Does study subject diversity influence cardiology research site performance?: Insights from 2 U.S. National Coronary Stent Registries.

BACKGROUND: Minorities and women are underrepresented in cardiovascular research. Whether their higher enrollment can be predicted or influences research site performance is unclear. METHODS: We evaluated 104 sites that enrolled 4,184 patients in the U.S. Platinum Diversity (PD) and Promus Element Plus (PE Plus) studies (2012 to 2016). Research sites were ranked from lowest to highest minority and female enrollment, respectively. United States Census Bureau division and core-based statistical area (CBSA) populations were determined for each site and the following study performance metrics compared across quartiles of minority and female enrollment, respectively: (1) study subject enrollment rate (SER), (2) time to first patient enrolled, (3) rate of follow-up visits not done, (4) rate of follow-up visits out of window, and (5) protocol deviation rate (PDR). Multivariable regression was used to predict SER and PDR. RESULTS: Minority enrollment varied by region (P = .025) and population (P = .024) with highest recruitment noted in the Pacific, West South Central, South Atlantic, Mid-Atlantic and East North Central divisions. Female enrollment bore no relationship to region (P = .67) or population (P = .40). Median SER was similar in sites withi the highest vs lowest quartile of minority enrollment (SER of 4 vs 5 patients per month, respectively, P =0.78) and highest vs. lowest female enrollment (SER of 4 vs 4, respectively, P = .21). Median PDR was lower in sites within the highest vs lowest minority enrollment (0.23 vs 0.50 PDs per patient per month, respectively, P = .01) and highest vs. lowest female enrollment (0.28 vs. 0.37 PDs per patient per month, respectively, P = .04). However, this relationship did not persist after multivariable adjustment. All other site performance metrics were comparable across quartiles of minority and female enrollment. CONCLUSIONS: Minority, but not female enrollment, correlated with research site geographic region and surrounding population. High enrollment of minorities and women did not influence study performance metrics. These findings help inform future strategies aimed at increasing clinical trial diversity. TRIAL REGISTRATION: The PD and PE Plus studies are registered at www.clinicaltrials.gov under identifiers NCT02240810 and NCT01589978, respectively. KEY POINTS: Question: Does the enrollment of more Blacks, Hispanics and women in US cardiovascular research studies influence the overall rate of study subject enrollment and/or other key study site performance metrics and can diverse enrollment be predicted? FINDINGS: In this pooled analysis of 104 sites that enrolled 4,184 patients in the Platinum Diversity and Promus Element Plus Post-Approval Studies, we found that the enrollment of higher proportions of underrepresented minorities and women was univariately associated with lower protocol deviation rates while having no effect on other site performance metrics. A site's geographic location and surrounding population predicted minority, but not female enrollment. Meaning: These findings suggest that cardiovascular research subject diversity may be predicted from site characteristics and enhanced without compromising key study performance metrics. These insights help inform future strategies aimed at improving clinical trial diversity.

Transradial access in acute myocardial infarction complicated by cardiogenic shock: Stratified analysis by shock severity.

BACKGROUND: Transradial access (TRA) is associated with improved survival and reduced vascular complications in acute myocardial infarction (AMI). Limited data exist regarding TRA utilization and outcomes for AMI complicated by cardiogenic shock (CS). We sought to assess the safety, feasibility, and clinical outcomes of TRA in AMI-CS. METHODS: One-hundred and fifty-three patients with AMI-CS were stratified into tertiles of disease severity using the CardShock score. The primary endpoint was successful percutaneous coronary intervention (PCI), defined as Thrombolysis in Myocardial Infarction III flow with survival to 30 days. RESULTS: Mean age was 66 years, 72% were men, and 47% had diabetes. TRA was the preferred access site in patients with low and intermediate disease severity. Overall, 50 (32%) patients experienced major adverse cardiac and cerebrovascular events; most events (78%) occurred in patients undergoing transfemoral access (TFA) in the intermediate-high tertiles of CS severity. Of the 41 (27%) total bleeding events, 32% occurred at the coronary angiography access site, of which 92% were in the TFA group. The use of ultrasound (US) guidance for TFA resulted in reduced coronary access-site bleeding (8.5 vs. 33.0%, p = .01). In a hierarchical logistic regression model, utilizing TRA did not result in lower odds of successful PCI (Odds ratio [OR]: 1.36; 95% confidence interval [CI]: 0.54-3.40). CONCLUSION: This study suggests that TRA is feasible across the entire spectrum of AMI-CS and is associated with reduced coronary access-site bleeding. In addition, US-guided TFA is associated with reductions in access-site bleeding and vascular complications. Concerted efforts should be made to incorporate vascular access protocols into existing CS algorithms in dedicated shock care centers.

