Faculty Bibliography

When selecting an anticoagulant, clinicians consider individual patient characteristic, the treatment indication, drug pharmacology, and safety and efficacy as demonstrated in randomized trials. An ideal anticoagulant prevents thrombosis with little or no increase in bleeding. Direct oral anticoagulants represent a major advance over traditional anticoagulants (e.g., unfractionated heparin, warfarin) but still cause bleeding, particularly from the gastrointestinal tract which can limit their use. Epidemiological studies indicate that patients with congenital factor XI (FXI) deficiency have a lower risk of venous thromboembolism (VTE) and ischemic stroke (IS) than non-deficient individuals, and do not have an increased risk of spontaneous bleeding, even with severe deficiency. These observations provide the rationale for targeting FXI as a new class of anticoagulant. Multiple FXI inhibitors have been introduced and several are being evaluated in Phase III trials. In this review, we explain why drugs that target FXI may be associated with a lower risk of bleeding than currently available anticoagulants and summarize the completed and ongoing trials.

BACKGROUND/UNASSIGNED:Calcified coronary lesions are a challenge for percutaneous coronary interventions (PCIs). Coronary intravascular lithotripsy (IVL) is a novel calcium modification technology approved for commercial use in February 2021, but little is known about its uptake in US clinical practice. METHODS/UNASSIGNED:We described trends in use of calcium modification strategies, variation in use across hospitals, and predictors of calcium modification and IVL use in PCI. We included National Cardiovascular Data Registry CathPCI Registry patients who underwent PCI between April 1, 2018, and December 31, 2022. We examined trends and hospital variation in calcium modification and IVL use. We used multivariate hierarchical logistic regression to identify predictors of calcium modification and IVL use at hospitals in 2022. RESULTS/UNASSIGNED:Of 2,733,494 PCIs across 1676 hospitals over 4.75 years, 11.4% were performed with calcium modification. Coronary IVL use increased rapidly from 0% of PCIs in Q4 2020 to 7.8% of PCIs in Q4 2022, which was accompanied by an overall increase in use of all calcium modification strategies (11.1%-16.0%) during this period with a slight corresponding decrease in coronary atherectomy use (5.4%-4.4%). In 2022, there was wide variation in IVL use across hospitals (median, 3.86%; IQR, 0%-8.19%), with IVL being the most common calcium modification strategy in 48% of hospitals. The treating hospital was the strongest predictor of calcium modification (median odds ratio [OR], 2.49; 95% CI, 2.40-2.57) and IVL use (median OR, 2.89; 95% CI, 2.74-3.04). CONCLUSIONS/UNASSIGNED:IVL has rapidly changed the landscape of calcium modification use for PCI, although there remains wide variation across hospitals.

(1) Background: Cardiogenic shock (CS) is associated with high morbidity and mortality. Frailty and cardiovascular diseases are intertwined, commonly sharing risk factors and exhibiting bidirectional relationships. The relationship of frailty and non-acute myocardial infarction with cardiogenic shock (non-AMI-CS) is poorly described. (2) Methods: We retrospectively analyzed the National Inpatient Sample from 2016 to 2020 and identified all hospitalizations for non-AMI-CS. We classified them into frail and non-frail groups according to the hospital frailty risk score cut-off of 5 and compared in-hospital outcomes. (3) Results: A total of 503,780 hospitalizations for non-AMI-CS were identified. Most hospitalizations involved frail adults (80.0%). Those with frailty had higher odds of in-hospital mortality (adjusted odds ratio [aOR] 2.11, 95% confidence interval [CI] 2.03-2.20, p < 0.001), do-not-resuscitate status, and discharge to a skilled nursing facility compared with those without frailty. They also had higher odds of in-hospital adverse events, such as acute kidney injury, delirium, and longer length of stay. Importantly, non-AMI-CS hospitalizations in the frail group had lower use of mechanical circulatory support but not rates of cardiac transplantation. (4) Conclusions: Frailty is highly prevalent among non-AMI-CS hospitalizations. Those accompanied by frailty are often associated with increased rates of morbidity and mortality compared to those without frailty.

