Newer P2Y12 blockers (prasugrel and ticagrelor) demonstrated significant ischaemic benefit over clopidogrel after acute coronary syndrome (ACS). However, both drugs are associated with an increase in ...bleeding complications. The objective of the present study was to evaluate the benefit of switching dual antiplatelet therapy (DAPT) from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS.
We performed an open-label, monocentric, and randomized trial. From March 2014 to April 2016, patients admitted with ACS requiring coronary intervention, on aspirin and a newer P2Y12 blocker and without adverse event at 1 month, were assigned to switch to aspirin and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged DAPT). The primary outcome was a composite of cardiovascular death, urgent revascularization, stroke and bleeding as defined by the Bleeding Academic Research Consortium (BARC) classification ≥2 at 1 year post ACS. Six hundred and forty six patients were randomized and 645 analysed, corresponding to 322 patients in the switched DAPT and 323 in the unchanged DAPT group. The primary endpoint occurred in 43 (13.4%) patients in the switched DAPT group and in 85 (26.3%) patients in the unchanged DAPT (HR 95%CI 0.48 (0.34-0.68), P < 0.01). No significant differences were reported on ischaemic endpoints, while BARC ≥ 2 bleeding occurred in 13 (4.0%) patients in the switched DAPT and in 48 (14.9%) in the unchanged DAPT group (HR 95%CI 0.30 (0.18-0.50), P < 0.01).
A switched DAPT is superior to an unchanged DAPT strategy to prevent bleeding complications without increase in ischaemic events following ACS.
To evaluate the safety, efficacy, and performance of the TriGuard™ HDH Embolic Deflection Device (TriGuard) compared with no cerebral protection in patients undergoing transcatheter aortic valve ...implantation (TAVI).
From February 2014 to March 2015, 85 subjects undergoing TAVI at 13 centres in Europe and Israel were randomized to TriGuard protection vs. no protection. Subjects underwent neurologic and cognitive evaluation at baseline, pre-discharge and 30 days; cerebral diffusion-weighted magnetic resonance imaging was performed at 4 ± 2 days post-procedure and at 30 days. Technical success, which included complete 3-vessel cerebral coverage, was achieved in 88.9% (40/45) of cases. The primary in-hospital procedural safety endpoint (death, stroke, life-threatening or disabling bleeding, stage 2 or 3 acute kidney injury, or major vascular complications) occurred in 21.7% of TriGuard and 30.8% of control subjects (P = 0.34). In the Per Treatment population (subjects with complete three-vessel cerebral coverage), TriGuard use was associated with greater freedom from new ischaemic brain lesions (26.9 vs. 11.5%), fewer new neurologic deficits detected by the National Institutes of Health Stroke Scale (3.1 vs. 15.4%), improved Montreal Cognitive Assessment (MoCA) scores, better performance on a delayed memory task (P = 0.028) at discharge, and a >2-fold increase in recovery of normal cognitive function (MoCA score >26) at 30 days.
TriGuard cerebral protection during TAVI is safe and complete cerebral vessel coverage was achieved in 89% of subjects. In this exploratory study, subjects undergoing protected TAVI had more freedom from ischaemic brain lesions, fewer neurologic deficits, and improved cognitive function in some domains at discharge and 30 days compared with controls.
Summary Background Optimum duration of dual antiplatelet treatment (DAPT) after coronary stenting remains uncertain, with an unknown efficacy to safety ratio of extended treatment leading to ...discrepancies between international guidelines and clinical practice. We assessed whether DAPT continuation beyond 1 year after coronary stenting is beneficial. Methods This analysis was a planned extension of the previously published ARCTIC-Monitoring trial, in which we randomly allocated 2440 patients to a strategy of platelet function testing with antiplatelet treatment adjustment or a conventional strategy after coronary stenting with drug-eluting stent (DES). We recruited patients (aged 18 years or older) scheduled for planned DES implantation at 38 centres in France. After 1 year of follow-up, patients without contraindication to interruption of DAPT were eligible for a second randomisation to this second phase of the study (ARCTIC-Interruption). Using a computer-generated randomisation sequence (1:1; stratified by centre), we allocated patients to a strategy of interruption of DAPT where the thienopyridine was interrupted and single aspirin antiplatelet treatment was maintained (interruption group) or a strategy of DAPT continuation for 6–18 months (continuation group). The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularisation, analysed by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00827411. Findings Between Jan 4, 2011, and March 3, 2012, 1259 eligible patients were randomly allocated to treatment in ARCTIC-Interruption: 624 to the interruption group and 635 to the continuation group. After a median follow-up of 17 months (IQR 15–18), the primary endpoint occurred in 27 (4%) patients in the interruption group and 24 (4%) patients in the continuation group (hazard ratio HR 1·17 95% CI 0·68–2·03; p=0·58). STEEPLE major bleeding events occurred more often in the continuation group (seven 1% patients) compared with the interruption group (one <0·5% patient; HR 0·15 0·02–1·20; p=0·073). Major or minor bleedings were also more common in the continuation group compared with the interruption group (12 2% patients vs three 1% patients; HR 0·26 0·07–0·91; p=0·04). Interpretation Our finding suggests no apparent benefit but instead harm with extension of DAPT beyond 1 year after stenting with DES when no event has occurred within the first year after stenting. No conclusion can be drawn for high-risk patients who could not be randomised. The consistency between findings from all trials of such interruption suggests the need for a reappraisal of guidelines for DAPT after coronary stenting towards shorter duration of treatment. Funding Allies in Cardiovascular Trials Initiatives and Organized Networks (ACTION Study Group), Fondation de France, Sanofi-Aventis, Cordis, Medtronic, Boston Scientific, Fondation SGAM.
