Cognitive Impairment in Heart Failure: A Heart Failure Society of America Scientific Statement.

Cognitive impairment is common among adults with heart failure (HF), as both diseases are strongly related to advancing age and multimorbidity (including both cardiovascular and noncardiovascular conditions). Moreover, HF itself can contribute to alterations in the brain. Cognition is critical for a myriad of self-care activities that are necessary to manage HF, and it also has a major impact on prognosis; consequently, cognitive impairment has important implications for self-care, medication management, function and independence, and life expectancy. Attuned clinicians caring for patients with HF can identify clinical clues present at medical encounters that suggest cognitive impairment. When present, screening tests such as the Mini-Cog, and consideration of referral for comprehensive neurocognitive testing may be indicated. Management of cognitive impairment should focus on treatment of underlying causes of and contributors to cognitive impairment, medication management/optimization, and accommodation of deficiencies in self-care. Given its implications on care, it is important to integrate cognitive impairment into clinical decision making. Although gaps in knowledge and challenges to implementation exist, this scientific statement is intended to guide clinicians in caring for and meeting the needs of an increasingly complex and growing subpopulation of patients with HF.

Pragmatic Clinical Trial to Improve Patient Experience Among Adults During Transitions from Hospital to Home: the PArTNER study.

INTRODUCTION: Minority-serving hospitals (MSHs) need evidence-based strategies tailored to the populations they serve to improve patient-centered outcomes after hospitalization. METHODS: We conducted a pragmatic randomized clinical trial (RCT) from October 2014 to January 2017 at a MSH comparing the effectiveness of a stakeholder-supported Navigator intervention vs. Usual care on post-hospital patient experience, outcomes, and healthcare utilization. Community health workers and peer coaches delivered the intervention which included (1) in-hospital visits to assess barriers to health/healthcare and to develop a personalized Discharge Patient Education Tool (DPET); (2) a home visit to review the DPET; and (3) telephone-based peer coaching. The co-primary outcomes were between-group comparisons of 30-day changes in Patient-Reported Outcomes Measurement Information System (PROMIS) measures of anxiety and informational support (minimum important difference is 2 to 5 units change); a p-value <0.025 was considered significant using intention-to-treat analysis. Secondary outcomes included death, ED visits, or readmissions and measures of emotional, social, and physical health at 30 and 60 days. RESULTS: We enrolled 1029 adults hospitalized with heart failure (28%), pneumonia (22%), MI (10%), COPD (11%), or sickle cell disease (29%). Over 80% were non-Hispanic Black. Overall, there were no significant between-group differences in the 30-day change in anxiety (adjusted difference: -1.6, 97.5% CI -3.3 to 0.1, p=0.03), informational support (adjusted difference: -0.01, 97.5% CI -2.0 to 1.9, p=0.99), or any secondary outcomes. Exploratory analyses suggested the Navigator intervention improved anxiety among participants with COPD, a primary care provider, a hospitalization in the past 12 months, or higher baseline anxiety; among participants without health insurance, the intervention improved informational support (all p-values <0.05). CONCLUSIONS: In this pragmatic RCT at a MSH, the Navigator intervention did not improve post-hospital anxiety, informational support, or other outcomes compared to Usual care. Benefits observed in participant subgroups should be confirmed in future studies. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02114515.

Survey of Anticoagulation Practices with the Impella Percutaneous Ventricular Assist Device at High-Volume Centers.

OBJECTIVES: To characterize anticoagulation practices with the Impella percutaneous ventricular assist device (pVAD). BACKGROUND: Managing anticoagulation in patients being supported by the Impella pVAD is made challenging by several unique features of the device. These include the release of a dextrose-based purge solution containing unfractionated heparin (UFH), the need to concurrently administer systemic anticoagulation with intravenous UFH, and the lack of an alternative strategy in patients with contraindications to UFH. METHODS: To characterize anticoagulation practices with the Impella pVAD, we conducted a survey of centers in the United States performing a high volume of Impella cases, which we defined as > 1 per month. Centers were contacted via email or phone and individuals who agreed to participate were provided with a link to complete the survey online. The primary measures of interest were variations in practice across centers and variations from the manufacturer's recommendations. RESULTS: Practices varied considerably among respondents (65 of 182 centers, or 35.7%) and often diverged from manufacturer recommendations. Approximately half of centers (52.4%) reported using a UFH concentration of 50 units/mL in the purge solution, whereas most of the remaining centers (41.3%) reported using lower concentrations. Strategies for the initiation and adjustment of systemic therapy also varied, as did practices for routinely monitoring for hemolysis. Nearly one-fifth of centers (16.7%) had not developed an alternative strategy for the purge solution in patients with contraindications to UFH. Most centers (58.4%) reported using argatroban or bivalirudin in this scenario, a strategy that diverges from the manufacturer's recommendations. CONCLUSIONS: Given these findings, studies to determine a systematic approach to anticoagulation with the Impella device are warranted.

