Showing papers by "Marco Valgimigli published in 2021"

2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).

Abstract: Supplementary Table 9, column 'Edoxaban', row 'eGFR category', '95 mL/min' (page 15). The cell should be coloured green instead of yellow. It should also read "60 mg"instead of "60 mg (use with caution in 'supranormal' renal function)."In the above-indicated cell, a footnote has also been added to state: "Edoxaban should be used in patients with high creatinine clearance only after a careful evaluation of the individual thromboembolic and bleeding risk."Supplementary Table 9, column 'Edoxaban', row 'Dose reduction in selected patients' (page 16). The cell should read "Edoxaban 60 mg reduced to 30 mg once daily if any of the following: creatinine clearance 15-50 mL/min, body weight <60 kg, concomitant use of dronedarone, erythromycin, ciclosporine or ketokonazole"instead of "Edoxaban 60 mg reduced to 30 mg once daily, and edoxaban 30 mg reduced to 15mg once daily, if any of the following: creatinine clearance of 30-50 mL/min, body weight <60 kg, concomitant us of verapamil or quinidine or dronedarone."

2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS)

Abstract: Supplementary Table 9, column 'Edoxaban', row 'eGFR category', '95 mL/min' (page 15). The cell should be coloured green instead of yellow. It should also read "60 mg"instead of "60 mg (use with caution in 'supranormal' renal function)."In the above-indicated cell, a footnote has also been added to state: "Edoxaban should be used in patients with high creatinine clearance only after a careful evaluation of the individual thromboembolic and bleeding risk."Supplementary Table 9, column 'Edoxaban', row 'Dose reduction in selected patients' (page 16). The cell should read "Edoxaban 60 mg reduced to 30 mg once daily if any of the following: creatinine clearance 15-50 mL/min, body weight <60 kg, concomitant use of dronedarone, erythromycin, ciclosporine or ketokonazole"instead of "Edoxaban 60 mg reduced to 30 mg once daily, and edoxaban 30 mg reduced to 15mg once daily, if any of the following: creatinine clearance of 30-50 mL/min, body weight <60 kg, concomitant us of verapamil or quinidine or dronedarone."

P2Y12 inhibitor monotherapy or dual antiplatelet therapy after coronary revascularisation: individual patient level meta-analysis of randomised controlled trials

Abstract: Objective To assess the risks and benefits of P2Y12 inhibitor monotherapy compared with dual antiplatelet therapy (DAPT) and whether these associations are modified by patients’ characteristics. Design Individual patient level meta-analysis of randomised controlled trials. Data sources Searches were conducted in Ovid Medline, Embase, and three websites (www.tctmd.com, www.escardio.org, www.acc.org/cardiosourceplus) from inception to 16 July 2020. The primary authors provided individual participant data. Eligibility criteria Randomised controlled trials comparing effects of oral P2Y12 monotherapy and DAPT on centrally adjudicated endpoints after coronary revascularisation in patients without an indication for oral anticoagulation. Main outcome measures The primary outcome was a composite of all cause death, myocardial infarction, and stroke, tested for non-inferiority against a margin of 1.15 for the hazard ratio. The key safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or type 5 bleeding. Results The meta-analysis included data from six trials, including 24 096 patients. The primary outcome occurred in 283 (2.95%) patients with P2Y12 inhibitor monotherapy and 315 (3.27%) with DAPT in the per protocol population (hazard ratio 0.93, 95% confidence interval 0.79 to 1.09; P=0.005 for non-inferiority; P=0.38 for superiority; τ2=0.00) and in 303 (2.94%) with P2Y12 inhibitor monotherapy and 338 (3.36%) with DAPT in the intention to treat population (0.90, 0.77 to 1.05; P=0.18 for superiority; τ2=0.00). The treatment effect was consistent across all subgroups, except for sex (P for interaction=0.02), suggesting that P2Y12 inhibitor monotherapy lowers the risk of the primary ischaemic endpoint in women (hazard ratio 0.64, 0.46 to 0.89) but not in men (1.00, 0.83 to 1.19). The risk of bleeding was lower with P2Y12 inhibitor monotherapy than with DAPT (97 (0.89%) v 197 (1.83%); hazard ratio 0.49, 0.39 to 0.63; P Conclusions P2Y12 inhibitor monotherapy was associated with a similar risk of death, myocardial infarction, or stroke, with evidence that this association may be modified by sex, and a lower bleeding risk compared with DAPT. Registration PROSPERO CRD42020176853.

Short dual antiplatelet therapy followed by P2Y12 inhibitor monotherapy vs. prolonged dual antiplatelet therapy after percutaneous coronary intervention with second-generation drug-eluting stents: a systematic review and meta-analysis of randomized clinical trials.

