Bleeding and thrombotic risk of different antiplatelet regimens posttranscatheter edge-to-edge mitral valve repair in patients with an indication for oral anticoagulation: Results from an all-comers national registry.

BACKGROUND: Evidence-based recommendations for antithrombotic treatment in patients who have an indication for oral anticoagulation (OAC) after transcatheter edge-to-edge mitral valve repair (TEER) are lacking. AIMS: To compare bleeding and thrombotic risk for different antithrombotic regimens post-TEER with MitraClip in an unselected population with the need for OACs. METHODS: Bleeding and thrombotic complications (stroke and myocardial infarction) up to 3 months after TEER with mitraclip were evaluated in 322 consecutive pts with an indication for OACs. These endpoints were defined by the Mitral Valve Academic Research Consortium criteria and were compared between two antithrombotic regimens: single antithrombotic therapy with OAC (single ATT) and double/triple ATT with a combination of OAC and aspirin and/or clopidogrel (combined ATT). RESULTS: Collectively, 108 (34%) patients received single ATT, 203 (63%) received double ATT and 11 (3%) received triple ATT. Bleeding events occurred in 67 patients (20.9%), with access site related events being the most frequent cause (37%). Bleeding complications were observed more frequently in the combined ATT group than in the single ATT group: 24% versus 14% [p = 0.03, adjusted RR: 0.55 (0.3-0.98)]. Within the combined group, the bleeding risk was 23% in the double ATT and 45% in the triple ATT group. Thrombotic complications occurred in only three patients (0.9%), and all belonged to the combined ATT group. CONCLUSIONS: In patients with an indication for OACs, withholding of antiplatelet therapy post-TEER with Mitraclip was associated with a 45% reduction in bleeding and without a signal of increased thrombotic risk.

Less bleeding by omitting aspirin in non-ST-segment elevation acute coronary syndrome patients: Rationale and design of the LEGACY study.

BACKGROUND: Early aspirin withdrawal, also known as P2Y12-inhibitor monotherapy, following percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can reduce bleeding without a trade-off in efficacy. Still the average daily bleeding risk is highest during the first months and it remains unclear if aspirin can be omitted immediately following PCI. METHODS: The LEGACY study is an open-label, multicenter randomized controlled trial evaluating the safety and efficacy of immediate P2Y12-inhibitor monotherapy versus dual antiplatelet therapy (DAPT) for 12 months in 3,090 patients. Patients are randomized immediately following successful PCI for NSTE-ACS to 75-100 mg aspirin once daily versus no aspirin. The primary hypothesis is that immediately omitting aspirin is superior to DAPT with respect to major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, while maintaining noninferiority for the composite of all-cause mortality, myocardial infarction and stroke compared to DAPT. CONCLUSIONS: The LEGACY study is the first randomized study that is specifically designed to evaluate the impact of immediately omitting aspirin, and thus treating patients with P2Y12-inhibitor monotherapy, as compared to DAPT for 12 months on bleeding and ischemic events within 12 months following PCI for NSTE-ACS.

A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI.

BACKGROUND: It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors. METHODS: We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome). RESULTS: For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04). CONCLUSIONS: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.).

Antithrombotic strategies in patients needing oral anticoagulation undergoing percutaneous coronary intervention: A network meta-analysis.

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.

Efficacy and Safety of the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation and Concomitant Aspirin Therapy: A Meta-Analysis of Randomized Trials.

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.

Value of Relative Myocardial Perfusion at MRI for Fractional Flow Reserve-Defined Ischemia: A Pilot Study.

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.

A clinical risk score to identify patients at high risk of very late stent thrombosis.

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.

Optimal antithrombotic treatment in patients with atrial fibrillation and coronary stents: an update.

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.

Triple therapy for atrial fibrillation and percutaneous coronary intervention.

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.

Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial.