Relationship Between Operator Volume and Long-Term Outcomes After Percutaneous Coronary Intervention.

BACKGROUND: Although many studies show an inverse association between operator procedural volume and short-term adverse outcomes after percutaneous coronary intervention (PCI), the association between procedural volume and longer-term outcomes is unknown. METHODS: Using the National Cardiovascular Data Registry CathPCI registry data linked with Medicare claims data, we examined the association between operator PCI volume and long-term outcomes among patients ≥65 years of age. Operators were stratified by average annual PCI volume (counting PCIs performed in patients of all ages): low- (<50 PCIs), intermediate- (50-100), and high- (>100) volume operators. One-year unadjusted rates of death and major adverse coronary events (MACEs; defined as death, readmission for myocardial infarction, or unplanned coronary revascularization) were calculated with Kaplan-Meier methods. The proportional hazards assumption was not met, and risk-adjusted associations between operator volume and outcomes were calculated separately from the time of PCI to hospital discharge and from hospital discharge to 1-year follow-up. RESULTS: Between July 1, 2009, and December 31, 2014, 723 644 PCI procedures were performed by 8936 operators: 2553 high-, 2878 intermediate-, and 3505 low-volume operators. Compared with high- and intermediate-volume operators, low-volume operators more often performed emergency PCI, and their patients had fewer cardiovascular comorbidities. Over 1-year follow-up, 15.9% of patients treated by low-volume operators had a MACE compared with 16.9% of patients treated by high-volume operators ( P=0.004). After multivariable adjustment, intermediate- and high-volume operators had a significantly lower rate of in-hospital death than low-volume operators (odds ratio, 0.91; 95% CI, 0.86-0.96 for intermediate versus low; odds ratio, 0.79; 95% CI, 0.75-0.83 for high versus low). There were no significant differences in rates of MACEs, death, myocardial infarction, or unplanned revascularization between operator cohorts from hospital discharge to 1-year follow-up (adjusted hazard ratio for MACEs, 0.99; 95% CI, 0.96-1.01 for intermediate versus low; hazard ratio, 1.01; 95% CI, 0.99-1.04 for high versus low). CONCLUSIONS: Unadjusted 1-year outcomes after PCI were worse for older adults treated by operators with higher annual volume; however, patients treated by these operators had more cardiovascular comorbidities. After risk adjustment, higher operator volume was associated with lower in-hospital mortality and no difference in postdischarge MACEs.

Periprocedural Outcomes of Direct Oral Anticoagulants Versus Warfarin in Nonvalvular Atrial Fibrillation.

BACKGROUND: Direct oral anticoagulants (DOACs) are surpassing warfarin as the anticoagulant of choice for stroke prevention in nonvalvular atrial fibrillation. DOAC outcomes in elective periprocedural settings have not been well elucidated and remain a source of concern for clinicians. The aim of this meta-analysis was to evaluate the periprocedural safety and efficacy of DOACs versus warfarin in patients with nonvalvular atrial fibrillation. METHODS: We reviewed the literature for data from phase III randomized controlled trials comparing DOACs with warfarin in the periprocedural period among patients with nonvalvular atrial fibrillation. Substudies from 4 trials (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation], and ENGAGE-AF [Effective Anticoagulation With Factor xA Next Generation in Atrial Fibrillation]) were included in the meta-analysis. DOACs as a group and warfarin were compared in terms of the 30-day pooled risk for stroke/systemic embolism, major bleeding, and death, according to whether the study drug was interrupted or not periprocedurally. The overall relative risk (RR) was estimated with a random-effects model. The I2 test was used to assess heterogeneity in RR among the studies. RESULTS: In the uninterrupted anticoagulant strategy, there were no differences in the rates of stroke/systemic embolism (pooled risk, 0.6% [29 events/4519 procedures] versus 1.1% [31/2971]; RR, 0.70; 95% confidence interval [CI], 0.41-1.18) and death (1.4% versus 1.8%; RR, 0.77; 95% CI, 0.53-1.12) between DOACs and warfarin and significantly fewer major bleeding events (2.0% versus 3.3%; RR, 0.62; 95% CI, 0.47-0.82) with DOACs compared to warfarin. Under an interrupted strategy, there was no significant difference between DOACs versus warfarin for stroke/systemic embolism (0.4% [41/9260] versus 0.5% [31/7168]; RR, 0.95; 95% CI, 0.59-1.55), major bleeding (2.1% versus 2.0%; RR, 1.05; 95% CI, 0.85-1.30), and death (0.7% versus 0.6%; RR, 1.24; 95% CI, 0.76-2.04). The studies were homogeneous ( I2=0.0%) for all calculated pooled associations except for the RR of death in the interrupted strategy ( I2=26.3%). CONCLUSIONS: The short-term safety and efficacy of DOACs and warfarin are not different in patients with nonvalvular atrial fibrillation periprocedurally. Under an uninterrupted anticoagulation strategy, DOACs are associated with a 38% lower risk of major bleeding compared with warfarin.

