Clinical outcomes according to lesion complexity in patients with high bleeding risk treated with 1-month dual antiplatelet therapy following pci: analysis from the onyx one clear study

BACKGROUND Safety and effectiveness outcomes were examined at 1 year among high bleeding risk (HBR) patients treated with 1 month of dual antiplatelet therapy (DAPT) following PCI with zotarolimus eluting stents (ZES) (Resolute Onyx, Medtronic, Santa Rosa, Califor nia) according to lesion complexity (Table). METHODS The 1-year clinical outcomes were evaluated in HBR pa tients treated with ZES who were event-free following 1-month DAPT post-procedure with planned single antiplatelet therapy thereafter. Propensity score adjustment was performed to account for baseline differences (Table). RESULTS A total of 1,506 patients were stratified by complex (n » 395) or noncomplex (n » 1,111) PCI criteria (Table). Complex patients were more frequently men (72.2% vs. 66.1%; p » 0.03) and had higher rates of prior myocardial infarction (MI) (34.4% vs. 23.4%), prior CABG (24.1% vs. 8.9%), multivessel disease (78.2% vs. 39.8%), and B2/C lesion classification (84.2% vs. 75.6%), all p < 0.001. Complex patients had more lesions treated (1.7 vs. 1.2), longer stent length per patient (65.1 mm vs. 26.9 mm), and longer procedure time (58.8 min vs. 35.3 min), all p < 0.001. Procedural success was higher among noncomplex patients (90.8% vs. 82.0%; p < 0.001). In unadjusted analysis, the rate of MI was higher in patients with complex lesions (p » 0.04). How ever, no significant differences in any outcomes between patients with and without complex lesions were present after propensity score adjustment (Table). CONCLUSION Despite greater anatomic and procedural complexity, similar safety and effectiveness were observed in complex and noncomplex patients treated with 1-month DAPT following PCI with Resolute Onyx ZES after propensity score adjustment. These findings support 1-month DAPT among selected HBR patients undergoing PCI with Resolute Onyx ZES irrespective of lesion and procedural complexity.

The urgent need for integrated science to fight COVID-19 pandemic and beyond.

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world's scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic's consequences and prevent recurrences of similar pandemics.

Big Data: uma nova fronteira na pesquisa e na prática médica / Big Data: a new frontier in research and medical practice

Espera-se que a integração contínua dos avanços tecnológicos e da digitalização revolucione os sistemas de saúde e a prestação de assistência ao paciente. Esses desen-volvimentos permitiram a geração de dados detalhados associados à assistência médica, os quais podem ser aproveitados, compilados e analisados com a ajuda de ferramentas sofisticadas. O ramo da ciência que lida com o armazenamento, processamento e imple-mentação desses grandes volumes de dados foi apropriadamente denominado "big data analytics" (BDA, Análise de grandes volumes de dados). Apesar do crescente interesse no potencial da BDA no campo da assistência médica, não há uma definição concisa, sendo que a BDA é descrita de acordo com o valor que ela pode fornecer. Como as ferramentas estatísticas tradicionais não estão equipadas para lidar com esses grandes e complexos conjuntos de dados, é preciso implementar ferramentas de inteligência artificial de alta di-mensão. A BDA foi explorada em várias vias em todo o espectro de serviços de saúde, desde a automação de tarefas, até ferramentas de previsão de risco, interpretação de imagens e realização de estudos clínicos. Contudo, como essas ferramentas são diferentes da medicina tradicional, existem várias preocupações referentes a implementação, uso e segurança e privacidade de dados. Todavia, a BDA detém imenso potencial para melhorar os serviços de saúde, sendo que todas as partes envolvidas devem envidar esforços deliberados para promover a aplicação dessa área emergente da medicina.

A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement.

BACKGROUND: Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. METHODS: We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. RESULTS: After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). CONCLUSIONS: In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.).

