Coronary Artery Bypass Graft Failure in Women: Incidence and Clinical Implications.

BACKGROUND: Women have worse outcomes after coronary artery bypass surgery (CABG) than men. OBJECTIVES: This study aimed to determine the incidence of CABG graft failure in women, its association with cardiac events, and whether it contributes to sex-related differences in outcomes. METHODS: A pooled analysis of individual patient data from randomized clinical trials with systematic imaging follow-up was performed. Multivariable logistic regression models were used to assess the association of graft failure with myocardial infarction and repeat revascularization between CABG and imaging (primary outcome) and death after imaging (secondary outcome). Mediation analysis was performed to evaluate the effect of graft failure on the association between female sex and risk of death. RESULTS: Seven randomized clinical trials (N = 4,413, 777 women) were included. At a median imaging follow-up of 1.03 years, graft failure was significantly more frequent among women than men (37.3% vs 32.9% at the patient-level and 20.5% vs 15.8% at the graft level; P = 0.02 and P < 0.001, respectively). In women, graft failure was associated with an increased risk of myocardial infarction and repeat revascularization (OR: 3.94; 95% CI: 1.79-8.67) and death (OR: 3.18; 95% CI: 1.73-5.85). Female sex was independently associated with the risk of death (direct effect, HR: 1.84; 95% CI: 1.35-2.50) but the association was not mediated by graft failure (indirect effect, HR: 1.04; 95% CI: 0.86-1.26). CONCLUSIONS: Graft failure is more frequent in women and is associated with adverse cardiac events. The excess mortality risk associated with female sex among CABG patients is not mediated by graft failure.

Association between overweight and obesity with coronary artery bypass graft failure: an individual patient data analysis of clinical trials.

OBJECTIVES: The association between obesity and graft failure after coronary artery bypass grafting has not been previously investigated. METHODS: We pooled individual patient data from randomized clinical trials with systematic postoperative coronary imaging to evaluate the association between obesity and graft failure at the individual graft and patient levels. Penalized cubic regression splines and mixed-effects multivariable logistic regression models were performed. RESULTS: Six trials comprising 3928 patients and 12 048 grafts were included. The median time to imaging was 1.03 (interquartile range 1.00-1.09) years. By body mass index (BMI) category, 800 (20.4%) patients were normal weight (BMI 18.5-24.9), 1668 (42.5%) were overweight (BMI 25-29.9), 983 (25.0%) were obesity class 1 (BMI 30-34.9), 344 (8.8%) were obesity class 2 (BMI 35-39.9) and 116 (2.9%) were obesity class 3 (BMI 40+). As a continuous variable, BMI was associated with reduced graft failure [adjusted odds ratio (aOR) 0.98 (95% confidence interval (CI) 0.97-0.99)] at the individual graft level. Compared to normal weight patients, graft failure at the individual graft level was reduced in overweight [aOR 0.79 (95% CI 0.64-0.96)], obesity class 1 [aOR 0.81 (95% CI 0.64-1.01)] and obesity class 2 [aOR 0.61 (95% CI 0.45-0.83)] patients, but not different compared to obesity class 3 [aOR 0.94 (95% CI 0.62-1.42)] patients. Findings were similar, but did not reach significance, at the patient level. CONCLUSIONS: In a pooled individual patient data analysis of randomized clinical trials, BMI and obesity appear to be associated with reduced graft failure at 1 year after coronary artery bypass grafting.

Prehospital Tirofiban Increases the Rate of Disrupted Myocardial Infarction in Patients with ST-Segment Elevation Myocardial Infarction: Insights From the On-TIME 2 Trial.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), prehospital tirofiban significantly improved myocardial reperfusion. However, its impact on the rate of disrupted myocardial infarction (MI), particularly in the context of high-sensitive cardiac troponin (hs-cTn) assays, is still unclear. METHODS: The On-TIME 2 (The Ongoing Tirofiban In Myocardial infarction Evaluation 2) trial randomly assigned STEMI patients to prehospital tirofiban or placebo before transportation to a percutaneous coronary intervention (PCI) centre. In this post hoc analysis, we evaluated STEMI patients that underwent primary PCI and had measured hs-cTn levels. Troponin T levels were collected at 18-24 h and 72-96 h after PCI. Disrupted MI was defined as peak hs-cTn T levels ≤10 times the upper limit of normal (≤140 ng/L). RESULTS: Out of 786 STEMI patients, 47 (6%) had a disrupted MI. Disrupted MI occurred in 31 of 386 patients (8.0%) in the tirofiban arm and in 16 of 400 patients (4.0%) in the placebo arm (p=0.026). After multivariate adjustment, prehospital tirofiban remained independently associated with disrupted MI (OR 2.03; 95% CI 1.10 to 3.87; P= 0.027). None of the patients with disrupted MI died during the one-year follow-up, compared to a mortality rate of 2.6% among those without disrupted MI. CONCLUSION: Among STEMI patients undergoing primary PCI, the use of prehospital tirofiban was independently associated with a higher rate of disrupted MI. These results, highlighting a potential benefit, underscore the need for future research focusing on innovative pretreatment approaches which may increase the rate of disrupted MI.

