DaJuanicia N. Holmes

The association of in-hospital major bleeding with short-, intermediate-, and long-term mortality among older patients with non-ST-segment elevation myocardial infarction

AIMS Bleeding complications have been associated with short-term mortality in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Their association with long-term outcomes is less clear. This study examines mortality associated with in-hospital bleeding during NSTEMI over time intervals starting from hospital discharge and extending past 3 years. METHODS AND RESULTS We studied 32 895 NSTEMI patients aged ≥65 years, using patient-level data from the CRUSADE registry linked with Medicare claims data. We assessed the association of in-hospital major bleeding with short (30 days), intermediate (1 year), and long-term (3 years) mortality among hospital survivors overall, as well as in those patients treated with or without a percutaneous coronary intervention (PCI). We calculated adjusted hazard ratios (HRs) for mortality for bleeders vs. non-bleeders over time intervals from: (i) discharge to 30 days; (ii) 31 days to 1 year; (iii) 1 year to 3 years; and (iv) beyond 3 years. Overall, 11.9% (n = 3902) had an in-hospital major bleeding event. Cumulative mortality was higher in those who had a major bleed vs. those without at 30 days, 1 year, and 3 years. Even after adjustment, major bleeding continued to be significantly associated with higher mortality over time in the overall population: (i) discharge to 30 days [adjusted HR 1.33; 95% confidence interval (CI) 1.18-1.51]; (ii) 31 days to 1 year (1.19; 95% CI 1.10-1.29); (iii) 1 year to 3 years (1.09; 95% CI 1.01-1.18), and (iv) attenuating beyond 3 years (1.14; 95% CI 0.99-1.31). In-hospital bleeding among patients treated with PCI continued to be significantly associated with higher adjusted mortality even beyond 3 years (1.25; 95% CI 1.01-1.54). CONCLUSION In-hospital major bleeding is associated with short-, intermediate-, and long-term mortality among older patients hospitalized for NSTEMI-this association is strongest within the first 30 days, but remains significant long term, particularly among PCI-treated patients. Despite a probable early hazard related to bleeding, the longer duration of risk in patients who bleed casts doubt on its causal relationship with long-term mortality. Rather, major bleeding likely identifies patients with an underlying risk for mortality.

Impact of obstructive sleep apnea and continuous positive airway pressure therapy on outcomes in patients with atrial fibrillation—Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF)

BACKGROUND Obstructive sleep apnea (OSA) is common in patients with atrial fibrillation (AF). Little is known about the impact of OSA on AF treatment and long-term outcomes. We studied whether patients with OSA have a greater likelihood of progressing to more persistent forms of AF or require more hospitalizations and/or worse outcomes compared with patients without OSA. METHODS A total of 10,132 patients were enrolled between June 2010 and August 2011 in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) and followed for up to 2 years. The prevalence of OSA and continuous positive airway pressure (CPAP) treatment was captured at baseline. The association between OSA and major cardiovascular outcomes was analyzed using multivariable hierarchical logistic regression modeling and Cox frailty regression model. RESULTS Of the 10,132 patients with AF, 1,841 had OSA. Patients with OSA were more symptomatic (22% vs 16% severe/disabling symptoms; P < .0001) and more often on rhythm control therapy (35% vs 31%; P = .0037). In adjusted analyses, patients with OSA had higher risk of hospitalization (hazard ratio [HR], 1.12; 95% CI, 1.03-1.22; P = .0078), but no difference in the risks of death (HR, 0.94; 95% CI, 0.77-1.15; P = .54); the composite of CV death, myocardial infarction, and stroke/transient ischemic attack (HR, 1.07; 95% CI, 0.85-1.34; P = .57); major bleeding (HR, 1.18; 95% CI, 0.96-1.46; P = .11); or AF progression (HR, 1.06; 95% CI, 0.89-1.28; P = .51). Patients with OSA on CPAP treatment were less likely to progress to more permanent forms of AF compared with patients without CPAP (HR, 0.66; 95% CI, 0.46-0.94; P = .021). CONCLUSION Compared with those without, AF patients with OSA have worse symptoms and higher risks of hospitalization, but similar mortality, major adverse cardiovascular outcome, and AF progression rates. CLINICAL TRIAL REGISTRATION NCT01165710 (http://www.clinicaltrials.gov).