Apixaban following acute coronary syndromes in patients with prior stroke: Insights from the APPRAISE-2 trial.

BACKGROUND AND PURPOSE: Patients with prior stroke are at greater risk for recurrent cardiovascular events post-acute coronary syndromes (ACS) and may have a different risk/benefit profile with antithrombotic therapy than patients without prior stroke. METHODS: We studied 7391 patients with ACS from APPRAISE-2, stratified by the presence or absence of prior stroke. Baseline characteristics and outcomes of cardiovascular death, myocardial infarction (MI), or stroke were compared between groups. Interactions between prior stroke, treatment assignment (apixaban vs placebo), and outcomes were tested before and after multivariable adjustment with Cox proportional hazards models. RESULTS: A total of 902 patients (12%) had prior stroke. Those with prior stroke were older (69 vs 67 years), had more hypertension (91% vs 77%), peripheral vascular disease (22% vs18%), and impaired renal function (38% vs 30%) but less diabetes (44% vs 48%) than those without prior stroke. Patients with prior stroke vs no prior stroke had higher unadjusted rates of cardiovascular death (4.8% vs 4.0%), MI (11.2% vs 7.1%), and ischemic stroke (3.2% vs 0.9%). Patients with prior stroke assigned to apixaban had similar rates of the composite of cardiovascular death, MI, or stroke compared with those assigned to placebo (HR 1.39; 95% CI 0.92-2.08). Patients without prior stroke assigned to apixaban had similar rates of cardiovascular death, MI, or ischemic stroke compared with those assigned to placebo (HR 0.87; 95% CI 0.73-1.04; P-interaction=.041). Median follow-up was 240 days. CONCLUSIONS: Patients with prior stroke are at higher risk for recurrent cardiovascular events post-ACS and had a differential risk/benefit profile with oral anticoagulation.

Percutaneous coronary intervention and antiplatelet therapy in patients with atrial fibrillation receiving apixaban or warfarin: Insights from the ARISTOTLE trial.

BACKGROUND: We assessed antiplatelet therapy use and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ARISTOTLE trial. METHODS: Patients were categorized based on the occurrence of PCI during follow-up (median 1.8 years); PCI details and outcomes post-PCI are reported. Of the 18,201 trial participants, 316 (1.7%) underwent PCI (152 in apixaban group, 164 in warfarin group). RESULTS: At the time of PCI, 84% (267) were on study drug (either apixaban or warfarin). Of these, 19% did not stop study drug during PCI, 49% stopped and restarted <5 days post-PCI, and 30% stopped and restarted >5 days post-PCI. At 30 days post-PCI, 35% of patients received dual -antiplatelet therapy (DAPT), 23% received aspirin only, and 13% received a P2Y12 inhibitor only; 29% received no antiplatelet therapy. Triple therapy (DAPT + oral anticoagulant [OAC]) was used in 21% of patients, 23% received OAC only, 15% received OAC plus aspirin, and 9% received OAC plus a P2Y12 inhibitor; 32% received antiplatelet agents without OAC. Post-PCI, patients assigned to apixaban versus warfarin had numerically similar rates of major bleeding (5.93 vs 6.73 events/100 patient-years; P = .95) and stroke (2.74 vs 1.84 events/100 patient-years; P = .62). CONCLUSIONS: PCI occurred infrequently during follow-up. Most patients on study drug at the time of PCI remained on study drug in the peri-PCI period; 19% continued the study drug without interruption. Antiplatelet therapy use post-PCI was variable, although most patients received DAPT. Additional data are needed to guide the use of antithrombotics in patients undergoing PCI.

