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BackgroundAntithrombotic treatment choices are complicated when patients have both atrial fibrillation (AF) and acute coronary syndrome and/or undergo percutaneous coronary intervention (PCI). In this study, we aimed to gain insight into antithrombotic management strategies in daily clinical practice.MethodsWe invited interventional cardiologists to complete the WOEST (What is the Optimal antiplatElet & Anticoagulant Therapy in Patients With Oral Anticoagulation and Coronary StenTing) survey 2018. In this questionnaire, we presented a patient with a non-ST-elevation myocardial infarction (NSTEMI) and an elective PCI case.ResultsThe results were based on 118 completed questionnaires (response rate 69.4%). In the case of the AF patient with NSTEMI, most cardiologists indicated they would initiate dual antiplatelet therapy (acetylsalicylic acid and clopidogrel) and continue non-vitamin K antagonist oral anticoagulant (NOAC) therapy at admission and during coronary angiography/PCI. At discharge, 70.3% would prescribe triple antithrombotic therapy (oral anticoagulation, acetylsalicylic acid and clopidogrel), mostly for 1 month. One year after NSTEMI, 83.1% would cancel the antiplatelet therapy and prescribe NOAC monotherapy. For the AF patient undergoing elective PCI, 51.7% would start dual antiplatelet therapy prior to the procedure and 52.5% would discontinue NOAC therapy prior to the PCI. At discharge, 55.1% would start triple antithrombotic therapy. Furthermore, 25.4% responded they routinely prescribe a reduced dose of NOAC after discharge. One year after PCI, 89.0% would continue NOAC monotherapy.ConclusionThe WOEST survey demonstrated heterogeneity in antithrombotic management strategies among interventional cardiologists. This observed variety mirrors the heterogeneity of the many guidelines and consensus documents. Further research is needed to guide patient-tailored medicine for AF patients undergoing PCI.

INTRODUCTION: The POPular Genetics trial demonstrated that a CYP2C19 genotype-guided P2Y12 inhibitor strategy reduced bleeding rates compared with standard treatment with ticagrelor or prasugrel without increasing thrombotic event rates after primary percutaneous coronary intervention (PCI).OBJECTIVE: In this analysis, we aimed to evaluate the cost effectiveness of a genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel.METHODS: A 1-year decision tree based on the POPular Genetics trial in combination with a lifelong Markov model was developed to compare costs and quality-adjusted life-years (QALYs) between a genotype-guided and a standard P2Y12 inhibitor strategy in patients with myocardial infarction undergoing primary PCI. The cost-effectiveness analysis was conducted from a Dutch healthcare system perspective. Within-trial survival and utility data were combined with lifetime projections to evaluate lifetime cost effectiveness for a cohort of 1000 patients. Costs and utilities were discounted at 4 and 1.5%, respectively, according to Dutch guidelines for health economic studies. Besides deterministic and probabilistic sensitivity analyses, several scenario analyses were also conducted (different time horizons, different discount rates, equal prices for P2Y12 inhibitors, and equal distribution of thrombotic events between the two strategies).RESULTS: Base-case analysis with a hypothetical cohort of 1000 subjects demonstrated 8.98 QALYs gained and €725,550.69 in cost savings for the genotype-guided strategy (dominant). The deterministic and probabilistic sensitivity analysis confirmed the robustness of the model and the cost-effectiveness results. In scenario analyses, the genotype-guided strategy remained dominant.CONCLUSION: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel resulted in QALYs gained and cost savings.TRIAL REGISTRATION: Clinicaltrials.gov number: NCT01761786, Netherlands trial register number: NL2872.

BACKGROUND Direct-acting oral anticoagulant use for stroke prevention in atrial fibrillation is limited by bleeding concerns. Asundexian, a novel, oral small molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal effect on haemostasis. We aimed to determine the optimal dose of asundexian and to compare the incidence of bleeding with that of apixaban in patients with atrial fibrillation. METHODS In this randomised, double-blind, phase 2 dose-finding study, we compared asundexian 20 mg or 50 mg once daily with apixaban 5 mg twice daily in patients aged 45 years or older with atrial fibrillation, a CHA2DS2-VASc score of at least 2 if male or at least 3 if female, and increased bleeding risk. The study was conducted at 93 sites in 14 countries, including 12 European countries, Canada, and Japan. Participants were randomly assigned (1:1:1) to a treatment group using an interactive web response system, with randomisation stratified by whether patients were receiving a direct-acting oral anticoagulant before the study start. Masking was achieved using a double-dummy design, with participants receiving both the assigned treatment and a placebo that resembled the non-assigned treatment. The primary endpoint was the composite of major or clinically relevant non-major bleeding according to International Society on Thrombosis and Haemostasis criteria, assessed in all patients who took at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT04218266, and EudraCT, 2019-002365-35. FINDINGS Between Jan 30, 2020, and June 21, 2021, 862 patients were enrolled. 755 patients were randomly assigned to treatment. Two patients (assigned to asundexian 20 mg) never took any study medication, resulting in 753 patients being included in the analysis (249 received asundexian 20 mg, 254 received asundexian 50 g, and 250 received apixaban). The mean age of participants was 73·7 years (SD 8·3), 309 (41%) were women, 216 (29%) had chronic kidney disease, and mean CHA2DS2-VASc score was 3·9 (1·3). Asundexian 20 mg resulted in 81% inhibition of FXIa activity at trough concentrations and 90% inhibition at peak concentrations; asundexian 50 mg resulted in 92% inhibition at trough concentrations and 94% inhibition at peak concentrations. Ratios of incidence proportions for the primary endpoint were 0·50 (90% CI 0·14-1·68) for asundexian 20 mg (three events), 0·16 (0·01-0·99) for asundexian 50 mg (one event), and 0·33 (0·09-0·97) for pooled asundexian (four events) versus apixaban (six events). The rate of any adverse event occurring was similar in the three treatment groups: 118 (47%) with asundexian 20 mg, 120 (47%) with asundexian 50 mg, and 122 (49%) with apixaban. INTERPRETATION The FXIa inhibitor asundexian at doses of 20 mg and 50 mg once daily resulted in lower rates of bleeding compared with standard dosing of apixaban, with near-complete in-vivo FXIa inhibition, in patients with atrial fibrillation. FUNDING Bayer.