Cost-Effectiveness of Strategies to Personalize the Selection of P2Y12 Inhibitors in Patients with Acute Coronary Syndrome.

PURPOSE: Perform a cost-effectiveness analysis comparing strategies for selecting P2Y12 inhibitors in acute coronary syndrome (ACS). METHODS: Six strategies for selection of P2Y12 inhibitors in ACS were compared from the US healthcare system perspective: (1) clopidogrel for all (universal clopidogrel); (2) ticagrelor guided by platelet reactivity assay (PRA; clopidogrel + phenotype); (3) ticagrelor use only in CYP2C19 poor metabolizers (genotype + conservative ticagrelor); (4) ticagrelor use in both CYP2C19 intermediate and poor metabolizers (genotype + liberal ticagrelor); (5) ticagrelor use only in patients with CYP2C19 polymorphisms and clopidogrel nonresponse by PRA (genotype + phenotype); and (6) ticagrelor for all (universal ticagrelor). A decision model was developed to model major adverse cardiovascular events and bleeding during 1 year of treatment with a P2Y12 inhibitor. Model inputs were identified from the literature. Lifetime costs were adjusted to 2017 US dollars; quality-adjusted life-years (QALYs) were projected using a Markov model. The primary endpoint was the incremental cost-effectiveness compared to the next best option along the cost-effectiveness continuum. Sensitivity analyses were performed on all model inputs to assess their influence on the incremental cost-effectiveness. RESULTS: In the base case analysis, incremental cost-effectiveness ratios (ICER) for the clopidogrel + phenotype, genotype + liberal ticagrelor, and universal ticagrelor strategies were $12,119/QALY, $29,412/QALY, and $142,456/QALY, respectively. Genotype + conservative ticagrelor and genotype + phenotype were not cost-effective due to second-order dominance. Genotype + liberal ticagrelor compared to clopidogrel + phenotype demonstrated the highest acceptance (97%) at a willingness to pay (WTP) threshold of $100,000/QALY. CONCLUSION: Cost-effective strategies to personalize P2Y12 inhibition in ACS include clopidogrel +phenotype and genotype + liberal ticagrelor. Universal ticagrelor may be considered cost-effective at a higher WTP threshold ($150,000/QALY). Genotype + liberal ticagrelor exhibited the highest acceptability compared to clopidogrel + phenotype over the widest range of WTP thresholds and may be preferred.

Comparison of practice patterns between inpatient cardiology pharmacists with and without added qualifications in cardiology.

BACKGROUND: There is a paucity of data comparing practice patterns between board-certified specialists with added qualifications in cardiology (AQCV) and cardiovascular pharmacists without these credentials. PURPOSE: The purpose is to characterize differences in practice between inpatient pharmacists with and without AQCV. METHODS: We conducted a multicenter, retrospective, cross-sectional, case-controlled survey. An AQCV pharmacist list was extracted from the Board of Pharmacy Specialties Web site. Hospitals with AQCV pharmacists comprised the case group. Hospitals were excluded if the AQCV pharmacists did not provide direct patient care, practiced in the outpatient setting, or were in a Veterans Affairs hospital. Each case hospital was matched to hospitals without an AQCV pharmacist in a 1:3 ratio (case:control) by region, cardiovascular discharges, and teaching hospital status. Institutions completed a survey characterizing their pharmacy services. RESULTS: Fifty-six hospitals completed the survey (21 AQCV, 35 non-AQCV). More AQCV pharmacists participated on rounds (100% vs 82.9%, P = .04) and devoted more time performing administrative tasks (20.5% ± 15.3% vs 11.1% ± 8.1%, P = .001) than non-AQCV pharmacists. Conversely, AQCV pharmacists spent less time providing clinical care (52.4% ± 14.5% vs 66.2% ± 19.8%, P = .007), were less involved with drug protocol management (71.4% vs 91.4%, P = .05), and performed less order verification than non-AQCV pharmacists. CONCLUSIONS: Practice patterns differ between inpatient pharmacists with and without AQCV. Further research is needed to determine whether AQCV credentialing improves patient outcomes and to delineate what specific tasks performed by inpatient cardiology pharmacists may improve patient outcomes.