Variation in post-TAVR antiplatelet therapy utilization and associated outcomes: Insights from the STS/ACC TVT Registry.

BACKGROUND: Dual antiplatelet therapy (DAPT) is recommended following transcatheter aortic valve replacement (TAVR); however, the optimal antiplatelet strategy is undefined, and little is known about practice patterns. We aimed to describe contemporary practice patterns of antiplatelet therapy and their relationship to outcomes post-TAVR. METHODS: The population was derived from the National Cardiovascular Data Registry, Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry with Center for Medical Services linkage for 1-year outcomes from October 1, 2011 to June 30,2016. The primary outcome measured was DAPT use in patients without anticoagulation. Secondary outcomes included death, major bleeding, myocardial infarction (MI), and stroke at 1 year. RESULTS: Overall, 16,694 patients underwent transfemoral TAVR at 444 hospitals and were discharged without anticoagulation. Among these, 13,546 (81.1%) patients were discharged on DAPT, whereas 3,148 patients (18.9%) were discharged on monotherapy. Patients discharged on DAPT versus monotherapy were similar in age, sex, and most comorbid illnesses but had higher rates of coronary artery disease (64.6% vs 52.3%; P < .01) and peripheral artery disease (25.2% vs 22.3%; P < .01). Hospital prescribing patterns varied significantly (median frequency of DAPT 85.7%, interquartile range 94.1%-74.2%). DAPT (vs monotherapy) patients had a similar mortality risk at 1 year (adjusted hazard ratio 0.92, 95% CI 0.81-1.05), significantly higher risk for major bleeding (1.48, 1.10-1.99), and similar hazard for stroke (1.04, 0.83-1.31) and MI (1.00, 0.72-1.39). CONCLUSIONS: In the United States, most patients were discharged on DAPT following TAVR. Practice patterns varied significantly among hospitals. Patients discharged with DAPT had a similar adjusted risk of mortality, stroke, and MI compared to antiplatelet monotherapy, although risk for bleeding was significantly higher. Future investigation is needed to define the optimal antiplatelet therapy for patients undergoing TAVR.

Challenges in Aortic Stenosis: Review of Antiplatelet/Anticoagulant Therapy Management with Transcatheter Aortic Valve Replacement (TAVR): TAVR with Recent PCI, TAVR in the Patient with Atrial Fibrillation, and TAVR Thrombosis Management.

PURPOSE OF REVIEW: This review aims to describe the current evidence and consensus recommendations around antiplatelet and anticoagulant management in three common clinical scenarios in transcatheter aortic valve replacement (TAVR): (1) recent percutaneous coronary intervention (PCI) preceding TAVR, (2) atrial fibrillation (AF) management in patients undergoing TAVR, and (3) bioprosthetic valve thrombosis management in TAVR. RECENT FINDINGS: Several small clinical trials have evaluated the use of single vs. dual antiplatelet therapy in patients undergoing TAVR, with most recent data favoring single antiplatelet therapy. There are several trials currently enrolling and in follow-up that evaluate the use of anticoagulants in combination with single and dual antiplatelet therapy for patients with AF undergoing TAVR, but as yet, there is no data to support a clear strategy. The use of DAPT after PCI continues to potentially shorten in patients undergoing elective PCI, thus prolonged DAPT may not be necessary post TAVR for the sake of PCI. Bioprosthetic valve thrombosis occurs more commonly than previously thought, but has uncertain clinical significance. In observational studies, antiplatelet therapy has little effect on bioprosthetic valve thrombosis, whereas anticoagulation is effective in both prevention and treatment of thrombosis. DAPT is currently recommended for 1-6 months for all patients without an indication for oral anticoagulation who undergo TAVR; however, there is a growing amount of evidence for single antiplatelet therapy. In the special situation of patients who have recently undergone PCI, the length of DAPT will depend on stent selection (BMS vs. DES), but may not be significantly prolonged unless the patient experienced an acute coronary syndrome prior to TAVR. There is no clear, optimal antithrombotic strategy for patients with AF who undergo TAVR, but avoidance of triple therapy by using OAC and low-dose ASA seems to be reasonable. OAC, not DAPT, is now known to prevent bioprosthetic valve thrombosis in TAVR and SAVR patients; however, the optimal therapy remains unknown. For patients who develop bioprosthetic valve thrombosis, OAC for 3-6 months, and repeat imaging is recommended to document resolution.

