Racial Differences in Presentation and Outcomes After Peripheral Arterial Interventions: Insights From the NCDR-PVI Registry.

BACKGROUND: We assess the rates of device use and outcomes by race among patients undergoing lower extremity peripheral arterial intervention using the American College of Cardiology National Cardiovascular Data Registry-Peripheral Vascular Intervention (PVI) registry. METHODS: Patients who underwent PVI between April 2014 and March 2019 were included. Socioeconomic status was evaluated using the Distressed Community Index score for patients' zip codes. Multivariable logistic regression was used to assess factors associated with utilization of drug-eluting technologies, intravascular imaging, and atherectomy. Among patients with Centers for Medicare and Medicaid Services data, we compared 1-year mortality, rates of amputation, and repeat revascularizations. RESULTS: Of 63 150 study cases, 55 719 (88.2%) were performed in White patients and 7431 (11.8%) in Black patients. Black patients were younger (67.9 versus 70.0 years), had higher rates of hypertension (94.4% versus 89.5%), diabetes (63.0% versus 46.2%), less likely to be able to walk 200 m (29.1% versus 24.8%), and higher Distressed Community Index scores (65.1 versus 50.6). Black patients were provided drug-eluting technologies at a higher rate (adjusted odds ratio, 1.14 [95% CI, 1.06-1.23]) with no difference in atherectomy (adjusted odds ratio, 0.98 [95% CI, 0.91-1.05]) or intravascular imaging (adjusted odds ratio, 1.03 [95% CI, 0.88-1.22]) use. Black patients experienced a lower rate of acute kidney injury (adjusted odds ratio, 0.79 [95% CI, 0.72-0.88]). In Centers for Medicare and Medicaid Services-linked analyses of 7429 cases (11.8%), Black patients were significantly less likely to have surgical (adjusted hazard ratio, 0.40 [95% CI, 0.17-0.96]) or repeat PVI revascularization (adjusted hazard ratio, 0.42 [95% CI, 0.30-0.59]) at 1 year compared with White patients. There was no difference in mortality (adjusted hazard ratio [0.8-1.4]) or major amputation (adjusted hazard ratio, 2.5 [95% CI, 0.8-7.6]) between Black and White patients. CONCLUSIONS: Black patients presenting for PVI were younger, had higher prevalence of comorbidities and lower socioeconomic status. After adjustment, Black patients were less likely to have surgical or repeat PVI revascularization after the index PVI procedure.

Impact of prior oral anticoagulant use and outcomes on patients from secondary analysis in the AUGUSTUS trial.

OBJECTIVE: Managing antithrombotic therapy in patients with atrial fibrillation (AF) and an acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) is challenging and can be affected by prior oral anticoagulant (OAC) treatment. We examined the relationship between prior OAC use and outcomes in the AUGUSTUS trial. METHODS: This prespecified secondary analysis is from AUGUSTUS, an open-label, 2-by-2 factorial, RCT to evaluate the safety of apixaban versus vitamin K antagonist (VKA) and aspirin versus placebo in patients with AF and ACS and/or PCI. The primary endpoint, major or clinically relevant non-major bleeding and clinical outcomes were compared in patients receiving (n=2262) or not receiving (n=2352) an OAC prior to enrolment. RESULTS: Patients with prior OAC use had more comorbidities, higher CHA2DS2-VASC and HAS-BLED scores, and were more likely enrolled following elective PCI. There was no difference in major or clinically relevant non-major bleeding with or without prior OAC (30 days: 5.1% vs 5.9% (adjusted HR (aHR) 0.82, 95% CI 0.63 to 1.06); 180 days: 13.5% vs 13.5% (aHR 0.98, 95% CI 0.83 to 1.16)). Patients with prior OAC use had a lower risk of death or ischaemic events (30 days: 1.7% vs 2.8% (aHR 0.61, 95% CI 0.41 to 0.92); 180 days: 5.4% vs 7.6% (aHR 0.70, 95% CI 0.55 to 0.88)). No interactions between randomised treatment (apixaban vs VKA, aspirin vs placebo) and prior OAC status were observed for outcomes, apart from apixaban (vs VKA) being associated with a lower risk of myocardial infarction with prior OAC use (180 days: 2.0% vs 3.7% (aHR 0.56, 95% CI 0.33 to 0.91(). CONCLUSIONS: In AUGUSTUS, prior OAC use was associated with fewer ischaemic events but not more bleeding. In patients with AF and ACS and/or undergoing PCI, clinicians can be assured that the trial results can be applied to patients regardless of their prior OAC status. TRIAL REGISTRATION NUMBER: NCT02415400.