Cost-effectiveness of systematic screening and treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) in patients with heart failure with preserved ejection fraction (HFpEF) in United States.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure in clinical practice. 99mTc-pyrophosphate scintigraphy (PYP-scan) improves the accuracy of ATTR-CM detection, enabling timely initiation of tafamidis, a drug that slows the progression of ATTR-CM and lowers the risk of adverse cardiac events. PYP-scans, serum free light-chain (FLC) test and immunofixation electrophoresis (IFE) are critical components of a systematic screening. We assessed the cost-effectiveness of universal systematic screening (USS) compared to standard-of-care (SoC) selected clinical referrals for the systematic screening in patients aged 60 years or older with heart failure with preserved ejection fraction (HFpEF) and ventricular wall thickness of at least 12 mm. METHODS: Two screening strategies, USS versus SoC screening for ATTR-CM were compared in a model-based assessment. Treatment decisions were based upon the accuracy of each screening strategy, which was followed by Markov state transitions across New York Heart Association (NYHA) functional classes and death. Model inputs were identified from a literature review. We calculated lifetime cost in 2022 US dollars and quality adjusted life-years (QALYs) of each strategy. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: The USS was associated with a significant increase in lifetime costs ($124,380 vs. $70,412) and modest improvement in QALYs (4.42 QALYs vs 4.36 QALYs). The ICER for the USS was $919,509 per QALY gained. ICER was sensitive to the age at the time of ATTR-CM diagnosis, true prevalence rate of ATTR-CM, and daily cost of tafamidis. CONCLUSIONS: Owing to the high cost of treatment with tafamidis, USS along with PYP scan for ATTR-CM in older HFpEF patients with ventricular wall thickening is unlikely to become a cost-effective strategy at a liberal WTP threshold.

Clinical pharmacy services in heart failure: an opinion paper from the Heart Failure Society of America and American College of Clinical Pharmacy Cardiology Practice and Research Network.

BACKGROUND: Heart failure (HF) care takes place in multiple settings, with a variety of providers, and generally involves patients who have multiple comorbidities. This situation is a "perfect storm" of factors that predispose patients to medication errors. METHODS AND RESULTS: The goals of this paper are to outline potential roles for clinical pharmacists in a multidisciplinary HF team, to document outcomes associated with interventions by clinical pharmacists, to recommend minimum training for clinical pharmacists engaged in HF care, and to suggest financial strategies to support clinical pharmacy services within a multidisciplinary team. As patients transition from inpatient to outpatient settings and between multiple caregivers, pharmacists can positively affect medication reconciliation and education, assure consistency in management that results in improvements in patient satisfaction and medication adherence, and reduce medication errors. For mechanical circulatory support and heart transplant teams, the Centers for Medicare and Medicaid Services considers the participation of a transplant pharmacology expert (e.g., clinical pharmacist) to be a requirement for accreditation, given the highly specialized and complex drug regimens used. Although reports of outcomes from pharmacist interventions have been mixed owing to differences in study design, benefits such as increased use of evidence-based therapies, decreases in HF hospitalizations and emergency department visits, and decreases in all-cause readmissions have been demonstrated. Clinical pharmacists participating in HF or heart transplant teams should have completed specialized postdoctoral training in the form of residencies and/or fellowships in cardiovascular and/or transplant pharmacotherapy, and board certification is recommended. Financial mechanisms to support pharmacist participation in the HF teams are variable. CONCLUSIONS: Positive outcomes associated with clinical pharmacist activities support the value of making this resource available to HF teams.

Reversal of Oral Anticoagulants: A Survey of Contemporary Practice Trends (ReACT).