Early adoption of dabigatran and its dosing in US patients with atrial fibrillation: results from the outcomes registry for better informed treatment of atrial fibrillation.

Background Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown. Methods and Results We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974 atrial fibrillation patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years, P<0.0001), more likely to be white (92% versus 89%, P=0.005), more likely to have private insurance (33% versus 25%, P<0.0001), and less likely to have prior cardiovascular disease (4% versus 33%, P<0.0001). They had more new‐onset atrial fibrillation (8.8% versus 4.1%, P<0.0001), lower CHADS2 scores (estimated risk based on the presence of congestive heart failure, hypertension, aged ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3, P<0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8, P<0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during follow‐up. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73, P=0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4, P<0.0001). Conclusions Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted. Clinical Trial Registration URL: Clinicaltrials.gov. Unique identifier: NCT01165710.

Rate versus rhythm control for management of atrial fibrillation in clinical practice: results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry.

BACKGROUND All patients with atrial fibrillation (AF) require optimization of their ventricular rate. Factors leading to use of additional rhythm control in clinical practice have not been thoroughly defined. METHODS The ORBIT-AF registry enrolled patients with AF from a broad range of practice settings and collected data on rate versus rhythm control, as indicated by the treating physician. Multivariable logistic regression analysis was performed to identify factors associated with each strategy. RESULTS Of 10,061 patients enrolled, 6,859 (68%) were managed with rate only control versus 3,202 (32%) with rhythm control. Patients managed with rate control were significantly older and more likely to have hypertension, heart failure, prior stroke, and gastrointestinal bleeds. They also had fewer AF-related symptoms (41% with no symptoms vs 31% for rhythm control). Systemic anticoagulation was prescribed for 5,448 (79%) rate-control patients versus 2,219 (69%) rhythm-control patients (P < .0001). After multivariable adjustment, patients with higher symptom scores (severe symptoms vs. none, OR 1.62, 95% CI 1.41-1.87) and those referred to electrophysiologists (OR 1.64, 95% CI 1.45-1.85) were more likely to be managed with a rhythm control strategy. CONCLUSIONS In this outpatient registry of US clinical practice, the majority of patients with AF were managed with rate control alone. Patients with more symptoms and who were treated by an electrophysiologist were more likely to receive rhythm-control therapies. A significant proportion of AF patients, regardless of treatment strategy, were not treated with anticoagulation for thromboembolism prophylaxis.

Fibrinolysis Use Among Patients Requiring Interhospital Transfer for ST-Segment Elevation Myocardial Infarction Care: A Report From the US National Cardiovascular Data Registry

IMPORTANCE Guidelines for patients with ST-segment elevation myocardial infarction (STEMI) recommend timely reperfusion with primary percutaneous coronary intervention (pPCI) or fibrinolysis. Among patients with STEMI who require interhospital transfer, it is unclear how reperfusion strategy selection and outcomes vary with interhospital drive times. OBJECTIVE To assess the association of estimated interhospital drive times with reperfusion strategy selection among transferred patients with STEMI in the United States. DESIGN, SETTING, AND PARTICIPANTS We identified 22,481 patients eligible for pPCI or fibrinolysis who were transferred from 1771 STEMI referring centers to 366 STEMI receiving centers in the Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines database between July 1, 2008, and March 31, 2012. MAIN OUTCOMES AND MEASURES In-hospital mortality and major bleeding. RESULTS The median estimated interhospital drive time was 57 minutes (interquartile range [IQR], 36-88 minutes). When the estimated drive time exceeded 30 minutes, only 42.6% of transfer patients treated with pPCI achieved the first door-to-balloon time within 120 minutes. Only 52.7% of eligible patients with a drive time exceeding 60 minutes received fibrinolysis. Among 15,437 patients with estimated drive times of 30 to 120 minutes who were eligible for fibrinolysis or pPCI, 5296 (34.3%) received pretransfer fibrinolysis, with a median door-to-needle time of 34 minutes (IQR, 23-53 minutes). After fibrinolysis, the median time to transfer to the STEMI receiving center was 49 minutes (IQR, 34-69 minutes), and 97.1% underwent follow-up angiography. Patients treated with fibrinolysis vs pPCI had no significant mortality difference (3.7% vs 3.9%; adjusted odds ratio, 1.13; 95% CI, 0.94-1.36) but had higher bleeding risk (10.7% vs 9.5%; adjusted odds ratio, 1.17; 95% CI, 1.02-1.33). CONCLUSIONS AND RELEVANCE In the United States, neither fibrinolysis nor pPCI is being optimally used to achieve guideline-recommended reperfusion targets. For patients who are unlikely to receive timely pPCI, pretransfer fibrinolysis, followed by early transfer for angiography, may be a reperfusion option when potential benefits of timely reperfusion outweigh bleeding risk.