BACKGROUND: If percutaneous coronary intervention (PCI) is required in patients taking oral anticoagulants, antiplatelet therapy with aspirin and clopidogrel is indicated, but such triple therapy increases the risk of serious bleeding. We investigated the safety and efficacy of clopidogrel alone compared with clopidogrel plus aspirin. METHODS: We did an open-label, multicentre, randomised, controlled trial in 15 centres in Belgium and the Netherlands. From November, 2008, to November, 2011, adults receiving oral anticoagulants and undergoing PCI were assigned clopidogrel alone (double therapy) or clopidogrel plus aspirin (triple therapy). The primary outcome was any bleeding episode within 1 year of PCI, assessed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769938. FINDINGS: 573 patients were enrolled and 1-year data were available for 279 (98·2%) patients assigned double therapy and 284 (98·3%) assigned triple therapy. Mean ages were 70·3 (SD 7·0) years and 69·5 (8·0) years, respectively. Bleeding episodes were seen in 54 (19·4%) patients receiving double therapy and in 126 (44·4%) receiving triple therapy (hazard ratio [HR] 0·36, 95% CI 0·26-0·50, p<0·0001). In the double-therapy group, six (2·2%) patients had multiple bleeding events, compared with 34 (12·0%) in the triple-therapy group. 11 (3·9%) patients receiving double therapy required at least one blood transfusion, compared with 27 (9·5%) patients in the triple-therapy group (odds ratio from Kaplan-Meier curve 0·39, 95% CI 0·17-0·84, p=0·011). INTERPRETATION: Use of clopiogrel without aspirin was associated with a significant reduction in bleeding complications and no increase in the rate of thrombotic events. FUNDING: Antonius Ziekenhuis Foundation, Strect Foundation.

CYP2C19 genotype-guided antiplatelet therapy in ST-segment elevation myocardial infarction patients-Rationale and design of the Patient Outcome after primary PCI (POPular) Genetics study.

RATIONALE: In patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (pPCI), the use of dual antiplatelet therapy is essential to prevent atherothrombotic complications. Therefore, patients are treated with acetylsalicylic acid and clopidogrel, prasugrel, or ticagrelor. Clopidogrel, however, shows a major interindividual variation in antiplatelet effect, which is correlated to an increase in atherothrombotic events in patients with high platelet reactivity. This interindividual variation is partly a result of CYP2C19 genetic variants. Ticagrelor and prasugrel reduce atherothrombotic events but increase bleeding rate and drug costs, as compared with clopidogrel. CYP2C19-based tailoring of antiplatelet therapy might be beneficial to STEMI patients. STUDY DESIGN: POPular Genetics (NCT01761786) is a randomized, open-label, multicenter trial involving 2,700 STEMI patients who undergo pPCI. Patients are randomized to CYP2C19 genotyping or routine ticagrelor or prasugrel treatment. In the genotyping group, *1/*1 (wild-type) patients receive clopidogrel, and patients carrying 1 or 2 *2 or *3 loss-of-function alleles receive ticagrelor or prasugrel. The primary net clinical benefit end point is the composite of death, (recurrent) myocardial infarction, definite stent thrombosis, stroke, and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding at 1 year. Primary safety end point is the composite of (PLATO) major and minor bleeding. Cost-effectiveness and quality of life will be assessed by calculating quality-adjusted life-years, net costs per life-year, and per quality-adjusted life-year gained. CONCLUSION: The POPular Genetics study is the first large-scale trial comparing CYP2C19 genotype-guided antiplatelet therapy to a nontailored strategy in terms of net clinical benefit, safety, and cost-effectiveness.

Atrial fibrillation and coronary artery disease: which antithrombotic treatment strategy?

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.

Impact of the number of modifiable risk factors on clinical outcomes after percutaneous coronary intervention: An analysis from the e-Ultimaster registry.

