Faculty Bibliography

Background: Potent P2Y12 inhibitors are recommended in patients with acute coronary syndrome (ACS), although the optimal antithrombotic strategy should be tailored based on patients thrombotic and hemorrhagic risk profile. We evaluated if the benefits associated with prasugrel vs. clopidogrel in ACS patients undergoing percutaneous coronary intervention (PCI) are similar in patients with different thrombotic risk profiles.
Method(s): PROMETHEUS was a multicenter observational study comparing prasugrel vs. clopidogrel in ACS patients undergoing PCI. Patients were defined at high thrombotic risk if presenting with a clinical and a procedural risk feature. The primary endpoint was major adverse cardiac events (MACE), composite of death, myocardial infarction, stroke, or unplanned revascularization. Hazard ratio (HR) and 95% confidence intervals (CI) were calculated using propensity-stratified analysis and with multivariable Cox regression.
Result(s): Among 16,065 patients, 4,293 were defined at high and 11,772 at low-to-moderate thrombotic risk. Patients receiving prasugrel had less comorbidities and risk factors than those treated with clopidogrel, both in the high and low-to-moderate thrombotic risk strata. High thrombotic risk patients had increased rates of ischemic and bleeding events at 90-day and 1-year follow-up. Patients treated with prasugrel had a lower adjusted 1-year risk of MACE (HR 0.86, 95% CI 0.77-0.96), irrespective of their thrombotic risk (pinteraction =0.32). Stratifying the study population by number of risk factors there was a significant interaction (pinteraction =0.026) for a greater reduction in MACE with prasugrel among patients with <=1 thrombotic risk factor. The risk of clinically significant bleeding was similar in patients treated with prasugrel and clopidogrel.
Conclusion(s): Patients with ACS at high thrombotic risk who undergo PCI are at increased risk of adverse events at 1 year. Prasugrel, mainly reserved to patients with less comorbidities, reduced the risk of ischemic events both in patients at high and low-to-moderate thrombotic risk as compared with clopidogrel.

BACKGROUND:Emerging evidence from randomized clinical trials (RCTs) comparing distal radial access (DRA) with conventional radial access (RA) is available. OBJECTIVES/OBJECTIVE:The aim of this study was to provide a quantitative appraisal of the effects of DRA) vs conventional RA for coronary angiography with or without intervention. METHODS:The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for RCT comparing DRA vs conventional RA for coronary angiography and/or intervention. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was radial artery occlusion (RAO) at the longest available follow-up. RESULTS:Fourteen studies enrolling 6,208 participants were included. Compared with conventional RA, DRA was associated with a significant lower risk of RAO, either detected at latest follow-up (risk ratio [RR]: 0.36; 95% CI: 0.23-0.56; P < 0.001; number needed to treat [NNT] = 30) or in-hospital (RR: 0.32; 95% CI: 0.19-0.53; P < 0.001; NNT = 28), as well as EASY (Early Discharge After Transradial Stenting of Coronary Arteries) ≥II hematoma (RR: 0.51; 95% CI: 0.27-0.96; P = 0.04; NNT = 107). By contrast, DRA was associated with a higher risk of access site crossover (RR: 3.08; 95% CI: 1.88-5.06; P < 0.001; NNT = 12), a longer time for radial puncture (standardized mean difference [SMD]: 3.56; 95% CI: 0.96-6.16; P < 0.001), a longer time for sheath insertion (SMD: 0.37; 95% CI: 0.16-0.58; P < 0.001), and a higher number of puncture attempts (SMD: 0.59, 95% CI: 0.48-0.69; P < 0.001). CONCLUSIONS:Compared with conventional RA, DRA is associated with lower risks of RAO and EASY ≥II hematoma but requires longer time for radial artery cannulation and sheath insertion, more puncture attempts, and a higher access site crossover.