BACKGROUND Nonadherence to antiplatelet therapy after percutaneous coronary intervention (PCI) is common, even in clinical trials. OBJECTIVES The purpose of this study was to investigate the impact of nonadherence to study protocol regimens in the MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen) trial. METHODS At 1-month after PCI, 4,579 high bleeding risk patients were randomized to single antiplatelet therapy (SAPT) for 11 months (or 5 months in patients on oral anticoagulation [OAC]) or dual antiplatelet therapy (DAPT) for ≥2 months followed by SAPT. Coprimary outcomes included net adverse clinical events (NACE), major adverse cardiac and cerebral events (MACE), and major or clinically relevant nonmajor bleeding (MCB) at 335 days. Inverse probability-of-censoring weights were used to correct for nonadherence Academic Research Consortium type 2 or 3. RESULTS In total, 464 (20.2%) patients in the abbreviated-treatment and 214 (9.4%) in the standard-treatment groups incurred nonadherence Academic Research Consortium type 2 or 3. At inverse probability-of-censoring weights analyses, NACE (HR: 1.01; 95% CI: 0.88-1.27) or MACE (HR: 1.07; 95% CI: 0.83-1.40) did not differ, and MCB was lower with abbreviated compared with standard treatment (HR: 0.51; 95% CI: 0.60-0.73) consistently across OAC subgroups; among OAC patients, SAPT discontinuation 6 months after PCI was associated with similar MACE and lower MCB (HR: 0.47; 95% CI: 0.22-0.99) compared with SAPT continuation. CONCLUSIONS In the MASTER DAPT adherent population, 1-month compared with ≥3-month DAPT was associated with similar NACE or MACE and lower MCB. Among OAC patients, SAPT discontinuation after 6 months was associated with similar MACE and lower MCB than SAPT continuation (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).

Background: Guidelines favor ticagrelor or prasugrel over clopidogrel in patients with myocardial infarction. However, the POPular Genetics trial (Patient Outcome After Primary Percutaneous Coronary Intervention [PCI]) showed that in patients with primary PCI, a CYP2C19 genotype–guided strategy was associated with a lower bleeding risk without increasing thrombotic risk, compared with routine ticagrelor/prasugrel treatment. Nevertheless, optimal P2Y 12 inhibitor treatment in specific CYP2C19 genetic subgroups is still a subject of debate. Methods: A prespecified subanalysis of the POPular Genetics trial was performed, using patients in whom CYP2C19 *2, *3, and *17 genotypes was determined. Two different analyses were planned. The first assessed the effect of the CYP2C19 *17 allele in clopidogrel-treated patients. The second compared the effect of clopidogrel in noncarriers of a loss-of-function allele with ticagrelor/prasugrel–treated patients, irrespective of CYP2C19 genotype. Main outcomes were a thrombotic outcome (cardiovascular death, myocardial infarction, stent thrombosis, and stroke) and a bleeding outcome (PLATO [Platelet Inhibition and Patient Outcomes] major and minor bleeding) after 12 months. Results: A total of 2429 patients were used for analyses. In the first analysis, the CYP2C19 *17 polymorphism was not found to have a significant influence on thrombotic (adjusted hazard ratio, 0.95 [95% CI, 0.45–2.02]) or bleeding outcomes (adjusted hazard ratio, 0.74 [95% CI, 0.48–1.18]). In the second analysis, clopidogrel was associated with a lower number of bleeding events compared with ticagrelor/prasugrel (9.9% versus 11.7%, adjusted hazard ratio, 0.74 [95% CI, 0.56–0.96]), without a significant increase in thrombotic events (3.4% versus 2.5%, adjusted hazard ratio, 1.14 [95% CI, 0.68–1.90]). Conclusions: In patients with primary PCI not carrying a CYP2C19 loss-of-function allele, the use of clopidogrel compared with ticagrelor or prasugrel was associated with lower bleeding rates, without an increase in thrombotic events. No effect on clinical outcomes was found for the CYP2C19 *17 polymorphism. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01761786. URL: https://www.trialregister.nl/ ; Unique identifier: NL2872.

Introduction: The POPular Genetics trial demonstrated that a genotype-guided strategy to select antiplatelet therapy in patients with ST-elevation myocardial infarction (STEMI) compared to universal treatment with ticagrelor or prasugrel, resulted in a reduction in bleedings without an increase in the thrombotic risk. The objective of this analysis was to assess the cost-effectiveness of the genotype-guided strategy. Methods: In the POPular Genetics trial, STEMI patients who underwent primary percutaneous coronary intervention were randomized to an intervention or a control arm. In the intervention arm CYP2C19 genetic testing for the *2 and *3 loss-of-function alleles took place. Carriers of a loss-of-function allele were treated with ticagrelor or prasugrel, while noncarriers were treated with clopidogrel. In the control arm patients were treated with ticagrelor or prasugrel. An alongside clinical-trial cost-effectiveness analysis was conducted based on a decision-model with 1000 patients in both groups. A hybrid model, consisting of a 1-year decision tree combined with a 25-years Markov model was developed, to estimate the life-time cost-effectiveness from a societal perspective. Outcome measures were costs, quality-adjusted life-years (QALYs) and incremental cost per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to account for the uncertainty around the key parameters. In an exploratory analysis the price for ticagrelor and prasugrel was the same as clopidogrel, to simulate the effect of generic ticagrelor and prasugrel in the future. Results: The genotype-guided strategy resulted in 26.87 QALY gained with cost-savings of є601,807 indicating that the genotype-guided strategy is a cost-saving intervention. The exploratory analysis - keeping the price of antithrombotic therapies at the same price level - resulted in cost-savings of є137,980. Deterministic and probabilistic sensitivity analyses confirmed the robustness of the base-case analysis. Conclusion: Based on the POPular Genetics trial, a genotype-guided strategy compared to universal ticagrelor or prasugrel treatment resulted in favorable cost-effectiveness with QALYs gained and cost-savings.

