Monotherapy with P2Y12-inhibitors after dual antiplatelet therapy: Filling gaps in evidence.

BACKGROUND: Whether P2Y12 inhibitor monotherapy (P2Y12-I) is superior to aspirin following DAPT discontinuation post-PCI remains to be established. METHODS: We updated our prior network meta-analysis where P2Y12-I and aspirin had been compared with DAPT or directly with each other. The focus is specifically on the available direct evidence, now consisting of the three head-to-head comparisons of P2Y12-I and aspirin in event-free PCI patients after DAPT. We include a Trial Sequential Analysis of the direct evidence based on meta-analytical literature. RESULTS: The main finding reveals a 39% significantly lower risk of myocardial infarction with P2Y12-I (RR 0.61, 95% CI 0.47-0.78, p = 0.0001, I2 = 0%) with no difference in bleeding. Trial Sequential Analysis demonstrates clinically meaningful evidence for a reduction in the incidence of myocardial infarction with P2Y12-I that is also supported by statistical significance. CONCLUSIONS: Accruing data highlight that P2Y12-I following DAPT discontinuation after PCI is associated with lower risk for MI and a similar risk for bleeding as compared with ASA. In light of potential limitations to the widespread adoption of life-long P2Y12-I treatment, clinicians should consider identifying selected patients who are expected to derive the highest benefit.

P2Y12 Inhibitor or Aspirin Following Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Network Meta-Analysis.

BACKGROUND: It is still unknown which antiplatelet monotherapy should be continued after a period of dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI). OBJECTIVES: The aim of this study was to compare aspirin vs P2Y12 inhibitor (P2Y12-I) monotherapy after dual antiplatelet therapy (DAPT) discontinuation in patients undergoing percutaneous coronary intervention (PCI). METHODS: Randomized studies enrolling patients undergoing PCI with second-generation drug-eluting stents and comparing aspirin or P2Y12-I monotherapy after DAPT discontinuation vs prolonged DAPT or aspirin vs P2Y12-I monotherapy after DAPT were included. Primary efficacy and safety endpoints were myocardial infarction (MI) and major bleeding (MB), respectively. Point estimates for dichotomous outcomes were pooled using frequentist and Bayesian frameworks. Sensitivity analyses and treatment hierarchy were performed. RESULTS: Nineteen studies encompassing 73,126 patients were included. The transitivity assumption was met. Under the frequentist framework, patients receiving aspirin had a significantly higher risk for MI compared with P2Y12-I monotherapy (risk ratio: 1.32; 95% CI: 1.08-1.62). Compared with DAPT, both monotherapies reduced MB, but only P2Y12-I showed equivalent efficacy in preventing MI. No significant differences in MB, death, and other thrombotic outcomes were observed. However, point estimates for the risk for stent thrombosis and stroke favored P2Y12-I monotherapy. Consistent results were found in a fixed-effects model and the Bayesian framework, with all models having adequate convergence. P2Y12-I vs aspirin monotherapy had the highest probability of being ranked first for reduction of all assessed outcomes. CONCLUSIONS: P2Y12-I monotherapy following DAPT discontinuation after PCI is associated with a significantly lower risk for MI and similar risk for MB, suggesting a potentially relevant net clinical benefit vs aspirin monotherapy. These findings strengthen the rationale for further studies directly comparing the 2 monotherapies after DAPT in PCI patients.

Impact of direct oral anticoagulants on evolution of post-thrombotic syndrome.

BACKGROUND: The effect of direct oral anticoagulants (DOACs) on evolution of a post-thrombotic syndrome (PTS) is unknown. METHODS AND RESULTS: This retrospective study included patients (n = 98) with a PTS occurring after a proximal deep-vein thrombosis (DVT). The PTS progression was assessed by the Villalta scale change over time from when patients were started on DOACs for the prevention of DVT recurrence according to current guidelines. The PTS evolution was compared between patients with good (n = 63) vs. poor (n = 35) DOACs adherence, defined by using a medication possession ratio cut point of 0.80. The mean follow-up was 41.7 ± 17.7 and 27.5 ± 10.5 months in patients with good or poor adherence, respectively. The primary endpoint of PTS improvement (defined when the Villalta score became <5 and/or decreased by ≥30% from baseline) was higher in patients with good vs. poor adherence (66.7% vs. 20%, p < 0.001). None of the patients in the good adherence group experienced at any time of follow-up the co-primary endpoint of PTS worsening (defined as the Villalta score increase ≥30%), which instead occurred in 12 (34.3%) of those with poor adherence (p < 0.001). All study-defined primary endpoints occurred within 2 years. The mean values of the Villalta partial scores related to the subjective symptoms (patient-rated) and to the potentially reversible physician-rated signs were significantly improved in the good adherence group, while they were unchanged among patients with poor adherence. CONCLUSIONS: In this study a good vs. poor DOACs adherence was associated with a more favorable progression of PTS over a long-term follow-up. Larger studies are needed to explore the clinical efficacy of DOACs on PTS manifestations.