BACKGROUND:Accumulating evidence from clinical trials suggests that a lower (restrictive) hemoglobin threshold (<8% g/dL) for red blood cell (RBC) transfusion, compared with a higher (liberal) threshold (≥10 g/dL) is safe. However, in anemic patients with acute myocardial infarction (MI), maintaining a higher hemoglobin level may increase oxygen delivery to vulnerable myocardium resulting in improved clinical outcomes. Conversely, RBC transfusion may result in increased blood viscosity, vascular inflammation, and reduction in available nitric oxide resulting in worse clinical outcomes. We hypothesize that a liberal transfusion strategy would improve clinical outcomes as compared to a more restrictive strategy. METHODS:We will enroll 3500 patients with acute MI (type 1, 2, 4b or 4c) as defined by the Third Universal Definition of MI and a hemoglobin <10 g/dL at 144 centers in the United States, Canada, France, Brazil, New Zealand, and Australia. We randomly assign trial participants to a liberal or restrictive transfusion strategy. Participants assigned to the liberal strategy receive transfusion of RBCs sufficient to raise their hemoglobin to at least 10 g/dL. Participants assigned to the restrictive strategy are permitted to receive transfusion of RBCs if the hemoglobin falls below 8 g/dL or for persistent angina despite medical therapy. We will contact each participant at 30 days to assess clinical outcomes and at 180 days to ascertain vital status. The primary endpoint is a composite of all-cause death or recurrent MI through 30 days following randomization. Secondary endpoints include all-cause mortality at 30 days, recurrent adjudicated MI, and the composite outcome of all-cause mortality, nonfatal recurrent MI, ischemia driven unscheduled coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), or readmission to the hospital for ischemic cardiac diagnosis within 30 days. The trial will assess multiple tertiary endpoints. CONCLUSIONS:The MINT trial will inform RBC transfusion practice in patients with acute MI.

Importance/UNASSIGNED:In patients with multivessel coronary artery disease (CAD) presenting with ST-segment elevation myocardial infarction (STEMI), complete revascularization reduces major cardiovascular events compared with culprit lesion-only percutaneous coronary intervention (PCI). Whether complete revascularization also improves angina-related health status is unknown. Objective/UNASSIGNED:To determine whether complete revascularization improves angina status in patients with STEMI and multivessel CAD. Design, Setting, and Participants/UNASSIGNED:This secondary analysis of a randomized, multinational, open label trial of patient-reported outcomes took place in 140 primary PCI centers in 31 countries. Patients presenting with STEMI and multivessel CAD were randomized between February 1, 2013, and March 6, 2017. Analysis took place between July 2021 and December 2021. Interventions/UNASSIGNED:Following PCI of the culprit lesion, patients with STEMI and multivessel CAD were randomized to receive either complete revascularization with additional PCI of angiographically significant nonculprit lesions or to no further revascularization. Main Outcomes and Measures/UNASSIGNED:Seattle Angina Questionnaire Angina Frequency (SAQ-AF) score (range, 0 [daily angina] to 100 [no angina]) and the proportion of angina-free individuals by study end. Results/UNASSIGNED:Of 4041 patients, 2016 were randomized to complete revascularization and 2025 to culprit lesion-only PCI. The mean (SD) age of patients was 62 (10.7) years, and 3225 (80%) were male. The mean (SD) SAQ-AF score increased from 87.1 (17.8) points at baseline to 97.1 (9.7) points at a median follow-up of 3 years in the complete revascularization group (score change, 9.9 [95% CI, 9.0-10.8]; P < .001) compared with an increase of 87.2 (18.4) to 96.3 (10.9) points (score change, 8.9 [95% CI, 8.0-9.8]; P < .001) in the culprit lesion-only group (between-group difference, 0.97 points [95% CI, 0.27-1.67]; P = .006). Overall, 1457 patients (87.5%) were free of angina (SAQ-AF score, 100) in the complete revascularization group compared with 1376 patients (84.3%) in the culprit lesion-only group (absolute difference, 3.2% [95% CI, 0.7%-5.7%]; P = .01). This benefit was observed mainly in patients with nonculprit lesion stenosis severity of 80% or more (absolute difference, 4.7%; interaction P = .02). Conclusions and Relevance/UNASSIGNED:In patients with STEMI and multivessel CAD, complete revascularization resulted in a slightly greater proportion of patients being angina-free compared with a culprit lesion-only strategy. This modest incremental improvement in health status is in addition to the established benefit of complete revascularization in reducing cardiovascular events.