Novel Oral Anticoagulant Based Versus Vitamin K Antagonist Based Double Therapy Among Stented Patients With Atrial Fibrillation: Insights From the PIONEER AF-PCI Trial.

BACKGROUND: Among stented patients with atrial fibrillation, double therapy with a novel oral anticoagulant plus single antiplatelet therapy (SAPT) reduces bleeding or cardiovascular rehospitalizations compared with a vitamin K antagonist (VKA) based triple therapy regimen. A recent study demonstrated that apixaban based double therapy reduced bleeding compared with VKA based double therapy. However, it remains unknown whether rivaroxaban based double therapy is superior to a VKA based double therapy. METHODS: Patient with stented atrial fibrillation (n=2124) were randomized to 3 groups: rivaroxaban 15 mg od plus a P2Y12 inhibitor (Group 1, n=709); rivaroxaban 2.5 mg bid plus dual antiplatelet therapy (DAPT; Group 2, n=709); and warfarin plus DAPT (Group 3, n=706). Before randomization, subjects were stratified according to a prespecified duration of DAPT (1, 6, or 12 months). After the prespecified DAPT duration, subjects in Group 2 were switched to rivaroxaban 15 mg plus low dose aspirin, and those in Group 3 were switched to VKA plus low dose aspirin. The Wei, Lin, and Weissfeld time to multiple events method was used to compare the occurrence of all bleeding and cardiovascular rehospitalizations among subjects on a novel oral anticoagulant versus VKA based double therapy. RESULTS: A total of 906 subjects were prespecified to a 1 or 6 months DAPT duration and received at least one dose of study drug. Twenty subjects (3.3%) assigned to novel oral anticoagulant+SAPT, and 15 (5.1%) subjects assigned to VKA+SAPT experienced multiple rehospitalizations. In total, 124 (20.3%) events occurred among subjects on novel oral anticoagulant+SAPT compared with 87 (29.6%) among subjects on VKA+SAPT (hazard ratio=0.65 [95% CI, 0.45-0.93], P=0.008). CONCLUSIONS: Among stented patients with atrial fibrillation, rivaroxaban plus SAPT was superior to warfarin plus SAPT in lowering total bleeding and cardiovascular rehospitalization. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01830543.

Cost Implications of Anticoagulation Strategies After Percutaneous Coronary Intervention Among Patients With Atrial Fibrillation (A PIONEER-AF PCI Analysis).

The PIONEER AF-PCI trial demonstrated that in atrial fibrillation patients who underwent intracoronary stenting, either rivaroxaban 15 mg daily plus P2Y12 inhibitor monotherapy (Group 1) or 2.5 mg rivaroxaban twice daily plus dual antiplatelet therapy (DAPT) (Group 2) was associated with fewer recurrent hospitalizations, primarily for bleeding and cardiovascular events, compared with standard-of-care vitamin K antagonist and DAPT (Group 3). Associated costs are unknown. This study estimates costs associated with rivaroxaban strategies compared with vitamin K antagonist and DAPT. Medication costs were estimated using wholesale acquisition costs, medication discontinuation rates, and costs of monitoring. Using a large US healthcare claims database, the mean adjusted increase in 1-year cost of care for individuals with atrial fibrillation and percutaneous coronary intervention (PCI) rehospitalized for bleeding, cardiovascular, and other events was compared with those not rehospitalized. Using adjudicated rehospitalization rates from PIONEER AF-PCI, cost differences were estimated. Rates of rehospitalization for bleeding were 6.5%, 5.4%, 10.5%, and 20.3%, 20.3%, 28.4% for cardiovascular events in Groups 1, 2, and 3. Medication and monitoring costs were $3,942, $4,115, and $1,703. One-year costs for all recurrent hospitalization costs and/or patient for the groups were $24,535, $20,205, and $29,756. One-year cost increase associated with bleeding rehospitalizations and/or patient was $4,160, $3,212, and $6,876 and was $13,264, $11,545, and $17,220 for cardiovascular rehospitalizations and/or patient. Overall estimated cost per patient was $28,476, $24,320, and $31,458. Compared with warfarin, both rivaroxaban treatment strategies had higher medication costs, but these were more than accounted for by fewer hospitalizations.