Suitability for elderly with heart disease of a QR code-based feedback of drug intake: Overcoming limitations of current medication adherence telemonitoring systems.

BACKGROUND: Current medication adherence telemonitoring systems have several limitations prompting the need for simpler, low-cost and widely applicable tools. To meet these needs, we propose a novel method consisting in sending a digital feedback of medication intake by just reading a pre-defined Quick Response (QR) code attached on the pills box. METHODS: To assess the potential clinical applicability of the proposed QR code-based task, its feasibility was tested among elderly with heart diseases. The primary endpoint was the learning success defined as a correct execution of all QR code-based digital task steps within 10 min. Study outcomes were compared between patients 65-75 years old (younger cohort) and those aged >75 years (older cohort) admitted to the Cardiology ward of a tertiary center. RESULTS: A total of 262 patients were included: 128 (48.9%) were younger and 134 (51.1%) older. Despite a baseline low smartphone use in the overall population (41.2%), patients learning success of the digital task was as high as 75.6%, with lower rates among older vs. younger (67.9% vs. 83.6%, p = 0.005). After adjustment no significant independent association between age and success in learning the QR code-based task was found. Differently, increasing age was a negative independent predictor of smartphone use. The learning time was overall small, but longer in the older group (126 ± 100 vs. 100 ± 60 s, p = 0.03). CONCLUSIONS: The QR code-based digital task was highly feasible for elderly with heart diseases suggesting its potential large-scale clinical application and encouraging the investigation of QR code-based systems for medication adherence telemonitoring.

[Management of antithrombotic therapy in patients with bleeding after percutaneous coronary intervention]. / Gestione della terapia antitrombotica nei pazienti con sanguinamento dopo angioplastica coronarica.

Bleeding is a frequently encountered complication in patients undergoing percutaneous coronary intervention (PCI) treated with a dual antiplatelet therapy regimen with aspirin plus an oral inhibitor of the P2Y12 platelet receptor (clopidogrel, prasugrel, ticagrelor) or with the combination of antiplatelet drugs and an anticoagulant in patients who have a specific indication for chronic anticoagulation therapy such as atrial fibrillation. The management of antithrombotic therapy during post-PCI bleeding is considerably challenging due to the intrinsic difficulty in estimating the balance between the bleeding risk - increased by antiplatelet and/or anticoagulant therapy - and the thrombotic risk associated with the possible discontinuation of these drugs. Currently, there are no data derived from dedicated studies in this setting and therefore the management of antithrombotic therapy in patients who suffer a hemorrhagic complication after PCI is guided by consensus documents that provide suggestions for the different types of bleeding, based on the severity of the latter. In light of the European documents available, this article will discuss the possible management strategies of antithrombotic therapy (antiplatelet and/or anticoagulant) in the different types of bleeding that can occur in patients undergoing PCI.

Pharmacodynamics During Transition Between Platelet P2Y12 Inhibiting Therapies.

Several platelet P2Y12 inhibiting agents, both oral and intravenous, are available for clinical use. The oral P2Y12 inhibitors comprise clopidogrel, prasugrel, and ticagrelor. Cangrelor is the only intravenous P2Y12 inhibitor. Numerous pharmacodynamic studies have been performed to assess the impact of P2Y12 inhibitor switching on platelet reactivity profiles and to define the optimal strategy if switching is needed, with the goal of minimizing the risk of having inadequate platelet inhibition due to potential drug-drug interactions occurring during the drug overlap phase. This article provides an overview of pharmacodynamic studies assessing switching between P2Y12 inhibitors and recommendations on switching modalities based on these findings.