Variation in Antithrombotic Therapy and Clinical Outcomes in Patients With Preexisting Atrial Fibrillation Undergoing Transcatheter Aortic Valve Replacement: Insights From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.

BACKGROUND: Optimal antithrombotic management of patients with preexisting atrial fibrillation undergoing transcatheter aortic valve replacement is challenging given the need to balance the risk of bleeding and thromboembolism. We aimed to examine variation in care and association of antithrombotic therapies with 1-year outcomes of stroke, bleeding, and mortality in patients undergoing transcatheter aortic valve replacement with concomitant atrial fibrillation in the United States. METHODS: Patients who underwent transcatheter aortic valve replacement with preexisting atrial fibrillation from November 2011 through September 2015 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy registry linked to the Medicare database were examined according to receipt of oral anticoagulants (OACs) or antiplatelet therapies (APTs) or a combination of these (OAC+APT) at discharge. To assess the associations of antithrombotic therapies with 1-year outcomes of stroke, bleeding, and mortality, we utilized inverse probability weighting for antithrombotic therapies and multivariable regression modeling to adjust for patient- and hospital-level variables. RESULTS: In the 11 382 patients included in our study, 5833 (51.2%) were discharged on OAC+APT, 4786 (42.0%) on APT alone, and 763 (6.7%) on OAC alone. There was significant variability in discharge medication patterns, including 42% of patients discharged without OAC therapy. In adjusted analyses, the risk for all-cause mortality and stroke was not significantly different when comparing the 3 different antithrombotic strategies. Risk of bleeding was higher with OAC+APT compared with APT alone (hazard ratio, 1.16 [95% CI, 1.05­1.27]) and similar compared with OAC alone (hazard ratio, 1.17 [95% CI, 0.93­1.47]). CONCLUSIONS: There was significant variability in discharge medication patterns across US sites in patients with atrial fibrillation undergoing transcatheter aortic valve replacement, including significant underuse of OAC in this high-risk cohort. The use of OAC+APT (versus OAC alone or APT alone) was not associated with a lower risk of stroke or mortality but was associated with increased risk of bleeding complications at 1 year compared with APT alone.

Incidence, Management, and Associated Clinical Outcomes of New-Onset Atrial Fibrillation Following Transcatheter Aortic Valve Replacement: An Analysis From the STS/ACC TVT Registry.