Abstract: AIMS After percutaneous coronary intervention (PCI) with second-generation drug-eluting stent (DES), whether short dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) with a P2Y12 receptor inhibitor confers benefits compared with prolonged DAPT is unclear. METHODS AND RESULTS Multiple electronic databases, including PubMed, Scopus, Web of Sciences, Ovid, and ScienceDirect, were searched to identify randomized clinical trials comparing ≤3 months of DAPT followed by P2Y12 inhibitor SAPT vs. 12 months of DAPT after PCI with second-generation DES implantation. The primary and co-primary outcomes of interest were major bleeding and stent thrombosis 1 year after randomization. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by fixed-effect and random-effects models. Multiple sensitivity analyses including random-effects models 95% CI adjustment were applied. A sensitivity analysis comparing trials using P2Y12 inhibitor SAPT with those using aspirin SAPT was performed. A total of five randomized clinical trials (32 145 patients) were available. Major bleeding was significantly lower in the patients assigned to short DAPT followed by P2Y12 inhibitor SAPT compared with those assigned to 12-month DAPT (random-effects model: HR 0.63, 95% 0.45-0.86). No significant differences between groups were observed in terms of stent thrombosis (random-effects model: HR 1.19, 95% CI 0.86-1.65) and the secondary endpoints of all-cause death (random-effects model: HR 0.85, 95% CI 0.70-1.03), myocardial infarction (random-effects model: HR 1.05, 95% CI 0.89-1.23), and stroke (random-effects model: HR 1.08, 95% CI 0.68-1.74). Sensitivity analyses showed overall consistent results. By comparing trials testing ≤3 months of DAPT followed by P2Y12 inhibitor SAPT vs. 12 months of DAPT with trials testing ≤3 months of DAPT followed by aspirin SAPT vs. 12-month of DAPT, there was no treatment-by-subgroup interaction for each endpoint. By combining all these trials, regardless of the type of SAPT, short DAPT was associated with lower major bleeding (random-effects model: HR 0.63, 95% CI 0.48-0.83) and no differences in stent thrombosis, all-cause death, myocardial infarction, and stroke were observed between regimens. CONCLUSION After second-generation DES implantation, 1-3 months of DAPT followed by P2Y12 inhibitor SAPT is associated with lower major bleeding and similar stent thrombosis, all-cause death, myocardial infarction, and stroke compared with prolonged DAPT. Whether P2Y12 inhibitor SAPT is preferable to aspirin SAPT needs further investigation.

Cardiac mortality in patients randomised to elective coronary revascularisation plus medical therapy or medical therapy alone: a systematic review and meta-analysis.

Abstract: © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/)

Assessing the Risks of Bleeding vs Thrombotic Events in Patients at High Bleeding Risk After Coronary Stent Implantation: The ARC-High Bleeding Risk Trade-off Model.

Abstract: Importance Patients who are candidates for percutaneous coronary intervention (PCI) and are at high bleeding risk constitute a therapeutic challenge because they often also face an increased risk of thrombotic complications. Objectives To develop and validate models to predict the risks of major bleeding (Bleeding Academic Research Consortium [BARC] types 3 to 5 bleeding) and myocardial infarction (MI) and/or stent thrombosis (ST) for individual patients at high bleeding risk and provide assistance in defining procedural strategy and antithrombotic regimens. Design, setting, and participants This prognostic study used individual patient data from 6 studies conducted from July 1, 2009, to September 5, 2017, for 6641 patients at more than 200 centers in Europe, the US, and Asia who underwent PCI and were identified as being at high bleeding risk using the Academic Research Consortium criteria. In 1 year of follow-up (excluding periprocedural events), individual patient risks of MI and/or ST and major bleeding were evaluated using 33 baseline variables. To validate these models, a subgroup of 1458 patients at high bleeding risk from the ONYX ONE trial were analyzed. Statistical analysis was performed from February 1, 2019, to April 30, 2020. Exposures All patients underwent PCI with bare metal, drug-coated, or drug-eluting stent implants. Main outcomes and measures Forward, stepwise multivariable proportional hazards models were used to identify highly significant predictors of MI and/or ST and BARC types 3 to 5 bleeding. Results A total of 6641 patients (4384 men [66.0%]; median age, 77.9 years [interquartile range, 70.0-82.6 years]) were included in this study. Over 365 days, nonperiprocedural MI and/or ST occurred in 350 patients (5.3%), and BARC types 3 to 5 bleeding occurred in 381 patients (5.7%). Eight independent baseline predictors of risk of MI and/or ST and 8 predictors for risk of BARC types 3 to 5 bleeding were identified. Four of these predictors were in both risk models. Both risk models showed moderate discrimination: C statistic = 0.69 for predicting MI and/or ST and 0.68 for predicting BARC types 3 to 5 bleeding. Applying these same models to the validation cohort gave a similar strength of discrimination (C statistic = 0.74 for both MI and/or ST and BARC types 3-5 bleeding). Patients with MI and/or ST had a mortality hazard ratio of 6.1 (95% CI, 4.8-7.7), and those with BARC types 3 to 5 bleeding had a mortality hazard ratio of 3.7 (95% CI, 2.9-4.8) compared with patients free of both events. Taking these data into account, the risk scores facilitate investigation of the individual patient trade-off between these 2 risks: 2931 patients (44.1%) at high bleeding risk in the 6 studies had a greater risk of MI and/or ST than of BARC 3 to 5 bleeding, 1555 patients (23.4%) had a greater risk of BARC 3 to 5 bleeding than of MI and/or ST, and 2155 (32.4%) had a comparable risk of both events. Conclusions and relevance In a large cohort of patients at high bleeding risk undergoing PCI, 2 prognostic models have been developed to identify individual patients' risk of major coronary thrombotic and bleeding events. In future clinical practice, using an application on a smartphone to evaluate the trade-off between these 2 quantifiable risks for each patient may help clinicians choose the most appropriate revascularization strategy and tailor the duration and intensity of antithrombotic regimens.