Total bleeding with rivaroxaban versus warfarin in patients with atrial fibrillation receiving antiplatelet therapy after percutaneous coronary intervention.

Among atrial fibrillation (AF) patients undergoing percutaneous coronary intervention (PCI), rivaroxaban with background antiplatelet therapy significantly reduced the first occurrence of bleeding compared to triple therapy with warfarin. This study hypothesized that total bleeding events, including those beyond the first event, would be reduced with rivaroxaban-based regimens. In the PIONEER AF-PCI trial, 2099 patients in the modified intention-to-treat population were randomized to three groups and followed for 12 months: (1) rivaroxaban 15 mg once daily plus a P2Y12 inhibitor (N = 696); (2) rivaroxaban 2.5 mg twice daily plus dual antiplatelet therapy (DAPT) (N = 706); and (3) dose-adjusted warfarin plus DAPT (N = 697). Descriptive statistics for the number of subjects who experienced one or more bleeding events were calculated. The total number of bleeding events was compared across treatment groups using the Wei, Lin, and Weissfeld method. A total of 514 and 439 events of clinically significant bleeding and bleeding requiring medical attention occurred throughout the study. Compared to triple therapy with warfarin, rivaroxaban-based regimen was associated with a reduction in total events of clinically significant bleeding (Group 1 vs. Group 3: HR 0.64 [95% CI 0.49-0.85], p < 0.001, NNT = 11; Group 2 vs. Group 3: HR 0.62 [95% CI 0.48-0.80], p < 0.001, NNT = 10). Similarly, rivaroxaban reduced the total bleeding events requiring medical attention (Group 1 vs. Group 3: HR 0.66 [95% CI 0.49-0.89], p < 0.001, NNT = 14; Group 2 vs. Group 3: HR 0.64 [95% CI 0.48-0.85], p = 0.002, NNT = 13). Rivaroxaban-based regimen reduced the total bleeding events compared with VKA-based triple therapy in stented AF patients. One clinically significant bleeding event could be prevented with rivaroxaban use for every 10-11 patients treated, and one bleeding requiring medical attention could be prevented with rivaroxaban for every 13-14 patients treated. These data provide evidence that total bleeding events, including those beyond the first event, are reduced with rivaroxaban-based antithrombotic regimens. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01830543 (PIONEER AF-PCI).

Intracoronary Imaging, Cholesterol Efflux, and Transcriptomes After Intensive Statin Treatment: The YELLOW II Study.

BACKGROUND: Despite extensive evidence demonstrating the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects remain elusive. OBJECTIVES: This study assessed changes in plaque morphology using intravascular imaging, with a comprehensive evaluation of cholesterol efflux capacity (CEC) and peripheral blood mononuclear cell (PBMC) transcriptomics in patients receiving high-dose statin therapy. METHODS: In a prospective study, 85 patients with stable coronary artery disease underwent percutaneous coronary intervention for a culprit lesion, followed by intracoronary multimodality imaging, including optical coherence tomography (OCT) of an obstructive nonculprit lesion. All subjects received 40 mg of rosuvastatin daily for 8 to 12 weeks, when the nonculprit lesion was reimaged and intervention performed. Blood samples were drawn at both times to assess CEC and transcriptomic profile in PBMC. RESULTS: Baseline OCT minimal fibrous cap thickness (FCT) was 100.9 ± 41.7 µm, which increased to 108.6 ± 39.6 µm at follow-up, and baseline CEC was 0.81 ± 0.14, which increased at follow-up to 0.84 ± 0.14 (p = 0.003). Thin-cap fibroatheroma prevalence decreased from 20.0% to 7.1% (p = 0.003). Changes in FCT were independently associated with CEC increase by multivariate analysis (ß: 0.30; p = 0.01). PBMC microarray analysis detected 117 genes that were differentially expressed at follow-up compared to baseline, including genes playing key roles in cholesterol synthesis (SQLE), regulation of fatty acids unsaturation (FADS1), cellular cholesterol uptake (LDLR), efflux (ABCA1 and ABCG1), and inflammation (DHCR24). Weighted coexpression network analysis revealed unique clusters of genes associated with favorable FCT and CEC changes. CONCLUSIONS: The study demonstrated an independent association between fibrous cap thickening and improved CEC that may contribute to morphological changes suggesting plaque stabilization among patients taking intensive statin therapy. Furthermore, the significant perturbations in PBMC transcriptome may help determine the beneficial effects of statin on plaque stabilization. (Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering [YELLOW II]; NCT01837823).