This study evaluated practice patterns and factors influencing treatment decisions regarding urgent or emergent reversal of oral anticoagulants (OACs). A 30-question survey was electronically distributed to anticoagulation members of the Anticoagulation Forum. Questions were designed to capture practice trends in the reversal of warfarin, factor Xa inhibitors, and factor IIa inhibitors. Continuous and categorical data were analyzed to generate descriptive statistics. Open-ended questions were summarized by thematic categories. 173 responses were collected most from US-based pharmacists with direct patient care responsibilities. The majority of the respondents' institutions (90.2%) utilized a guideline or protocol for OACs reversal. Vitamin K (91.3%), activated charcoal (80.4%), and fresh frozen plasma (72.8%) were the most common reversal agents on formulary without restrictions. Most institutions (87.0%) reported having 4-factor prothrombin complex concentrate (4F-PCC) and idarucizumab on formulary, but most commonly (52.2%) with restrictions. Andexanet alfa was only reported on formulary at 35.9% of institutions. In contrast to current guideline recommendations, vitamin K (98.8%) was preferred over 4F-PCC and 4F-PCC (71.6%) was preferred over andexanet alfa as first-line agents used to reverse warfarin and factor Xa inhibitors, respectively. Weight-based dosing strategies for 4F-PCC were commonly utilized for different reversals (41.2%-59.4%). Cost, efficacy, and safety of 4F-PCC were identified as top facilitators and barriers for 4F-PCC adoption in practice. Our findings revealed that guideline recommendations for reversal of warfarin and factor Xa and IIa inhibitors are not followed by a majority of institutions. Studies are needed to investigate strategies to overcome barriers for implementing and following guideline recommendations.

Stratification of burnout in health-system pharmacists during the COVID-19 pandemic: A focus on the ambulatory care pharmacist.

Introduction: Burnout is defined as high emotional exhaustion and depersonalization, and low personal accomplishment from work. Prevalence of burnout among health-system and ambulatory care pharmacists is unknown during the COVID-19 pandemic. Objectives: The purpose of this research is to analyze burnout prevalence among health-system pharmacists (HSPs) and ambulatory care pharmacists (ACPs) using the Oldenburg Burnout Inventory and Maslach Burnout Inventory. Methods: An electronic survey was sent to HSPs at two academic health systems in Chicago, IL. Demographics, risk of burnout based on two validated assessments (the Oldenburg Burnout Inventory [OLBI] and the Maslach Burnout Inventory [MBI]), burnout contributors, burnout mitigation strategies, and change in burnout due to COVID-19 were collected. Burnout was defined as meeting any one criterion for high burnout on the following dimensions: exhaustion score and disengagement on the OLBI, and emotional exhaustion and depersonalization on the MBI. The co-primary outcomes were the prevalence of burnout among HSPs, and the comparison of ACP burnout to that of non-ambulatory HSPs. Secondary outcomes were comparison of burnout between the OLBI and MBI assessments, conceptualization of the causes and contributors of burnout and mitigation strategies among HSPs, and the self-perceived effect of COVID-19 on burnout severity. Results: Of the 113 pharmacists included in the study, HSP burnout prevalence as defined above was 87.6%, ACP burnout was 88.4%, and non-ambulatory HSP burnout was 87.1%. There was no statistical difference between ACP and non-ambulatory HSP burnout prevalence, either overall or in any specific burnout dimension. The OLBI and MBI captured similar rates of burnout. The commonly reported burnout causes were staffing and scheduling issues, precepting requirements, and patient needs. Participants' most reported coping strategies were spending time with family/friends, sleep, exercise, and recreational/relaxation activities. A majority of HSPs (78.2%) reported higher levels of burnout due to COVID-19. Conclusion: HSP burnout during COVID-19 pandemic is higher than cited in the pre-COVID literature. Individual coping strategies are poor buffers for work-related burnout.

Influence of digoxin on mortality in patients with atrial fibrillation: Overview of systematic reviews.

Once a routine part of atrial fibrillation (AF) management, digoxin use has declined. Likely hastening this decline are findings from several studies and systematic reviews identifying a potential association between digoxin use and all-cause mortality in AF populations. However, inconsistency exists within some of these studies potentially leading to confusion among clinicians. To critically evaluate the current literature to contextualize the associations between digoxin and mortality risk in patients with AF by performing an overview of systematic reviews. We searched MEDLINE, Cochrane Central Database of Systematic Reviews, and SCOPUS from their earliest date through October 12, 2020, to identify systematic reviews (SRs) that included studies enrolling patients with AF or atrial flutter and evaluated the association between digoxin use and all-cause mortality. We used the AMSTAR 2 tool to assess the risk of bias for each included SR. Results from reviews are qualitatively synthesized. Our search identified 10 SRs that met our inclusion criteria. Of the 41 unique AF studies included in these SRs, 41% were cohort studies, 29% were post hoc analyses of randomized controlled trials (RCTs), 15% were RCTs, and 15% were registry studies. Based on our AMSTAR 2 assessment, the overall confidence in the results of the 10 reviews was rated as "moderate" in three SRs, "low" in three SRs, and "critically low" in the rest. Except for one review, each included SR shows that digoxin use in AF is associated with a 15 to 38% higher risk of all-cause mortality. This association may be greater when AF-only populations are considered compared with a mix of AF and heart failure populations. Serum digoxin concentration (SDC) data were infrequently considered, but available data suggested a greater association between increasing SDC and all-cause mortality. This overview of reviews found general consistency regarding the association between digoxin use and higher all-cause mortality in AF populations. However, heterogeneity exists among and between SRs and an unmet need exists for additional study in a RCT setting with close monitoring and reporting of SDC to better inform clinical practice.