3- or 1-Month DAPT in Patients at High Bleeding Risk Undergoing Everolimus-Eluting Stent Implantation.

Abstract: Objectives The aim of this study was to evaluate 2 abbreviated dual-antiplatelet therapy (DAPT) regimens in patients at high bleeding risk (HBR) undergoing percutaneous coronary interventi...

Device-Related Thrombus After Left Atrial Appendage Closure: Data on Thrombus Characteristics, Treatment Strategies, and Clinical Outcomes From the EUROC-DRT-Registry.

Abstract: Background Left atrial appendage closure is an established therapy in patients with atrial fibrillation. Although device-related thrombosis (DRT) is relatively rare, it is potentially linked to adverse events. As data on DRT characteristics, outcome, and treatment regimen are scarce, we aimed to assess these questions in a multicenter approach. Methods One hundred fifty-six patients with the diagnosis of DRT after left atrial appendage closure were included in the multinational EUROC-DRT registry. Baseline characteristics included clinical and echocardiographic data. After inclusion, all patients underwent further clinical and echocardiographic follow-up to assess DRT dynamics, treatment success, and outcome. Results DRT was detected after a median of 93 days (interquartile range, 54–161 days) with 17.9% being detected >6 months after left atrial appendage closure. Patients with DRT were at high ischemic and bleeding risk (CHA2DS2-VASc 4.5±1.7, HAS-BLED 3.3±1.2) and had nonparoxysmal atrial fibrillation (67.3%), previous stroke (53.8%), and spontaneous echo contrast (50.6%). The initial treatment regimens showed comparable resolution rates (antiplatelet monotherapy: 57.1%, dual antiplatelet therapy: 85.7%, vitamin K antagonists: 80.0%, novel oral anticoagulants: 75.0%, and heparin: 68.6%). After intensification or switch of treatment, complete DRT resolution was achieved in 79.5% of patients. Two-year follow-up revealed a high risk of mortality (20.0%) and ischemic stroke (13.8%) in patients with DRT. Patients with incomplete DRT resolution showed numerically higher stroke rates and increased mortality rates (stroke: 17.6% versus 12.3%, P=0.29; mortality: 31.3% versus 13.1%, P=0.05). Conclusions A substantial proportion of DRT is detected >6 months after left atrial appendage closure, highlighting the need for imaging follow-up. Patients with DRT appear to be at a high risk for stroke and mortality. While DRT resolution was achieved in most patients, incomplete DRT resolution appeared to identify patients at even higher risk. Optimal DRT diagnostic criteria and treatment regimens are warranted.

Impact of Clinical Presentation on Bleeding Risk after Percutaneous Coronary Intervention and Implications for the ARC-HBR Definition.

Abstract: Background The identification of bleeding risk factors in patients undergoing percutaneous coronary intervention (PCI) is essential to inform subsequent management. Whether clinical presentation per se affects bleeding risk after PCI remains unclear. Aims We aimed to assess whether clinical presentation per se predisposes to bleeding in patients undergoing PCI and if the Academic Research Consortium (ARC)-high bleeding risk (HBR) criteria perform consistently among acute (ACS) and chronic (CCS) coronary syndrome patients. Methods Consecutive patients undergoing PCI from the Bern PCI Registry were stratified by clinical presentation. Bleeding events at 1 year were compared in ACS versus CCS patients, and the originally-defined ARC-HBR criteria were assessed. Results Among 16,821 patients, 9,503 (56.5%) presented with ACS. At 1 year, BARC 3 or 5 bleeding occurred in 4.97% and 3.60% of patients with ACS and CCS, respectively. After adjustment, ACS remained associated with higher BARC 3 or 5 bleeding risk (adjusted HR: 1.21; 95% CI: 1.01-1.43; p=0.034), owing to non-access site-related occurrences, which mainly accrued within the first 30 days after PCI. The ARC-HBR score had lower discrimination among ACS compared with CCS patients, and its performance slightly improved when ACS was computed as a minor criterion. Conclusions ACS presentation per se predicts 1-year major bleeding risk after PCI. The ARC-HBR score discrimination appeared lower in ACS than CCS, and its overall performance improved numerically when ACS was computed as an additional minor risk criterion.

