Antithrombotic Treatment after Transcatheter Heart Valves Implant.

Transcatheter heart valve replacement technology was introduced as alternative to surgery for the growing high-risk profile population. Developed first, aortic valve replacement (TAVR) became a standard of care for patients with severe aortic stenosis at high operative risk, with a potential future use also for low-risk subjects. In the last decade, a multitude of transcatheter mitral valve replacement (TMVR) devices have been developed for the treatment of severe mitral regurgitation, with encouraging results coming from first-in-man and feasibility studies. As for biological surgical-type valves, transcatheter implanted valves still preserve the risk of thrombosis and embolic events and anticoagulation- or antiplatelet-based strategies are the most widely used options. Unfortunately, these last remain recommended on the basis of empirical or not widely validated evidence. Therefore, given the exponential rise of TAVR and TMVR procedures, it is important to identify the optimal antithrombotic strategies that best fit the risk of thromboembolic and bleeding events. Hereafter, this review evaluates the current guidelines, trials, and observational data discussing antithrombotic strategy after transcatheter aortic or mitral valve replacement.

Prasugrel use and clinical outcomes by age among patients undergoing PCI for acute coronary syndrome: from the PROMETHEUS study.

BACKGROUND: Prasugrel is a potent thienopyridine that may be preferentially used in younger patients with lower bleeding risk. OBJECTIVE: We compared prasugrel use and outcomes by age from the PROMETHEUS study. We also assessed age-related trends in treatment effects with prasugrel versus clopidogrel. METHODS: PROMETHEUS was a multicenter acute coronary syndrome (ACS) percutaneous coronary intervention (PCI) registry. We compared patients in age tertiles (T1 < 60 years, T2 60-70 years, T3 > 70 years). Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke or unplanned revascularization. Data were adjusted using multivariable Cox regression for age-related risks and propensity score stratification for thienopyridine effects. RESULTS: The study included 19,914 patients: 7045 (35.0%) in T1, 6489 (33.0%) in T2 and 6380 (32.0%) in T3. Prasugrel use decreased from T1 to T3 (29.2% vs. 23.5% vs. 7.5%, p < 0.001). Crude 1-year MACE rates were highest in T3 (17.4% vs. 16.8% vs. 22.7%, p < 0.001), but adjusted risk was similar between the groups (p-trend 0.52). Conversely, crude incidence (2.8% vs. 3.8% vs. 6.9%, p < 0.001) and adjusted bleeding risk were highest in T3 (HR 1.24, 95% CI 0.99-1.55 in T2; HR 1.83, 95% CI 1.46-2.30 in T3; p-trend < 0.001; reference = T1). Treatment effects with prasugrel versus clopidogrel did not demonstrate age-related trends for MACE (p-trend = 0.91) or bleeding (p-trend = 0.28). CONCLUSIONS: Age is a strong determinant of clinical risk as well as prasugrel prescription in ACS PCI with much lower use among older patients. Prasugrel did not have a differential treatment effect by age for MACE or bleeding. Frequency of prasugrel use and age-related temporal risks of all-cause death and bleeding after ACS PCI.

Incidence, predictors, and outcomes of DAPT disruption due to non-compliance vs. bleeding after PCI: insights from the PARIS Registry.

BACKGROUND: The disruption of dual antiplatelet therapy (DAPT) due to non-compliance or bleeding is known to significantly increase the risk of adverse outcomes after percutaneous coronary intervention (PCI). However, it is currently unknown if there are differences in the predictors and clinical impact of disruption due to non-compliance compared with bleeding. METHODS: The patterns of non-adherence to antiplatelet regimens in stented patients (PARIS) registry was an international, multicenter prospective study of PCI patients discharged on DAPT (aspirin + a P2Y12 receptor). We analyzed the incidence, patient characteristics, predictors, and outcomes in patients with DAPT disruption due to non-compliance as compared to DAPT disruption due to bleeding in the PARIS registry. Predictors of non-recommended disruption and bleeding disruption were assessed using logistic regression. Risks associated with disruption on major adverse cardiac events (MACE, a composite of cardiac death, definite or probable stent thrombosis, spontaneous myocardial infarction, and target lesion revascularization) were analyzed using time-updated Cox regression over 2-year follow-up. RESULTS: Out of 5018 patients, the rate of non-compliant DAPT disruption was 1.6% at 30 days (n = 79), 6.5% at 12 months (n = 328), and 9.1% at 2 years from PCI (n = 457). The rate of bleeding DAPT disruption was 0.6% at 30 days (n = 32), 3.1% at 12 months (n = 156), and 4.6% at 2 years (n = 229). Multivariate predictors of non-compliant disruption included female gender, history of smoking, acute coronary syndrome, and US patients which were associated with greater risk; and dyslipidemia and discharge PPI which were associated with lower risk. Multivariate predictors of bleeding disruption included older age, prior MI, and discharge warfarin which were associated with greater risk; and US region and intervention to the LAD which were associated with lower risk. Non-compliant disruption was associated with a significantly greater risk for MACE (HR 1.73, 95% CI 1.17-2.54, p = 0.006) and spontaneous myocardial infarction (HR 2.93, 95% CI 1.85-4.65, p < 0.001). Bleeding disruption was associated with a significantly greater risk for all-cause death (HR 1.93, 95% CI 1.22-3.08, p = 0.005). CONCLUSION: Approximately 1 in 10 patients disrupts DAPT due to non-compliance and 1 in 20 disrupts DAPT due to bleeding. Disruption due to non-compliance resulted in higher risk for ischemic events and disruption due to bleeding had higher subsequent mortality. These data warrant efforts to focus on patient education in those at high risk of non-compliance.