BACKGROUND:Evidence supporting anticoagulation with unfractionated heparin (UFH) in patients with an intra-aortic balloon pump (IABP) to prevent limb ischaemia remains limited, while bleeding risks remain high. Monitoring heparin in this setting with anti-factor Xa (anti-Xa) is not previously described. OBJECTIVES/OBJECTIVE:The study objective is to describe the incidence of thromboembolic and bleeding events with the use of UFH in patients with an IABP utilising monitoring with both anti-Xa and activated partial thromboplastin time (aPTT). METHODS:This is a retrospective study of adults who received an IABP and UFH for ≥24 hours. Electronic medical records were reviewed for pertinent data. The primary outcome was the incidence of limb ischaemia during IABP. Secondary outcomes included myocardial infarction, thrombus on IABP, or stroke. Exploratory outcomes included any venous thromboembolism and bleeding events. RESULTS:Of 159 patients, 88% received an IABP for cardiogenic shock and median duration of IABP support was 118 hours (interquartile range, 67-196). Limb ischaemia occurred in four of 159 patients (2.5%). Strokes occurred in 3.8% of the cohort, and bleeding events occurred in 33%. Despite anticoagulation use in all patients, 11% experienced a venous thromboembolism, with most identified upon asymptomatic screening with concern for heparin-induced thrombocytopenia. We found no differences in outcomes that occurred with a hybrid anti-Xa and aPTT versus aPTT monitoring alone. CONCLUSIONS:We observed a high rate of thrombotic and bleeding complications with the use of UFH in patients with an IABP. Use of anti-Xa versus aPTT for monitoring was not associated with complications. These data suggest safer anticoagulation strategies are needed in this setting.

BACKGROUND:Optimal duration and choice of antiplatelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention remain controversial. METHODS AND RESULTS/RESULTS:Digital databases (PubMed, Cochrane, and Embase) were queried to select all randomized controlled trials on a post-percutaneous coronary intervention population with acute coronary syndrome. Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel for 12 months was compared with 4 major strategies: high-potency, high- to low-potency, low-dose, and short-duration DAPT. A network meta-analysis was performed to compare the safety and efficacy of different antiplatelet strategies. This study was the second updated manuscript under the International Prospective Register of Systematic Review registration (CRD42021286552). Thirty-two randomized controlled trials comprising 103 459 (51 750 experimental, 51 709 control) patients were included. Compared with DAPT with aspirin and clopidogrel for 12 months, high- to low-potency DAPT (risk ratio [RR], 0.69 [95% CI, 0.52-0.92]) and aspirin+prasugrel containing DAPT for 12 months (RR, 0.84 [95% CI, 0.72-0.98]) had a significantly lower, whereas DAPT for 1 month followed by clopidogrel only (RR, 1.59 [95% CI, 1.06-2.39]) had a higher, incidence of major adverse cardiovascular events at 1 year (median follow-up). Prasugrel (RR, 1.35 [95% CI, 1.09-1.66]) and ticagrelor (RR, 1.38 [95% CI, 1.17-1.62]) containing DAPT for 12 months had significantly higher rates, whereas high- to low-potency DAPT (RR, 0.85 [95% CI, 0.63-1.15]) had no significant risk of major bleeding. CONCLUSIONS:Aspirin and ticagrelor for 3 months, followed by aspirin and clopidogrel for the remaining duration, can be considered the optimal strategy for treating post-percutaneous coronary intervention patients with acute coronary syndrome because of a significantly reduced risk of major adverse cardiovascular events without increasing the risk of bleeding.

The optimal antiplatelet strategy after coronary artery bypass graft (CABG) surgery in patients with chronic coronary syndromes (CCS) is unclear. Adding the P2Y₁₂ inhibitor, ticagrelor, to low-dose aspirin for 1 year is associated with a reduction in graft failure, particularly saphenous vein grafts, at the expense of an increased risk of clinically important bleeding. As the risk of thrombotic graft failure and ischaemic events is highest early after CABG surgery, a better risk-to-benefit profile may be attained with short-term dual antiplatelet therapy followed by single antiplatelet therapy. The One Month Dual Antiplatelet Therapy With Ticagrelor in Coronary Artery Bypass Graft Patients (ODIN) trial is a prospective, randomised, double-blind, placebo-controlled, international, multicentre study of 700 subjects that will evaluate the effect of short-term dual antiplatelet therapy with ticagrelor plus low-dose aspirin after CABG in patients with CCS. Patients will be randomised 1:1 to ticagrelor 90 mg twice daily or matching placebo, in addition to aspirin 75-150 mg once daily for 1 month; after the first month, antiplatelet therapy will be continued with aspirin alone. The primary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, revascularisation and graft failure at 1 year. The key secondary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, Bleeding Academic Research Consortium (BARC) type 3 bleeding, revascularisation and graft failure at 1 year (net clinical benefit). ODIN will report whether the addition of ticagrelor to low-dose aspirin for 1 month after CABG reduces ischaemic events and provides a net clinical benefit in patients with CCS. (ClinicalTrials.gov: NCT05997693).