Patient-tailored antithrombotic therapy following percutaneous coronary intervention

Abstract: Dual antiplatelet therapy has long been the standard of care in preventing coronary and cerebrovascular thrombotic events in patients with chronic coronary syndrome and acute coronary syndrome undergoing percutaneous coronary intervention, but choosing the optimal treatment duration and composition has become a major challenge. Numerous studies have shown that certain patients benefit from either shortened or extended treatment duration. Furthermore, trials evaluating novel antithrombotic strategies, such as P2Y12 inhibitor monotherapy, low-dose factor Xa inhibitors on top of antiplatelet therapy, and platelet function- or genotype-guided (de-)escalation of treatment, have shown promising results. Current guidelines recommend risk stratification for tailoring treatment duration and composition. Although several risk stratification methods evaluating ischaemic and bleeding risk are available to clinicians, such as the use of risk scores, platelet function testing , and genotyping, risk stratification has not been broadly adopted in clinical practice. Multiple risk scores have been developed to determine the optimal treatment duration, but external validation studies have yielded conflicting results in terms of calibration and discrimination and there is limited evidence that their adoption improves clinical outcomes. Likewise, platelet function testing and genotyping can provide useful prognostic insights, but trials evaluating treatment strategies guided by these stratification methods have produced mixed results. This review critically appraises the currently available antithrombotic strategies and provides a viewpoint on the use of different risk stratification methods alongside clinical judgement in current clinical practice.

Antithrombotic Therapy in Patients Undergoing Transcatheter Interventions for Structural Heart Disease.

Abstract: Contemporary evidence supports device-based transcatheter interventions for the management of patients with structural heart disease. These procedures, which include aortic valve implantation, mitr...

European position paper on the management of patients with patent foramen ovale. Part II - Decompression sickness, migraine, arterial deoxygenation syndromes and select high-risk clinical conditions.

Abstract: Patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions but to date only one official position paper related to left circulation thromboembolism has been published. This interdisciplinary paper, prepared with the involvement of eight European scientific societies, reviews the available evidence and proposes a rationale for decision making for other PFO-related clinical conditions. In order to guarantee a strict evidence-based process, we used a modified grading of recommendations, assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements were weighed and graded according to predefined scales. Despite being based on limited and observational or low-certainty randomised data, a number of position statements were made to frame PFO management in different clinical settings, along with suggestions for new research avenues. This interdisciplinary position paper, recognising the low or very low certainty of existing evidence, provides the first approach to several PFO-related clinical scenarios beyond left circulation thromboembolism and strongly stresses the need for fresh high-quality evidence on these topics.

Mortality after bleeding versus myocardial infarction in coronary artery disease: a systematic review and meta-analysis.

Abstract: BACKGROUND Bleeding is the principal safety concern of antithrombotic therapy and occurs frequently among patients with coronary artery disease (CAD). AIMS We aimed to evaluate the prognostic impact of bleeding on mortality compared with that of myocardial infarction (MI) in patients with CAD. METHODS We searched Medline and Embase for studies that included patients with CAD and that reported both the association between the occurrence of bleeding and mortality, and between the occurrence of MI and mortality within the same population. Adjusted hazard ratios (HRs) for mortality associated with bleeding and MI were extracted and ratios of hazard ratios (rHRs) were pooled by using inverse variance weighted random effects meta-analyses. Early events included periprocedural or within 30-day events after revascularisation or acute coronary syndrome (ACS). Late events included spontaneous or beyond 30-day events after revascularisation or ACS. RESULTS A total of 141,059 patients were included across 16 studies; 128,660 (91%) underwent percutaneous coronary intervention. Major bleeding increased the risk of mortality to the same extent as MI (rHRsbleedingvsMI 1.10, 95% CI: 0.71-1.71, p=0.668). Early bleeding was associated with a higher risk of mortality than early MI (rHRsbleedingvsMI 1.46, 95% CI: 1.13-1.89, p=0.004), although this finding was not present when only randomised trials were included. Late bleeding was prognostically comparable to late MI (rHRsbleedingvsMI 1.14, 95% CI: 0.87-1.49, p=0.358). CONCLUSIONS Compared with MI, major and late bleeding is associated with a similar increase in mortality, whereas early bleeding might have a stronger association with mortality.