Optimizing anticoagulation for patients receiving Impella support.

Anticoagulation of patients treated with the Impella percutaneous mechanical circulatory support (MCS) devices is complex and lacks consistency across centers, potentially increasing the risk of complications. In order to optimize safety and efficacy, an expert committee synthesized all available evidence evaluating anticoagulation for patients receiving Impella support in order to provide consensus recommendations for the management of anticoagulation with these devices. The evidence synthesis led to the creation of 42 recommendations to improve anticoagulation management related to the use of the Impella devices. Recommendations address purge solution management, intravenous anticoagulation, monitoring, evaluation and management of heparin-induced thrombocytopenia (HIT), and management during combination MCS support. The use of a heparinized, dextrose-containing purge solution is critical for optimal device function, and a bicarbonate-based purge solution may be an alternative in certain situations. Likewise, intravenous (ie, systemic) anticoagulation with heparin is often necessary, although evidence supporting the optimal assay and target range for monitoring the level of anticoagulation is generally lacking. Patients treated with an Impella MCS device may develop HIT, which is more difficult to evaluate and treat in this setting. Lastly, the use of Impella with extracorporeal membrane oxygenation or for biventricular support creates additional anticoagulation challenges.

Beyond Heart Failure and Ischemic Heart Disease: A Scoping Review of Novel Uses of Ivabradine in Adults.

Ivabradine lowers heart rate by inhibiting the hyperpolarization-activated current in pacemaker cells, and its use for the treatment of heart failure (HF) and ischemic heart disease (IHD) is well described. Ivabradine may be an attractive treatment option for other conditions for which a reduction in heart rate is desirable but less is known about its role in these settings. The primary objective was to perform a scoping review summarizing the literature evaluating novel uses for ivabradine other than HF and IHD in adults. PubMed and EMBASE were searched for articles for all dates through September 2019. Search strategies combined terms generic, commercial/trade, and international names for ivabradine. Manual search of references was also performed to identify additional articles. Studies were included if they were published in English, evaluated the efficacy of ivabradine for indications other than HF or IHD in patients aged 18 years or older, and the primary outcome included clinically relevant end points. Articles were screened first by title and abstract followed by full-text screening of the remaining articles. After removal of duplicates, 1807 records were screened for inclusion and 84 studies were included in this scoping review. Novel uses of ivabradine were reported for various tachyarrhythmias, valvular heart disease, premedication for coronary computed tomography angiography, perioperative risk reduction, sepsis with and without multi-organ dysfunction syndrome, cor pulmonale, reactive airway disease, and erectile dysfunction. This scoping review identified several potential novel uses for ivabradine in adults. This review may help to identify existing gaps where further research is needed to elucidate the role of ivabradine for indications beyond HF and IHD.

Comparison of Cardiac Events Associated With Azithromycin vs Amoxicillin.