Regional Systems of Care Demonstration Project: American Heart Association Mission: Lifeline STEMI Systems Accelerator.

BACKGROUND: Up to 50% of patients fail to meet ST-segment-elevation myocardial infarction (STEMI) guideline goals recommending a first medical contact-to-device time of <90 minutes for patients directly presenting to percutaneous coronary intervention-capable hospitals and <120 minutes for transferred patients. We sought to increase the proportion of patients treated within guideline goals by organizing coordinated regional reperfusion plans. METHODS: We established leadership teams, coordinated protocols, and provided regular feedback for 484 hospitals and 1253 emergency medical services (EMS) agencies in 16 regions across the United States. RESULTS: Between July 2012 and December 2013, 23 809 patients presented with acute STEMI (direct to percutaneous coronary intervention hospital: 11 765 EMS transported and 6502 self-transported; 5542 transferred). EMS-transported patients differed from self-transported patients in symptom onset to first medical contact time (median, 47 versus 114 minutes), incidence of cardiac arrest (10% versus 3%), shock on admission (11% versus 3%), and in-hospital mortality (8% versus 3%; P<0.001 for all comparisons). There was a significant increase in the proportion of patients meeting guideline goals of first medical contact-to-device time, including those directly presenting via EMS (50% to 55%; P<0.001) and transferred patients (44%-48%; P=0.002). Despite regional variability, the greatest gains occurred among patients in the 5 most improved regions, increasing from 45% to 57% (direct EMS; P<0.001) and 38% to 50% (transfers; P<0.001). CONCLUSIONS: This Mission: Lifeline STEMI Systems Accelerator demonstration project represents the largest national effort to organize regional STEMI care. By focusing on first medical contact-to-device time, coordinated treatment protocols, and regional data collection and reporting, we were able to increase significantly the proportion of patients treated within guideline goals.

Challenges in Aortic Valve Stenosis: Low-Flow States Diagnosis, Management, and a Review of the Current Literature.

PURPOSE OF REVIEW: We will describe and define the current diagnosis, management, and potential therapy for low-flow aortic stenosis (AS) states, as well as summarize the available evidence underlying these recommendations. RECENT FINDINGS: Low-flow aortic stenosis syndromes have worse prognoses than traditionally defined normal flow severe aortic stenosis. In this setting, aortic valve replacement is the only therapy that improves outcomes. Transcatheter aortic valve replacement has an ever-expanding role in the treatment of aortic stenosis, and there is growing evidence that TAVR may be a preferred therapy for low-flow AS states. Aortic stenosis remains one of the most common valvular diseases requiring therapy. Low-flow AS represents up to 40% of all patients with AS and is associated with significant mortality. This condition requires further testing for appropriate diagnosis and treatment. Low-flow AS states have poor prognoses, thus AVR and especially TAVR have a growing role in treatment of this challenging subset of AS patients.

Use and outcomes associated with bridging during anticoagulation interruptions in patients with atrial fibrillation: findings from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF).