Only one-third of intermediate-grade coronary artery stenosis (i.e. 40–70% diameter narrowing) causes myocardial ischemia, requiring most often additional invasive work-up with invasive fractional flow reserve (FFR). To evaluate the correlations between FFR estimates derived from computed tomography (FFRCT) and adenosine perfusion cardiac magnetic resonance (CMR) with invasive FFR in intermediate-grade stenosis. Thirty-seven patients (mean age 61 ± 9 years; 25 men) who underwent adenosine perfusion CMR, quantitative coronary angiography and FFR in the work-up for intermediate-grade stenoses (n = 39) diagnosed at coronary CT angiography were retrospectively evaluated. Blinded FFRCT analysis was computed on each intermediate-grade lesion and correlated to the FFR values. On adenosine CMR, subendocardial time-enhancement maximal upslopes, normalized by respective left ventricle cavity upslopes, were obtained distal to a coronary stenosis (RISK area) and in remote myocardium (REMOTE area). The perfusion was subsequently assessed without (uncorrected RISK) and after correction for remote perfusion (relative myocardial perfusion index = REMOTE/RISK ratio), and then correlated to the FFR values. Differences in correlations were tested with z statistics and considered statistically significant different at a p

Background: Current guidelines recommend non–vitamin K antagonist oral anticoagulants (NOACs) as the first-choice therapy in patients with nonvalvular atrial fibrillation because these drugs have several benefits over the vitamin K antagonists (VKAs). It is unknown whether these benefits remain when NOACs have to be combined with aspirin therapy. To assess the efficacy and safety of NOACs compared with VKAs in patients with atrial fibrillation and concomitant aspirin therapy, we conducted a systematic review and study–based meta-analysis of published randomized controlled trials. Methods: A systematic electronic literature search was done in MEDLINE, EMBASE, and Cochrane CENTRAL Register of Controlled Trials for studies including published data of patients ≥18 years of age with nonvalvular atrial fibrillation, randomized to either VKAs or NOACs, or receiving aspirin therapy at any time during the study that report all-cause stroke or systemic embolism, vascular death, myocardial infarction, major bleeding, or intracranial hemorrhage as an outcome. Hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome were extracted from the individual studies and pooled with random-effects meta-analysis. Results: This study-based meta-analysis was restricted to the subgroups of patients on aspirin therapy (n=21 722) from 4 randomized controlled trials comparing VKAs and NOACs (n=71 681) in nonvalvular atrial fibrillation. In this meta-analysis including patients on mainly low-dose aspirin, NOACs were found to be more effective (outcome of stroke or systemic embolism: HR, 0.78; 95% CI, 0.67–0.91; vascular death: HR, 0.85; 95% CI, 0.76–0.93) and as safe as VKAs with respect to major bleeding (HR, 0.83; 95% CI, 0.69–1.01). NOACs were safer with respect to the reduction of intracranial hemorrhage (HR, 0.38; 95% CI, 0.26–0.56). Conclusions: This study-based meta-analysis shows that it may be both safer and more effective to use NOACs compared with VKAs to treat patients with nonvalvular atrial fibrillation and concomitant aspirin therapy.

Objectives: The aim of this study was to determine predictors of very late stent thrombosis (VLST; >1 year after stenting), and to evaluate whether addition of these predictors to the dual antiplatelet therapy (DAPT) score would improve the ability to identify patients at high risk of VLST who might benefit from DAPT. Background: VLST is a severe complication of percutaneous coronary intervention (PCI). Extended knowledge about the predictors of VLST is needed to prevent this life-threatening complication. Recent data showed a reduction in VLST after treatment with prolonged DAPT. The DAPT study developed a prediction score to identify patients after PCI who might benefit from prolonged DAPT duration. Methods: The Dutch stent thrombosis study is a multi-center case-control study. Consecutive patients with definite VLST were included between 2007 and 2014. Baseline characteristics from the index PCI were collected. Independent predictors of VLST were identified and added to the DAPT score to develop the VLST score. Results: In total, 155 VLST cases and 155 matched controls were included. Suboptimal result of stenting, right coronary artery as target vessel, and diffuse coronary artery ectasia were independent predictors of VLST, and added to the DAPT score. The power of the VLST score to identify patients who experienced VLST was increased (AUC, 95%CI; DAPT score: 0.64, 0.57-0.70; VLST score: 0.70, 0.63-0.76, P = 0.010). Conclusions: Addition of newly identified independent predictors of VLST resulted in a prediction model with a higher ability to identify patients at high risk of VLST who might benefit from prolonged DAPT.

International audience; Objective: Correcting the perfusion in areas distal to coronary stenosis (risk) according to that of normal (remote) areas defines the relative myocardial perfusion index, which is similar to the fractional flow reserve (FFR) concept. The aim of this study was to assess the value of relative myocardial perfusion by MRI in predicting lesion-specific inducible ischemia as defined by FFR.Materials and methods: Forty-six patients (33 men and 13 women; mean [± SD] age, 61 ± 9 years) who underwent adenosine perfusion MRI and FFR measurement distal to 49 coronary artery stenoses during coronary angiography were retrospectively evaluated. Subendocardial time-enhancement maximal upslopes, normalized by the respective left ventricle cavity upslopes, were obtained in risk and remote subendocardium during adenosine and rest MRI perfusion and were correlated to the FFR values.Results: The mean FFR value was 0.84 ± 0.09 (range, 0.60-0.98) and was less than or equal to 0.80 in 31% of stenoses (n = 15). The relative subendocardial perfusion index (risk-to-remote upslopes) during hyperemia showed better correlations with the FFR value (r = 0.59) than the uncorrected risk perfusion parameters (i.e., both the upslope during hyperemia and the perfusion reserve index [stress-to-rest upslopes]; r = 0.27 and 0.29, respectively). A cutoff value of 0.84 of the relative subendocardial perfusion index had an ROC AUC of 0.88 to predict stenosis at an FFR of less than or equal to 0.80.Conclusion: Using adenosine perfusion MRI, the relative myocardial perfusion index enabled the best prediction of FFR-defined lesion-specific myocardial ischemia. This index could be used to noninvasively determine the need for revascularization of known coronary stenoses.