Trial design: Rivaroxaban for the prevention of major cardiovascular events after transcatheter aortic valve replacement: Rationale and design of the GALILEO study.

BACKGROUND: Optimal antithrombotic treatment after transcatheter aortic valve replacement (TAVR) is unknown and determined empirically. The direct factor Xa inhibitor rivaroxaban may potentially reduce TAVR-related thrombotic complications and premature valve failure. DESIGN: GALILEO is an international, randomized, open-label, event-driven, phase III trial in more than 1,520 patients without an indication for oral anticoagulation who underwent a successful TAVR (ClinicalTrials.govNCT02556203). Patients are randomized (1:1 ratio), 1 to 7days after a successful TAVR, to either a rivaroxaban-based strategy or an antiplatelet-based strategy. In the experimental arm, subjects receive rivaroxaban (10mg once daily [OD]) plus acetylsalicylic acid (ASA, 75-100mg OD) for 90days followed by rivaroxaban alone. In the control arm, subjects receive clopidogrel (75mg OD) plus ASA (as above) for 90days followed by ASA alone. In case new-onset atrial fibrillation occurs after randomization, full oral anticoagulation will be implemented with maintenance of the original treatment assignment. The primary efficacy end point is the composite of all-cause death, stroke, myocardial infarction, symptomatic valve thrombosis, pulmonary embolism, deep venous thrombosis, and systemic embolism. The primary safety end point is the composite of life-threatening, disabling, and major bleeding, according to the Valve Academic Research Consortium definitions. CONCLUSIONS: GALILEO will test the hypothesis that a rivaroxaban-based antithrombotic strategy reduces the risk of thromboembolic complications post-TAVR with an acceptable risk of bleeding compared with the currently recommended antiplatelet therapy-based strategy in subjects without need of chronic oral anticoagulation.

Recurrent Hospitalization Among Patients With Atrial Fibrillation Undergoing Intracoronary Stenting Treated With 2 Treatment Strategies of Rivaroxaban or a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy.

