Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation.

BACKGROUND: Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation has been limited. METHODS: We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2DS2VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis. RESULTS: Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, -76 days; 95% confidence interval [CI], -121 to -31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted. CONCLUSIONS: Among patients with rheumatic heart disease-associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.).

Effect of Corticosteroid Therapy in Patients With Cardiac Sarcoidosis on Frequency of Venous Thromboembolism.

Sarcoidosis is a multisystem inflammatory condition with occasional cardiac involvement (CS), which may be associated with risk of venous thromboembolism (VTE). As data on VTE in CS are sparse and corticosteroid therapy has not been previously examined, we aim to determine the association between CS, corticosteroid treatment for CS, and VTE. Patients referred to our institution with concern for sarcoidosis and underwent a positron emission tomography (PET) scan were retrospectively assessed. Chi-squared and multivariate regression analyses were conducted to determine the association between a diagnosis of sarcoidosis, CS, corticosteroid use, and VTE events. Six hundred and forty nine patients were split into 3 categories: 235 with no sarcoidosis (NS), 91 with extra-cardiac sarcoidosis only (ECS), and 323 with CS (isolated CS and/or CS with extra cardiac sarcoid). Thirty nine CS, 7 ECS, and 9 NS patients developed PE while 44 CS, 3 ECS, and 18 NS patients developed DVT. On multivariate regression, neither CS nor ECS was an independent risk factor for VTE (p >0.05) but corticosteroid use was independently associated with VTE (HR 3.06, p = 0.007 for PE, HR 6.21, p <0.0001 for DVT). On logistic regression analysis, corticosteroid dose was found to be independently associated with both PE (p = 0.001) and DVT (p = 0.007). Optimal threshold for defining VTE risk with corticosteroid therapy was a prednisone-equivalent dose of 17.5 mg. In conclusion, contrary to previous studies, this current study found that neither sarcoidosis nor CS is an independent risk factor for VTE. Rather, corticosteroid therapy was associated with an increased risk of VTE.

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation.

BACKGROUND: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need. METHODS: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD. CONCLUSION: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.

Effectiveness of theophylline in preventing contrast-induced nephropathy after coronary angiographic procedures.

BACKGROUND: Contrast-induced nephropathy (CIN) is the third most common cause of hospital acquired acute renal failure and is associated with increased morbidity and mortality. The use of theophylline for prevention of CIN has yielded conflicting results. This study aimed at examining the effectiveness of theophylline in prevention of CIN when added to IV hydration and N-acetylcysteine (NAC). METHODS: Patients with stable serum creatinine and at least moderate risk for CIN according to Mehran's risk score were included in this parallel group, 1:1, single-blind, randomized controlled trial. All patients received IV hydration (1 mL/kg per hour for 24 hours) and NAC (600 mg bid for 2 days). Patients were randomized to placebo (group P) or theophylline (200 mg in 100 mL 0.9% saline, as IV infusion 30 minutes before contrast medium (CM) administration; group T). Patients underwent standard coronary angiography ± angioplasty. Serum creatinine (SCr) was assessed just before and 72 hours after contrast administration and estimated glomerular filtration rate (eGFR) was calculated. RESULTS: This study included 60 patients with mean SCr 1.44 ± 0.7 mg/dL and eGFR 60.2 ± 29.2 mL/min. Mean SCr among group T was 1.54 ± 0.7 mg/dL with eGFR 58.6 ± 28.6 mL/min, while group P showed mean SCr of 1.34 ± 0.7 mg/dL and eGFR of 61.8 ± 30.1 mL/min. Among group P, 6 (20%) patients developed CIN while none of the patients in group T developed CIN. In comparison to placebo, theophylline significantly decreased SCr (P = 0.0001) and increased eGFR (P = 0.001) at 72 hours. Multivariate regression analysis showed that receiving placebo instead of theophylline, anemia, congestive heart failure, chronic renal impairment, and high-contrast load are all independent predictors for deteriorating renal function after CM administration. CONCLUSION: Theophylline seems to be an effective prophylaxis against CIN for moderate- and high-risk patients undergoing coronary angiography or angioplasty. It offers additive protection when added to IV hydration and NAC.

Impact of bifurcation lesions on clinical outcome and prognosis of primary angioplasty in acute myocardial infarction.

AIMS: The aim of this study was to determine the impact of bifurcation lesions on outcomes after primary percutaneous intervention (PCI) for acute myocardial infarction. METHODS AND RESULTS: We retrospectively reviewed a single-centre database of 646 patients admitted for primary angioplasty within 12 hours after AMI. We compared baseline characteristics and outcomes between bifurcation and non-bifurcation lesions. Bifurcation lesions were found in 23% of patients. They predominantly involved the left anterior descending artery. Provisional T-stenting was used in 89.3% of patients (with stenting of the main branch in 82% and of both branches in 7.3%), side-branch protection in 54.6%, and final kissing balloon inflation in 33%. The procedural success rate was 92% for the main branch of bifurcation lesions compared with 93% for non-bifurcation lesions (P=0.65). Major adverse cardiac event (MACE) rates were comparable in the two groups: in-hospital MACE was 13.3% in the bifurcation group versus 11.4% in the non-bifurcation group (P=0.72), and the 1-year total MACE rate was 22.6% in the bifurcation group versus 19.5% in the non-bifurcation group (P=0.56). CONCLUSIONS: Bifurcation lesions are common in patients with AMI. In a population with AMI, immediate and mid-term outcomes of primary PCI were similar in patients with and without bifurcation lesions.

Comparison of real-time coherent contrast imaging to dipyridamole thallium-201 single-photon emission computed tomography for assessment of myocardial perfusion and left ventricular wall motion.

Real-time coherent contrast imaging (CCI) echocardiography has the ability to evaluate wall motion and myocardial perfusion simultaneously, but its clinical applicability in the diagnosis of coronary artery disease (CAD) remains to be determined. This study examines the level of agreement between real-time CCI echocardiography and thallium-201 single-photon emission computed tomography (SPECT) following stress vasodilation. Forty-two patients with known or suspected CAD underwent real-time CCI using octafluoropropane-filled microspheres infusion before and after dipyridamole and thallium-201 injections. The apical 4- and 2-chamber views were each divided into 6 segments to assess wall motion and perfusion. Real-time CCI and SPECT were interpreted independently. Thirty-eight patients successfully completed tests, and 4 had suboptimal contrast images. Each vascular territory was classified as normal or abnormal by CCI perfusion, wall motion, and SPECT at baseline and at stress. Of the 114 territories (3 in each of the 38 patients), 3 (3.5%) were not analyzed; however, all territories corresponding to the left anterior descending artery were suitable for analysis. Concordance between CCI echocardiography and thallium-201 SPECT perfusion for left anterior descending, left circumflex, and right coronary artery territories were 91%, 86%, and 69%, respectively; between CCI perfusion and wall motion, the correlations were 93%, 93%, and 91%, respectively. When CCI perfusion and wall motion analysis were combined, their concordance to thallium-201 SPECT uptake improved to 94%, 89%, and 79%, respectively. In conclusion, real-time CCI echocardiography agrees very closely with thallium-201 SPECT in assessing myocardial perfusion following vasodilatory stress. Assessment of myocardial perfusion, in addition to segmental wall motion analysis, during stress echocardiography may be a significant contribution to the noninvasive evaluation of patients with ischemic heart disease.