Background: Patients with acute coronary syndrome (ACS) who are carrying CYP2C19 loss-of-function alleles derive less benefit from clopidogrel treatment. Despite this, in elderly patients, clopidogrel might be preferred over more potent P2Y12 inhibitors due to a lower bleeding risk. Whether CYP2C19 genotype-guided antiplatelet treatment in the elderly could be of benefit has not been studied specifically.Methods: Patients aged 70 years and older with known CYP2C19*2 and *3 genotype were identified from the POPular Genetics and POPular Age trials. Noncarriers of loss-of-function alleles treated with clopidogrel were compared to patients, irrespective of CYP2C19 genotype, treated with ticagrelor and to clopidogrel treated carriers of loss-of-function alleles. We assessed net clinical benefit (all-cause death, myocardial infarction, stroke and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding), atherothrombotic outcomes (cardiovascular & nbsp;death, myocardial infarction, stroke) and bleeding outcomes (PLATO major and minor bleeding).Results: A total of 991 patients were assessed. There was no significant difference in net clinical benefit (17.2% vs. 15.1%, adjusted hazard ratio (adjHR) 1.05, 95% confidence interval (CI) 0.77 & ndash;1.44), atherothrombotic outcomes (9.7% vs. 9.2%, adjHR 1.00, 95%CI 0.66 & ndash;1.50), and bleeding outcomes (17.7% vs. 19.8%, adjHR 0.80, 95%CI 0.62 & ndash;1.12) between clopidogrel in noncarriers of loss-of-function alleles and ticagrelor respectively.Conclusion: In ACS patients aged 70 years and older, there was no significant difference in net clinical benefit and atherothrombotic outcomes between noncarriers of a loss-of-function allele treated with clopidogrel and pa-tients treated with ticagrelor. The bleeding rate was numerically; though not statistically significant, lower in pa-tients using clopidogrel.(c) 2021 Published by Elsevier B.V.

The POPular Genetics trial demonstrated that a genotype-guided strategy benefits patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) compared to standard treatment with ticagrelor or prasugrel by reducing bleedings, without increasing

Background Biatrial, extensive, and complex ablation strategies have been published for the treatment of neurally mediated syncope, sinus node dysfunction, and functional atrioventricular block. We have developed a less extensive and more specific approach compared with previously published cardioneuroablation strategies, called cardio-neuromodulation. It is based on tailored vagolysis of the sinoatrial node through partial ablation of the anterior right-ganglionated plexus, preferentially through a right-sided approach. Methods Patients with syncope were enrolled between December 2016 and December 2017. They were assigned to group A if they had a positive head-up tilt test and to group B if they presented with a pause ≥3 seconds. The area to target during cardio-neuromodulation was designed offline on a computed tomographic scan. Slow heart rates and pauses were compared during 24-hour rhythm registration at baseline, at 1-month follow-up, and 6-month follow-up. Syncope burden was assessed before the procedure and at 3- and 6-month follow-up. Results Twenty patients underwent cardio-neuromodulation through a right-sided approach (12 in group A, 8 in group B). The first application of radiofrequency energy led to a P-P interval shortening >120 ms in all 20 patients. After a mean±SD ablation time of 7±4 minutes and mean ablated surface area of 11±6 mm 2 , the P-P interval shortened by 219±160 ms ( P P P Conclusions These data indicate that cardio-neuromodulation, through a right-sided and computed tomographic–guided procedure, is safe, fast, and highly reproducible in preventing inappropriate functional sinus bradycardia and syncope recurrence.

Aims We aimed to assess the safety and performance of a novel sirolimus-eluting stent with biodegradable polymer under real-world conditions. Methods and results This prospective, multicentre, observational, all-comers registry enrolled 1,356 patients. The primary endpoint was target lesion failure at 12 months: it occurred in 5.1% (95% CI: 4.0-6.4) of patients in the overall population and in 7.7% (95% CI: 5.5-10.9), 5.8% (95% CI: 4.2-8.1), 1.8% (95% CI: 0.2-11.8) and 7.2% (95% CI: 5.1-10.0) of patients with diabetes mellitus, small vessels, chronic total occlusion and acute myocardial infarction, respectively. Conclusions This novel stent platform demonstrated good clinical outcomes in an all-comers population, even in predefined high-risk groups. ClinialTrials.gov identifier: NCT01553526

Fractional flow reserve (FFR) during invasive coronary angiography has become an established tool for guiding treatment. However, only one-third of intermediate-grade coronary artery stenosis (ICAS) are hemodynamically significant and require coronary revascularization. Additionally, the severity of stenosis visually established by coronary computed tomography angiography (CCTA) does not reliably correlate with the functional severity. Therefore, additional angiographic morphologic descriptors affecting hemodynamic significance are required. To evaluate quantitative stenosis analysis and plaque descriptors by CCTA in predicting the hemodynamic significance of ICAS and to compare it with quantitative catheter coronary angiography (QCA). QCA was performed in 65 patients (mean age 63 ± 9 years; 47 men) with 76 ICAS (40-70%) on CCTA. Plaque descriptors were determined including circumferential extent of calcification, plaque composition, minimal lumen diameter (MLD) and area, diameter stenosis percentage (Ds %), area stenosis percentage and stenosis length on CCTA. MLD and Ds % were also analyzed on QCA. FFR was measured on 52 ICAS lesions on CCTA and QCA. The diagnostic values of the best CCTA and QCA descriptors were calculated for ICAS with FFR ≤ 0.80. Of the 76 ICAS on CCTA, 52 (68%) had a Ds % between 40 and 70% on QCA. Significant intertechnique correlations were found between CCTA and QCA for MLD and Ds % (p < 0.001). In 17 (33%) of the 52 ICAS lesions on QCA, FFR values were ≤ 0.80. Calcification circumference extent (p = 0.50) and plaque composition assessment (p = 0.59) did not correlate with the hemodynamic significance. Best predictors for FFR ≤ 0.80 stenosis were ≤ 1.35 mm MLD (82% sensitivity, 66% specificity), and ≤ 2.3 mm(²) minimal lumen area (88% sensitivity, 60% specificity) on CCTA, and ≤ 1.1 mm MLD (59% sensitivity, 77% specificity) on QCA. Quantitative CCTA and QCA poorly predict hemodynamic significance of ICAS, though CCTA seems to have a better sensitivity than QCA. In this range of stenoses, additional functional evaluation is required.