Decision Analytic Markov Model Weighting Expected Benefits and Current Limitations of First-Generation Bioresorbable Vascular Scaffolds: Implications for Manufacturers and Next Device Iterations.

BACKGROUND: Relative benefits of bioresorbable vascular scaffolds (BVS) compared with everolimus-eluting stents (EES) are expected to accrue after complete bioresorption. METHODS AND RESULTS: We built a decision analytic Markov model comparing BVS and EES for a contemporary percutaneous coronary intervention population. Procedure-related morbidity and outcome data from the available literature were used to derive model probabilities. The net benefit of BVS and EES was estimated in terms of quality-adjusted life expectancy. Under the assumption of no risk for device thrombosis and target lesion revascularization with BVS beyond 3 years, the equipoise in quality-adjusted life expectancy (12.86) between BVS and EES was achieved 19 years after implantation. The maximum tolerable excess risk of 3-year BVS thrombosis equalizing the model-predicted quality-adjusted life expectancy of BVS and EES at 10 years was 1.40, corresponding to an absolute tolerable rate of 1.45%. CONCLUSIONS: At the currently observed relative increase in device thrombosis and under the extreme hypothesis of no scaffold thrombosis and target lesion revascularization beyond 3 years, the incremental benefit of BVS over EES becomes apparent only after 19 years. This simulation suggests that there is a small degree of benefit that clinicians and decision-makers may expect from the first-generation BVS at the current risk of device thrombosis. Manufacturers should target scaffold thrombosis rates <1.45% at 3 years to make their technologies attractive during a 10-year horizon.

Clinical Outcomes Following Intravascular Imaging-Guided Versus Coronary Angiography-Guided Percutaneous Coronary Intervention With Stent Implantation: A Systematic Review and Bayesian Network Meta-Analysis of 31 Studies and 17,882 Patients.

OBJECTIVES: The authors sought to explore the comparative clinical efficacy of different imaging modalities for guiding percutaneous coronary interventions (PCI). BACKGROUND: Coronary angiography (CA) is the standard imaging modality for intraprocedural guidance of PCI. Intracoronary imaging techniques, including intravascular ultrasound (IVUS) and optical coherence tomography (OCT), can overcome some limitations of CA. METHODS: Comprehensive hierarchical Bayesian network meta-analysis of randomized clinical trials and adjusted observational studies comparing clinical outcomes of PCI with stent implantation guided by CA, IVUS, or OCT. RESULTS: A total of 31 studies encompassing 17,882 patients were included. Compared with CA guidance, the risks of all-cause death (odds ratio [OR]: 0.74; 95% credible interval [CrI]: 0.58 to 0.98), myocardial infarction (OR: 0.72; 95% CrI: 0.52 to 0.93), target lesion revascularization (OR: 0.74, 95% CrI: 0.58 to 0.90) and stent thrombosis (OR: 0.42; 95% CrI: 0.20 to 0.72) were significantly reduced by IVUS guidance. PCI guidance using either IVUS or OCT was associated with a significant reduction of major adverse cardiovascular events (OR: 0.79; 95% CrI: 0.67 to 0.91 and OR: 0.68; 95% CrI: 0.49 to 0.97, respectively) and cardiovascular death (OR: 0.47; 95% CrI: 0.32 to 0.66 and OR: 0.31; 95% CrI: 0.13 to 0.66, respectively). No differences in terms of comparative clinical efficacy were found between IVUS and OCT for all the investigated outcomes. Pooled estimates were consistent across several sensitivity analyses. However, the treatment effect of IVUS on all-cause death was neutralized in the analysis restricted to randomized clinical trials (OR: 1.03; 95% CrI: 0.41 to 2.14). CONCLUSIONS: Compared with CA, the use of intravascular imaging techniques for PCI guidance reduces the risk of cardiovascular death and adverse events.

Update on clinical evidence (Part II): A summary of the main post market studies.

Bioresorbable vascular scaffolds (BVS, Absorb, Abbott Vascular, Santa Clara, CA) received the CE mark in October 2011, and were approved by the Food and Drug Administration in July 2016. After their introduction in clinical practice a broad amount of post-marketing clinical experience with BVS has been generated so far in Europe and outside the United States. The available BVS registries differ in many aspects, including their being single-center or multicenter, single-arm or controlled, sponsored or investigator-initiated, published or presented at a large-scale international meeting. This article provides an overview of clinical results of the main post-marketing studies of BVS available. © 2016 Wiley Periodicals, Inc.