Importance: Conflicting evidence exists on the association between azithromycin use and cardiac events. Objective: To compare the odds of cardiac events among new users of azithromycin relative to new users of amoxicillin using real-world data. Design, Setting, and Participants: This retrospective cohort study used data from Truven Health Analytics MarketScan database from January 1, 2009, to June 30, 2015. Patients receiving either amoxicillin or azithromycin and enrolled in a health care plan 365 days before (baseline period) the dispensing date (index date) were included in the study. Patients were matched 1:1 on high-dimensional propensity scores. Data were analyzed from October 1, 2018, to December 31, 2019. Exposures: New use of azithromycin compared with new use of amoxicillin. Main Outcomes and Measures: The primary outcome consisted of cardiac events, including syncope, palpitations, ventricular arrhythmias, cardiac arrest, or death as a primary diagnosis for hospitalization at 5, 10, and 30 days from the index date. Logistic regression models were used to estimate odds ratios (ORs) with 95% CIs. Results: After matching, the final cohort included 2 141 285 episodes of each index therapy (N = 4 282 570) (mean [SD] age of patients, 35.7 [22.3] years; 52.6% female). Within 5 days after therapy initiation, 1474 cardiac events (0.03%) occurred (708 in the amoxicillin cohort and 766 in the azithromycin cohort). The 2 most frequent events were syncope (1032 [70.0%]) and palpitations (331 [22.5%]). The odds of cardiac events with azithromycin compared with amoxicillin were not significantly higher at 5 days (OR, 1.08; 95% CI, 0.98-1.20), 10 days (OR, 1.05; 95% CI, 0.97-1.15), and 30 days (OR, 0.98; 95% CI, 0.92-1.04). Among patients receiving any concurrent QT-prolonging drug, the odds of cardiac events with azithromycin were 1.40 (95% CI, 1.04-1.87) greater compared with amoxicillin. Among patients 65 years or older and those with a history of cardiovascular disease and other risk factors, no increased risk of cardiac events with azithromycin was noted. Conclusions and Relevance: This study found no association of cardiac events with azithromycin compared with amoxicillin except among patients using other QT-prolonging drugs concurrently. Although azithromycin is a safe therapy, clinicians should carefully consider its use among patients concurrently using other QT-prolonging drugs.

Risk of cardiac events with azithromycin-A prediction model.

Previous studies have suggested an increased risk of cardiac events with azithromycin, but the predictors of such events are unknown. We sought to develop and validate two prediction models to identify such predictors. We used data from Truven Marketscan Database (01/2009 to 06/2015). Using a split-sample approach, we developed two prediction models, which included baseline demographics, clinical conditions (Model 1), concurrent use of any drug (Model 1) and therapeutic class (Model 2) with a risk of QT-prolongation (CQT-Rx). Patients enrolled in a health plan for 365 days before and five days after dispensing of azithromycin (episodes). Cardiac events included syncope, palpitations, ventricular arrhythmias, cardiac arrest as a primary diagnosis for hospitalization including death. For each model, a backward elimination of predictors using logistic regression was applied to identify predictors in 100 random samples of the training cohort. Predictors prevalent in >50% of the models were included in the final model. A score for the Assessment of Cardiac Risk with Azithromycin (ACRA) was generated using the training cohort then tested in the validation cohort. A cohort of 20,134,659 episodes with 0.03% cardiac events were included. Over 60% included females with mean age of 40.1±21.3 years. Age, sex, history of syncope, cardiac dysrhythmias, non-specific chest pain, and presence of a CQT-Rx were included as predictors for Model-1 (c-statistic = 0.68). For Model-2 (c-statistic = 0.64), predictors included age, sex, anti-arrhythmic agents, anti-emetics, antidepressants, loop diuretics, and ACE inhibitors. ACRA score is available online (bit.ly/ACRA_2020). The ACRA score may help identify patients who are at higher risk of cardiac events following treatment with azithromycin. Providers should assess the risk-benefit of using azithromycin and consider alternative antibiotics among high-risk patients.

Prevalence of Cardiac Risk Factors in Patients Prescribed Azithromycin before and after the 2012 FDA Warning on the Risk of Potentially Fatal Heart Rhythms.

STUDY OBJECTIVE: To measure the prevalence of cardiac risk factors among patients prescribed azithromycin before and after the United States Food and Drug Administration (FDA) issued a warning on May 17, 2012, on the risk of potentially fatal heart rhythms associated with the drug. DESIGN: Retrospective cohort study using administrative claims data. DATA SOURCE: Truven Health Analytics MarketScan database. PATIENTS: A total of 12,971,078 unique patients with 23,749,652 azithromycin prescriptions dispensed between January 2009 and June 2015 were included. Patients had to be continuously enrolled in a health plan for at least 365 days (baseline) before the date of azithromycin dispensing (index date). Cohorts were assigned based on the index dates of the azithromycin prescriptions, either before (January 1, 2009-May 1, 2012) or after (June 1, 2012-June 30, 2015) the FDA warning was issued. MEASUREMENTS AND MAIN RESULTS: A cardiac risk factor included either a cardiac condition (heart failure or dysrhythmias) or concurrent use of drugs that prolong the QT interval. The unit of analysis was each prescription of azithromycin. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the prevalence of cardiac risk factors. Mean age of the patients was 40.1 ± 21.3 years old, with 60.8% females. Prior to the FDA warning, 11,596,022 (48.8%) azithromycin prescriptions were identified, and 12,153,630 (51.2%) were identified after the warning. The prevalence of a preexisting cardiac condition was 7.3% versus 7.9% (p<0.0001) before and after the FDA warning, respectively. Concurrent use of a QT-interval-prolonging drug was 23.3% versus 24.2% (p<0.0001) before and after the FDA warning, respectively. After controlling for confounders, the odds of having a cardiac risk factor after the FDA warning were significantly lower (odds ratio 0.938, 95% CI 0.936-0.940) compared with before the FDA warning. CONCLUSION: Despite the 2012 FDA warning, a nontrivial number of azithromycin prescriptions was prescribed concurrently in patients with preexisting a cardiac condition (1 of 12 azithromycin prescriptions) and in those using a QT-interval-prolonging drug (1 of 5 azithromycin prescriptions). After adjusting for confounders, the odds of cardiac risk factors being present in patients prescribed azithromycin were modestly lower after the warning; however, the prevalence remained essentially unchanged before and after the FDA warning was issued.

