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Objectives This study sought to assess whether there were significant interactions of procedural access strategies and lesion characteristics with bleeding and ischemic events among atrial fibrillation (AF) patients anticoagulated with rivaroxaban or warfarin following a percutaneous coronary intervention. Background Among stented AF patients, the impact of procedural access strategies or lesion characteristics on antithrombotic safety and efficacy outcomes is unclear. Methods In the PIONEER AF-PCI (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) trial, 2,124 patients were randomized to 3 groups and followed for 12 months: 1) rivaroxaban 15 mg once daily plus a P2Y12 inhibitor (n = 709); 2) rivaroxaban 2.5 mg twice a day plus dual antiplatelet therapy (DAPT) (n = 709); and 3) dose-adjusted warfarin plus DAPT (n = 706). Kaplan-Meier rates of clinically significant bleeding and major adverse cardiovascular events were compared between treatments stratified by subgroups of procedure type and lesion characteristics. Results Compared with warfarin, both rivaroxaban regimens consistently reduced clinically significant bleeding across subgroups of radial versus femoral arterial access and by vascular closure device use. Treatment effect of rivaroxaban on major adverse cardiovascular events did not vary when stratified by ischemia-driven revascularization, urgency of revascularization, location of culprit artery, presence of bifurcation lesion, presence of thrombus, type, and length of stent or number of stents (interaction p > 0.05 for all subgroups). Conclusions Among stented AF patients requiring long-term oral anticoagulation, there was no effect modification by procedure or lesion characteristics of either clinically significant bleeding or major adverse cardiovascular events. Rivaroxaban-based therapy was superior to warfarin plus DAPT in bleeding outcomes regardless of the type of stent or arterial access during the index coronary revascularization. (A Study Exploring Two Strategies of Rivaroxaban [JNJ39039039; BAY-59-7939] and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention [PIONEER AF-PCI]; NCT01830543)

Background: The risk of tuberculosis (TB) is greater for individuals with human immunodeficiency virus (HIV) who are on combined antiretroviral therapy (c-ART) than for the normal population. Therefore, the detection and treatment of latent tuberculosis infections is recommended for all HIV-positive persons with positive tuberculin skin tests (TSTs). Materials and Methods: This retrospective cohort study included all HIV-positive individuals with CD4 lymphocyte counts greater than 200 cells/μL and negative TST results, who were taking antiretroviral drugs and had been referred to Imam Khomeini Teaching Hospital Consultation Centre for Clients with Risky Behaviors in Tehran, Iran, from 2008 to 2013. TST conversion to positivity is defined as an induration increase of at least 5 mm compared with a previously negative TST result within a 1-year period. Conversion rates are expressed in person-years of observation. Results: A total of 113 patients were included in our study. At 1 year, 9 of the 113 TST-negative patients taking c-ART became TST-positive (8%; 8 males and 1 female). The TST conversion incidence rate was 10.09/100 person-years. TST conversion was only found to be associated with sex (odds ratio: 8.64; 95% confidence interval: 1.04–7.56, p = 0.032). Conclusion: Our results suggest that TSTs should be administered to all HIV-positive patients before beginning isoniazid preventive therapy in Iran.

Supported by evidence from basic science, clinical, and epidemiological studies, the high-density lipoprotein (HDL) hypothesis posits that reduction in HDL levels may accelerate the development of coronary heart disease (CHD). HDL may also exert cardiovascular protection via anti- oxidative, anti-thrombotic, anti-inflammatory, and anti-apoptotic properties. However, controversial results from clinical trials involving HDL- raising interventions have cast doubts on the validity of HDL hypothesis. The coevolution of HDL physiology and CHD pathogenesis has prompted the revision of hypothesis, with an alternative focus on the functionality of HDL particles. Instead of raising the quantity of HDL, improving the quality of HDL by promoting reverse cholesterol transport may be a more appropriate strategy in preventing adverse cardiovascular events. Preliminary data suggest that administration of apolipoprotein A1 mimetic peptides and reconstituted HDL particles could be safe and effective in promoting plaque stabilization and regression. Future studies are warranted to clarify the effect of HDL subspecies on atherosclerosis and determine whether the effect could translate into cardiovascular benefits.