BACKGROUND: Patients with atrial fibrillation who undergo intracoronary stenting traditionally are treated with a vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT), yet this treatment leads to high risks of bleeding. We hypothesized that a regimen of rivaroxaban plus a P2Y12 inhibitor monotherapy or rivaroxaban plus DAPT could reduce bleeding and thereby have a favorable impact on all-cause mortality and the need for rehospitalization. METHODS: Stented subjects with nonvalvular atrial fibrillation (n=2124) were randomized 1:1:1 to administration of reduced-dose rivaroxaban 15 mg daily plus a P2Y12 inhibitor for 12 months (group 1); rivaroxaban 2.5 mg twice daily with stratification to a prespecified duration of DAPT of 1, 6, or 12 months (group 2); or the reference arm of dose-adjusted VKA daily with a similar DAPT stratification (group 3). The present post hoc analysis assessed the end point of all-cause mortality or recurrent hospitalization for an adverse event, which was further classified as the result of bleeding, a cardiovascular cause, or another cause blinded to treatment assignment. RESULTS: The risk of all-cause mortality or recurrent hospitalization was 34.9% in group 1 (hazard ratio=0.79; 95% confidence interval, 0.66-0.94; P=0.008 versus group 3; number needed to treat=15), 31.9% in group 2 (hazard ratio=0.75; 95% confidence interval, 0.62-0.90; P=0.002 versus group 3; number needed to treat=10), and 41.9% in group 3 (VKA+DAPT). Both all-cause death plus hospitalization potentially resulting from bleeding (group 1=8.6% [P=0.032 versus group 3], group 2=8.0% [P=0.012 versus group 3], and group 3=12.4%) and all-cause death plus rehospitalization potentially resulting from a cardiovascular cause (group 1=21.4% [P=0.001 versus group 3], group 2=21.7% [P=0.011 versus group 3], and group 3=29.3%) were reduced in the rivaroxaban arms compared with the VKA arm, but other forms of rehospitalization were not. CONCLUSIONS: Among patients with atrial fibrillation undergoing intracoronary stenting, administration of either rivaroxaban 15 mg daily plus P2Y12 inhibitor monotherapy or 2.5 mg rivaroxaban twice daily plus DAPT was associated with a reduced risk of all-cause mortality or recurrent hospitalization for adverse events compared with standard-of-care VKA plus DAPT. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01830543.

Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI.

BACKGROUND: In patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) with placement of stents, standard anticoagulation with a vitamin K antagonist plus dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor and aspirin reduces the risk of thrombosis and stroke but increases the risk of bleeding. The effectiveness and safety of anticoagulation with rivaroxaban plus either one or two antiplatelet agents are uncertain. METHODS: We randomly assigned 2124 participants with nonvalvular atrial fibrillation who had undergone PCI with stenting to receive, in a 1:1:1 ratio, low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 months (group 1), very-low-dose rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, or 12 months (group 2), or standard therapy with a dose-adjusted vitamin K antagonist (once daily) plus DAPT for 1, 6, or 12 months (group 3). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to Thrombolysis in Myocardial Infarction [TIMI] criteria or bleeding requiring medical attention). RESULTS: The rates of clinically significant bleeding were lower in the two groups receiving rivaroxaban than in the group receiving standard therapy (16.8% in group 1, 18.0% in group 2, and 26.7% in group 3; hazard ratio for group 1 vs. group 3, 0.59; 95% confidence interval [CI], 0.47 to 0.76; P<0.001; hazard ratio for group 2 vs. group 3, 0.63; 95% CI, 0.50 to 0.80; P<0.001). The rates of death from cardiovascular causes, myocardial infarction, or stroke were similar in the three groups (Kaplan-Meier estimates, 6.5% in group 1, 5.6% in group 2, and 6.0% in group 3; P values for all comparisons were nonsignificant). CONCLUSIONS: In participants with atrial fibrillation undergoing PCI with placement of stents, the administration of either low-dose rivaroxaban plus a P2Y12 inhibitor for 12 months or very-low-dose rivaroxaban plus DAPT for 1, 6, or 12 months was associated with a lower rate of clinically significant bleeding than was standard therapy with a vitamin K antagonist plus DAPT for 1, 6, or 12 months. The three groups had similar efficacy rates, although the observed broad confidence intervals diminish the surety of any conclusions regarding efficacy. (Funded by Janssen Scientific Affairs and Bayer Pharmaceuticals; PIONEER AF-PCI ClinicalTrials.gov number, NCT01830543 .).

Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction: The AEGIS-I Trial (ApoA-I Event Reducing in Ischemic Syndromes I).