BACKGROUND/UNASSIGNED:Complete revascularization improves cardiovascular outcomes compared with culprit-only revascularization in patients with acute myocardial infarction ([MI]; ST-segment-elevation MI or non-ST-segment-elevation MI) and multivessel coronary artery disease. However, the timing of complete revascularization (single-setting versus staged revascularization) is uncertain. The aim was to compare the outcomes of single-setting complete, staged complete, and culprit vessel-only revascularization in patients with acute MI and multivessel disease. METHODS/UNASSIGNED:PubMed, EMBASE, and clinicaltrials.gov databases were searched for randomized controlled trials that compared 3 revascularization strategies. RESULTS/UNASSIGNED:From 16 randomized controlled trials that randomized 11 876 patients with acute MI and multivessel disease, both single-setting complete and staged complete revascularization reduced primary outcome (cardiovascular mortality/MI; odds ratio [OR], 0.52 [95% CI, 0.41-0.65]; OR, 0.74 [95% CI, 0.62-0.88]), composite of all-cause mortality/MI (OR, 0.52 [95% CI, 0.40-0.67]; OR, 0.78 [95% CI, 0.67-0.91]), major adverse cardiovascular event (OR, 0.42 [95% CI, 0.32-0.56]; OR, 0.62 [95% CI, 0.47-0.82]), MI (OR, 0.39 [95% CI, 0.26-0.57]; OR, 0.73 [95% CI, 0.59-0.90]), and repeat revascularization (OR, 0.30 [95% CI, 0.18-0.47]; OR, 0.46 [95% CI, 0.30-0.71]) compared with culprit-only revascularization. Single-setting complete revascularization reduced cardiovascular mortality/MI (OR, 0.70 [95% CI, 0.55-0.91]), major adverse cardiovascular event (OR, 0.67 [95% CI, 0.50-0.91]), and all-cause mortality/MI driven by a lower risk of MI (OR, 0.53 [95% CI, 0.36-0.77]) compared with staged complete revascularization. Single-setting complete revascularization ranked number 1, followed by staged complete revascularization (number 2) and culprit-only revascularization (number 3) for all outcomes. The results were largely consistent in subgroup analysis comparing ST-segment-elevation MI versus non-ST-segment-elevation MI cohorts. CONCLUSIONS/UNASSIGNED:Single-setting complete revascularization may offer the greatest reductions in cardiovascular events in patients with acute MI and multivessel disease. A large-scale randomized trial of single-setting complete versus staged complete revascularization is warranted to evaluate the optimal timing of complete revascularization.

BACKGROUND/UNASSIGNED:Radial artery access for coronary angiography or percutaneous coronary intervention (PCI) reduces the risk of death, bleeding, and vascular complications and is preferred over femoral artery access, leading to a class 1 indication by clinical practice guidelines. However, alternate upper extremity access such as distal radial and ulnar access are not mentioned in the guidelines despite randomized trials. We aimed to evaluate procedural outcomes with femoral, radial, distal radial, and ulnar access sites in patients undergoing coronary angiography or PCI. METHODS/UNASSIGNED:PubMed, EMBASE, and clinicaltrials.gov databases were searched for randomized clinical trials that compared at least 2 of the 4 access sites in patients undergoing PCI or angiography. Primary outcomes were major bleeding and access site hematoma. Intention-to-treat mixed treatment comparison meta-analysis was performed. RESULTS/UNASSIGNED:From 47 randomized clinical trials that randomized 38 924 patients undergoing coronary angiography or PCI, when compared with femoral access, there was a lower risk of major bleeding with radial access (odds ratio [OR], 0.46 [95% CI, 0.35-0.59]) and lower risk of access site hematoma with radial (OR, 0.34 [95% CI, 0.24-0.48]), distal radial (OR, 0.33 [95% CI, 0.20-0.56]), and ulnar (OR, 0.50 [95% CI, 0.31-0.83]) access. However, when compared with radial access, there was higher risk of hematoma with ulnar access (OR, 1.48 [95% CI, 1.03-2.14]). CONCLUSIONS/UNASSIGNED:Data from randomized trials support guideline recommendation of class 1 for the preference of radial access over femoral access in patients undergoing coronary angiography or PCI. Moreover, distal radial and ulnar access can be considered as a default secondary access site before considering femoral access. REGISTRATION/UNASSIGNED:URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: 42024512365.