SummaryPatients exhibiting high on-clopidogrel platelet reactivity (HPR) are at an increased risk of atherothrombotic events following percutaneous coronary interventions (PCI). The use of concomitant medication which is metabolised by the hepatic cytochrome P450 system, such as phenprocoumon, is associated with HPR. We assessed the level of platelet reactivity on clopidogrel in patients who received concomitant treatment with acenocoumarol (another coumarin derivative). Patients scheduled for PCI were included in a prospective, single centre, observational registry. Patients who were adequately pre-treated with clopidogrel were eligible for this analysis, which included 1,582 patients, of whom 104 patients (6.6 %) received concomitant acenocoumarol treatment. Platelet reactivity, as measured with the VerifyNow P2Y12 assay and expressed in P2Y12 Reaction Units (PRU), was significantly higher in patients on concomitant acenocoumarol treatment (mean PRU 229 ± 88 vs 187 ± 95; p< 0.001). In patients with concomitant acenocoumarol use, the proportion of patients with HPR was higher, defined as PRU > 208 (57.7 % vs 41.1 %; p=0.001) and PRU236 (49.0 % vs 31.4 %; p< 0.001). In multivariable analysis, concomitant acenocoumarol use was independently associated with a higher PRU and the occurrence of HPR defined as PRU236 (OR 2.00, [1.07–3.79]), but not with HPR defined as PRU > 208 (OR 1.37, [0.74–2.54]). PRU also was significantly increased after 1:1 propensity matching (+28.2; p< 0.001). As this was an observational study, confounding by indication cannot be excluded, although multivariable analyses and propensity matching were performed. The impact of the findings from this hypothesis-generating study on clinical outcome requires further investigation.

Item does not contain fulltext AIMS: To investigate the optimal periprocedural antithrombotic strategy in patients on long-term oral anticoagulation (OAC) who require percutaneous coronary intervention with stenting. METHODS AND RESULTS: The WOEST study was a randomised controlled trial which recruited 573 patients on long-term OAC who underwent PCI. The periprocedural treatment strategy was left to the operator's discretion. To assess the safety and feasibility of uninterrupted oral anticoagulation (UAC) and bridging therapy (BT), bleeding complications and MACCE were assessed in patients treated according to UAC (n=241) and BT (n=322) regimen. After 30 days, as well as after one year, there were no significant differences in bleeding complications (HR 1.14, 95% CI: 0.77-1.69, p=0.51, and HR 1.26, 95% CI: 0.94-1.69, p=0.12, respectively) and MACCE. MACCE tended to be less frequent in the UAC group (respectively HR 0.48, 95% CI: 0.15-1.51, p=0.21, and HR 0.72, 95% CI: 0.46-1.14, p=0.16). Additionally, adjustment with a propensity score revealed no significant differences. Periprocedural INR was not associated with bleeding or MACCE. CONCLUSIONS: In the WOEST study, UAC was not associated with an increase of bleeding or MACCE compared to bridging therapy. This is the largest study up to now to support the current guidelines. The WOEST trial is registered with ClinicalTrials.gov, number NCT00769938.

Chronic oral anticoagulant therapy is recommended (class I) in patients with mechanical heart valves and in patients with atrial fibrillation with a CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or transient ischemic attack or thromboembolism, Vascular disease, Age 65 to 74 years, Sex category) score ≥1. When these patients undergo percutaneous coronary intervention with stenting, treatment with aspirin and a P2Y12 receptor inhibitor also becomes indicated. Before 2014, guidelines recommended the use of triple therapy (vitamin K antagonists, aspirin, and clopidogrel) for these patients. However, major bleeding is increasingly recognized as the Achilles’ heel of the triple therapy regimen. Lately, various studies have investigated this topic, including a prospective randomized trial, and the evidence for adding aspirin to the regimen of vitamin K antagonists and clopidogrel seems to be weakened. In this group of patients, the challenge is finding the optimal equilibrium to prevent thromboembolic events, such as stent thrombosis and thromboembolic stroke, without increasing bleeding risk.

PURPOSE OF REVIEW The optimal antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) is still debated. This review is an update of a previous review and aims to summarize new published data regarding the management of this group of atrial fibrillation patients. RECENT FINDINGS Recent data report an underuse of oral anticoagulation in patients with atrial fibrillation undergoing PCI while indicated. However, tools for risk assessment and thus better guidance for decision-making are lacking, especially for elderly atrial fibrillation patients. New evidence suggests that the combination of oral anticoagulation and clopidogrel without aspirin may improve clinical outcomes in comparison with triple therapy; however, there is little data regarding the role of non-vitamin K oral anticoagulants and newer P2Y12 inhibitors in these regimens. SUMMARY Despite accumulating data on the assessment of bleeding and thrombotic risk, the management of elderly atrial fibrillation patients, new treatment regimens, and the role of more potent antithrombotic agents, the optimal antithrombotic therapy for patients with atrial fibrillation after PCI is still unclear. In the meantime, careful assessment of both thrombotic and bleeding risk and individualized decision-making are paramount to ensure the best patient outcomes.