Pre-hospital evaluation of chest pain patients using the modified HEART-score: rationale and design.

Background: This study assesses how ambulance paramedics using the modified HEART-score with a point-of-care cardiac troponin (cTn) compare to the emergency physicians using the modified HEART-score with a high-sensitive cTn (hs-cTn) in patients with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS), focusing on interobserver agreement and diagnostic performance. Methods: In this prospective multicenter cohort, we compare four cTn testing strategies (serial point of care and hs-cTn cTn measurement) with and without the HEART-score. Outcomes include the HEART-score's interobserver agreement, NSTE-ACS at discharge, major adverse cardiovascular events (MACE) after 30 days, and diagnostic accuracy of the different strategies. Conclusion: The POPular HEART study aims to improve NSTE-ACS diagnostic pathways, promoting pre-hospital detection and ruling out of NSTE-ACS to minimize unnecessary hospitalizations and associated costs.Clinical Trial Registration: NCT04851418 (ClinicalTrials.gov).

What & why? Many people visit the emergency department (ED) due to chest pain, often worried about the possibility of a heart attack. While acute heart attacks can often be detected through an electrocardiogram (ECG; a test of the heart's electrical activity), a significant number of patients with a heart attack have a normal ECG. These patients require further testing to measure cardiac troponin (cTn; an indicator of heart damage) in the hospital to rule out a heart attack, known as non-ST-elevation acute coronary syndrome (NSTE-ACS). To improve diagnosis and care for these patients, we compared two approaches: ambulance paramedics using a quick bedside cTn test and the HEART-score, versus hospital doctors using a more sensitive cTn test with the HEART-score. The HEART score combines factors like the patient's medical history, ECG results, age, risk factors, and cTn levels to assess the risk of heart problems. In this comparison, the key difference lies in how cTn levels are measured ­ either through a quick finger prick test in an ambulance using a point-of-care device or a more detailed analysis in a hospital laboratory.How? We focused on patients visited by emergency medical services for chest pain suspected of a heart attack and transported to the hospital. We assessed the quick bedside test by paramedics and the detailed hospital test by doctors, alongside the use of the HEART score in both settings. Our evaluation looked at the agreement between these methods and their effectiveness in identifying or excluding an NSTE-ACS.What? Our research, known as the POPular HEART study, seeks to simplify the early identification or rule-out of an NSTE-ACS in patients with chest pain directly by ambulance. This approach aims to decrease unnecessary hospital admissions and reduce healthcare costs.Main points We're exploring innovative methods to safely identify patients with a very low risk of NSTE-ACS in individuals with chest pain outside the hospital. Our objective is to safely minimize hospital admissions that may not be necessary, thereby saving resources. By doing so, we aim to alleviate the pressure on EDs and contribute to more cost-effective healthcare.

Defining high bleeding risk in patients undergoing transcatheter aortic valve implantation: a VARC-HBR consensus document.

The identification and management of patients at high bleeding risk (HBR) undergoing transcatheter aortic valve implantation (TAVI) are of major importance, but the lack of standardised definitions is challenging for trial design, data interpretation, and clinical decision-making. The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) is a collaboration among leading research organisations, regulatory authorities, and physician-scientists from Europe, the USA, and Asia, with a major focus on TAVI-related bleeding. VARC-HBR is an initiative of the CERC (Cardiovascular European Research Center), aiming to develop a consensus definition of TAVI patients at HBR, based on a systematic review of the available evidence, to provide consistency for future clinical trials, clinical decision-making, and regulatory review. This document represents the first pragmatic approach to a consistent definition of HBR evaluating the safety and effectiveness of procedures, devices and drug regimens for patients undergoing TAVI..

P2Y12 Inhibition in Patients Requiring Oral Anticoagulation After Percutaneous Coronary Intervention: The SWAP-AC-2 Study.