OBJECTIVES: The aim of this study was to evaluate incidence, care patterns, and clinical outcomes in patients developing new-onset atrial fibrillation (AF) following transcatheter aortic valve replacement (TAVR). BACKGROUND: Pre-procedural AF has been associated with adverse outcomes in patients undergoing TAVR, but the incidence of new-onset AF, associated anticoagulant management, and subsequent clinical outcomes are unclear. METHODS: Using the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry linked with Medicare claims, patients undergoing TAVR from 2011 to 2015 who developed post-procedural AF were evaluated. Patients with known AF prior to TAVR were excluded. Outcomes of interest included in-hospital mortality and stroke and all-cause mortality, stroke, and bleeding at 12 months. Multivariate adjustment was then performed to determine differences in 1-year outcomes among those with and without new post-procedural AF, stratified by anticoagulation status. RESULTS: We identified 1,138 of 13,556 patients (8.4%) who developed new onset AF (4.4% of transfemoral [TF]-access patients, 16.5% of non-TF-access patients). Patients developing AF were older, more likely female, had higher Society of Thoracic Surgeons risk scores, and were often treated using non-TF access. Despite having a median CHA2DS2-VASc score of 5 (25th and 75th percentile: 5 to 6), only 28.9% of patients with new AF were discharged on oral anticoagulation. In-hospital mortality (7.8% vs. 3.4%; p < 0.01) and stroke (4.7% vs. 2.0%; p < 0.01) were higher among patients who developed post-procedural AF compared with those who did not. At 1 year, rates of death (adjusted hazard ratio [HR]: 1.37; 95% confidence interval [CI]: 1.19 to 1.59), stroke (adjusted HR: 1.50; 95% CI: 1.14 to 1.98), and bleeding (adjusted HR: 1.24; 95% CI: 1.10 to 1.40) were higher among patients with new-onset AF. One-year mortality rates were highest among patients who developed new-onset AF but were not discharged on anticoagulation. CONCLUSIONS: Post-TAVR AF occurred in 8.4% of patients (4.4% with TF access, 16.5% with non-TF access), with fewer than one-third of patients receiving anticoagulation at discharge, and was associated with increased risk for in-hospital and 1-year mortality and stroke. Given the clinical significance of post-TAVR AF, additional studies are necessary to delineate the optimal management strategy in this high-risk population.

Data monitoring committees: Promoting best practices to address emerging challenges.

BACKGROUND AND PURPOSE: Data monitoring committees are responsible for safeguarding the interests of study participants and assuring the integrity and credibility of clinical trials. The independence of data monitoring committees from sponsors and investigators is essential in achieving this mission. Creative approaches are needed to address ongoing and emerging challenges that potentially threaten data monitoring committees' independence and effectiveness. METHODS: An expert panel of representatives from academia, industry and government sponsors, and regulatory agencies discussed these challenges and proposed best practices and operating principles for effective functioning of contemporary data monitoring committees. RESULTS AND CONCLUSIONS: Prospective data monitoring committee members need better training. Options could include didactic instruction as well as apprenticeships to provide real-world experience. Data monitoring committee members should be protected against legal liability arising from their service. While avoiding breaches in confidentiality of interim data remains a high priority, data monitoring committees should have access to unblinded efficacy and safety data throughout the trial to enable informed judgments about risks and benefits. Because overly rigid procedures can compromise their independence, data monitoring committees should have the flexibility necessary to best fulfill their responsibilities. Data monitoring committee charters should articulate principles that guide the data monitoring committee process rather than list a rigid set of requirements. Data monitoring committees should develop their recommendations by consensus rather than through voting processes. The format for the meetings of the data monitoring committee should maintain the committee's independence and clearly establish the leadership of the data monitoring committee chair. The independent statistical group at the Statistical Data Analysis Center should have sufficient depth of knowledge about the study at hand and experience with trials in general to ensure that the data monitoring committee has access to timely, reliable, and readily interpretable insights about emerging evidence in the clinical trial. Contracts engaging data monitoring committee members for industry-sponsored trials should have language customized to the unique responsibilities of data monitoring committee members rather than use language appropriate to consultants for product development. Regulatory scientists would benefit from experiencing data monitoring committee service that does not conflict with their regulatory responsibilities.

Association Between Chronic Kidney Disease and Rates of Transfusion and Progression to End-Stage Renal Disease in Patients Undergoing Transradial Versus Transfemoral Cardiac Catheterization-An Analysis From the Veterans Affairs Clinical Assessment Reporting and Tracking (CART) Program.

BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk for bleeding, transfusion, and dialysis after cardiac catheterization. Whether rates of these complications are increased in this high-risk population undergoing transradial access compared with transfemoral access is unknown. METHODS AND RESULTS: From the Veterans Affairs (VA) Clinical Assessment Reporting and Tracking program, we identified 229 108 patients undergoing cardiac catheterization between 2007 and 2014, of which 48 155 (21.0%) had baseline glomerular filtration rate (GFR) between 15 and 59 mL/min. We used multivariable Cox modeling to determine the independent association between transradial access and postprocedure transfusion as well as progression to new dialysis by degree of renal dysfunction. Overall, 35 979 (15.7%) of patients underwent Transradial access. Transradial patients tended to be slightly younger, but, overall, had similar rates of CKD compared to transfemoral patients (24.3% vs 27.1%). Transradial patients had longer fluoroscopy times (7.2 vs 6.0 minutes; P<0.001), but lower contrast use (85.0 vs 100.0 mL; P<0.001). The estimated rate of blood transfusion within 48 hours was lower among transradial patients (0.85% vs 1.01%) as were rates of new dialysis at 1 year (0.58% vs 0.71%). After multivariable adjustment, transradial access was associated with lower rates of progression to dialysis at 1 year overall (hazard ratio [HR], 0.83; 95% CI, 0.70-0.98), with no trend of increased risk for dialysis by degree of CKD compared with transfemoral access. Transradial access was associated with greater reduction in transfusion rates with increasing degree of CKD (P value for trend=0.04: non-CKD: HR, 0.99; 95% CI, 0.73-1.34; GFR 45-59 mL/min: HR, 0.93; 95% CI, 0.70-1.23; GFR 30-44 mL/min: HR, 0.73; 95% CI, 0.51-1.03; GFR 15-29 mL/min: HR, 0.43; 95% CI, 0.20-0.90). CONCLUSIONS: Among patients undergoing cardiac catheterization in the VA health system, transradial access was associated with lower risk for postprocedure transfusion within 48 hours among patients with more-severe CKD, and with lower risk of progression to end-stage renal disease at 1 year compared with transfemoral access. These data provide additional evidence that transradial access may provide significant benefit in this high-risk population.

Factors Associated With Initial Prasugrel Versus Clopidogrel Selection for Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: Insights From the Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) Study.

BACKGROUND: Few studies have examined how antiplatelet therapies are selected during the routine care of acute myocardial infarction patients, particularly relative to the patient's estimated mortality and bleeding risks. METHODS AND RESULTS: We examined patients presenting with acute myocardial infarction treated with percutaneous coronary intervention at 233 US hospitals in the TRANSLATE-ACS observational study from April 2010 to October 2012. We developed a multivariable logistic regression model to identify factors associated with prasugrel selection. Prasugrel use rates and associated 1-year risk-adjusted major adverse cardiovascular events and Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) moderate/severe bleeding outcomes were also examined in relation to predicted mortality and bleeding using the validated Acute Coronary Treatment and Intervention Outcomes (ACTION) risk prediction scores. Among 11 969 patients, 3123 (26%) received prasugrel at the time of percutaneous coronary intervention. The strongest factors associated with prasugrel use included cardiogenic shock (odds ratio [OR] 1.68, 95% CI 1.25-2.26), drug-eluting stent use (OR 1.45, 95% CI 1.31-1.62), and ST-segment elevation myocardial infarction presentation (OR 1.23, 95% CI 1.12-1.35). Older age (OR 0.57, 95% CI 0.0.53-0.61), dialysis (OR 0.56, 95% CI 0.32-0.96), prior history of stroke/transient ischemic attack (OR 0.52, 95% CI 0.38-0.73), and interhospital transfer (OR 0.50, 95% CI 0.46-0.55) were associated with lowest prasugrel selection. Prasugrel was used less often than clopidogrel in patients at higher predicted bleeding risk (21.9% versus 29.7%, P<0.001). Yet paradoxically, prasugrel was also less likely than clopidogrel to be used in patients with higher predicted mortality risk (21.1% versus 30.2%, P<0.001). Adjusted bleeding and outcomes events were similar among those receiving prasugrel and clopidogrel in the 4 subgroups of patients based on bleeding risk and ischemic benefits. CONCLUSIONS: In community practice, prasugrel use may be driven more by bleeding risk rather than ischemic benefit. This may result in underutilization of higher potency ADP receptor inhibitor among patients more likely to derive ischemic benefit.