We thank Drs. Capodanno and Lip for their interest in and valuable comments on our recent review [(1)][1] on triple therapy for atrial fibrillation (AF) and percutaneous coronary intervention (PCI). The conclusion of our review was that it might be a reasonable option to treat with a combination of

Contains fulltext : 89856.pdf (Publisher’s version ) (Closed access) Chronic oral anticoagulant treatment is obligatory in patients (class I) with mechanical heart valves and in patients with atrial fibrillation with CHADS2 score >1. When these patients undergo percutaneous coronary intervention with placement of a stent, there is also an indication for treatment with aspirin and clopidogrel. Unfortunately, triple therapy is known to increase the bleeding risk. For this group of patients, the bottom line is to find the ideal therapy in patients with indications for both chronic anticoagulation therapy and percutaneous intervention to prevent thromboembolic complications such as stent thrombosis without increasing the risk of bleeding. (Neth Heart J 2010;18:444-50.). 01 september 2010

Background Long-term oral anticoagulant treatment is obligatory in patients (class I) with mechanical heart valves and most patients with atrial fibrillation. When these patients undergo percutaneous coronary intervention with stenting, there is also an indication for treatment with aspirin and clopidogrel. However, triple therapy is known to increase the risk of bleeding complications. Unfortunately, there are no prospective data available to resolve this issue. Nevertheless, it all comes down to finding the ideal therapy in patients with indications of both chronic anticoagulation therapy and percutaneous intervention to prevent thrombotic complications (eg, stent thrombosis) without increasing the risk of bleeding. Objectives This prospective randomized multicenter study will assess the hypothesis that after percutaneous coronary intervention with stent implantation in patients on oral anticoagulant therapy, the combination of oral anticoagulation therapy and clopidogrel 75 mg/d reduces the risk of bleeding and is not inferior to triple therapy treatment with respect to the prevention of thrombotic complications. Design Multicenter, international, open-label randomized trial evaluating triple therapy (clopidogrel + oral anticoagulants + aspirin) in patients with an indication for oral anticoagulants who undergo coronary stenting versus the combination of oral anticoagulants and clopidogrel. The primary outcome is the combination of TIMI and GUSTO minor and major bleeding up to 30 days and 1 year. The secondary outcomes are major adverse cardiac events. The sample size is 496. Conclusions No prospective randomized study has yet addressed the issue of optimal antiplatelet therapy in patients with chronic oral anticoagulant therapy undergoing coronary stenting. Therefore, the WOEST trial will help to define new guidelines for patients with indication for chronic anticoagulation who need coronary stenting.

Background — Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is associated with sudden death in the young and heart failure in the elderly. The purpose is to review 15 symptomatic ARVD/C cases and also to describe the use of MRI as a diagnostic tool.Methods and results — This retrospective analysis includes 15 patients who presented with symptomatic ARVD/C. Diagnosis was made upon the criteria proposed by the European Society of Cardiology.In all patients there was at least 1 or more abnormal MRI sign.The most frequent abnormalities were focal right ventricular dyskinesia (64%), MRI fatty infiltration (57%) and right ventricular aneurysm or right ventricular outflow tract microaneurysms (57%).Presenting symptoms were palpitations (60%), atypical chest pain (46%), syncope (40%), and aborted sudden death (26%).T-inversion in V2-V3 was seen in 60% of the patients. Thirteen patients (86%) received an ICD implantation. The mean follow-up per patient was 89 months, which resulted in a total f...

Purpose of review Patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) require treatment with oral anticoagulation (OAC) and additional dual antiplatelet therapy with aspirin and clopidogrel (DAPT), i.e. triple therapy. However, triple therapy produces a high annual bleeding risk outweighing the benefits. To improve safety of antithrombotic treatment in these patients, the risks and benefits of all possible treatment options should be evaluated. This review provides an overview of current guidelines and new evidence for optimizing treatment of atrial fibrillation patients with an indication for combined treatment with OAC and DAPT. Recent findings To reduce bleeding risks during PCI, new evidence suggests that uninterrupted anticoagulation, radial access and the use of newer-generation drug eluting stent (DES) should be preferred. The use of glycoprotein receptor inhibitors should be avoided. After PCI, omitting aspirin seems to result in less bleeding compared with triple therapy, and the use of proton pump inhibitors further reduces bleeding risk. Summary These new strategies seem to further improve the safety of antithrombotic treatment in patients with atrial fibrillation undergoing PCI.

An 87 year old woman was referred because of suspected atrial fibrillation. Past history includes nefrectomy due to malignancy 4 years earlier and recurrent diverticultis. Home Treatment consisted of telmisartan/ hydrochlorothiade, aspirin, spironolactone and butenamide. The patient was referred after disopyramide was administered because of irregular pulse with no effect. On admission patient was dyspnoeic at rest (NYHA IV). Clinical investigation revealed an irregular pulse, bilateral basal crackles and severe peripheral pitting oedema. ECG showed an undetermined rhythm with left bundle branch

The optimal antiaggregant therapy after coronary stenting in patients receiving oral anticoagulants (OACs) is currently debated. MEDLINE and Cochrane Library were searched for studies reporting outcomes of patients who underwent PCI and who were on triple therapy (TT) or dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel or dual therapy (DT) with OAC and clopidogrel. Major bleeding was the primary end point, whereas all-cause death, myocardial infarction (MI), stent thrombosis, and stroke were secondary ones. Results were reported for all studies and separately for those deriving from randomized controlled trials or multivariate analysis. In 9 studies, 1,317 patients were treated with DAPT and 1,547 with TT. DAPT offered a significant reduction of major bleeding at 1 year for overall studies and for the subset of observational works providing adjusted data (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.39 to 0.68, I 2 60% and OR 0.36, 95% CI 0.28 to 0.46) compared to TT. No increased risk of major adverse cardiac events (MACE: death, MI, stroke, and stent thrombosis) was reported (OR 0.71, 95% CI 0.46 to 1.08), although not deriving from randomized controlled trials or multivariate analysis. Six studies tested OAC and clopidogrel (1,263 patients) versus OAC, aspirin, and clopidogrel (3,055 patients) with a significant reduction of bleeding (OR 0.79, 95% CI 0.64 to 0.98), without affecting rates of death, MI, stroke, and stent thrombosis (OR 0.90, 95% CI 0.69 to 1.23) also when including clinical data from randomized controlled trials or multivariate analysis. In conclusion, compared to TT, both aspirin and clopidogrel and clopidogrel and OAC reduce bleeding. No difference in major adverse cardiac events is present for clopidogrel and OAC, whereas only low-grade evidence is present for aspirin and clopidogrel.