BACKGROUND: Among patients treated with a novel oral anticoagulant (NOAC) undergoing percutaneous coronary intervention (PCI), combination therapy with clopidogrel (ie, known as dual antithrombotic therapy [DAT]) is the treatment of choice. However, there are concerns for individuals with impaired response to clopidogrel. OBJECTIVES: The authors sought to assess the pharmacodynamic (PD) effects of clopidogrel vs low-dose ticagrelor in patients with impaired clopidogrel response assessed by the ABCD-GENE score. METHODS: This was a prospective, randomized PD study of NOAC-treated patients undergoing PCI. Patients with an ABCD-GENE score ≥10 (n = 39), defined as having impaired clopidogrel response, were randomized to low-dose ticagrelor (n = 20; 60 mg twice a day) or clopidogrel (n = 19; 75 mg once a day). Patients with an ABCD-GENE score <10 (n = 42) were treated with clopidogrel (75 mg once a day; control cohort). PD assessments at baseline and 30 days post-randomization (trough and peak) were performed to assess P2Y12 signaling (VerifyNow P2Y12 reaction units [PRU], light transmittance aggregometry, and vasodilator-stimulated phosphoprotein); makers of thrombosis not specific to P2Y12 signaling were also assessed. The primary endpoint was PRU (trough levels) at 30 days. RESULTS: At 30 days, PRU levels were reduced with ticagrelor-based DAT compared with clopidogrel-based DAT at trough (23.0 [Q1-Q3: 3.0-46.0] vs 154.5 [Q1-Q3: 77.5-183.0]; P < 0.001) and peak (6.0 [Q1-Q3: 4.0-14.0] vs 129.0 [Q1-Q3: 66.0-171.0]; P < 0.001). Trough PRU levels in the control arm (104.0 [Q1-Q3: 35.0-167.0]) were higher than ticagrelor-based DAT (P = 0.005) and numerically lower than clopidogrel-based DAT (P = 0.234). Results were consistent by light transmittance aggregometry and vasodilator-stimulated phosphoprotein. Markers measuring other pathways leading to thrombus formation were largely unaffected. CONCLUSIONS: In NOAC-treated patients undergoing PCI with an ABCD-GENE score ≥10, ticagrelor-based DAT using a 60-mg, twice-a-day regimen reduced platelet P2Y12 reactivity compared with clopidogrel-based DAT. (Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After PCI [SWAP-AC-2]; NCT04483583).

Upper extremity versus lower extremity for secondary access during transcatheter aortic valve implantation: rationale and design of the randomised TAVI XS trial.

BACKGROUND: During transcatheter aortic valve implantation (TAVI), secondary access is required for angiographic guidance and temporary pacing. The most commonly used secondary access sites are the femoral artery (angiographic guidance) and the femoral vein (temporary pacing). An upper extremity approach using the radial artery and an upper arm vein instead of the lower extremity approach using the femoral artery and femoral vein may reduce clinically relevant secondary access site-related bleeding complications, but robust evidence is lacking. TRIAL DESIGN: The TAVI XS trial is a multicentre, randomised, open-label clinical trial with blinded evaluation of endpoints. A total of 238 patients undergoing transfemoral TAVI will be included. The primary endpoint is the incidence of clinically relevant bleeding (i.e. Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding) of the randomised secondary access site (either diagnostic or pacemaker access, or both) within 30 days after TAVI. Secondary endpoints include time to mobilisation after TAVI, duration of hospitalisation, any BARC type 2, 3 or 5 bleeding, and early safety at 30 days according to Valve Academic Research Consortium­3 criteria. CONCLUSION: The TAVI XS trial is the first randomised trial comparing an upper extremity approach to a lower extremity approach with regard to clinically relevant secondary access site-related bleeding complications. The results of this trial will provide important insights into the safety and efficacy of an upper extremity approach in patients undergoing transfemoral TAVI.