Ticagrelor Monotherapy Versus Dual-Antiplatelet Therapy After PCI: An Individual Patient-Level Meta-Analysis

Abstract: Objectives The aim of this study was to compare ticagrelor monotherapy with dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents. Background The role of abbreviated DAPT followed by an oral P2Y12 inhibitor after PCI remains uncertain. Methods Two randomized trials, including 14,628 patients undergoing PCI, comparing ticagrelor monotherapy with standard DAPT on centrally adjudicated endpoints were identified, and individual patient data were analyzed using 1-step fixed-effect models. The protocol was registered in PROSPERO ( CRD42019143120 ). The primary outcomes were the composite of Bleeding Academic Research Consortium type 3 or 5 bleeding tested for superiority and, if met, the composite of all-cause death, myocardial infarction, or stroke at 1 year, tested for noninferiority against a margin of 1.25 on a hazard ratio (HR) scale. Results Bleeding Academic Research Consortium type 3 or 5 bleeding occurred in fewer patients with ticagrelor than DAPT (0.9% vs. 1.7%, respectively; HR: 0.56; 95% confidence interval [CI]: 0.41 to 0.75; p Conclusions Ticagrelor monotherapy was associated with a lower risk for major bleeding compared with standard DAPT, without a concomitant increase in ischemic events.

Access-Site Crossover in Patients With Acute Coronary Syndrome Undergoing Invasive Management.

Abstract: Objectives The aim of this study was to assess the impact of access-site crossover in patients with acute coronary syndrome undergoing invasive management via radial or femoral access. Background There are limited data on the clinical implications of access-site crossover. Methods In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox)–Access trial, 8,404 patients with acute coronary syndrome were randomized to radial or femoral access. Patients undergoing access-site crossover or successful access site were investigated. Thirty-day coprimary outcomes were a composite of death, myocardial infarction, or stroke (major adverse cardiovascular events [MACE]) and a composite of MACE or Bleeding Academic Research Consortium type 3 or 5 bleeding (net adverse clinical events [NACE]). Results Access-site crossover occurred in 183 of 4,197 patients (4.4%) in the radial group (mainly to femoral access) and 108 of 4,207 patients (2.6%) in the femoral group (mainly to radial access). In multivariate analysis, the risk for coprimary outcomes was not significantly higher with radial crossover compared with successful radial (MACE: adjusted rate ratio [adjRR]: 1.25; 95% confidence interval [CI]: 0.81 to 1.93; p = 0.32; NACE: adjRR: 1.40; 95% CI: 0.94 to 2.06; p = 0.094) or successful femoral access (MACE: adjRR: 1.17; 95% CI: 0.76 to 1.81; p = 0.47; NACE: adjRR: 1.26; 95% CI: 0.86 to 1.86; p = 0.24). Access site–related Bleeding Academic Research Consortium type 3 or 5 bleeding was higher with radial crossover than successful radial access. Femoral crossover remained associated with higher risks for MACE (adjRR: 1.84; 95% CI: 1.18 to 2.87; p = 0.007) and NACE (adjRR: 1.69; 95% CI: 1.09 to 2.62; p = 0.019) compared with successful femoral access. Results remained consistent after excluding patients with randomized access not attempted. Conclusions Crossover from radial to femoral access abolishes the bleeding benefit offered by the radial over femoral artery but does not appear to increase the risk for MACE or NACE compared with successful radial or femoral access. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox [MATRIX]; NCT01433627 )

Safety and efficacy of double vs. triple antithrombotic therapy in patients with atrial fibrillation with or without acute coronary syndrome undergoing percutaneous coronary intervention: a collaborative meta-analysis of non-vitamin K antagonist oral anticoagulant-based randomized clinical trials.

Abstract: AIMS Safety and efficacy of antithrombotic regimens in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) may differ based on clinical presentation. We sought to compare double vs. triple antithrombotic therapy (DAT vs. TAT) in AF patients with or without acute coronary syndrome (ACS) undergoing PCI. METHODS AND RESULTS A systematic review and meta-analysis was performed using PubMed to search for non-vitamin K antagonist oral anticoagulant (NOAC)-based randomized clinical trials. Data on subgroups of ACS or elective PCI were obtained by published reports or trial investigators. A total of 10 193 patients from four NOAC trials were analysed, of whom 5675 presenting with ACS (DAT = 3063 vs. TAT = 2612) and 4518 with stable coronary artery disease (SCAD; DAT = 2421 vs. TAT = 2097). The primary safety endpoint of ISTH major bleeding or clinically relevant non-major bleeding was reduced with DAT compared with TAT in both ACS (12.2% vs. 19.4%; RR 0.63, 95% CI 0.56-0.71; P < 0.0001; I2 = 0%) and SCAD (14.6% vs. 22.0%; RR 0.68, 95% CI 0.55-0.85; P = 0.0008; I2 = 66%), without interaction (P-int = 0.54). Findings were consistent for secondary bleeding endpoints, including intra-cranial haemorrhage. In both subgroups, there was no difference between DAT and TAT for all-cause death, major adverse cardiovascular events, or stroke. Myocardial infarction and stent thrombosis were numerically higher with DAT vs. TAT consistently in ACS and SCAD (P-int = 0.60 and 0.86, respectively). Findings were confirmed by multiple sensitivity analyses, including a separate analysis on dabigatran regimens and a restriction to PCI population. CONCLUSIONS DAT, compared with TAT, is associated with lower bleeding risks, including intra-cranial haemorrhage, and a small non-significant excess of cardiac ischaemic events in both patients with or without ACS.