Safety and efficacy of the COMBO bio-engineered stent in an all-comer PCI cohort: 1-Year final clinical outcomes from the MASCOT post-marketing registry.

BACKGROUND: The COMBO stent (OrbusNeich Medical, Ft. Lauderdale, Florida) is a new-generation bio-engineered drug eluting stent, combining an abluminal coating of a bioabsorbable polymer matrix for sustained release of sirolimus and luminal anti-CD34 coating for endothelial progenitor cell capture and rapid endothelialization. METHODS: The Multinational Abluminal Sirolimus Coated BiO-Engineered StenT (MASCOT) registry was a prospective post-marketing study conducted from June 2014-May 2017 across 60 centers globally. Patients were eligible if COMBO stent implantation was attempted, and they received dual antiplatelet therapy (DAPT) per local guidelines. Follow-up was conducted by trained research staff at 1, 6 and 12 months by phone or clinic visit to capture clinical events and DAPT cessation events. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, non-fatal myocardial infarction not clearly attributable to a non-target vessel, or ischemia-driven target lesion revascularization. RESULTS: A total of 2614 patients were enrolled over the study period with 96.7% completion of 1-year follow-up. The mean age of enrolled patients was 62.9 ±â€¯11.2 years and 23.0% were female. Diabetes mellitus was present at baseline in 33.5%. A total of 56.1% patients underwent PCI for acute coronary syndrome (ACS). The 1-year primary endpoint of TLF occurred in 3.4% patients (n = 88). Definite stent thrombosis occurred in 0.5% patients (n = 12). CONCLUSION: The MASCOT post marketing registry provides comprehensive safety and efficacy outcomes following contemporary PCI using the novel COMBO stent in an all-comer population. This platform is associated with low rates of 1-year TLF and ST. CLINICALTRIALS. GOV IDENTIFIER: NCT02183454.

Impact of Discharge Location After Transcatheter Aortic Valve Replacement on 1-Year Outcomes in Women: Results From the WIN-TAVI Registry.

BACKGROUND: Several clinical and procedural factors determine outcomes after transcatheter aortic valve replacement (TAVR), but data are scarce on the impact of post-TAVR discharge disposition on long-term outcomes. We sought to analyse whether discharge location after TAVR is associated with 1-year outcomes in women undergoing contemporary TAVR. METHODS: The Women's INternational Transcatheter Aortic Valve Implantation (WIN-TAVI) registry is the first all-female TAVR registry to study the safety and performance of contemporary TAVR in women (n = 1019). Information on discharge location was available in 817 patients (80.2%). We compared women discharged home vs those discharged to another location (nursing home, rehabilitation, or other hospital). One-year outcomes were adjusted using multivariable Cox regression methods with discharge home as the reference group. RESULTS: Of the study subjects, 75.2% (n = 614) were discharged home and 24.8% (n = 203) to another location. Women discharged to other locations were older with a greater prevalence of severe lung disease requiring home oxygen and renal failure on dialysis but were less frequently considered frail or at high surgical risk compared with women discharged home. After multivariable adjustment, non-home discharge was associated with greater hazard for 1-year Valve Academic Research Consortium 2 efficacy (21.3% vs 10.8%, hazards ratio [HR] 1.9, 95% confidence interval [CI] 1.2-2.9) and safety endpoints (31.5% vs 15.2%, HR 2.1, 95% CI 1.5-3.0), cardiovascular death (12.7% vs 5.5%, HR 2.0, 95% CI 1.1-3.6), and stroke (6.5% vs 0.8%, HR 8.5, 95% CI 2.9-25.6). CONCLUSIONS: In women undergoing contemporary TAVR, discharge disposition significantly affects 1-year risk of outcomes even after adjustment for recorded baseline differences. This might suggest the necessity of considering additional factors beyond comorbidities in the TAVR decision-making process.

Cooperative Behavior Emerges among Drosophila Larvae.

Spectacular examples of cooperative behavior emerge among a variety of animals and may serve critical roles in fitness [1, 2]. However, the rules governing such behavior have been difficult to elucidate [2]. Drosophila larvae are known to socially aggregate [3, 4] and use vision, mechanosensation, and gustation to recognize each other [5-8]. We describe here a model experimental system of cooperative behavior involving Drosophila larvae. While foraging in liquid food, larvae are observed to align themselves and coordinate their movements in order to drag a common air cavity and dig deeper. Large-scale cooperation is required to maintain contiguous air contact across the posterior breathing spiracles. On the basis of a directed genetic screen we find that vision plays a key role in cluster dynamics. Our experiments show that blind larvae form fewer clusters and dig less efficiently than wild-type and that socially isolated larvae behave as if they were blind. Furthermore, we observed that blind and socially isolated larvae do not integrate effectively into wild-type clusters. Behavioral data indicate that vision and social experience are required to coordinate precise movements between pairs of larvae, therefore increasing the degree of cooperativity within a cluster. Hence, we hypothesize that vision and social experience allow Drosophila larvae to assemble cooperative digging groups leading to more effective feeding and potential evasion of predators. Most importantly, these results indicate that control over membership of such a cooperative group can be regulated.