Larry R. Jackson

Outcomes of Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention Receiving an Oral Anticoagulant and Dual Antiplatelet Therapy: A Comparison of Clopidogrel Versus Prasugrel From the TRANSLATE-ACS Study.

OBJECTIVES The purpose of this study was to determine whether bleeding risk varies depending on which P2Y12 receptor inhibitor agent is used. BACKGROUND Prior studies have shown significant bleeding risk among patients treated with triple therapy (i.e., oral anticoagulant, P2Y12 receptor inhibitor, and aspirin). METHODS We evaluated patients with acute myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) at 233 hospitals in the United States enrolled in the TRANSLATE-ACS (Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study (April 2010 to October 2012). Using inverse probability-weighted propensity modeling, we compared 6-month adjusted risks of Bleeding Academic Research Consortium (BARC) bleeding, stratifying by whether or not bleeding was associated with rehospitalization among patients discharged on aspirin + anticoagulant + clopidogrel (triple-C), aspirin + anticoagulant + prasugrel (triple-P), aspirin + clopidogrel (dual-C), or aspirin + prasugrel (dual-P). RESULTS Of 11,756 MI patients, 526 (4.5%) were discharged on triple-C, 91 (0.8%) on triple-P, 7,715 (66%) on dual-C, and 3,424 (29%) on dual-P. Compared with dual-therapy patients, triple-therapy patients had significantly higher any BARC-defined bleeding. Triple-P was associated with a greater risk of any BARC-defined bleeding events compared with triple-C. This finding was driven mostly by an increased risk of bleeding events that were patient-reported only and did not require rehospitalization. There were no significant differences in bleeding requiring rehospitalization between the triple-P and -C groups. CONCLUSIONS Among MI patients, the addition of an oral anticoagulant was associated with a significantly greater risk of any BARC-defined bleeding relative to dual antiplatelet therapy, regardless of which P2Y12 receptor inhibitor was selected. Among patients on triple therapy, prasugrel use was associated with higher patient-reported-only bleeding, but not bleeding requiring rehospitalization, than clopidogrel-treated patients.

Novel oral anticoagulants: pharmacology, coagulation measures, and considerations for reversal

Novel oral anticoagulants (NOAC) provide an effective and, in some cases, superior alternative to traditional, oral vitamin K antagonists such as warfarin. These drugs differ in their pharmacokinetic and pharmacodynamics profiles, which is important for selecting the right drug for the right patient. A concern among clinicians is a virtual absence of guidance from clinical trials for reversing the anticoagulant effects of these drugs in clinical settings such as life-threatening bleeding or a need for emergent procedures that carry bleeding risk. In this review, we discuss NOAC, the role of coagulation assays to assess their systemic anticoagulants effects, and the available data supporting strategies designed to reverse or attenuate these effects.

Racial/ethnic differences in atrial fibrillation symptoms, treatment patterns, and outcomes: Insights from Outcomes Registry for Better Informed Treatment for Atrial Fibrillation Registry.

BACKGROUND Significant racial/ethnic differences exist in the incidence of atrial fibrillation (AF). However, less is known about racial/ethnic differences in quality of life (QoL), treatment, and outcomes associated with AF. METHODS Using data from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we compared clinical characteristics, QoL, management strategies, and long-term outcomes associated with AF among various racial/ethnic groups. RESULTS We analyzed 9,542 participants with AF (mean age 74 ± 11 years, 43% women, 91% white, 5% black, 4% Hispanic) from 174 centers. Compared with AF patients identified as white race, patients identified as Hispanic ethnicity and those identified as black race were younger, were more often women, and had more cardiac and noncardiac comorbidities. Black patients were more symptomatic with worse QoL and were less likely to be treated with a rhythm control strategy than other racial/ethnic groups. There were no significant racial/ethnic differences in CHA2DS2-VASc stroke or ATRIA bleeding risk scores and rates of oral anticoagulation use were similar. However, racial and ethnic minority populations treated with warfarin spent a lower median time in therapeutic range of international normalized ratio (59% blacks vs 68% whites vs 62% Hispanics, P < .0001). There was no difference in long-term outcomes associated with AF between the 3 groups at a median follow-up of 2.1 years. CONCLUSION Relative to white and Hispanic patients, black patients with AF had more symptoms, were less likely to receive rhythm control interventions, and had lower quality of warfarin management. Despite these differences, clinical events at 2 years were similar by race and ethnicity.

