ALBERT

Description: Introduction US Food and Drug Administration has recently approved the use of rivaroxaban 2.5mg BID in patients with coronary heart disease based on Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial. However, it's unclear whether there is net clinical benefit with use of rivaroxaban in such patients. Therefore, we did a systematic review and meta-analysis to evaluate the effects of rivaroxaban on clinical outcomes in coronary heart disease patients. Methods: Embase, Ovid, Pubmed and Scopus were extensively searched from inception of these databases to April 2019 by two independent reviewers. Only randomized controlled trials of low dose rivaroxaban (2.5 mg BID) reporting mortality and cardiovascular outcomes of interest in baseline coronary heart disease patients (≥ 18 years) with at least 1000 patients and follow-up of ≥ 1 year were included. The co-primary outcomes were cardiovascular mortality and all-cause mortality. The secondary endpoints were myocardial infarction (MI), stroke, major adverse cardiovascular events, major bleeding and cerebral nervous system (CNS) bleeding. Cochrane Collaboration's tool was used for risk of bias assessment. Statistical heterogeneity was quantified using I2 statistics whereas publication bias was assessed with Eggers regression test. We combined estimates using DerSimonian and Laird random effects models. Outcomes were reported as hazard ratios (HR) with 95% confidence intervals (CI). Results: Five randomized control trials including 39,979 patients were included in our meta-analysis. Trials ATLAS and Commander HF used placebo as their control while COMPASS and GEMINI ACS-1 used aspirin as control. Pioneer AF-PCI used vitamin K antagonist as the control. Mean age (SD) of the patients was 65.6 ± 3.7 years with 74.3% females. Mean follow up in years was 1.6 ±0.5. Majority of the patients in each trial had hypertension. Our pooled analysis showed reduction in all-cause mortality (HR, 0.85, 95% CI, 0.72-1.00, P=0.05), cardiovascular mortality (HR, 0.83, 95% CI, 0.70-1.00, P=0.05), MI (HR, 0.88, 95% CI, 0.78-1.00, P=0.05) and stroke (HR, 0.70, 95% CI, 0.53-0.94, P=0.02) with low dose rivaroxaban. No significant difference in risk of bleeding was observed (HR, 1.45, 95% CI, 0.83-2.51, P=0.19). Our pooled analysis also showed reduction in major cardiovascular events (HR, 0.91, 95% CI, 0.85-0.98, P=0.01). CNS bleeding was only reported by ATLAS and COMPASS trials and net effect showed no statistically significant bleeding risk (HR, 1.63, 95% CI, 0.70-3.79, P=0.26). Conclusion: Our data suggest that the use of rivaroxaban is associated with reduction in all-cause and cardiovascular mortality in coronary heart disease patients without significantly increasing the risk of bleeding. To further decrease the residual risk of cardiovascular events in coronary heart disease patients, low dose rivaroxaban can be considered by clinicians. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Current expert recommendations recommend double therapy (DT) over triple therapy (TT) in atrial fibrillation patients post percutaneous coronary intervention (PCI) to prevent the incidence of stroke. Though previous studies have focused on DT (oral anticoagulant [OAC] + P2Y12 inhibitor (including clopidogrel, ticagrelor and prasugrel)) versus TT (OAC + P2Y12 inhibitor and aspirin) strategy, no study assessed which OAC was more effective in the prevention of cardiovascular events and stroke. To this end we performed a systematic review and meta-analysis to assess whether non-vitamin K oral anticoagulants (NOAC) based DT strategy is comparable with vitamin K antagonist-based TT in patients with AF after PCI. Methods: Embase, Ovid, Pubmed and Scopus were extensively searched for only phase 2 and 3 clinical trials comparing NOAC based DT with VKA based TT from inception of these databases till June 2019 by two independent reviewers. The endpoints were all-cause mortality, Thrombolysis in Myocardial Infarction (TIMI) major bleeding, cardiovascular mortality and myocardial infarction. Cochrane Collaboration's tool was used for risk of bias assessment. Statistical heterogeneity