In the United States, the frequency of using percutaneous mechanical circulatory support devices for acute myocardial infarction complicated by cardiogenic shock is increasing. These devices require large-bore vascular access to provide left, right, or biventricular cardiac support, frequently under urgent/emergent circumstances. Significant technical and logistical variability exists in device insertion, care, and removal in the cardiac catheterization laboratory and in the cardiac intensive care unit. This variability in practice may contribute to adverse outcomes observed in centers that receive patients with cardiogenic shock, who are at higher risk for circulatory insufficiency, venous stasis, bleeding, and arterial hypoperfusion. In this position statement, we aim to: 1) describe the public health impact of bleeding and vascular complications in cardiogenic shock; 2) highlight knowledge gaps for vascular safety and provide a roadmap for a regulatory perspective necessary for advancing the field; 3) propose a minimum core set of process elements, or "vascular safety bundle"; and 4) develop a possible study design for a pragmatic trial platform to evaluate which structured approach to vascular access drives most benefit and prevents vascular and bleeding complications in practice.

BACKGROUND:Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI). METHODS:We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo. RESULTS:The median age was 68 years, 23% of participants were women, 51% had ST-segment-elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71-1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69-1.61]). CONCLUSIONS:In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI. REGISTRATION:URL: https://www. CLINICALTRIALS:gov; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search; Unique identifier: 2019-003244-79.

BACKGROUND:The relative safety and efficacy of de-escalation, extended duration (ED) (>12-months) and standard dual antiplatelet therapy for 12-months (DAPT-12) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains controversial. METHODS:Online databases were queried to identify relevant randomized control trials (RCTs). ED-DAPT, high-potency (HP) DAPT, shorter duration (SD) DAPT and low-dose (LD) DAPT were compared with DAPT-12. A trial sequential, bivariate, influential and frequentist network meta-analysis (NMA) was performed to determine the pooled estimates. RESULTS:A total of 30 RCTs comprising 81 208 (40 839 experimental, 40 369 control arm) patients with CAD were included in the quantitative analysis. On NMA, compared with DAPT-12, all types of de-escalation, HP-DAPT-12 and ED-DAPT strategies had a statistically non-significant difference in the incidence of MACE at a median follow-up of 1-year. Similarly, there was no significant difference in the incidence of stroke, stent thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR) and all-cause mortality between DAPT-12 and all other strategies. The network estimates showed a significantly lower incidence of major bleeding with DAPT for 3-months followed by P2Y12-inhibitor monotherapy (RR 0.62, 95% CI 0.45-0.84), while a higher risk of bleeding with HP-DAPT for 12 months (RR 1.55, 95% CI 1.16-2.06). The net clinical benefit and rankograms also favored DAPT-3 (P2Y12) and discouraged the use of HP-DAPT-12 and ED-DAPT. A subgroup analysis of 19 RCTs restricted to patients who presented with acute coronary syndrome (ACS) mirrored the findings of pooled analysis. A sensitivity analysis revealed no influence of any individual study or individual strategy on net ischemic estimates. The trial sequential analysis (TSA) illustrated a consistently non-significant difference at the interim analysis of trials, reaching the futility area for MACE, while the cumulative Z-values line surpassed the monitoring boundary as well as the required information size for major bleeding favoring de-escalation strategy. CONCLUSION/CONCLUSIONS:DAPT for 3 months followed by ticagrelor-only and use of aspirin + clopidogrel after a short period of high potency DAPT appears to be a safe strategy for treating post-PCI patients. However, given the methodological limitations and inclusion of a small number of trials in novel de-escalation strategies, these findings need validation by future large scale RCTs.