Differences in Short- and Long-Term Outcomes Among Older Patients With ST-Elevation Versus Non-ST-Elevation Myocardial Infarction With Angiographically Proven Coronary Artery Disease.

BACKGROUND: Among older patients with acute myocardial infarction (MI), it remains uncertain whether there is a time-dependent difference in the risk of recurrent mortality and nonfatal cardiovascular and cerebrovascular events for those with ST-segment-elevation MI (STEMI) compared with those with non-ST-segment-elevation MI. METHODS AND RESULTS: Older patients ≥65 years with acute MI and significant coronary artery disease identified with coronary angiography from the ACTION Registry-GWTG (Get With the Guidelines) were linked to Medicare claims data from 2007 to 2010. We examined the unadjusted cumulative incidence of each outcome studied from hospital discharge through 2 years with log-rank tests and then performed a piece-wise proportional hazards modeling with 2 time periods: discharge to 90 days and 90 days to 2 years. Among the 46 199 patients linked with Medicare data, 17 287 (37.4%) presented with STEMI. Through 2 years, the unadjusted cumulative incidence of all-cause mortality (16.0% versus 19.8%; P<0.001) and the composite outcome (21.9% versus 27.9%; P<0.001) was lower for STEMI patients. Within the first 90 days, unadjusted rates of mortality (5.5% versus 5.3%) and the composite outcome (7.9% versus 8.1%) were similar but diverged from 90 days to 2 years (mortality, 11.1% versus 15.4%; P<0.001; composite outcome, 15.2% versus 21.5%; P<0.001). After multivariable adjustment, the adjusted risks of mortality and the composite outcome through 90 days were higher for STEMI patients, whereas risks of mortality and the composite outcome were attenuated from 90 days through 2 years. CONCLUSIONS: Among older acute MI patients with angiographically confirmed coronary artery disease discharged alive, STEMI patients (compared with non-ST-segment-elevation MI patients) were found to have a lower frequency of unadjusted postdischarge mortality and composite cardiovascular and cerebrovascular outcomes through 2 years after hospital discharge. This analysis provides unique insight into differential short- and long-term risks of ischemic cardiovascular and cerebrovascular outcomes by MI classification among older MI patients with confirmed coronary artery disease surviving to hospital discharge.

Care Transitions After Acute Myocardial Infarction for Transferred-In Versus Direct-Arrival Patients.

BACKGROUND: Many patients in the United States require transfer from one hospital to another for acute myocardial infarction (MI) care. How well these transferred-in patients are transitioned back to their local community is unknown. METHODS AND RESULTS: We used linked Medicare claims data to examine postdischarge outcomes of 39 136 patients with acute MI aged ≥65 years discharged alive from 451 US hospitals in Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines. Multivariable Cox modeling was used to compare the likelihood of outpatient clinic follow-up and risks of all-cause mortality and all-cause or cardiovascular readmission at 30 days post MI between transferred-in and direct-arrival patients. From 2007 to 2010, 14 060 of 39 136 patients (36%) required interhospital transfer for acute MI care, traveling a median of 43 miles (interquartile range, 27-68 miles; 77.6 km [interquartile range, 48.2-122.6 km]). Compared with those arriving directly, transferred-in patients with MI were slightly younger (median age, 73 versus 74; P<0.01) but less likely to have previous MI, heart failure, and previous revascularization than direct-arrival patients. Relative to direct-arrival patients, those transferred-in had a lower likelihood of outpatient follow-up within 30 days post discharge (risk-adjusted incidence, 69.9% versus 78.2%; hazard ratio [HR], 0.90; 95% confidence interval, 0.87-0.92) and higher adjusted 30-day all-cause and cardiovascular readmission risks (14.5% versus 14.0%; HRall-cause, 1.08; 95% confidence interval, 1.01-1.15 and 9.5% versus 9.1%; HRcardiovascular, 1.13; 95% confidence interval, 1.04-1.22). In contrast, risk-adjusted 30-day mortality was similar between transferred-in and direct arrivals (1.6% versus 1.6%; HR, 1.05; 95% confidence interval, 0.86-1.27). CONCLUSIONS: Transferred-in patients with acute MI are less likely to have outpatient clinic follow-up within 30 days and more likely to be readmitted within the first 30 days post discharge compared with direct-arrival patients. These results indicate room for improvement in the safe and seamless transition of care for transferred patients with MI traveling back to their home environments.