was quantified using I2 statistics. Publication bias was assessed with Eggers regression test. Estimates were reported as hazard ratios (HR) with 95% confidence intervals (CI) using random effect model. Rivaroxaban 15 mg once daily dose from PIONEER-AF was included. From REDUAL-PCI trial we included dabigatran 110 mg BID and 150 mg BID doses. AUGUSTUS trial used 5 mg BID or 2.5 mg BID dosing of apixaban. Results: 402 trials were retrieved in the initial search which were analyzed according to PRISMA (Preferred Reporting Items for Systematic review and Meta-Analyses) guidelines. Three trials (Augustus, PIONEER AF-PCI and RE-DUAL PCI) were extracted that met the inclusion criteria and included in the final analysis evaluating 8754 patients. Twenty seven percent were females. Mean age was 71 years. PCI was done for acute coronary syndrome in 44% of the patients. Mean calculated CHA2DS2-VASc was 4 which qualifies the use of oral anticoagulants. Only PIONEER AF-PCI and RE-DUAL PCI trials described the type of stent used for PCI. Drug eluting stents were used in 71% of the patients. There was no evidence of publication bias in our analysis (P=.78). The studies overall had low risk of bias. Our analysis showed no statistically significant difference in usage of NOAC + P2Y12 inhibitor compared to triple therapy consisting vitamin K antagonist in regards to all-cause mortality, (HR 0.92, 95% CI 0.72-1.18, P=.52), thrombolysis in myocardial infarction (TIMI) major bleeding (HR 0.91, 95% CI 0.38-2.16, P=.83), cardiovascular mortality (HR 0.95, 95% CI 0.71-1.28, P=.75), stroke (HR 1.07, 95% CI 0.67-1.71, P=.78),stent thrombosis (HR 0.72, 95% CI 0.42-1.23, P=0.23) and myocardial infarction (HR 0.88, 95% CI 0.68-1.13, P=.32). Conclusion: We conclude that there is no difference between the usage of NOAC including rivaroxaban, dabigatran and apixaban in dual regimen vs triple therapy with VKA (warfarin). However, some limitations need to be considered such as heterogeneity across patients in terms of indication for PCI (elective vs emergency), choice of P2Y12 inhibitor (clopidogrel vs ticagrelor vs prasugrel), mean duration of therapy (range 6-12 months) and mean length of follow-up (range 6-14 months). In future clinical practice, post-PCI antithrombotic regimens in AF will likely consist of a single P2Y12 inhibitor plus NOAC. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Spleen tyrosine kinase (Syk), a cytoplasmic tyrosine kinase, is a member of the non-receptor type protein kinase family. Apart from the hematopoietic cells, it is also expressed in the epithelial and endothelial cells. Fostamatinib, a Syk inhibitor, has been proven beneficial in autoimmune disease like rheumatoid arthritis (RA) and immune thrombocytopenia (ITP). Murine models have shown a direct correlation between hypertension and level of R406, the active metabolite of fostamatinib. In this study, we sought to examine the cardiovascular profile of fostamatinib in published and unpublished randomized controlled trials. Methods: A systematic search of Pubmed, Medline and Scopus databases were done from inception till date to identify all phase 2 and 3 clinical trials of fostamatinib in patients with ITP and RA by two independent reviewers. Trials were included if they reported side effects including but not limited to cerebral ischemia or infarction, myocardial ischemia and myocardial infarction, hypertension and cardiac rhythm disorders. 35 trials were retrieved in the initial search which were excluded according to PRISMA (Preferred Reporting Items for Systematic review and Meta-Analyses) guidelines. 11 trials met the eligibility criteria and were included in the final analysis. All statistical analysis was carried out using OpenMetaAnalyst software. Categorical variables from each study are presented as proportions. The proportions from each study were subjected to arcsine transformation and pooled using a random-effects model. This yielded the pooled estimate with 95% confidence intervals. The I2 statistic was used to assess heterogeneity and a value of I2 = 25%-50% was considered mild, 50%-75% as moderate, and 〉 75% as severe. A P value of