Frequency of "on-label" use of intravenous diltiazem for rate control in patients with acute-onset atrial fibrillation or atrial flutter.

PURPOSE: The study was designed to characterize "on-label" use of i.v. diltiazem in patients with acute atrial fibrillation or flutter (AFF). METHODS: An IRB-approved, single-center, retrospective, observational design was used. Eligible patients had acute AFF with heart rate >120 bpm and received i.v. diltiazem from June 1, 2012, to June 30, 2014. The primary outcome was frequency of on-label use of i.v. diltiazem, defined as use of at least one FDA-approved weight-based bolus dose followed by an infusion, if appropriate, in the absence of contraindications. RESULTS: A total of 300 patients were screened; 97 patients were included for analysis. I.V. diltiazem was used on-label in only 14 patients (14%). Of the 96 patients who received an initial diltiazem bolus injection, the median dose was significantly higher in patients for whom the diltiazem dose was on-label, as follows: 17.5 mg (interquartile range [IQR]), 10-20 mg vs. 10.0 mg (IQR, 10-20 mg), p < 0.02). Twenty-nine patients (35%) in the off-label group had a therapeutic response to diltiazem alone compared with 8 patients (57%) in the on-label group (p = 0.11). More patients treated with off-label diltiazem bolus injection required additional rate control medications (41% vs. 7%, p < 0.04). CONCLUSION: In most patients, i.v. diltiazem was not used in accordance with FDA labeling. For most, i.v. diltiazem doses were lower than recommended and many of these patients required additional rate control medications to achieve a therapeutic response.

Design of the patient navigator to Reduce Readmissions (PArTNER) study: A pragmatic clinical effectiveness trial.

Previous work indicates the potential for community health workers and peer coaches serving as patient navigators to improve processes of care and health outcomes during care transitions, but have not been sufficiently tested to determine if such programs improve measures of patient experience in minority serving institutions. The objectives of the Patient Navigator to Reduce Readmissions (PArTNER) study was to: 1) conduct a pragmatic clinical effectiveness trial comparing a multi-faceted, stakeholder-supported Navigator intervention (in-person CHW visits in the hospital and after hospital discharge, plus telephone-based peer coaching) versus usual care on the experience of hospital-to-home care transitions in patients hospitalized with heart failure, pneumonia, chronic obstructive pulmonary disease, myocardial infarction, or sickle cell disease; 2) examine the effectiveness of the Navigator intervention in patient subgroups; and 3) understand the barriers and facilitators of successfully implementing the Navigator intervention across patient populations. The co-primary outcomes are the 30-day changes in: 1) Patient Reported Outcomes Measurement Information System (PROMIS) emotional distress-anxiety, and 2) PROMIS informational support. Secondary outcomes at 30 and 60 days include other PROMIS health measures and hospital readmissions. Innovative features of the PArTNER study include early and continuous engagement of patients, their caregivers, clinicians, health system administrators, and other stakeholders to inform the design and implementation of the Navigator intervention. In this report, we describe the design of the PArTNER study.

Impact of treatment guidelines on clinical and economic outcomes of acute decompensated heart failure.