International comparisons of the management of patients with non-ST segment elevation acute myocardial infarction in the United Kingdom, Sweden, and the United States: The MINAP/NICOR, SWEDEHEART/RIKS-HIA, and ACTION Registry-GWTG/NCDR registries

Objectives To compare management of patients with acute non-ST segment elevation myocardial infarction (NSTEMI) in three developed countries with national ongoing registries. Background Results from clinical trials suggest significant variation in care across the world. However, international comparisons in “real world” registries are limited. Methods We compared the use of in-hospital procedures and discharge medications for patients admitted with NSTEMI from 2007 to 2010 using the unselective MINAP/NICOR [England and Wales (UK); n = 137,009], the unselective SWEDEHEART/RIKS-HIA (Sweden; n = 45,069), and the selective ACTION Registry-GWTG/NCDR [United States (US); n = 147,438] clinical registries. Results Patients enrolled among the three registries were generally similar except those in the US who were younger but had higher rates of smoking, diabetes, hypertension, prior heart failure, and prior MI than in Sweden or in UK. Angiography and percutaneous coronary intervention (PCI) were performed more often in the US (76% and 44%) and Sweden (65% and 42%) relative to the UK (32% and 22%). Discharge betablockers were also prescribed more often in the US (89%) and Sweden (89%) than in the UK (76%). In contrast, discharge statins, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), and dual antiplatelet agents (among those not receiving PCI) were higher in the UK (92%, 79%, and 71%) than in the US (85%, 65%, 41%) and Sweden (81%, 69%, and 49%). Conclusions The care for patients with NSTEMI differed substantially among the three countries. These differences in care among countries provide an opportunity for future comparative effectiveness research as well as identify opportunities for global quality improvement.

Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II: rationale and design of the ORBIT-AF II registry.

BACKGROUND Recent clinical trials have demonstrated the safety and efficacy of several non-vitamin K oral anticoagulants (NOACs) for the treatment of atrial fibrillation (AF). However, there are limited data on their use and outcomes in routine clinical practice, particularly among patients newly diagnosed as having AF and patients with AF recently transitioned to a NOAC. METHODS/DESIGN ORBIT-AF II is a multicenter, national registry of patients with AF that is enrolling up to 15,000 newly diagnosed patients with AF and/or those with AF recently transitioned to a NOAC from 300 US outpatient practices. These patients will be followed for up to 2 years, including clinical status, outcomes (major adverse cardiovascular events, bleeding), and management of anticoagulation surrounding bleeding events. In addition, detailed data regarding the use of these agents in and around cardiac procedures, their complications, and management of such complications will be collected. CONCLUSIONS The ORBIT-AF II registry will provide valuable insights into the safety and effectiveness of NOACs used in AF in community practice settings.

Provider specialty and atrial fibrillation treatment strategies in United States community practice: findings from the ORBIT-AF registry.

Background The prevalence of atrial fibrillation (AF) continues to increase; however, there are limited data describing the division of care among practitioners in the community and whether care differs depending on provider specialty. Methods and Results Using the Outcomes Registry for Better Informed Treatment of AF (ORBIT‐AF) Registry, we described patient characteristics and AF management strategies in ambulatory clinic practice settings, including electrophysiology (EP), general cardiology, and primary care. A total of 10 097 patients were included; of these, 1544 (15.3%) were cared for by an EP provider, 6584 (65.2%) by a cardiology provider, and 1969 (19.5%) by an internal medicine/primary care provider. Compared with those patients who were cared for by cardiologists or internal medicine/primary care providers, patients cared for by EP providers were younger (median age, 73 years [interquartile range, IQR, 64, 80 years, Q1, Q3] versus 75 years [IQR, 67, 82 years] for cardiology and versus 76 years [IQR, 68, 82 years] for primary care). Compared with cardiology and internal medicine/primary care providers, EP providers used rhythm control (versus rate control) management more often (44.2% versus 29.7% and 28.8%, respectively, P<0.0001; adjusted odds ratio [OR] EP versus cardiology, 1.66 [95% confidence interval, CI, 1.05 to 2.61]; adjusted OR for internal medicine/primary care versus cardiology, 0.91 [95% CI, 0.65 to 1.26]). Use of oral anticoagulant therapy was high across all providers, although it was higher for cardiology and EP providers (overall, 76.1%; P=0.02 for difference between groups). Conclusions Our data demonstrate important differences between provider specialties, the demographics of the AF patient population treated, and treatment strategies—particularly for rhythm control and anticoagulation therapy.