The addition of clopidogrel to aspirin treatment reduces ischemic events in a wide range of patients with cardiovascular disease. However, recurrent ischemic event occurrence during dual antiplatelet ...therapy, including stent thrombosis, remains a major concern. Platelet function measurements during clopidogrel treatment demonstrated a variable and overall modest level of P2Y12 inhibition. High on-treatment platelet reactivity to adenosine diphosphate (ADP) was observed in selected patients. Multiple studies have now demonstrated a clear association between high on-treatment platelet reactivity to ADP measured by multiple methods and adverse clinical event occurrence. However, the routine measurement of platelet reactivity has not been widely implemented and recommended in the guidelines. Reasons for the latter include: 1) a lack of consensus on the optimal method to quantify high on-treatment platelet reactivity and the cutoff value associated with clinical risk; and 2) limited data to support that alteration of therapy based on platelet function measurements actually improves outcomes. This review provides a consensus opinion on the definition of high on-treatment platelet reactivity to ADP based on various methods reported in the literature and proposes how this measurement may be used in the future care of patients.
Clopidogrel responsiveness has been proposed to be involved in recurrent ischemic events after stenting for non-ST elevation acute coronary syndromes (NSTE ACS). However, its biological definition is ...not consensual. We assess the value of ADP-induced platelet aggregation (ADP-Ag) and platelet reactivity index VASP (PRI VASP) in predicting recurrent ischemic events in patients with NSTE ACS undergoing percutaneous coronary intervention (PCI). We studied 195 consecutive NSTE ACS patients undergoing PCI after a 600 mg loading dose of clopidogrel. ADP-Ag and PRI VASP were analysed. The primary end-point was recurrent ischemic events within 30 days of PCI. It occurred in 14 patients (7%). Construction of ROC curves to examine the value of predictive models showed that sensitivity and specificity for primary endpoint were 79% and 76%, respectively, for a maximal intensity of ADP-Ag >or=70%, 93% and 50% for PRIVASP > 53%. The positive and negative predictive values were 21% and 98%, respectively, for ADP-Ag >or=70%, 12% and 99% for PRIVASP > 53%. In patients with NSTE ACS undergoing PCI, ADP-Ag and PRI VASP identify low responders to clopidogrel with an increased risk of recurrent ischemic events with respective cut-off values of 70% and 53%.
Genetic polymorphisms of cytochrome P450 (CYP) isoforms may promote variability in platelet response to clopidogrel. This study was conducted to analyze, in 603 patients with non–ST elevation acute ...coronary syndromes, the effect of CYP3A4, CYP3A5, and CYP2C19 gene polymorphisms on clopidogrel response and post-treatment platelet reactivity assessed by adenosine diphosphate (ADP)–induced platelet aggregation, vasodilator-stimulated phosphoprotein phosphorylation index, and ADP-induced P-selectin expression. The CYP2C19*2 polymorphism was significantly associated with ADP-induced platelet aggregation, vasodilator-stimulated phosphoprotein phosphorylation index, and ADP-induced P-selectin expression in recessive (p <0.01, p <0.007, and p <0.06, respectively) and codominant (p <0.08, p <0.0001, and p <0.009, respectively) models, but the CYP3A4*1B and CYP3A5*3 polymorphisms were not. The CYP2C19*2 allele carriers exhibited the highest platelet index levels in multivariate analysis (p = 0.03). After covariate adjustment, the CYP2C19*2 allele was more frequent in clopidogrel nonresponders, defined by persistent high post-treatment platelet reactivity (ADP-induced platelet aggregation >70%; p = 0.03). In conclusion, the present data suggest that the CYPC19*2 allele influences post-treatment platelet reactivity and clopidogrel response in patients with non–ST elevation acute coronary syndromes.