BACKGROUND: Temporary interruption of oral anticoagulation for procedures is often required, and some propose using bridging anticoagulation. However, the use and outcomes of bridging during oral anticoagulation interruptions in clinical practice are unknown. METHODS AND RESULTS: The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry is a prospective, observational registry study of US outpatients with atrial fibrillation. We recorded incident temporary interruptions of oral anticoagulation for a procedure, including the use and type of bridging therapy. Outcomes included multivariable-adjusted rates of myocardial infarction, stroke or systemic embolism, major bleeding, cause-specific hospitalization, and death within 30 days. Of 7372 patients treated with oral anticoagulation, 2803 overall interruption events occurred in 2200 patients (30%) at a median follow-up of 2 years. Bridging anticoagulants were used in 24% (n=665), predominantly low-molecular-weight heparin (73%, n=487) and unfractionated heparin (15%, n=97). Bridged patients were more likely to have had prior cerebrovascular events (22% versus 15%; P=0.0003) and mechanical valve replacements (9.6% versus 2.4%; P<0.0001); however, there was no difference in CHA2DS2-VASc scores (scores ≥ 2 in 94% versus 95%; P=0.5). Bleeding events were more common in bridged than nonbridged patients (5.0% versus 1.3%; adjusted odds ratio, 3.84; P<0.0001). The incidence of myocardial infarction, stroke or systemic embolism, major bleeding, hospitalization, or death within 30 days was also significantly higher in patients receiving bridging (13% versus 6.3%; adjusted odds ratio, 1.94; P=0.0001). CONCLUSIONS: Bridging anticoagulation is used in one quarter of anticoagulation interruptions and is associated with higher risk for bleeding and adverse events. These data do not support the use of routine bridging, and additional data are needed to identify best practices concerning anticoagulation interruptions. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01165710.

Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF).

BACKGROUND: During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. METHODS AND RESULTS: In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non-central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3-30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36-1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80-2.00]; P=0.32). CONCLUSIONS: TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

The periprocedural management of novel oral anticoagulants in patients with nonvalvular atrial fibrillation: rationale and a summary of the available evidence from phase 3 clinical trials.

The novel oral anticoagulants (NOACs) have rapidly emerged as an alternative therapy to warfarin. Several recent phase 3 randomized control trials have demonstrated the efficacy and safety of the NOACs in the treatment for patients with nonvalvular atrial fibrillation. As the NOACs are incorporated in clinical practice, questions have begun to arise concerning their optimal use in commonly encountered situations. In this review, we provide a summary of the available evidence from the phase 3 randomized control trials specifically with regard to 1 such scenario, the periprocedural management of NOACs, with a goal of providing guidance for practicing clinicians.

Regional systems of care demonstration project: Mission: Lifeline STEMI Systems Accelerator: design and methodology.

ST-segment elevation myocardial infarction (STEMI) systems of care have been associated with significant improvement in use and timeliness of reperfusion. Consequently, national guidelines recommend that each community should develop a regional STEMI care system. However, significant barriers continue to impede widespread establishment of regional STEMI care systems in the United States. We designed the Regional Systems of Care Demonstration Project: Mission: Lifeline STEMI Systems Accelerator, a national educational outcome research study in collaboration with the American Heart Association, to comprehensively accelerate the implementation of STEMI care systems in 17 major metropolitan regions encompassing >1,500 emergency medical service agencies and 450 hospitals across the United States. The goals of the program are to identify regional gaps, barriers, and inefficiencies in STEMI care and to devise strategies to implement proven recommendations to enhance the quality and consistency of care. The study interventions, facilitated by national faculty with expertise in regional STEMI system organization in partnership with American Heart Association representatives, draw upon specific resources with proven past effectiveness in augmenting regional organization. These include bringing together leading regional health care providers and institutions to establish common commitment to STEMI care improvement, developing consensus-based standardized protocols in accordance with national professional guidelines to address local needs, and collecting and regularly reviewing regional data to identify areas for improvement. Interventions focus on each component of the reperfusion process: the emergency medical service, the emergency department, the catheterization laboratory, and inter-hospital transfer. The impact of regionalization of STEMI care on clinical outcomes will be evaluated.

Patterns and outcomes of red blood cell transfusion in patients undergoing percutaneous coronary intervention.