One-year outcomes after Absorb bioresorbable vascular scaffold implantation in routine clinical practice.

AIMS: Our aim was to report one-year outcomes of Absorb bioresorbable scaffold implantation under real-world conditions in an all-comers population of patients with high proportions of complex lesions. METHODS AND RESULTS: Patients undergoing Absorb 1.1 implantation were included in a single-centre, prospective, all-comers registry. The primary outcome was target lesion failure (TLF), defined as the combination of cardiac death, target vessel myocardial infarction (MI), or clinically driven target lesion revascularisation (TLR). A total of 319 patients received 604 Absorb BVS in 406 lesions. Of note, 24.8% of patients had diabetes and 49.5% presented with an acute coronary syndrome. A total of 51% of lesions were type B2/C. The reference vessel diameter and lesion length were 2.9±0.5 and 21.2±16.8 mm, respectively. The one-year cumulative rate of TLF was 4.9%. Rates of cardiac death, target vessel MI and TLR were 0.9%, 1.3% and 4.2%, respectively. The cumulative one-year rate of definite/probable scaffold thrombosis was 1.3%, with all events occurring within 30 days. CONCLUSIONS: These data suggest that twelve-month clinical outcomes of Absorb use in "real-world" unselected patients with high proportions of complex lesions are reasonably good.

Bioresorbable vascular scaffold in patients with complex coronary artery disease.

The advent of fully bioresorbable stent technology is heralded as breakthrough technology in the current era of percutaneous coronary interventions (PCI). Bioresorbable scaffolds (BRS) have the potential to introduce a paradigm shift in interventional cardiology, representing an anatomical and functional "vascular restoration" therapy instead of an artificial stiff tube encased by persistent metallic foreign body. Among BRS, the everolimus-eluting scaffold (ABSORB, Abbott Vascular, Santa Clara, CA, USA) has been the most extensively investigated in clinical studies. The use of ABSORB in the treatment of relatively simple lesions appears to provide a similar degree of safety and efficacy compared with metallic drug-eluting stent (DES) treated under randomized trials conditions, but patients treated in real-world practice are far more complex than those included in randomized trials. Therefore, several ABSORB all-comers registries dealing with real world conditions are being performed. Their currently available results are summarized in the present overview.

Impact of residual platelet reactivity on reperfusion in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

AIM: Whether high platelet reactivity (HPR) immediately after diagnostic angiography is associated with worse coronary reperfusion prior to and after primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is unknown. This study aimed to assess the impact of P2Y12-mediated HPR on angiographic outcomes in patients with STEMI undergoing PPCI. METHODS: STEMI patients undergoing PPCI and pretreated with a P2Y12 receptor antagonist underwent platelet function testing with the VerifyNow™ assay at the time of angiography. Light transmission aggregometry (LTA) was performed in a subgroup. HPR was defined according to expert consensus definitions. Pre-PCI coronary patency, thrombotic burden and indices of impaired post-PCI reperfusion were compared between HPR and non-HPR patients. RESULTS: Among 164 patients, the prevalence of VerifyNow™-derived HPR was 71.3% at a median (interquartile range (IQR)) of 55 (40-75) minutes after a P2Y12 inhibitor loading dose. Compared with non-HPR patients, those with HPR had significantly lower rates of pre-PCI Thrombolysis in Myocardial Infarction (TIMI) flow grades 2 or 3 (51.1% vs. 32.5%, p = 0.04), higher rates of thrombus score (TS) grade 3/4 (29.8% vs. 52.1%, p = 0.015) and 4 (14.9% vs. 32.5%, p = 0.037) and lower median (IQR) corrected TIMI frame count (cTFC; 23.2 (15.8-32.5) vs. 26.0 (21.0-35.0), p = 0.02), respectively. These findings were consistent using LTA-based data. HPR and TS grade 4 were predictors of higher cTFC. CONCLUSIONS: In patients with STEMI undergoing PPCI pretreated with P2Y12 receptor inhibitors, pre-PPCI HPR was found to be associated with lower pre-PCI coronary patency, higher thrombotic burden and a worse index of post-PCI coronary reperfusion.