Expanding the benefits of implantable cardioverter-defibrillator therapy: "is less more"?

Implantable cardioverter-defibrillator (ICD) therapy improves survival in patients with significant left ventricular systolic dysfunction. Although this lifesaving therapy has many benefits, inappropriate ICD shocks may increase morbidity and mortality. With rates of inappropriate therapy quoted as high as 35% at 3 years after device implantation, numerous strategies have been evaluated to decrease the overall incidence of inappropriate therapy. Changes in programming algorithms, which allow for longer detection windows for rhythm analysis, extended the use of antitachycardia pacing, and improved supraventricular tachycardia discriminators, hold promise for decreasing inappropriate ICD therapy. In this review, we discuss the data summarizing the adverse effects of ICD shocks on outcomes, clinical trial-based programming algorithms to decrease inappropriate shocks, and the expanded role of antitachycardia pacing in ventricular arrhythmia management.

Sinus Node Dysfunction and Atrial Fibrillation: A Reversible Phenomenon?

Symptomatic sinus node dysfunction (SND) consists of a variety of manifestations, including tachycardia‐bradycardia syndrome. Atrial fibrillation (AF) is commonly associated with SND, which complicates the management of both conditions. This paper reviews the epidemiology, pathophysiology, and clinical trial data investigating therapeutic approaches for treatment of patients with both SND and AF.

Impact of Proton Pump Inhibitor Use on the Comparative Effectiveness and Safety of Prasugrel Versus Clopidogrel: Insights From the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE‐ACS) Study

Background Proton pump inhibitors (PPIs) reduce gastrointestinal bleeding events but may alter clopidogrel metabolism. We sought to understand the comparative effectiveness and safety of prasugrel versus clopidogrel in the context of proton pump inhibitor (PPI) use. Methods and Results Using data on 11 955 acute myocardial infarction (MI) patients treated with percutaneous coronary intervention at 233 hospitals and enrolled in the TRANSLATE‐ACS study, we compared whether discharge PPI use altered the association of 1‐year adjusted risks of major adverse cardiovascular events (MACE; death, MI, stroke, or unplanned revascularization) and Global Use of Strategies To Open Occluded Arteries (GUSTO) moderate/severe bleeding between prasugrel‐ and clopidogrel‐treated patients. Overall, 17% of prasugrel‐treated and 19% of clopidogrel‐treated patients received a PPI at hospital discharge. At 1 year, patients discharged on a PPI versus no PPI had higher risks of MACE (adjusted hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.21‐1.58) and GUSTO moderate/severe bleeding (adjusted HR 1.55, 95% CI 1.15‐2.09). Risk of MACE was similar between prasugrel and clopidogrel regardless of PPI use (adjusted HR 0.88, 95% CI 0.62‐1.26 with PPI, adjusted HR 1.07, 95% CI 0.90‐1.28 without PPI, interaction P=0.31). Comparative bleeding risk associated with prasugrel versus clopidogrel use differed based on PPI use but did not reach statistical significance (adjusted HR 0.73, 95% CI 0.36‐1.48 with PPI, adjusted HR 1.34, 95% CI 0.79‐2.27 without PPI, interaction P=0.17). Conclusions PPIs did not significantly affect the MACE and bleeding risk associated with prasugrel use, relative to clopidogrel. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01088503.

Racial and ethnic differences in the prevalence, management, and outcomes in patients with atrial fibrillation: A systematic review

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States and is associated with increased morbidity, mortality, and health care expenditures. In this review, our aim was to assess the racial and ethnic differences in the epidemiology, management, and outcomes of patients with AF. A search of relevant studies from January 1, 2007, to December 30, 2017, was conducted in PubMed, EMBASE, and Web of Science and supplemented by manual searches of the bibliographies of retrieved articles. We identified 152 studies of which 64 were subsequently included. We found that underrepresented racial and ethnic groups have a higher prevalence of established risk factors associated with the development of AF but an overall lower incidence and prevalence of AF as compared with non-Hispanic whites. Moreover, racial and ethnic differences exist in detection, awareness, and AF-associated symptoms. Nonwhite populations also experience decreased use of rhythm control modalities and anticoagulation for stroke prevention. Lastly, among those with AF, underrepresented racial and ethnic groups had increased morbidity and mortality relative to white groups. Racial and ethnic differences exist in the prevalence, quality of life, management, and outcomes of individuals with AF; however, the mechanisms for these differences have yet to be fully elucidated. Racial and ethnic differences in AF warrant further analysis to understand the factors contributing to the differences in prevalence and management to ensure the delivery of high quality care that prevents stroke, reduces deaths, and decreases expenses associated with caring for underrepresented populations with AF.