Background Individual response to oral antiplatelet therapy is subject to variability, and bedside monitoring offers the opportunity of individualizing therapy for stent implantation. Time and ...consequence of discontinuation of thienopyridine after stenting is also an unsolved issue after drug eluting stent (DES) implantation. Study Design The ARCTIC trial is designed to demonstrate the superiority of a strategy of platelet function monitoring with dose adjustment in suboptimal responders as compared to a more conventional strategy without monitoring and without dose adjustment to reduce the primary end point evaluated 1 year after DES implantation. At the end of the 1-year follow-up, all patients will be randomized again to test the superiority of a strategy of pursuit of dual antiplatelet therapy beyond 1 year as compared to a strategy of interruption. ARCTIC is a multicenter, prospective, open-label study with parallel arms and a double randomization. Two thousand four hundred sixty-six patients with stable angina/ischemia or non–ST-elevation Acute Coronary Syndrome undergoing percutaneous coronary intervention (PCI) with DES implantation are being enrolled. The primary end point for the 2 tested hypotheses is the time to first occurrence of all-cause mortality, nonfatal myocardial infarction, definite/probable stent thrombosis, urgent revascularization, or nonfatal stroke. Platelet function analyses will be performed at the time of PCI and repeated 2 to 4 weeks after PCI. Conclusion ARCTIC tests the hypothesis of personalized oral antiplatelet therapy at the time of and after DES implantation. It also examines the clinical impact of thienopyridine interruption 1 year after DES implantation.
Prosthesis−patient mismatch (PPM) is associated with worse outcomes following surgical aortic valve replacement (SAVR). PPM has been identified in a significant proportion of TAVR, particularly in ...patients with small aortic annuli. Our objective was to evaluate the hemodynamic performances of balloon-expandable (BE) (Sapiens 3TM) versus two different self-expandable (SE) (Evolut ProTM, Accurate NeoTM) TAVR devices in patients with small aortic annulus defined by a computed tomography aortic annulus area (AAA) between 330 and 440 mm2. We enrolled 131 consecutive patients corresponding to 76 Sapiens 3 23 mm (58.0%), 26 Evolut Pro (19.9%) and 29 Accurate Neo (22.1%). Mean age was 82.5 ± 7.06 years, 22.9% of patients were male and mean Euroscore was 4.0%. Mean AAA was 374 ± 27 mm2 for Sapiens 3, 383 ± 29 mm2 for Corevalve Evolut Pro and 389 ± 25 mm2 for Accurate Neo. BE devices were associated with significantly higher rates of PPM (39.5%) as compared to SE devices (15.4% for Corevalve Evolut Pro and 6.9% for Accurate Neo) (p < 0.0001). Paravalvular leaks ≥ 2/4 were more often observed in SE devices (15.4% for Corevalve Evolut Pro and 17.2% for Accurate Neo) than in BE devices (2.6%) (p = 0.007). In conclusion, SE TAVR devices did achieve better hemodynamic results despite higher rates of paravalvular leaks. Therefore, SE TAVI devices could be considered as first choice in small aortic anatomy.
Background: Transcatheter aortic valve implantation (TAVI) is the preferred treatment for symptomatic severe aortic stenosis (AS) in a majority of patients across all surgical risks. Patients and ...methods: Paravalvular leak (PVL) and patient–prosthesis mismatch (PPM) are two frequent complications of TAVI. Therefore, based on the large France-TAVI registry, we planned to report the incidence of both complications following TAVI, evaluate their respective risk factors, and study their respective impacts on long-term clinical outcomes, including mortality. Results: We identified 47,494 patients in the database who underwent a TAVI in France between 1 January 2010 and 31 December 2019. Within this population, 17,742 patients had information regarding PPM status (5138 with moderate-to-severe PPM, 29.0%) and 20,878 had information regarding PVL (4056 with PVL ≥ 2, 19.4%). After adjustment, the risk factors for PVL ≥ 2 were a lower body mass index (BMI), a high baseline mean aortic gradient, a higher body surface area, a lower ejection fraction, a smaller diameter of TAVI, and a self-expandable TAVI device, while for moderate-to-severe PPM we identified a younger age, a lower BMI, a larger body surface area, a low aortic annulus area, a low ejection fraction, and a smaller diameter TAVI device (OR 0.85; 95% CI, 0.83–0.86) as predictors. At 6.5 years, PVL ≥ 2 was an independent predictor of mortality and was associated with higher mortality risk. PPM was not associated with increased risk of mortality. Conclusions: Our analysis from the France-TAVI registry showed that both moderate-to-severe PPM and PVL ≥ 2 continue to be frequently observed after the TAVI procedure. Different risk factors, mostly related to the patient’s anatomy and TAVI device selection, for both complications have been identified. Only PVL ≥ 2 was associated with higher mortality during follow-up.
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