A commonly encountered scenario is the patient with atrial fibrillation (AF) on oral anticoagulation (OAC) who either develops an acute coronary syndrome or has to undergo percutaneous coronary intervention with stent placement. In such patients, separate indications suggest combining OAC and dual antiplatelet therapy (DAPT). This approach, however, increases the risk of bleeding as well as thromboembolic risk if bleeding does not occur. For optimal clinical results, the risks and benefits of all possible treatment options should be determined based on the best available data. This review provides an overview of the most recent data regarding the optimal treatment of AF patients with an indication for combined treatment with OAC and DAPT.

Purpose of review The optimal antithrombotic therapy in patients with atrial fibrillation and coronary artery disease is controversial. The benefit of the combination of antithrombotic therapies remains debatable, and, as the bleeding risk is substantial, this calls for knowledge of the duration, and which and how many agents should be used. Recent findings The first randomized trial to challenge current recommendations of triple therapy (oral anticoagulation plus clopidogrel plus aspirin) examined patients on warfarin undergoing percutaneous coronary intervention with stent implantation. A reduced risk of any bleeding (hazard ratio 0.36) was found with combination of clopidogrel compared with triple therapy without increasing major cardiovascular events. In real-life patients, a nationwide Danish registry supported these findings, and, relative to triple therapy, no significant difference was found for recurrent myocardial infarction when adding only clopidogrel (hazard ratio 0.69) or aspirin (hazard ratio 0.96) to vitamin K antagonist. However, the latter regimen was associated with significantly increased risk of death. Summary Within 1 year after myocardial infarction and/or percutaneous coronary intervention in patients with atrial fibrillation, current consensus papers endorse use of dual antiplatelet therapy on top of oral anticoagulation. A regimen consisting of oral anticoagulation and clopidogrel (without aspirin) could provide an alternative from a benefit and safety perspective.

Patients with essential thrombocythemia (ET) are at increased risk of developing arterial thrombosis. We report a case of a 36-year-man with unstable angina in the presence of occlusion of two coronary arteries with insufficient collateral perfusion. We also found essential thrombocythemia in this patient. The patient underwent coronary artery bypass grafting (CABG). Ten days before surgery, the aspirin was replaced by a prophylactic dose of low-molecular-weight heparin. Postoperative follow-up was complicated by pulmonary embolisms and a cardiac tamponade. We conclude that ET is a risk factor for coronary heart disease that should be treated with aspirin. If a patient needs CABG, aspirin should be continued because of the high risk of thromboembolic events in the high-risk ET patients. (Neth Heart J 2010;18:378-80.).

Karjalainen PP, Porela P, Ylitalo A et al.: Safety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting. Eur. Heart J. 28(6), 726–732 (2007). Chronic oral antithrombotic treatment is necessary in patients with mechanical heart valves and in the majority of patients with atrial fibrillation. Many of these patients also have ischemic heart disease. When these patients are required to undergo percutaneous coronary intervention with stenting, there is also an indication for treatment with aspirin and clopidogrel. However, triple therapy is known to augment the risk for bleeding complications. It is therefore unknown what the best antithrombotic treatment is, when considering both thrombotic (e.g., stent thrombosis) and bleeding complications. Unfortunately, no prospective (randomized) data are available to solve this issue.

Dewilde, Willem J M Verheugt, Freek W A Ten Berg, Jurrien M Comment Letter England Lancet. 2013 Jul 6;382(9886):25. doi: 10.1016/S0140-6736(13)61522-6.

To evaluate the current management, and adherence to recommendations, of patients on oral anticoagulation (OAC) undergoing coronary stent implantation (PCI-S).By means of a contact person who had been previously identified in 8 European countries, a questionnaire was electronically forwarded between April and July 2010 to the national institutions where PCI-S is performed.A total of 202 questionnaires (median response rate: 50%, range 33-78%) was received. The prevalence of OAC patients among those undergoing PCI-S is mostly reported 5-10% (97%). The peri-procedural pharmacological management mostly encompasses: preprocedural OAC interruption and bridging with low-molecular-weight heparin (59%), intraprocedural administration of an unfractionated heparin bolus (81%), and use of glycoprotein IIb/IIIa inhibitors on an individual basis (79%). The radial approach is reported as the preferred option (58%), as well as the implantation of bare metal stents (76%). Triple therapy (warfarin, aspirin, clopidogrel) is the most frequently prescribed (80%), generally for 1 month after bare metal stent (77%) and for at least 12 months after drug-eluting stent (60%). Throughout triple therapy, the International Normalized Ratio is mostly targeted to the lower end of the therapeutic range (77%), and gastric protection is routinely prescribed (69%), mostly by giving proton-pump inhibitors (70%).Among the 202 interventional cardiologists from the 8 European countries interviewed, the management of patients on OAC undergoing PCI-S appears variable and only partially adherent to currently available recommendations.