Representation of black patients in randomized clinical trials of heart failure with reduced ejection fraction

Background Black individuals have a disproportionately higher burden of heart failure with reduced ejection fraction (HFrEF) relative to other racial and ethnic populations. We conducted a systematic review to determine the representation, enrollment trends, and outcomes of black patients in historic and contemporary randomized clinical trials (RCTs) for HFrEF. Methods We searched PubMed and Embase for RCTs of patients with chronic HFrEF that evaluated therapies that significantly improved clinical outcomes. We extracted trial characteristics and compared them by trial type. Linear regression was used to assess trends in enrollment among HFrEF RCTs over time. Results A total of 25 RCTs, 19 for pharmacotherapies and 6 (n=9,501) for implantable cardioverter defibrillators, were included in this analysis. Among these studies, there were 78,816 patients, 4,640 black (5.9%), and the median black participation per trial was 162 patients. Black race was reported in the manuscript of 14 (56.0%) trials, and outcomes by race were available for 12 (48.0%) trials. Implantable cardiac defibrillator trials enrolled a greater percentage of black patients than pharmacotherapy trials (7.1% vs 5.7%). Overall, patient enrollment among the 25 RCTs increased over time (P = .075); however, the percentage of black patients has decreased (P = .001). Outcomes varied significantly between black and white patients in 6 studies. Conclusions Black patients are modestly represented among pivotal RCTs of individuals with HFrEF for both pharmacotherapies and implantable cardioverter defibrillators. The current trend for decreasing black representation in trials of HF therapeutics is concerning and must improve to ensure the generalizability for this vulnerable population.

Prevalence, Characteristics, and Outcomes of Valvular Heart Disease in Patients With Atrial Fibrillation: Insights From the ORBIT‐AF (Outcomes Registry for Better Informed Treatment for Atrial Fibrillation)

Background The presence of valvular heart disease (VHD) may affect the risk of stroke and mortality in patients with atrial fibrillation (AF). Community‐based estimates of prevalence and outcomes of specific forms of VHD in patients with AF are lacking. Methods and Results We examined the prevalence of VHD, anticoagulation use, mortality, stroke/transient ischemic attack, and bleeding among a community cohort of patients with AF. Significant VHD was defined as follows: (1) moderate/severe mitral stenosis or mechanical valve; (2) bioprosthetic valve, surgical repair, or balloon valvuloplasty; and (3) moderate/severe aortic regurgitation or stenosis, mitral regurgitation, or tricuspid regurgitation. Proportional hazards models were performed to test the association between VHD groups and outcomes. Among 9748 patients with AF, 2705 (27.7%) had significant VHD. Anticoagulation use was highest among patients with mitral stenosis/mechanical valve (91.8%). Compared with individuals with no significant VHD, individuals with aortic regurgitation/aortic stenosis, mitral regurgitation, or tricuspid regurgitation (hazard ratio, 1.23; 95% confidence interval, 1.07–1.42) had the highest risk of death. There were no differences in stroke or transient ischemic attack and major bleeding among individuals with and without significant VHD. Patients with AF and aortic stenosis had the highest risk of death (hazard ratio, 1.32; 95% confidence interval, 1.08–1.62). Conclusions Significant VHD is common among patients with AF in community practice. In a community cohort of patients with AF and CHA 2 DS 2‐VASc score ≥2, most were anticoagulated. Individuals with AF and moderate‐to‐severe biological VHD have more comorbidities and a higher mortality risk; however, stroke and major bleeding are similar among those with and without significant VHD.

Sinus Node Dysfunction Is Associated With Higher Symptom Burden and Increased Comorbid Illness: Results From the ORBIT-AF Registry

Patients with sinus node dysfunction (SND) have increased risk of atrial tachyarrhythmias, including atrial fibrillation (AF). To date, treatment patterns and outcomes of patients with SND and AF have not been well described.