Effectiveness and Safety of Aldosterone Antagonist Therapy Use Among Older Patients With Reduced Ejection Fraction After Acute Myocardial Infarction.

BACKGROUND: While aldosterone antagonists have proven benefit among post-myocardial infarction (MI) patients with low ejection fraction (EF), how this treatment is used among older MI patients in routine practice is not well described. METHODS AND RESULTS: Using ACTION Registry-GWTG linked to Medicare data, we examined 12 080 MI patients ≥65 years with EF ≤40% who were indicated for aldosterone antagonist therapy per current guidelines and without documented contraindications. Of these, 11% (n=1310) were prescribed aldosterone antagonists at discharge. Notably, 10% of patients prescribed an aldosterone antagonist were eligible for, but not concurrently treated with, an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Spironolactone was the predominantly prescribed aldosterone antagonist. At 2-year follow-up, aldosterone antagonist use was not associated with lower mortality (unadjusted 39% versus 38%; HR 0.99, 95% CI 0.88-1.33 using inverse probability-weighted propensity adjustment) except in symptomatic HF patients (HR 0.84, 95% CI 0.72-0.99, Pinteraction=0.009). Risks of hyperkalemia were low at 30 days, but significantly higher among patients prescribed aldosterone antagonists (unadjusted 2.3% versus 1.5%; adjusted HR 2.04, 95% CI 1.16-3.60), as was 2-year risk of acute renal failure (unadjusted 6.7% versus 4.8%; adjusted HR 1.39, 95% CI 1.01-1.92) compared with patients not prescribed aldosterone antagonists. CONCLUSIONS: Aldosterone antagonist use among eligible older MI patients in routine clinical practice was not associated with lower mortality except in patients with HF symptoms, but was associated with increased risks of hyperkalemia and acute renal failure. These results underscore the importance of close post-discharge monitoring of this patient population.

Diagnostic evaluation of the MRP-8/14 for the emergency assessment of chest pain.

Elevated levels of myeloid-related protein (MRP)-8/14 (S100A8/A9) are associated with first cardiovascular events in healthy individuals and worse prognosis in patients with acute coronary syndrome (ACS). The diagnostic utility of MRP-8/14 in patients presenting to the emergency room with symptoms concerning for ACS is uncertain. MRP-8/14 was measured in serial serum and plasma samples in a single center prospective cohort-study of patients presenting to the emergency room with non-traumatic chest pain concerning for ACS. Final diagnosis was adjudicated by an endpoint committee. Of patients with baseline MRP-8/14 results (n = 411), the median concentration in serum was 1.57 µg/ml (25th, 75th: 0.87, 2.68) and in plasma was 0.41 µg/ml (<0.4, 1.15) with only moderate correlation between serum and plasma (ρ = 0.40). A final diagnosis of MI was made in 106 (26%). Peak serum MRP-8/14 was higher in patients presenting with MI (p < 0.001). However, the overall diagnostic performance of MRP-8/14 was poor: sensitivity 28% (95% CI 20-38), specificity 82% (78-86), positive predictive value 36% (26-47), and negative predictive value 77% (72-81). The area under the ROC curve for diagnosis of MI with MRP-8/14 was 0.55 (95% CI 0.51-0.60) compared with 0.95 for cTnI. The diagnostic performance was not improved in early-presenters, patients with negative initial cTnI, or using later MRP-8/14 samples. Patients presenting with MI had elevated levels of serum MRP-8/14 compared to patients with non-cardiac chest pain. However, overall diagnostic performance of MRP-8/14 was poor and neither plasma nor serum MRP-8/14 offered diagnostic utility comparable to cardiac troponin.