Dual antiplatelet therapy (DAPT) has been the cornerstone of antithrombotic management for patients undergoing percutaneous coronary intervention (PCI). However, approximately 10% of these patients have concomitant atrial fibrillation (AF) and require chronic oral anticoagulant (OAC) in addition to DAPT. This traditional "triple therapy" has been associated with a three to four-fold increased risk of bleeding. The safety of non-vitamin K OAC (NOAC)-based strategies, using a NOAC plus a P2Y12 inhibitor, has been compared to vitamin K antagonist (VKA)-based triple therapy in the PIONEER AF-PCI and REDUAL PCI randomized trials, both of which have demonstrated that NOAC-based strategies are safer and provide an attractive alternative to VKA-based triple therapy among AF patients who undergo PCI. This article reviews the rationale, evidence, and recent evaluation of triple antithrombotic therapy among AF patients undergoing PCI.

The concurrence of atrial fibrillation and acute coronary syndrome poses a conundrum in the antithrombotic management as intensification of anticoagulation or antiplatelet therapy inevitably comes at the price of an increased bleeding risk. Various antithrombotic combinations have been attempted to prevent the recurrent cardiovascular events, however, there has been limited success in effective risk reduction for this high risk population. Given the overarching effect of interleukin 1β-driven inflammation on the arrhythmogenesis, thrombogenesis, and hypercoagulability, we hypothesize that the triple-pathway strategy (i.e., incorporating antiinflammatory therapy into anticoagulant and antiplatelet therapy) would grant incremental cardiovascular benefits for atrial fibrillation patients with coexisting acute coronary syndrome and stent placement.

This study sought to assess whether there were significant interactions of procedural access strategies and lesion characteristics with bleeding and ischemic events among atrial fibrillation (AF) patients anticoagulated with rivaroxaban or warfarin following a percutaneous coronary intervention.Among stented AF patients, the impact of procedural access strategies or lesion characteristics on antithrombotic safety and efficacy outcomes is unclear.In the PIONEER AF-PCI (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) trial, 2,124 patients were randomized to 3 groups and followed for 12 months: 1) rivaroxaban 15 mg once daily plus a P2YCompared with warfarin, both rivaroxaban regimens consistently reduced clinically significant bleeding across subgroups of radial versus femoral arterial access and by vascular closure device use. Treatment effect of rivaroxaban on major adverse cardiovascular events did not vary when stratified by ischemia-driven revascularization, urgency of revascularization, location of culprit artery, presence of bifurcation lesion, presence of thrombus, type, and length of stent or number of stents (interaction p0.05 for all subgroups).Among stented AF patients requiring long-term oral anticoagulation, there was no effect modification by procedure or lesion characteristics of either clinically significant bleeding or major adverse cardiovascular events. Rivaroxaban-based therapy was superior to warfarin plus DAPT in bleeding outcomes regardless of the type of stent or arterial access during the index coronary revascularization. (A Study Exploring Two Strategies of Rivaroxaban [JNJ39039039; BAY-59-7939] and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention [PIONEER AF-PCI]; NCT01830543).

Andexanet alfa is a recombinant factor Xa decoy molecule that inhibits direct and indirect factor Xa inhibitors to allow the normal coagulation process to resume. Its development arises in a space where novel oral anticoagulants are receiving expanded indications yet their use is limited by the lack of an effective reversal agent. Areas covered: This article reviews the biochemical properties, mechanism of action and the preclinical and clinical trials on andexanet alfa. It additionally aims to provide expert commentary and future perspectives on the efficacy, safety and challenges facing andexanet alfa as a universal antidote for direct and indirect factor Xa inhibitors. Expert commentary: Andexanet alfa shows promise to become a highly effective, novel antidote for factor Xa anticoagulation. Its biochemical profile and mechanism of action are immediately more attractive than other drugs on the market and under development due to its inert nature within the normal coagulation cascade, with minimal intrinsic procoagulant or anticoagulant properties. The anticoagulant antidote space will continue to develop as more specific and universal options become available for reversal of the effect of DOACs. Preliminary results of a pivotal phase 3b/4 trial demonstrate a favorable efficacy and safety profile in patients with acute hemorrhage.

Dual antiplatelet therapy (DAPT) has been the mainstay of antithrombotic management for acute coronary syndrome (ACS). Approximately 5-10% of patients experience recurrent events despite standard treatment, and there is an unmet demand for secondary cardiovascular prevention in the post-ACS setting