IMPORTANCE: Studies have shown variation in the use of red blood cell transfusion among patients with acute coronary syndromes. There are no definitive data for the efficacy of transfusion in improving outcomes, and concerning data exist about possible association with harm. Current transfusion practices in patients undergoing percutaneous coronary intervention (PCI) are not well understood. OBJECTIVE: To determine the current patterns of blood transfusion among patients undergoing PCI and the association of transfusion with adverse cardiac outcomes across hospitals in the United States. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of all patient visits from the CathPCI Registry from July 2009 to March 2013 that included PCI, excluding those with missing data on bleeding complications or who underwent in-hospital coronary artery bypass graft surgery (N = 2,258,711 visits). MAIN OUTCOMES AND MEASURES: Transfusion rates in the overall population and by hospital (N = 1431) were the primary outcomes. The association of transfusion with myocardial infarction, stroke, and death after accounting for a patient's propensity for transfusion was also measured. RESULTS: The overall rate of transfusion was 2.14% (95% CI, 2.13%-2.16%) and quarterly transfusion rates slightly declined from July 2009 to March 2013 (from 2.11% [95% CI, 2.03%-2.19%] to 2.04% [95% CI, 1.97%-2.12%]; P < .001). Patients who were more likely to receive transfusion were older (mean, 70.5 vs 64.6 years), were women (56.3% vs 32.5%), and had hypertension (86.4% vs 82.0%), diabetes (44.8% vs 34.6%), advanced renal dysfunction (8.7% vs 2.3%), prior myocardial infarction (33.0% vs 30.2%), or prior heart failure (27.0% vs 11.8%). Overall, 96.3% of sites gave a transfusion to less than 5% of patients and 3.7% of sites gave a transfusion to 5% of patients or more. Variation in hospital risk-standardized rates of transfusion persisted after adjustment, and hospitals showed variability in their transfusion thresholds. Receipt of transfusion was associated with myocardial infarction (42,803 events; 4.5% vs 1.8%; odds ratio [OR], 2.60; 95% CI, 2.57-2.63), stroke (5011 events; 2.0% vs 0.2%; OR, 7.72; 95% CI, 7.47-7.98), and in-hospital death (31,885 events; 12.5% vs 1.2%; OR, 4.63; 95% CI, 4.57-4.69), irrespective of bleeding complications. CONCLUSIONS AND RELEVANCE: Among patients undergoing PCI at US hospitals, there was considerable variation in blood transfusion practices, and receipt of transfusion was associated with increased risk of in-hospital adverse cardiac events. These observational findings may warrant a randomized trial of transfusion strategies for patients undergoing PCI.

Do Clinical Outcomes and Quality of Life Differ by the Number of Antianginals for Stable Ischemic Heart Disease? Insights from the BARI 2D Trial.

Medical therapy, including antianginal treatment, is the cornerstone in the management of stable ischemic heart disease (SIHD). However, it remains unclear whether combining antianginal agents provides benefits beyond monotherapy in terms of quality of life (QoL) and cardiovascular outcomes. We used data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, which compared cardiovascular and QoL outcomes in patients with SIHD and diabetes mellitus randomized to revascularization with intensive medical therapy or intensive medical therapy alone. We categorized patients into 3 groups: ≥2 versus 1 versus 0 antianginals. We compared patient characteristics, QoL metrics, and cardiovascular end points at baseline and at 5 years, creating a multivariable model to adjust for key clinical confounders. Of 2,368 patients, 348 patients (14.7%) were on 0 antianginals, 1,020 patients (43.1%) were on 1 antianginal, and 1,000 patients (42.2%) were on ≥2 antianginals at baseline. The most common antianginal class was ß blockers. At baseline, patients on 0 antianginals had better QoL metrics (self-health score, Duke activity status index, and energy rating) than patients on ≥2 antianginals. However, at the 1-year follow-up, patients taking only 1 antianginal showed greater QoL improvement than those taking 0 antianginal, without any incremental benefit in QoL metrics seen in patients taking ≥2 antianginal agents, even after adjusting for multiple covariates such as age, heart failure, diabetes control, and myocardial jeopardy index. Lastly, at the 5-year follow-up, after adjustment, there were no differences in all-cause mortality, major adverse cardiovascular events, or myocardial infarction between patients taking different numbers of antianginals. Adults on a single antianginal for SIHD and diabetes mellitus had similar or better improvements in QoL than those on 2 or more antianginal agents at 1 year of follow-up. These findings merit further research to better understand the impact of medical therapy intensity on QoL in patients with SIHD and associated co-morbidities.

Impact of anemia on outcomes and resource utilization in patients with myocardial infarction: A national database analysis.