BACKGROUND: Human or recombinant apolipoprotein A-I (apoA-I) has been shown to increase high-density lipoprotein-mediated cholesterol efflux capacity and to regress atherosclerotic disease in animal and clinical studies. CSL112 is an infusible, plasma-derived apoA-I that has been studied in normal subjects or those with stable coronary artery disease. This study aimed to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of CSL112 in patients with a recent acute myocardial infarction. METHODS: The AEGIS-I trial (Apo-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b trial. Patients with myocardial infarction were stratified by renal function and randomized 1:1:1 to CSL112 (2 g apoA-I per dose) and high-dose CSL112 (6 g apoA-I per dose), or placebo for 4 consecutive weekly infusions. Coprimary safety end points were occurrence of either a hepatic safety event (an increase in alanine transaminase >3 times the upper limit of normal or an increase in total bilirubin >2 times the upper limit of normal) or a renal safety event (an increase in serum creatinine >1.5 times the baseline value or a new requirement for renal replacement therapy). RESULTS: A total of 1258 patients were randomized, and 91.2% received all 4 infusions. The difference in incidence rates for an increase in alanine transaminase or total bilirubin between both CSL112 arms and placebo was within the protocol-defined noninferiority margin of 4%. Similarly, the difference in incidence rates for an increase in serum creatinine or a new requirement for renal replacement therapy was within the protocol-defined noninferiority margin of 5%. CSL112 was associated with increases in apoA-I and ex vivo cholesterol efflux similar to that achieved in patients with stable coronary artery disease. In regard to the secondary efficacy end point, the risk for the composite of major adverse cardiovascular events among the groups was similar. CONCLUSIONS: Among patients with acute myocardial infarction, 4 weekly infusions of CSL112 are feasible, well tolerated, and not associated with any significant alterations in liver or kidney function or other safety concern. The ability of CSL112 to acutely enhance cholesterol efflux was confirmed. The potential benefit of CSL112 to reduce major adverse cardiovascular events needs to be assessed in an adequately powered phase 3 trial. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02108262.

An open-label, randomized, controlled, multicenter study exploring two treatment strategies of rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in subjects with atrial fibrillation who undergo percutaneous coronary intervention (PIONEER AF-PCI).

BACKGROUND: Guidelines recommendations regarding anticoagulant therapy after percutaneous coronary intervention (PCI) among patients with atrial fibrillation (AF) rely on retrospective, nonrandomized observational data. Currently, patients are treated with triple-therapy (dual antiplatelet therapy [DAPT] + oral anticoagulation therapy), but neither the duration of DAPT nor the level of anticoagulation has been studied in a randomized fashion. Recent studies also suggest dual pathway therapy with clopidogrel plus oral anticoagulation therapy may be superior, and other studies suggest that novel oral anticoagulants such as rivaroxaban may further improve patient outcomes. DESIGN: PIONEER AF-PCI (ClinicalTrials.gov NCT01830543) is an exploratory, open-label, randomized, multicenter clinical study assessing the safety of 2 rivaroxaban treatment strategies and 1 vitamin K antagonist (VKA) treatment strategy in subjects who have paroxysmal, persistent, or permanent nonvalvular AF and have undergone PCI with stent placement. Approximately 2,100 subjects will be randomized in a 1:1:1 ratio to receive either rivaroxaban 15 mg once daily plus clopidogrel 75 mg daily for 12 months (a WOEST trial-like strategy), or rivaroxaban 2.5 mg twice daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, an ATLAS trial-like strategy), or dose-adjusted VKA once daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, traditional triple therapy). All patients will be followed up for 12 months for the primary composite end point of Thrombolysis in Myocardial Infarction major bleeding, bleeding requiring medical attention, and minor bleeding (collectively, clinically significant bleeding). CONCLUSION: The PIONEER AF-PCI study is the first randomized comparison of VKA vs novel oral anticoagulant therapy in patients with NVAF receiving antiplatelet therapy after PCI to assess the relative risks of bleeding complications.

Balancing ischaemia and bleeding risks with novel oral anticoagulants.

