can explain the variation of high-density lipoprotein cholesterol (HDL-C) plasma levels in familial hypercholesterolemia (FH). FH is characterized by elevated low-density lipoprotein cholesterol levels and premature cardiovascular disease (CVD). Although low HDL-C levels have been shown to affect the severity of the clinical phenotype, little is known about the factors that determine HDL-C levels in these patients. A cohort of 1002 heterozygous FH patients was genotyped for polymorphisms in the genes encoding for ATP-binding cassette transporter A1, apolipoprotein (apo) AIV, apoCIII, apoE, cholesteryl transfer ester protein, hepatic lipase, lipoprotein lipase, and two paraoxonases. Multiple linear regression showed that, together, these polymorphisms explain only 3.9% of the variation of HDL-C plasma levels. When significant two-way interactions between the polymorphisms were also taken into account, the explained variation rose to 12.5%. In a regression model that also incorporated sex, smoking, alcohol use, body mass index, and concomitant beta-blocker use as covariates, the explained variation of HDL-C plasma levels even increased to 32.5%. This study provides direct evidence that multiple, modestly penetrant, but highly prevalent, polymorphisms can explain a substantial part of the variation of HDL-C plasma levels in a representative large cohort of heterozygous FH patients.

639 Concomitant use of beta-blockers and levosimendan in patients with decompensated chronic heart failure improves prognosis

639 Concomitant use of beta-blockers and levosimendan in patients with decompensated chronic heart failure improves prognosis