BACKGROUND: Although anemia is common in patients with myocardial infarction (MI), management remains controversial. We quantified the association of anemia with in-hospital outcomes and resource utilization in patients admitted with MI using a large national database. METHODS: All hospitalizations with a primary diagnosis code for acute MI in the National Inpatient Sample (NIS) between 2014 and 2018 were identified. Among these hospitalizations, patients with anemia were identified using a secondary diagnosis code. Data on demographic and clinical variables were collected. Outcomes of interest included in-hospital adverse events, length of stay (LOS), and total cost. Multivariable logistic regression and generalized linear models were used to evaluate the relationship between anemia and outcomes. RESULTS: Among 1,113,181 MI hospitalizations, 254,816 (22.8%) included concomitant anemia. Anemic patients were older and more likely to be women. After adjustment for demographics and comorbidities, anemia was associated with higher mortality (7.1 vs. 4.3%; odds ratio 1.09; 95% confidence interval [CI] 1.07-1.12, p < 0.001). Anemia was also associated with a mean of 2.71 days longer LOS (average marginal effects [AME] 2.71; 95% CI 2.68-2.73, p < 0.05), and $ 9703 mean higher total costs (AME $9703, 95% CI $9577-$9829, p < 0.05). Anemic patients who received blood transfusions had higher mortality as compared with those who did not (8.2% vs. 7.0, p < 0.001). CONCLUSION: In MI patients, anemia was associated with higher in-hospital mortality, adverse events, total cost, and length of stay. Transfusion was associated with increased mortality, and its role in MI requires further research.

A Randomized Comparison of Radial Artery Intimal Hyperplasia Following Distal Versus Proximal Transradial Access for Coronary Angiography: PRESERVE RADIAL.

BACKGROUND: Distal transradial access (dTRA) is an alternative to conventional forearm transradial access (fTRA) for coronary angiography (CAG). Differences in healing of the radial artery (RA) in the forearm have not been evaluated between these 2 access strategies. We sought to compare the mean difference in forearm RA intimal-medial thickening (IMT) in patients randomized to dTRA versus fTRA. METHODS AND RESULTS: In this single-center randomized clinical trial, 64 patients undergoing nonemergent CAG were randomized (1:1) to dTRA versus fTRA. Ultra-high-resolution (55-MHz) vascular ultrasound of the forearm and distal RA was performed pre-CAG and at 90 days. The primary end point was the mean change in forearm RA IMT. Secondary end points included procedural characteristics, vascular injury, RA occlusion, and ipsilateral hand pain and function. Baseline demographics and clinical characteristics, mean forearm RA IMT, and procedural specifics were similar between the dTRA and fTRA cohorts. There was no difference in mean change in forearm RA IMT between the 2 cohorts (0.07 versus 0.07 mm; P=0.37). No RA occlusions or signs of major vascular injury were observed at 90 days. Ipsilateral hand pain and function (Borg pain scale score: 12 versus 11; P=0.24; Disabilities of the Arm, Shoulders, and Hand scale score: 6 versus 8; P=0.46) were comparable. CONCLUSIONS: Following CAG, dTRA was associated with no differences in mean change of forearm RA IMT, hand pain, and function versus fTRA for CAG. Further investigation is warranted to elucidate mechanisms and predictors of RA healing and identify effective strategies to preserving RA integrity for repeated procedures. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04801901.

Best practices for vascular arterial access and closure: a contemporary guide for the cardiac catheterization laboratory.

More than 1 million transcatheter-based cardiovascular procedures across the spectrum of interventional cardiology are performed annually in the United States. With the expanded indications for and increased complexities associated with these procedures, interventional cardiologists are expected to possess the requisite expertise to complete these interventions safely and effectively. While the art of vascular access and closure remains a prerequisite and critical skillset in contemporary practice, there remain significant variations in the techniques employed, resulting in the bleeding and vascular complications encountered in clinical practice. With an increasing recognition of the potential merits to standardized approaches to vascular access and closure, cardiovascular societies have put forth recommendations around best practices for performing these procedures in the cardiac catheterization laboratories. In this review, we aim to: (1) Examine the evolving definitions of bleeding and vascular complications; (2) Review best practices for transradial and transfemoral access and closure, including for large bore procedures; and (3) Highlight knowledge gaps and proposed areas of clinical research pertaining to vascular access which may inform clinical practice and potentially optimize the outcomes of patients undergoing transcatheter-based cardiac and vascular interventions.