BACKGROUND: No data exist that demonstrate the impact of comprehensive acute decompensated heart failure (ADHF) treatment guidelines on clinical and economic outcomes in hospitalized patients with this condition. OBJECTIVES: To compare clinical and economic outcomes before and after implementation of treatment guidelines for ADHF. METHODS: A single-center, retrospective, chart review study was conducted in a university hospital. ADHF treatment guidelines were developed and implemented on January 1, 2004. Patients hospitalized for ADHF between January 2003 and November 2004 were identified using the Acute Decompensated Heart Failure Registry. Study periods were 12 months prior to and the 11 months following guideline implementation. RESULTS: This cohort was comprised of 683 ADHF hospitalizations (357 preguideline, 326 postguideline); several patients were admitted more than once. There was a trend toward increased use of intravenous vasoactive drugs (VADs) following guideline implementation (19.9% vs 24.2%; p = 0.05). The duration of intravenous VAD use decreased by more than 40% following guideline implementation, but this was not statistically significant after risk adjustment (p = 0.22). The need for intensive care unit monitoring decreased from 45.1% before guideline implementation to 25.3% following guideline implementation (p < 0.02) in patients treated with intravenous VADs. The need for mechanical ventilation was reduced by nearly 80% (p = 0.04) following guideline implementation. Significantly more patients of the postguideline cohort were prescribed beta-blockers at discharge (54.9% vs 75.2%; p = 0.0001). Costs were not significantly different between the groups. CONCLUSIONS: Implementation of ADHF treatment guidelines was associated with reduced need for mechanical ventilation, improved utilization of beta-blockers at discharge, and trends toward increased use of intravenous VADs, while not significantly changing total costs. More rigorous studies need to be conducted to estimate the true effect of treatment guidelines on ADHF care and outcomes.

Comparison of 6-Month Costs Between Oral Antiplatelet Agents Following Acute Coronary Syndrome.

BACKGROUND: In patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI), newer antiplatelet agents prasugrel and ticagrelor have lower rates of cardiovascular events when compared with clopidogrel. However, it is unclear whether there are differences in economic outcomes when comparing these agents in ACS-PCI patients. OBJECTIVE: To assess aggregated costs and medical resource utilization among ACS-PCI patients prescribed prasugrel, ticagrelor, or generic clopidogrel, using a large commercial insurance claims database. METHODS: Costs attributable to any medical and pharmacy service and resource utilization including number of admissions, length of hospital stay, emergency room visits, and office visits over the 180-day postdischarge period were compared. All-cause and cardiovascular health care costs and resource utilization were separately analyzed for patients enrolled in the data over the continuous follow-up (CFU) period, and for patients continuously taking their initial treatment for 6 months (CTX). Potential confounders collected over a 6-month baseline assessment period were controlled for, using a generalized linear model. RESULTS: Over the 180-day follow-up, prasugrel and ticagrelor patients underwent fewer admissions (rate ratio [RR] = 0.87, 95% CI = 0.80-0.95) from CFU and RR = 0.81, 95% CI = 0.71-0.89 from CTX) compared with clopidogrel patients. The newer agent cohort incurred more overall health care costs than the generic clopidogrel group, with added costs of $957 (95% CI = $236-$1,725) in the CFU group and $1,122 (95% CI = $455-$1,865) in the CTX group, which were smaller than the increase in all-cause outpatient pharmacy costs associated with the newer agents versus clopidogrel (CFU: $1,175, 95% CI = $1,079-$1,278 and CTX: $1,360, 95% CI = $1,256-$1,487). Overall, there was no statistically significant difference in the economic outcomes associated with prasugrel and ticagrelor. There were, however, significant correlations between all-cause and cardiovascular-related outcomes. CONCLUSIONS: The higher price of prasugrel and ticagrelor was partially offset by a decrease in hospital admission compared with generic clopidogrel over a 6-month postdischarge period. Aggregated medical costs and resource utilization were not significantly different between prasugrel and ticagrelor patients. DISCLOSURES: No funding was received for this study. DiDomenico has received an honorarium from Amgen for preparation of a heart failure drug monograph for Pharmacy Practice News and serves as an advisory board member for a heart failure program at Otsuka America Pharmaceuticals and for Novartis Pharmaceuticals. Touchette has received unrestricted grant funding from Cardinal Health, Sunovion Pharmaceuticals, and Takeda and has served as a consultant to and director of the American College of Clinical Pharmacy Practice-Based Research Network on a study funded by Pfizer. Walton has served as a paid consultant for Bristol-Myers Squibb, Baxter, Merck, Genentech, Primus, Takeda, and Abbott. The other authors have nothing to disclose.