Preoperative computed tomography-imaging with patient-specific computer simulation in transcatheter aortic valve implantation: Design and rationale of the GUIDE-TAVI trial.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an established treatment option for patients with severe aortic valve stenosis, but is still associated with relatively high rates of pacemaker implantation and paravalvular regurgitation. Routine preoperative computed tomography (CT) combined with patient-specific computer modelling can predict the interaction between the TAVI device and the patient's unique anatomy, allowing physicians to assess the risk for paravalvular regurgitation and conduction disorders in advance to the procedure. The aim of this trial is to assess potential improvement in the procedural outcome of TAVI by applying CT-based patient-specific computer simulations in patients with suitable anatomy for TAVI. METHODS: The GUIDE-TAVI trial is an international multicenter randomized controlled trial including patients accepted for TAVI by the Heart Team. Patients enrolled in the study will be randomized into 2 arms of each 227 patients. In patients randomized to the use of FEops HEARTGuide (FHG), patient-specific computer simulation with FHG is performed in addition to routine preoperative CT imaging and results of the FHG are available to the operator(s) prior to the scheduled intervention. In patients randomized to no use of FHG, only routine preoperative CT imaging is performed. The primary objective is to evaluate whether the use of FHG will reduce the incidence of mild to severe PVR, according to the Valve Academic Research Consortium 3. Secondary endpoints include the incidence of new conduction disorders requiring permanent pacemaker implantation, the difference between preoperative and final selected valve size, the difference between target and final implantation depth, change of preoperative decision, failure to implant valve, early safety composite endpoint and quality of life. CONCLUSIONS: The GUIDE-TAVI trial is the first multicenter randomized controlled trial to evaluate the value of 3-dimensional computer simulations in addition to standard preprocedural planning in TAVI procedures.

Postoperative Myocardial Injury and Inflammatory Biomarkers in Patients Undergoing Vascular Surgery: A Subanalysis of the Platelet Reactivity and Postoperative Myocardial Injury after Major Vascular Surgery (PROMISE) Study.

BACKGROUND: Postoperative myocardial injury (PMI) is associated with morbidity and mortality, but the aetiology remains unclear. We studied whether PMI is associated with perioperative systemic inflammation. The objective is the examination of the relationship between inflammatory biomarkers (Interleukin 6[IL-6], C-reactive protein [CRP]) and PMI, detected by elevated cardiac troponin (cTn), in patients undergoing elective open abdominal aortic surgery. METHODS: This prospective, single-center, observational cohort study included 54 patients undergoing elective open abdominal aortic surgery between March 2018 and April 2021. Patients were routinely treated with aspirin. IL-6 and CRP were measured preoperatively, directly after surgery, 24 hr and 48 hr postoperatively. The primary outcome was cTn release assessed by a fifth-generation high-sensitive cTn assay. Multivariable generalized linear regression models were used to evaluate the association between inflammatory biomarkers and cTn concentrations. RESULTS: Fifteen patients (27.8%) developed PMI. IL-6 directly and 24 hr postoperatively was associated with elevated cTn concentrations (1.28 [1.07-1.54], P = 0.009) and 1.75 [1.18-2.59], P = 0.006, respectively). Also, CRP directly and 24 hr postoperatively was associated with elevated cTn concentrations (1.25 [1.06-1.47], P = 0.009) and 1.61 [1.1-2.33], P = 0.013, respectively). No association was found between IL-6 or CRP and cTn concentrations when measured at 48 hr postsurgery. CONCLUSIONS: Biomarkers of inflammation are associated with elevated postoperative cTn concentrations in the early postoperative period in patients undergoing elective open abdominal aortic surgery.

Treatment of elderly patients with non-ST-elevation myocardial infarction: the nationwide POPular age registry.

OBJECTIVE: We describe the current treatment of elderly patients with non-ST-elevation myocardial infarction (NSTEMI) enrolled in a national registry. METHODS: The POPular AGE registry is a prospective, multicentre study of patients ≥ 75 years of age presenting with NSTEMI, performed in the Netherlands. Management was at the discretion of the treating physician. Cardiovascular events consisted of cardiovascular death, myocardial infarction and ischaemic stroke. Bleeding was classified according to the Bleeding Academic Research Consortium (BARC) criteria. RESULTS: A total of 646 patients were enrolled between August 2016 and May 2018. Median age was 81 (IQR 77-84) years and 58% were male. Overall, 75% underwent coronary angiography, 40% percutaneous coronary intervention, and 11% coronary artery bypass grafting, while 49.8% received pharmacological therapy only. At discharge, dual antiplatelet therapy (aspirin and P2Y12 inhibitor) was prescribed to 56.7%, and 27.4% received oral anticoagulation plus at least one antiplatelet agent. At 1­year follow-up, cardiovascular death, myocardial infarction or stroke had occurred in 13.6% and major bleeding (BARC 3 and 5) in 3.9% of patients. The risk of both cardiovascular events and major bleeding was highest during the 1st month. However, cardiovascular risk was three times as high as bleeding risk in this elderly population, both after 1 month and after 1 year. CONCLUSIONS: In this national registry of elderly patients with NSTEMI, the majority are treated according to current European Society of Cardiology guidelines. Both the cardiovascular and bleeding risk are highest during the 1st month after NSTEMI. However, the cardiovascular risk was three times as high as the bleeding risk.