Background: In percutaneous coronary interventions (PCIs), radial (R) rather than femoral (F) access is recommended due to lower rates of bleeding and vascular complications. Although the safety and effectiveness of intravascular lithotripsy (IVL) for the treatment of coronary artery calcification have been shown, whether IVL procedural success or complication rates differ between R and F access sites is not known.
Method(s): Individual patient-level data were pooled from the Disrupt CAD III and CAD IV studies, which collected access site data and shared uniform study inclusion/exclusion criteria, endpoint definitions, and use of independent angiographic core laboratory and clinical event committee adjudication. Procedural success, defined as stent delivery with residual stenosis <=30% without in-hospital major adverse cardiovascular events (MACE), and vascular complications were compared based on R vs F access.
Result(s): The pooled population included 444 patients, with 281 (63.3%) cases performed using R access. Patient baseline comorbidities were similar between the 2 groups. All lesions in both groups were severely calcified by core lab assessment. Baseline diameter stenosis (R 66% +/- 11% vs F 64% +/- 11%; P = 0.14) and lesion length (R 27 +/- 12 mm vs F 26 +/- 11 mm; P = 0.62) were similar between the groups. Procedural success and rates of 30-day MACE were similar by access site (Table 1). [Formula presented]
Conclusion(s): The current pooled analysis represents the largest comparison of R vs F access with coronary IVL for target lesion preparation. In the Disrupt CAD III and CAD IV trials, the majority of patients enrolled had R access despite high lesion complexity and device profile. Successful IVL catheter delivery was achieved and procedural outcomes for treatment of coronary artery calcification were similar regardless of access site. Categories: CORONARY: Coronary Atherectomy, Plaque Modification, Lithotripsy, and Thrombectomy
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OBJECTIVES/OBJECTIVE:To assess whether contrast media type is associated with outcomes in veterans undergoing percutaneous coronary intervention (PCI). BACKGROUND:There is uncertainty about the impact of iso-osmolar contrast medium (IOCM) versus low-osmolar contrast medium (LOCM) on acute kidney injury (AKI) and other major adverse renal or cardiovascular events (MARCE) after PCI. We assessed the association between contrast media type and MARCE in patients who underwent PCI within the Veterans Administration Healthcare System. METHODS:We reviewed PCIs performed between 2009 and 2019 using data from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program. The primary endpoint was MARCE, a composite of myocardial infarction, stroke, all-cause death, AKI, and dialysis onset at 30 days. RESULTS:The analysis cohort consisted of 50,389 patients of whom 25,555 received LOCM and 24,834 received IOCM. There was significant variation in contrast type across sites. After adjustment for comorbidities, no significant association between contrast media type and MARCE was observed in both site-unadjusted (odds ratio [OR] for IOCM: 0.99; 95% confidence interval [CI]: 0.92-1.08; p = 0.97) and site-adjusted (OR: 1.06; 95% CI: 0.95-1.18; p = 0.30) analyses. Similar results were obtained when contrast volume was imputed or the data was subset to individuals with available contrast volume. CONCLUSION/CONCLUSIONS:In a large cohort of veterans undergoing PCI, we found considerable site variation in the type of contrast media used but no significant association between contrast media type and the incidence of MARCE, both before and after adjustment for the site.

BACKGROUND:Prior studies of radial access for cardiac catheterization have focused on early adopters of the technique, and some have described a risk/treatment paradox of low radial access use among high bleeding risk patients. This study aimed to determine (1) trends in radial access use over time, (2) if increasing use of radial access is driven by new invasive and interventional cardiologists (operators) or existing operators changing their practice, and (3) if increasing radial rates are associated with lower bleeding rates and elimination of the risk/treatment paradox. METHODS:In this cross-sectional study using data from the Clinical Assessment, Reporting, and Tracking Program, we calculated radial access rates and risk-adjusted postprocedural bleeding rates of patients undergoing diagnostic angiography or percutaneous coronary intervention (PCI) between 2011 and 2018 in Veterans Affairs hospitals. We used separate bleeding risk models for diagnostic angiography and PCI and assessed temporal trends with the Kendall Tau-b test. RESULTS:=0.20). Femoral access patients had a higher predicted risk for bleeding. CONCLUSIONS:A steady rise in radial access for diagnostic angiography and PCI was driven by increasing use among existing operators and high use by new operators. While this was associated with decreasing bleeding rates, a risk/treatment paradox for access site selection persists; patients at higher bleeding risk were still more likely to receive femoral access.