Biodegradable- Versus Durable-Polymer Drug-Eluting Stents for STEMI: Final 2-Year Outcomes of the BIOSTEMI Trial.

Abstract: Objectives The aim of this study was to investigate the safety and efficacy of biodegradable-polymer sirolimus-eluting stents (BP-SES) compared with durable-polymer everolimus-eluting stents (DP-EES) in patients with ST-segment elevation myocardial infarction (STEMI). Background Primary percutaneous coronary intervention (PCI) is an effective treatment for patients with STEMI, and long-term outcomes are determined by the safety and efficacy profile of the newest generation drug-eluting stents. Methods BIOSTEMI (A Comparison of an Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent With a Durable Polymer Everolimus-Eluting Stent for Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention) was an investigator-initiated, multicenter, assessor-blind, randomized superiority trial using Bayesian methods. Patients with STEMI undergoing primary PCI within 24 h of symptom onset were randomized in a 1:1 ratio to receive BP-SES (n = 649) or DP-EES (n = 651). The primary endpoint was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial reinfarction, and clinically indicated target lesion revascularization (TLR) at 2 years. Results Between April 2016 and March 2018, 1,300 patients were included. Baseline characteristics were comparable between the 2 treatment groups. Follow-up through 2 years was complete in 1,221 patients (94%). At 2 years, TLF occurred in 33 patients (5.1%) treated with BP-SES and in 53 patients (8.1%) treated with DP-EES (rate ratio: 0.58; 95% Bayesian credible interval: 0.40 to 0.84; posterior probability of superiority = 0.998). The difference was driven by a lower incidence of clinically indicated TLR in patients treated with BP-SES compared with DP-EES (2.5% vs. 5.1%; rate ratio: 0.52; 95% Bayesian credible interval: 0.30 to 0.87; posterior probability of superiority = 0.993). There were no significant differences in rates of cardiac death, target vessel myocardial reinfarction, and definite stent thrombosis between the 2 treatment arms. Conclusions In patients with STEMI undergoing primary PCI, BP-SES were superior to DP-EES with respect to TLF at 2 years. The difference was driven by lower rates of ischemia-driven TLR. (A Comparison of an Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent With a Durable Polymer Everolimus-Eluting Stent for Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention [BIOSTEMI]; NCT02579031 )

Management of acute coronary syndromes in older adults

Abstract: Older patients are underrepresented in prospective studies and randomized clinical trials of acute coronary syndromes (ACS). Over the last decade, a few specific trials have been conducted in this population, allowing more evidence-based management. Older adults are a heterogeneous, complex, and high-risk group whose management requires a multidimensional clinical approach beyond coronary anatomic variables. This review focuses on available data informing evidence-based interventional and pharmacological approaches for older adults with ACS, including guideline-directed management. Overall, an invasive approach appears to demonstrate a better benefit-risk ratio compared to a conservative one across the ACS spectrum, even considering patients' clinical complexity and multiple comorbidities. Conversely, more powerful strategies of antithrombotic therapy for secondary prevention have been associated with increased bleeding events and no benefit in terms of mortality reduction. An interdisciplinary evaluation with geriatric assessment should always be considered to achieve a holistic approach and optimize any treatment on the basis of the underlying biological vulnerability.

Efficacy and Safety of Ticagrelor Monotherapy by Clinical Presentation: Pre-Specified Analysis of the GLOBAL LEADERS Trial.

Abstract: Background The optimal duration of dual antiplatelet therapy after coronary drug‐eluting stent placement in adults with stable coronary artery disease (SCAD) versus acute coronary syndromes (ACS) r...

Sex-Based Differences in Bleeding Risk After Percutaneous Coronary Intervention and Implications for the Academic Research Consortium High Bleeding Risk Criteria.