Risk of Heart Failure Complication during Hospitalization for Acute Myocardial Infarction in a Contemporary Population: Insights from the National Cardiovascular Data ACTION Registry

Background—Patients with acute myocardial infarction (MI) complicated by heart failure (HF) are subject to higher mortality during the index hospitalization. Early risk prediction and intervention may help prevent HF-related morbidity and mortality. Methods and Results—We examined 77 675 ST-elevation MI and 110 128 non-ST-elevation patients with MI without cardiogenic shock or HF at presentation treated at 609 hospitals in Acute Coronary Treatment and Intervention Outcomes Network Registry (ACTION) Registry-Get With The Guidelines between January 1, 2007, and March 31, 2011. Logistic regression identified patient characteristics associated with development of in-hospital HF. Overall, 3.8% of patients with MI developed in-hospital HF, which was associated with higher mortality in both ST-elevation MI and non-ST elevation MI. In multivariable logistic regression, left ventricular ejection fraction ⩽30%, prior HF, diabetes mellitus, female sex, ST-elevation MI, and hypertension (all P<0.005) were independently associated with in-hospital HF. Patients who developed HF during non-ST-elevation MI were more likely to be medically managed without catheterization (30% versus 13% with HF, P<0.0001) or had longer delays to surgical or percutaneous revascularization. Patients with ST-elevation MI and HF were less likely to receive primary percutaneous coronary revascularization (84% versus 79% with HF, P<0.0001), and more likely to receive thrombolytic therapy (14% versus 11%; P=0.0001). Conclusions—Patients with MI who develop HF during hospitalization have a higher risk clinical profile and greater mortality, but may be less likely to receive revascularization in a timely fashion. Targeting these highest risk patients may improve outcome post-MI.

Mortality implications of primary percutaneous coronary intervention treatment delays: insights from the Assessment of Pexelizumab in Acute Myocardial Infarction trial.

Background— Prior studies demonstrate a direct relationship between treatment delays to primary percutaneous intervention and mortality in patients with ST-segment elevation myocardial infarction (STEMI). This analysis compared the relationship of symptom onset-to-balloon time and door-to-balloon time on mortality in patients with STEMI. Methods and Results— We analyzed different treatment delays (symptom onset-to-balloon time, door-to-balloon time) and mortality in 5745 STEMI patients. Baseline characteristics, flow grade, 90-day mortality, and clinical outcomes were compared in patients stratified by treatment delay. Multivariable logistic regression modeling was performed to assess the independent and relative effect of each treatment delay on 90-day mortality. Female sex, increased age, and worse thrombolysis in myocardial infarction flow grade were significantly associated with longer symptom onset-to-balloon times and door-to-balloon times. Longer symptom onset-to-balloon time was significantly associated with worse 90-day mortality (3.7%, 4.2%, and 6.5% for time delays <3 hours, 3 to 5 hours, and >5 hours, respectively, P<0.0001). Similarly, longer door-to-balloon times were significantly associated with worse 90-day mortality (3.2%, 4.0%, 4.6%, and 5.3% for delays <60 minutes, 60 to 90 minutes, 90 to 120 minutes, and ≥120 minutes respectively, P<0.0001). In a multivariate model of 90-day mortality, door-to-balloon time (&khgr;2 6.0, P<0.014), and symptom onset-to-hospital arrival (&khgr;2 9.8, P<0.007) remained independent determinants. Conclusions— Both symptom onset-to-balloon time and hospital door-to-balloon time are strongly associated with 90-day mortality following STEMI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00091637.