To the editor: We read the article by Schomig et al 1 with great interest. We learnt when and how doctors should prescribe triple antithrombotic therapy after stent implantation. Schomig states that further prospective clinical trials are needed in order to evaluate the best treatment strategy for patients receiving oral anticoagulation (OAC) who undergo percutaneous coronary interventions (PCI). Unfortunately, all present …

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is associated with sudden death in the young and heart failure in the elderly. The purpose is to review 15 symptomatic ARVD/C cases and also to describe the use of MRI as a diagnostic tool.This retrospective analysis includes 15 patients who presented with symptomatic ARVD/C. Diagnosis was made upon the criteria proposed by the European Society of Cardiology. In all patients there was at least 1 or more abnormal MRI sign. The most frequent abnormalities were focal right ventricular dyskinesia (64%), MRI fatty infiltration (57%) and right ventricular aneurysm or right ventricular outflow tract microaneurysms (57%). Presenting symptoms were palpitations (60%), atypical chest pain (46%), syncope (40%), and aborted sudden death (26%). T-inversion in V2-V3 was seen in 60% of the patients. Thirteen patients (86%) received an ICD implantation. The mean follow-up per patient was 89 months, which resulted in a total follow-up of 111 patient years. Forty-six percent of the patients with an ICD had one or more appropriate shocks during follow-up. To this date no mortality was reported.This retrospective study demonstrates that symptomatic ARVD/C patients typically present with symptoms of syncope, palpitations in association with ventricular tachycardia and in a quarter of the cases with aborted sudden cardiac death. The electrocardiogram mostly shows T inversion in the anterior leads. All patients were treated with medication and ICD-implantation or VT-ablation. The malignant nature of the disease in symptomatic ARVD/C patients is stressed by the fact that the presenting symptom is aborted sudden death in a quarter of the cases and the fact that nearly half of the patients with an ICD had at least one appropriate shock during follow-up. There was an abnormal MRI in 100% of the investigated patients. In 20% (3 patients), the MRI criterion (right ventricular dilatation/bulging/aneurysm) was necessary to meet the ESC criteria. Therefore it has become an important tool in our diagnostic work-up when ARVD/C is suspected. We also suggest a change in the diagnostic criteria of ARVD/C. Whereas fatty infiltration seen on RV biopsy is a major criterion, MRI fatty infiltration is not regarded as a diagnostic criterion by the task force to this day.

We report a case of a 78-year old man presenting with a pseudo aneurysm of a valve conduit in the ascending aorta 6 weeks after Bentall (Shiley conduit 25) operation because of aortic stenosis and aneurysmatic aorta. Further medical history includes hypertension, left ventricular hypertrophy, diabetes and chronic obstructive pulmonary disease. The patient presented with acute dyspnoea at rest and was unresponsive to furosemide treatment. Clinical investigation revealed blood pressure 96/46, a regular pulse 107 and saturation 90%. There were bilateral basal crackles and peripheral edema. A new systolic murmur 3/6 was heard on the left parasternal side. Electrocardiogram showed a left bundle branch block and serology revealed maximal creatine kinase level of 995 U/L. After admission there was anuria with a creatinine level of 341 μmol/L (normal 62–106). A transthoracic echocardiography showed a large pseudo aneurysm at the origin of the conduit. A massive paravalvular

Compression of superior vena cava, oesophagus and bronchus is well known, but atrial compression, especially left sided, in combination with right pulmonary vein compression is very rare. We report an unusual case in a Marfan patient of extrinsic biatrial and pulmonary vein compression caused by a descending thoracic aneurysm.

A 58-year old woman was referred because of progressive heart failure since three weeks. Because of peripheral oedema and the presence of a diastolic murmur an echocardiography is performed showing a mitral stenosis and the presence of a thrombus in the left atrium. We present 3-D Computed Tomography (CT) images that show the massive extent of the left atrial thrombus only sparing the ostia of the pulmonary veins. A clue for diagnosis for mitral stenosis is the presence of an rumbling mid-diastolic murmur.

Diagnostic image: An 80-year-old man is referred because of an acute posterior infarction. Because of persisting pain and apparition of a new murmur, an echocardiography is performed showing inferoposterolateral akinesis complicated by ventricular wall pseudoaneurysm. After discussing with patient and family, conservative therapy was continued. A clue for diagnosis of pseudoaneurysm is the presence of a systolic murmur.

Background The optimal antithrombotic regimen in patients with a concomitant indication for oral anticoagulation (OAT) presenting with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) remains unclear. Objectives To perform a network meta-analysis of all randomized controlled trials (RCTs) evaluating different antithrombotic regimens among patients with ACS or undergoing PCI requiring OAT. Methods Network meta-analysis was performed in a frequentist framework. Antithrombotic regimens were categorized by OAC type (vitamin K antagonist-based [VKA]; non-VKA OAT [NOAC]) and antiplatelet agents (P2Y inhibitor only: dual therapy [DAT]; P2Y plus aspirin: triple therapy [TAT]). Safety outcomes were Thrombolysis in Myocardial Infarction (TIMI) major bleeding and intracranial hemorrhage (ICH). Efficacy outcomes were cardiovascular death, myocardial infarction, stroke and stent-thrombosis (ST). Results Five RCTs were included, encompassing 10,797 patients (atrial fibrillation 69-100%, ACS 28-62%, PCI 77-100%). Both VKA and NOAC-based DAT regimens reduced the occurrence of TIMI major bleeding compared to VKA TAT (VKA DAT: RR 0.62, 95% CI 0.39-0.98; NOAC DAT: RR 0.52, 95% CI 0.39-0.70). Nevertheless, only NOAC DAT significantly reduced the occurrence of ICH compared to VKA TAT (RR 0.33, 95% CI 0.17-0.64). Ischemic outcomes were similar among the four treatment regimens. However, numerical, potentially clinically important, higher ST occurrence was observed for NOAC DAT as compared to both VKA TAT (1.50, 95% confidence interval [CI] 0.96-2.33) and NOAC TAT (1.86, 95% CI 0.93-3.73). Conclusion DAT regimens present the highest safety profile among antithrombotic strategies, with a NOAC-specific impact on ICH reduction. NOAC DAT might entail clinically important higher ST occurrence, warranting a case-by-case comprehensive evaluation that integrates patient- and procedure-related residual ischemic risk with the patient-specific bleeding risk.