Adding Surgical Edge-to-Edge Mitral Valve Repair to Myectomy in Hypertrophic Obstructive Cardiomyopathy: Long-Term Functional and Echocardiographic Outcome.

This study evaluates the early and long-term clinical and echocardiographic outcome of edge-to-edge (E2E) mitral valve repair (MVr) concomitant to septal myectomy (SM) in patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM). A retrospective single-center analysis was performed of patients who underwent isolated SM or SM with E2E MVr from 2011 to 2022. Exclusion criteria were primary mitral valve (MV) disease or concomitant valve surgery. Early and long-term safety, functional and echocardiographic outcomes were compared between groups. Between January 2011 and April 2022, 76 consecutive patients underwent SM for HOCM: 42 patients (55%) underwent SM without additional E2E MVr (Group 1) and 34 patients (45%) underwent SM with additional E2E MVr (Group 2). At latest follow-up, 87% of patients were in New York Heart Association (NYHA) class I-II with no significant differences in NYHA class between groups. Incidence of safety events was comparable between groups. Echocardiographic relief of left ventricular outflow tract (LVOT) obstruction was comparable at early follow-up (P = 0.68), with a significant but small difference in maximum LVOT pressure gradient at latest follow-up in favor of E2E MVr (P = 0.04). Furthermore, patients who underwent SM with E2E MVr showed less residual systolic anterior motion at early and latest follow-up (P = 0.020; P = 0.178). Reintervention on the MV was absent in both groups at 1 year and equally low at follow-up (P = 0.27). This study demonstrates that adding E2E MVr to septal myectomy is as safe as isolated myectomy for the treatment of HOCM. Moreover, the addition of E2E MVr is associated with similar excellent functional improvement and freedom from MV reintervention.

Critical Analysis of Thrombocytopenia Associated With Glycoprotein IIb/IIIa Inhibitors and Potential Role of Zalunfiban, a Novel Small Molecule Glycoprotein Inhibitor, in Understanding the Mechanism(s).

Thrombocytopenia is a rare but serious complication of the intravenous glycoprotein IIb/IIIa (GPIIb/IIIa; integrin αIIbß3) receptor inhibitors (GPIs), abciximab, eptifibatide, and tirofiban. The thrombocytopenia ranges from mild (50 000-100 000 platelets/µL), to severe (20 000 to <50 000/µL), to profound (<20 000/µL). Profound thrombocytopenia appears to occur in <1% of patients receiving their first course of therapy. Thrombocytopenia can be either acute (<24 hours) or delayed (up to ~14 days). Both hemorrhagic and thrombotic complications have been reported in association with thrombocytopenia. Diagnosis requires exclusion of pseudothrombocytopenia and heparin-induced thrombocytopenia. Therapy based on the severity of thrombocytopenia and symptoms may include drug withdrawals and treatment with steroids, intravenous IgG, and platelet transfusions. Abciximab-associated thrombocytopenia is most common and due to either preformed antibodies or antibodies induced in response to abciximab (delayed). Readministration of abciximab is associated with increased risk of thrombocytopenia. Evidence also supports an immune basis for thrombocytopenia associated with the 2 small molecule GPIs. The latter bind αIIbß3 like the natural ligands and thus induce the receptor to undergo major conformational changes that potentially create neoepitopes. Thrombocytopenia associated with these drugs is also immune-mediated, with antibodies recognizing the αIIbß3 receptor only in the presence of the drug. It is unclear whether the antibody binding depends on the conformational change and whether the drug contributes directly to the epitope. Zalunfiban, a second-generation subcutaneous small molecule GPI, does not induce the conformational changes; therefore, data from studies of zalunfiban will provide information on the contribution of the conformational changes to the development of GPI-associated thrombocytopenia.

The Clinical Implementation of CYP2C19 Genotyping in Patients with an Acute Coronary Syndrome: Insights From the FORCE-ACS Registry.