Aims: A substantial proportion of the patients undergoing percutaneous coronary intervention (PCI) have none of the of standard modifiable cardiovascular risk factors (SMuRFs): hypertension, diabetes, hypercholesterolaemia and smoking. The aim of this analysis was to compare clinical outcomes after PCI according to the number of SMuRFs. Methods: Patients with an indication for a PCI were stratified based upon the number of SMuRFs: 0, 1, 2 or 3-4. The primary outcome was target lesion failure (TLF), a composite of cardiac death, target vessel-related myocardial infarction or clinically driven target lesion revascularization at 1-year. Inverse weighted propensity score (IWPS) adjustment was performed to adjust for differences in baseline characteristics. Results: The prevalence of SMuRFs was: 0 SMuRF 16.4 %; 1 SMuRF 27.8 %; 2 SMuRFs 34.7 % and 3-4 SMuRFs 21.1 %. Patients without SMuRFs were younger, more likely to be male and had less complex coronary artery disease. The incidence of TLF increased with the number of SMuRFs: 2.65 %, 2.75 %, 3.23 %, and 4.24 %, Ptrend < 0.001. The relative risk (RR) for a TLF was 60 % higher (95 % confidence interval 1.32-1.93, p < 0.01) for patients with 3-4 SMuRFs compared to patients without SMuRFs. The trend remained (Ptrend < 0.01) after IWPS with TLF rates of 2.88 %, 2.64 %, 2.88 % and 3.65 %. The RR for a TLF was 27 % higher (95 % CI 1.05-1.53, p < 0.01). Conclusion: The incidence of clinical events at 1-year increased with the number of SMuRFs. While patients without SMuRFs have a relatively favourable risk profile, more research is needed to optimize therapeutic management in the majority of patients.

Complete versus incomplete revascularization in patients with a non-ST-elevation myocardial infarction: Analysis from the e-ULTIMASTER registry.

BACKGROUND: Incomplete revascularization (ICR) has been associated with a worse prognosis after a percutaneous coronary intervention (PCI). In NSTEMI patients with multivessel disease (MVD) however, the benefit of a complete revascularization (CR) remains unclear. METHODS: Patients presenting with an NSTEMI and MVD were selected from the global e-ULTIMASTER registry and grouped according to completeness of revascularization at index hospitalization discharge. The primary endpoint was the patient oriented composite endpoint (POCE) defined as all death, any myocardial infarction, and any revascularization at 1 year. Target lesion failure (TLF) was defined as the composite of cardiac death, target vessel related myocardial infarction and clinically driven target lesion revascularization. Inverse propensity score weighting (IPSW) was performed to harmonize the patient's baseline characteristics between the groups. RESULTS: CR was achieved in 1800 patients (47.0 %) and ICR in 2032 patients (53.0 %). The incidence of POCE at 1 year was lower in the CR group compared to the ICR group: 7.0 % vs. 12.9 %, p < 0.0001. Similarly for TLF at 1 year: 3.6 % vs. 5.5 %, p < 0.01. After IPSW, the incidence of POCE was 7.7 % vs. 12.0 %, p < 0.0001, due to a lower all-cause mortality: 2.7 % vs. 4.2 %, p = 0.02 and less revascularizations: 4.9 % vs. 7.9 %, p < 0.001. The incidence of TLF was no longer statistically significant: CR 3.9 % vs. IR 5.0 %, p = 0.10. CONCLUSIONS: Patients with a NSTEMI and multi vessel disease undergoing a percutaneous coronary revascularization with a complete revascularization during index hospitalization have better 1-year clinical outcomes. Randomized studies are warranted to confirm these results.

Temporary omission of oral anticoagulation in atrial fibrillation patients undergoing percutaneous coronary intervention: rationale and design of the WOEST-3 randomised trial.