Abstract: Background Female sex was not included among the high bleeding risk (HBR) criteria by the Academic Research Consortium (ARC) as it remains unclear whether it constitutes an HBR condition after percutaneous coronary intervention. We investigated whether female sex associates with HBR and assessed the performance of ARC HBR criteria separately in women and men. Methods and Results Among all consecutive patients undergoing percutaneous coronary intervention between 2009 and 2018, bleeding occurrences up to 1 year were prospectively collected and centrally adjudicated. All but one of the originally defined ARC HBR criteria were assessed, and the ARC HBR score generated accordingly. Among 16 821 patients, 25.6% were women. Compared with men, women were older and had lower creatinine clearance and hemoglobin values. After adjustment, female sex was independently associated with access-site (adjusted hazard ratio, 2.14; 95% CI, 1.22-3.74; P=0.008) but not with overall or non-access-site 1-year Bleeding Academic Research Consortium 3 or 5 bleeding. This association remained consistent when the femoral but not the radial approach was chosen. The ARC HBR score discrimination, using the original criteria, was lower among women than men (c-index 0.644 versus 0.688; P=0.048), whereas a revised ARC HBR score, in which age, creatinine clearance, and hemoglobin were modeled as continuous rather than dichotomized variables, performed similarly in both sexes. Conclusions Female sex is an independent predictor for access-site bleeding but not for overall bleeding events at 1 year after percutaneous coronary intervention. The ARC HBR framework shows an overall good performance in both sexes, yet is lower in women than men, attributable to dichotomization of age, creatinine clearance, and hemoglobin values, which are differently distributed between sexes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02241291.

Antithrombotic Therapy after Percutaneous Coronary Intervention of Bifurcation Lesions

Abstract: Coronary bifurcations exhibit localized turbulent flow and enhanced propensity for platelet deposition, plaque rupture, and atherothrombosis. Percutaneous coronary intervention (PCI) of bifurcation lesions is associated with an increased risk of thrombotic events. Such risk is modulated by anatomical complexity, intraprocedural factors and pharmacological therapy. There is no consensus on the appropriate PCI strategy or the optimal regimen and duration of antithrombotic treatment in order to decrease the risk of ischemic and bleeding complications in the setting of coronary bifurcation. A uniform therapeutic approach meets a clinical need. The present initiative, promoted by the European Bifurcation Club (EBC), involves opinion leaders from Europe, America, and Asia with the aim to analyze the currently available evidence. Although mainly derived from sub-studies of large trials or small studies, or from authors' opinions, an algorithm for the optimal management of patients undergoing bifurcation PCI, developed on the basis of clinical presentation, bleeding risk, and intraprocedural strategy is here proposed.

Guided and unguided de-escalation from potent P2Y12 inhibitors among patients with ACS: a meta-analysis.

Abstract: Aim Optimal dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) intends to balance ischemic and bleeding risks. Various DAPT de-escalation strategies, defined as switching from a full-dose potent to a reduced dose or less potent P2Y12 inhibitor, have been evaluated in several ACS-PCI trials. We aimed to compare DAPT de-escalation to standard DAPT with full dose potent P2Y12 inhibitors in ACS patients who underwent PCI. Methods & results PubMed, Google Scholar and Cochrane Central Register of Controlled Trials were searched for eligible randomised controlled trials. Aspirin monotherapy trials were excluded. Five randomised trials (n = 10,779 patients) that assigned DAPT de-escalation (genetically guided to clopidogrel n = 1,242; platelet function guided to clopidogrel n = 1,304; unguided to clopidogrel n = 1,672; unguided to lower dose n = 1,170) versus standard DAPT (control group n = 5,391) were included in this analysis. DAPT de-escalation was associated with a significant reduction in Bleeding Academic Research Consortium ≥ 2 bleeding (HR 0.57, 95% CI 0.42-0.78; I2 = 77%) as well as major adverse cardiac events, represented in most trials by the composite of cardiovascular mortality, myocardial infarction, stent thrombosis and stroke (HR 0.77, 95% CI 0.62-0.96; I2 = 0%). Notwithstanding the limited power, consistency was noted across various de-escalation strategies. Conclusion De-escalation of DAPT after PCI for ACS, both unguided and guided by genetic or platelet function testing, was associated with lower rates of clinically relevant bleeding and ischemic events as compared to standard DAPT with potent P2Y12 inhibitors based on five open-label RCTs reviewed.

Clinical risk predictors in atrial fibrillation patients following successful coronary stenting: ENTRUST-AF PCI sub-analysis