BACKGROUND: Guidelines recommend prasugrel or ticagrelor for acute coronary syndrome (ACS) patients. However, these P2Y12 inhibitors increase bleeding risk compared to clopidogrel. Although genotype-guided P2Y12-inhibitor selection has been shown to reduce bleeding risk, data on its clinical implementation is lacking. METHODS: The study included ACS patients receiving genotype-guided antiplatelet therapy, utilising either a point-of-care (POC) device or laboratory-based testing. We aimed to collect qualitative and quantitative data on genotyping, eligibility for de-escalation, physician adherence to genotype results, time to de-escalation and cost reduction. RESULTS: Of the 1,530 patients included in the ACS registry from 2021 to 2023, 738 ACS patients treated with ticagrelor received a CYP2C19 genotype test. The median turnover time of genotyping was 6.3 hours (interquartile range [IQR], 3.2-16.7), with 82.3% of the genotyping results known within 24 hours after admission. POC genotyping exhibited significantly shorter turnaround times compared to laboratory-based testing (with respective medians of 5.7 vs 47.8 hours; P < .001). Of the genotyped patients, 81.7% were eligible for de-escalation which was carried out within 24 hours in 70.9% and within 48 h in 93.0%. The time to de-escalation was significantly shorter using POC (25.4 hours) compared to laboratory-based testing (58.9 hours; P < .001). Implementing this strategy led to a reduction of €211,150.50 in medication costs. CONCLUSIONS: CYP2C19 genotype-guided-de-escalation in an all-comers ACS population is feasible. POC genotyping leads to shorter turnaround times and quicker de-escalation. Time to de-escalation from ticagrelor to clopidogrel in noncarriers was short, with high physician adherence to genotype results.

Conservative versus Invasive Strategy in Elderly Patients with Non-ST-Elevation Myocardial Infarction: Insights from the International POPular Age Registry.

This registry assessed the impact of conservative and invasive strategies on major adverse clinical events (MACE) in elderly patients with non-ST-elevation myocardial infarction (NSTEMI). Patients aged ≥75 years with NSTEMI were prospectively registered from European centers and followed up for one year. Outcomes were compared between conservative and invasive groups in the overall population and a propensity score-matched (PSM) cohort. MACE included cardiovascular death, acute coronary syndrome, and stroke. The study included 1190 patients (median age 80 years, 43% female). CAG was performed in 67% (N = 798), with two-thirds undergoing revascularization. Conservatively treated patients had higher baseline risk. After propensity score matching, 319 patient pairs were successfully matched. MACE occurred more frequently in the conservative group (total population 20% vs. 12%, adjHR 0.53, 95% CI 0.37-0.77, p = 0.001), remaining significant in the PSM cohort (18% vs. 12%, adjHR 0.50, 95% CI 0.31-0.81, p = 0.004). In conclusion, an early invasive strategy was associated with benefits over conservative management in elderly patients with NSTEMI. Risk factors associated with ischemia and bleeding should guide strategy selection rather than solely relying on age.

Periprocedural continuation versus interruption of oral anticoagulant drugs during transcatheter aortic valve implantation: rationale and design of the POPular PAUSE TAVI trial.

About one-third of patients undergoing transcatheter aortic valve implantation (TAVI) use oral anticoagulants (OAC), mainly due to atrial fibrillation. General guidelines advise interrupting OAC in patients with a high risk of bleeding undergoing interventions. However, preliminary observational data suggest that the continuation of OAC during TAVI is safe and may reduce the risk of periprocedural thromboembolic events. The Periprocedural Continuation Versus Interruption of Oral Anticoagulant Drugs During Transcatheter Aortic Valve Implantation (POPular PAUSE TAVI) is a multicentre, randomised clinical trial with open-label treatment and blinded endpoint assessment. Patients are randomised 1:1 to periprocedural continuation versus interruption of OAC and are stratified for vitamin K antagonist or direct oral anticoagulant use. The primary endpoint is a composite of cardiovascular mortality, all stroke, myocardial infarction, major vascular complications and type 2-4 bleeding within 30 days after TAVI, according to the Valve Academic Research Consortium-3 criteria. Secondary endpoints include separate individual and composite outcomes, quality of life and cost-effectiveness. Since continuation of OAC is associated with the ancillary benefit that it simplifies periprocedural management, the primary outcome is first analysed for non-inferiority; if non-inferiority is proven, superiority will be tested. Recruitment started in November 2020, and the trial will continue until a total of 858 patients have been included and followed for 90 days. In summary, POPular PAUSE TAVI is the first randomised clinical trial to assess the safety and efficacy of periprocedural continuation versus interruption of OAC in patients undergoing TAVI.