The optimal antithrombotic management of atrial fibrillation (AF) patients who require oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) remains unclear. Current guidelines recommend dual antithrombotic therapy (DAT; OAC plus P2Y12 inhibitor - preferably clopidogrel) after a short course of triple antithrombotic therapy (TAT; DAT plus aspirin). Although DAT reduces bleeding risk compared to TAT, this is counterbalanced by an increase in ischaemic events. Aspirin provides early ischaemic benefit, but TAT is associated with an increased haemorrhagic burden; therefore, we propose a 30-day dual antiplatelet therapy (DAPT; aspirin plus P2Y12 inhibitor) strategy post-PCI, temporarily omitting OAC. The study aims to compare bleeding and ischaemic risk between a 30-day DAPT strategy following PCI and a guideline-directed therapy in AF patients requiring OAC. WOEST-3 (ClinicalTrials.gov: NCT04436978) is an investigator-initiated, international, open-label, randomised controlled trial (RCT). AF patients requiring OAC who have undergone successful PCI will be randomised within 72 hours after PCI to guideline-directed therapy (edoxaban plus P2Y12 inhibitor plus limited duration of aspirin) or a 30-day DAPT strategy (P2Y12 inhibitor plus aspirin, immediately discontinuing OAC) followed by DAT (edoxaban plus P2Y12 inhibitor). With a sample size of 2,000 patients, this trial is powered to assess both superiority for major or clinically relevant non-major bleeding and non-inferiority for a composite of all-cause death, myocardial infarction, stroke, systemic embolism or stent thrombosis. In summary, the WOEST-3 trial is the first RCT temporarily omitting OAC in AF patients, comparing a 30-day DAPT strategy with guideline-directed therapy post-PCI to reduce bleeding events without hampering efficacy.

The management of patients on oral anticoagulation undergoing coronary stent implantation: a survey among interventional cardiologists from eight European countries.

PURPOSE: To evaluate the current management, and adherence to recommendations, of patients on oral anticoagulation (OAC) undergoing coronary stent implantation (PCI-S). METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Semi-Quantitative Versus Visual Analysis of Adenosine Perfusion Magnetic Resonance Imaging in Intermediate-Grade Coronary Artery Stenosis Using Fractional Flow Reserve as the Reference: A Pilot Study.

Background: To evaluate the diagnostic accuracy of semi-quantitative adenosine perfusion magnetic resonance imaging (MRI) to determine fractional flow reserve (FFR) ≤ 0.80 intermediate-grade coronary stenoses as compared to visual analysis. Methods: Forty-six patients (mean age 61 ± 9 years; 33 males) with 49 intermediate-grade stenoses (59 ± 7.6%; range, 42-70% minimal diameter reduction) underwent adenosine perfusion MRI and FFR measurement within four months in this retrospective study. MRI was visually assessed by two experienced readers twice with one-year interval, the second time with the knowledge of the diseased artery. The stress subendocardial myocardial enhancement maximal upslope was evaluated distal to the coronary stenosis (=RISK) and divided by the same value in remote myocardium supplied by normal arteries (=REMOTE) to obtain the relative myocardial perfusion index (RMPI). Results: The average FFR value was 0.84 ± 0.09 and 15/49(31%) intermediate-grade stenoses were FFR ≤ 0.80. The kappa-values for interobserver agreement assessing inducible perfusion defects on visual readings was 0.20 on the first reading and increased to 0.62 with the knowledge of the stenosis location. Consensus readings had a diagnostic accuracy of 82%(40/49) in identifying FFR ≤ 0.80 stenoses on both blinded and unblinded readings with regards to the knowledge of the stenosis location. Meanwhile, stress subendocardial RMPI had higher accuracy (43/49[88%]) than visual readings to predict FFR ≤ 0.80 stenoses, using a cutoff value of 0.84. Conclusion: By assessing perfusion changes in remote myocardium, semi-quantitative MRI analysis using stress subendocardial RMPI can provide an equal or more accurate alternative to visual analysis in identifying FFR ≤ 0.80 intermediate-grade stenoses. Larger cohorts of patients are required to validate this approach.

Antiplatelet therapy in patients with atrial fibrillation: a systematic review and meta-analysis of randomized trials.