Vitamin K antagonists (VKAs) have long been the standard of care for treatment of venous thromboembolism (VTE), and thromboprophylaxis in atrial fibrillation (AF). Despite their efficacy, their use requires frequent monitoring and is complicated by drug-drug interactions and the need to maintain a narrow therapeutic window. Since 2009, novel oral anticoagulants (NOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, have become alternative options to VKAs owing to their predictable and safe pharmacological profiles. The overall clinical effect of these drugs, which is a balance between ischaemic benefit and bleeding harm, varies according to the clinical scenario. As adjunctive therapy to dual antiplatelet therapy in patients with acute coronary syndrome, NOACs are associated with incremental bleeding risks and modest benefits. For treatment of VTE, NOACs have a safer profile than VKAs and a similar efficacy. In thromboprophylaxis in AF, NOACs are associated with the greatest benefits by reducing both ischaemic events and haemorrhagic complications and might reduce mortality compared with VKAs. The role of NOACs continues to evolve as these drugs are evaluated in different patient populations, including those with renal impairment or with AF and undergoing percutaneous coronary intervention.

Impact of time to treatment on myocardial reperfusion and infarct size with primary percutaneous coronary intervention for acute myocardial infarction (from the EMERALD Trial).

The impact of time to treatment on outcomes after primary percutaneous coronary intervention (PCI) is controversial, and there are few data about time to treatment and infarct size. The EMERALD trial randomly assigned 501 high-risk patients with ST-elevation myocardial infarction undergoing primary PCI to stenting with or without GuardWire (Medtronic, Santa Rosa, California) distal protection. Infarct size using sestamibi imaging at 5 to 14 days and clinical outcomes were examined by time to treatment. There were no differences in outcomes between distal protection and control patients. Shorter time to reperfusion (<2 vs 2 to 3 vs >3 to 4 vs >4 hours) was associated with smaller infarct size (2% vs 9% vs 12% vs 11%, p=0.026), trends for better myocardial blush (p=0.08), and lower 6-month mortality rates (0% vs 0% vs 2.4% vs 5.3%, p=0.06). Incremental delays in reperfusion after 2 hours had little impact on infarct size. Shorter time to reperfusion impacted on infarct size in patients with anterior infarction (0% vs 17% vs 20.5% vs 30.5%, p=0.026), but not nonanterior infarction (3% vs 7% vs 7.5% vs 10%, p=0.23, p=0.022 for interaction). In conclusion, very early reperfusion with primary PCI is associated with smaller infarct size and has a much greater impact in anterior versus nonanterior infarction. Incremental delays in reperfusion after 2 hours have less effect on infarct size. These data have implications regarding the triage of patients for primary PCI.

Estrogen-eluting, phosphorylcholine-coated stent implantation is associated with reduced neointimal formation but no delay in vascular repair in a porcine coronary model.

Estrogen can inhibit intimal proliferation and accelerate endothelial regeneration after angioplasty. This suggests that estrogen may prevent in-stent restenosis. Unlike other therapies to prevent restenosis, estrogen may also not delay endothelial regrowth, thereby avoiding the risk of late stent thrombosis. The purpose of this work was to determine the effect of a 17beta-estradiol-eluting stent on neointimal formation in a porcine model. Each artery of six pigs was randomized to either a control, low-dose, or high-dose 17beta-estradiol-eluting stent. All animals were sacrificed at 30 days for histopathological analysis. There was a 40% reduction in intimal area in the high-dose stents compared with control stents (2.54 +/- 1.0 vs. 4.13 +/- 1.1 mm(2), for high dose vs. control, respectively; P < 0.05). There was complete endothelial regeneration at 30 days and similar inflammatory response to stenting on histopathology in all the stent groups. This is the first study to show that 17beta-estradiol-eluting stents are associated with reduced neointimal formation without affecting endothelial regeneration in the pig model of in-stent restenosis. Estrogen-coated stents may have a potential benefit in the prevention and treatment of in-stent restenosis.