Abstract: This subgroup analysis of the ENTRUST-AF PCI trial (ClinicalTrials.gov Identifier: NCT02866175; Date of registration: August 2016) evaluated type of AF, and CHA2DS2-VASc score parameters as predictors for clinical outcome. Patients were randomly assigned after percutaneous coronary intervention (PCI) to either edoxaban (60 mg/30 mg once daily [OD]; n = 751) plus a P2Y12 inhibitor for 12 months or a vitamin K antagonist [VKA] (n = 755) plus a P2Y12 inhibitor and aspirin (100 mg OD, for 1–12 months). The primary outcome was a composite of major/clinically relevant non-major bleeding (CRNM) within 12 months. The composite efficacy endpoint consisted of cardiovascular death, stroke, systemic embolic events, myocardial infarction (MI), and definite stent thrombosis. Major/CRNM bleeding event rates were 20.7%/year and 25.6%/year with edoxaban and warfarin, respectively (HR [95% CI]: 0.83 [0.654–1.047]). The event rates of composite outcome were 7.26%/year and 6.86%/year, respectively (HR [95% CI]): 1.06 [0.711–1.587]), and of overall net clinical benefit were 12.48%/year and 12.80%/year, respectively (HR [(95% CI]: 0.99 [(0.730; 1.343]). Increasing CHA2DS2-VASc score was associated with increased rates of all outcomes. CHA2DS2-VASc score ≥ 5 was a marker for stent thrombosis. Paroxysmal AF was associated with a higher occurrence of MI (4.87% versus 2.01%, p = 0.0024). After PCI in AF patients, increasing CHA2DS2-VASc score was associated with increased bleeding rates and CHA2DS2-VASc score (≥ 5) predicted the occurrence of stent thrombosis. Paroxysmal AF was associated with MI. These findings may have important clinical implications in AF patients.

Questions and answers on diagnosis and risk assessment: a companion document of the 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation

Abstract: Q1: You are a practicing cardiologist and receive a call from a 60-year-old patient with hypertension, diabetes mellitus and hypercholesterolemia as cardiovascular risk factors (CVRFs). His check-up 6 months earlier was unremarkable. He reports ongoing moderate to severe retrosternal chest pain with

Impact of Echocardiographic Guidance on Safety and Efficacy of Left Atrial Appendage Closure: An Observational Study

Abstract: Objectives The aim of this study was to evaluate the impact of echocardiographic guidance on the safety and efficacy of left atrial appendage closure (LAAC). Background Expert consensus documents recommend intraprocedural imaging by means of either transesophageal echocardiography or intracardiac echocardiography to guide LAAC. However, no evidence exists that intraprocedural echocardiographic guidance in addition to fluoroscopy improves the safety and efficacy of LAAC. Methods Consecutive LAAC procedures performed at a high-volume center between January 2009 and October 2020 were stratified on the basis of intraprocedural imaging modalities, including fluoroscopic guidance (FG) only or intraprocedural echocardiographic guidance (EG) in addition to fluoroscopy. The primary safety endpoint was the composite of procedure-related complications occurring within 7 days after the procedure. Technical success at 7 days and at follow-up were secondary endpoints. Results Among 811 LAAC procedures, 549 (67.7%) and 262 (32.3%) were assigned to the FG and EG groups, respectively. After adjusting for confounders, EG remained associated with a lower rate of the primary safety endpoint (3.4% vs 9.1%; P = 0.004; adjusted odds ratio [OR]: 0.31; 95% CI: 0.11-0.90; P = 0.030). Technical success trended higher at 7 days (92.1% vs 87.2%; P = 0.065; adjusted OR: 1.68; 95% CI: 0.95-3.01; P = 0.079) and was significantly improved with EG compared with FG (87.6% vs 79.9%; P = 0.018; OR: 4.06; 95% CI: 1.60-10.27; P = 0.003) after a median follow-up period of 4.9 months (interquartile range: 3.4 months-6.2 months). Conclusions In a large cohort of consecutive LAACs, the use of intraprocedural echocardiography to guide intervention in addition to standard fluoroscopy was associated with lower risks for procedural complications and higher mid-term technical success rates.

Comparing methods for estimating patient‐specific treatment effects in individual patient data meta‐analysis

Abstract: Meta-analysis of individual patient data (IPD) is increasingly used to synthesize data from multiple trials. IPD meta-analysis offers several advantages over meta-analyzing aggregate data, including the capacity to individualize treatment recommendations. Trials usually collect information on many patient characteristics. Some of these covariates may strongly interact with treatment (and thus be associated with treatment effect modification) while others may have little effect. It is currently unclear whether a systematic approach to the selection of treatment-covariate interactions in an IPD meta-analysis can lead to better estimates of patient-specific treatment effects. We aimed to answer this question by comparing in simulations the standard approach to IPD meta-analysis (no variable selection, all treatment-covariate interactions included in the model) with six alternative methods: stepwise regression, and five regression methods that perform shrinkage on treatment-covariate interactions, that is, least absolute shrinkage and selection operator (LASSO), ridge, adaptive LASSO, Bayesian LASSO, and stochastic search variable selection. Exploring a range of scenarios, we found that shrinkage methods performed well for both continuous and dichotomous outcomes, for a variety of settings. In most scenarios, these methods gave lower mean squared error of the patient-specific treatment effect as compared with the standard approach and stepwise regression. We illustrate the application of these methods in two datasets from cardiology and psychiatry. We recommend that future IPD meta-analysis that aim to estimate patient-specific treatment effects using multiple effect modifiers should use shrinkage methods, whereas stepwise regression should be avoided.