AIMS: The aim of this study was to systematically assess the effects of antiplatelets on clinical outcomes in patients with atrial fibrillation (AF), treated and not-treated with oral anticoagulation. METHODS AND RESULTS: We searched MEDLINE, Embase, and CENTRAL from inception until September 2020. From 5446 citations, we selected randomized trials allocating patients with AF to antiplatelet therapy vs. control. We applied random-effects models for meta-analysis and assessed potential effect modification with background anticoagulation use. Eighteen trials including 21 518 participants met our prespecified eligibility criteria. In 10 studies without background anticoagulation, antiplatelets reduced all-cause stroke [486/6165 (events/patients) vs. 621/6061; risk ratio (RR) 0.77, 95% confidence interval (CI) 0.69-0.86, I2 = 0%]. In eight studies with background anticoagulation, there was a signal for an increase in all-cause stroke with antiplatelets (97/4608 vs. 72/4684; RR 1.33, 95% CI 0.98-1.79, I2 = 0%, P-value for interaction <0.001). A similar pattern emerged for ischaemic stroke. Irrespective of background anticoagulation use, antiplatelets increased major bleeding (509/10 402 vs. 328/10 496; RR 1.54, 95% CI 1.35-1.77, I2 = 0%) and intracranial haemorrhage (107/10 221 vs. 65/10 232; RR 1.64, 95% CI 1.20-2.24, I2 = 0%), and reduced myocardial infarction (201/9679 vs. 260/9751; RR 0.79, 95% CI 0.65-0.94, I2 = 0%, all P-values for interaction ≥0.36). Antiplatelets did not affect mortality (1221/10 299 vs. 1211/10 287; RR 1.02, 95% CI 0.89-1.17, I2 = 29%, P-value for interaction = 0.23). CONCLUSIONS: In patients with AF not receiving oral anticoagulation, antiplatelet therapy modestly reduced stroke. There was a corresponding signal for harm when used on top of anticoagulation. Irrespective of background anticoagulation use, antiplatelet therapy significantly increased bleeding, moderately reduced myocardial infarction, and did not affect mortality.

Cost Effectiveness of a CYP2C19 Genotype-Guided Strategy in Patients with Acute Myocardial Infarction: Results from the POPular Genetics Trial.

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.

Dual versus triple antithrombotic therapy after percutaneous coronary intervention: the prospective multicentre WOEST 2 Study.

BACKGROUND: For patients on oral anticoagulants (OAC) undergoing percutaneous coronary intervention (PCI), European guidelines have recently changed their recommendations to dual antithrombotic therapy (DAT; P2Y12 inhibitor and OAC) without aspirin. AIMS: The prospective WOEST 2 registry was designed to obtain contemporary real-world data on antithrombotic regimens and related outcomes after PCI in patients with an indication for OAC. METHODS: In this analysis, we compare DAT (P2Y12 inhibitor and OAC) to triple antithrombotic therapy (TAT; aspirin, P2Y12 inhibitor, and OAC) on thrombotic and bleeding outcomes after one year. Clinically relevant bleeding was defined as Bleeding Academic Research Consortium classification (BARC) grade 2, 3, or 5; major bleeding as BARC grade 3 or 5. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause mortality, myocardial infarction, stent thrombosis, ischaemic stroke, and transient ischaemic attack. RESULTS: A total of 1,075 patients were included between 2014 and 2021. Patients used OAC for atrial fibrillation (93.6%) or mechanical heart valve prosthesis (4.7%). Non-vitamin K oral anticoagulants (NOAC) were prescribed in 53.1% and vitamin K antagonists in 46.9% of patients. At discharge, 60.9% received DAT, and 39.1% TAT. DAT was associated with less clinically relevant and similar major bleeding (16.8% vs 23.4%; p<0.01 and 7.6% vs 7.7%, not significant), compared to TAT. The difference in MACCE between the two groups was not statistically significant (12.4% vs 9.7%; p=0.17). Multivariable adjustment and propensity score matching confirmed these results. CONCLUSIONS: Dual antithrombotic therapy is associated with a substantially lower risk of clinically relevant bleeding without a statistically significant penalty in ischaemic events.