Major Bleeding in Patients With Coronary or Peripheral Artery Disease Treated With Rivaroxaban Plus Aspirin.

Background: In patients with coronary or peripheral artery disease, the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced major adverse cardiovascular events and mortality and increased bleeding.

Objectives: This study sought to explore the effects of the combination of rivaroxaban and aspirin compared with aspirin on sites, timing, severity, and management of bleeding in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) study.

Bleeding and New Cancer Diagnosis in Patients With Atherosclerosis.

Background: Patients treated with antithrombotic drugs are at risk of bleeding. Bleeding may be the first manifestation of underlying cancer.

Methods: We examined new cancers diagnosed in relation to gastrointestinal or genitourinary bleeding among patients enrolled in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) and determined the hazard of new cancer diagnosis after bleeding at these sites.

Rivaroxaban Plus Aspirin Versus Aspirin in Relation to Vascular Risk in the COMPASS Trial.

Background: The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial showed that the combination of low-dose rivaroxaban and aspirin reduced major vascular events in patients with stable vascular disease.

Objectives: The purpose of this study was to identify subsets of patients at higher risk of recurrent vascular events, which may help focus the use of rivaroxaban and aspirin therapy.

Methods: COMPASS patients with vascular disease were risk stratified using 2 methods: the REACH (REduction of Atherothrombosis for Continued Health) atherothrombosis risk score and CART (Classification and Regression Tree) analysis.

Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin.

Background & Aims: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial.

Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-Blind, Placebo-Controlled Trial.

Background & Aims: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk.

Methods: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease.

Stroke Outcomes in the COMPASS Trial.

Background: Strokes were significantly reduced by the combination of rivaroxaban plus aspirin in comparison with aspirin in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies). We present detailed analyses of stroke by type, predictors, and antithrombotic effects in key subgroups.

Methods: Participants had stable coronary artery or peripheral artery disease and were randomly assigned to receive aspirin 100 mg once daily (n=9126), rivaroxaban 5 mg twice daily (n=9117), or rivaroxaban 2.

Rationale, design, and baseline participant characteristics in the MRI and cognitive substudy of the cardiovascular outcomes for people using anticoagulation strategies trial.

Background: Covert vascular disease of the brain manifests as infarcts, white matter hyperintensities, and microbleeds on MRI. Their cumulative effect is often a decline in cognition, motor impairment, and psychiatric disorders. Preventive therapies for covert brain ischemia have not been established but represent a huge unmet clinical need.

Major Adverse Limb Events and Mortality in Patients With Peripheral Artery Disease: The COMPASS Trial.

Background: Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There is limited information on the prognosis of patients who experience MALE.

Objectives: Among participants with lower extremity PAD, this study investigated: 1) if hospitalizations, MACE, amputations, and deaths are higher after the first episode of MALE compared with patients with PAD who do not experience MALE; and 2) the impact of treatment with low-dose rivaroxaban and aspirin compared with aspirin alone on the incidence of MALE, peripheral vascular interventions, and all peripheral vascular outcomes over a median follow-up of 21 months.

Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease.

Background: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention.

Methods: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily).

Rationale, Design and Baseline Characteristics of Participants in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) Trial.

Background: Long-term aspirin prevents vascular events but is only modestly effective. Rivaroxaban alone or in combination with aspirin might be more effective than aspirin alone for vascular prevention in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). Rivaroxaban as well as aspirin increase upper gastrointestinal (GI) bleeding and this might be prevented by proton pump inhibitor therapy.

The treatment of missing data in a large cardiovascular clinical outcomes study.

Background: The potential impact of missing data on the results of clinical trials has received heightened attention recently. A National Research Council study provides recommendations for limiting missing data in clinical trial design and conduct, and principles for analysis, including the need for sensitivity analyses to assess robustness of findings to alternative assumptions about the missing data. A Food and Drug Administration advisory committee raised missing data as a serious concern in their review of results from the ATLAS ACS 2 TIMI 51 study, a large clinical trial that assessed rivaroxaban for its ability to reduce the risk of cardiovascular death, myocardial infarction or stroke in patients with acute coronary syndrome.

Agents with vasodilator properties in acute heart failure: how to design successful trials.

Agents with vasodilator properties (AVDs) are frequently used in the treatment of acute heart failure (AHF). AVDs rapidly reduce preload and afterload, improve left ventricle to aorta and right ventricle to pulmonary artery coupling, and may improve symptoms. Early biomarker changes after AVD administration have suggested potentially beneficial effects on cardiac stretch, vascular tone, and renal function.

Rivaroxaban: a novel oral anticoagulant for the prevention and treatment of several thrombosis-mediated conditions.

The development of rivaroxaban (XARELTO®) is an important new medical advance in the field of oral anticoagulation. Thrombosis-mediated conditions constitute a major burden for patients, healthcare systems, and society. For more than 60 years, the prevention and treatment of these conditions have been dominated by oral vitamin K antagonists (such as warfarin) and the injectable heparins.

Rivaroxaban in patients with a recent acute coronary syndrome.

Background: Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome.

Methods: In this double-blind, placebo-controlled trial, we randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.

Rationale and design of the Anti-Xa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome-thrombolysis in myocardial infarction 51 (ATLAS-ACS 2 TIMI 51) trial: a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of rivaroxaban in subjects with acute coronary syndrome.

Background: Although therapy with aspirin or aspirin plus a thienopyridine reduces the incidence of long-term adverse cardiovascular events among patients with acute coronary syndrome (ACS), there remains a significant residual risk of cardiovascular death, recurrent myocardial infarction (MI), and stroke. In a phase 2 trial (ClinicalTrials.gov NCT00402597) in which the addition of the factor Xa inhibitor rivaroxaban was compared with placebo, among ACS patients receiving either aspirin alone or dual-antiplatelet therapy with aspirin and a thienopyridine, the end point of death, MI, or stroke compared with placebo was reduced (87/2331 [3.

Predictors of improved renal function after percutaneous stent-supported angioplasty of severe atherosclerotic ostial renal artery stenosis.

Background: Percutaneous stent-supported angioplasty is a treatment option for atherosclerotic ostial renal artery stenosis. Improvement of renal function by such intervention, however, is controversial and thought to be limited to specific subsets, such as nondiabetic patients and bilateral stenoses. In this prospective study, we investigated predictors for improvement of renal function and blood pressure after renal artery stent placement.

Stent angioplasty of severe atherosclerotic ostial renal artery stenosis in patients with diabetes mellitus and nephrosclerosis.

Atherosclerotic renal artery stenosis (ARAS) may lead to deterioration of renal function or hypertension. The clinical outcome after stent angioplasty of ARAS on renal function and blood pressure control in patients with diabetes and nephrosclerosis is the subject of some controversy. We have analyzed the results of our single-center experience with stent angioplasty for severe (>/= 70%) ostial ARAS and present here the results of a subgroup analysis of those patients who had diabetes mellitus and nephrosclerosis.