Xarelto plus Acetylsalicylic acid: Treatment patterns and Outcomes in patients with Atherosclerosis (XATOA): Rationale and design of a prospective registry study to assess rivaroxaban 2.5 mg twice daily plus aspirin for prevention of atherothrombotic events in coronary artery disease, peripheral artery disease, or both.

Patients with coronary artery disease (CAD), peripheral artery disease (PAD), or both remain at risk of cardiovascular events (including peripheral ischemic events), even when they receive the current guideline-recommended treatment. The phase III COMPASS trial demonstrated that treatment with rivaroxaban vascular dose 2.5 mg twice daily plus aspirin (dual pathway inhibition [DPI] regimen) significantly reduced the risk of major adverse cardiovascular events (including peripheral ischemic events) and increased the risk of major bleeding, but not fatal bleeding or intracranial hemorrhage, versus aspirin alone in patients with CAD, PAD, or both. The results of the COMPASS trial supported the regulatory approval of the DPI regimen in several geographic regions. However, it is unclear whether the patients selected for treatment with the DPI regimen in clinical practice will have a similar risk profile and event rates compared with the COMPASS trial population. The prospective post-approval XATOA registry study aims to assess treatment patterns, as well as ischemic and bleeding outcomes in patients with CAD, PAD, or both, who receive DPI therapy in routine clinical practice. Up to 10,000 patients from at least 400 centers in 22 countries will be enrolled and followed up for a minimum of 12 months, and all treatment will be at the discretion of the prescribing physician. The primary objective of the XATOA study will be to describe early treatment patterns, while ischemic and bleeding outcomes will be described as a secondary objective. TRIAL REGISTRATION NUMBER: NCT03746275.

Association of Multiple Enrichment Criteria With Ischemic and Bleeding Risks Among COMPASS-Eligible Patients.

BACKGROUND: The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial found clinical benefit of low-dose rivaroxaban plus aspirin, but at the expense of increased bleeding risk in patients with stable vascular disease. OBJECTIVES: This study evaluated the balance of ischemic and bleeding risks according to the presence of ≥1 enrichment criteria in "COMPASS-eligible" patients. METHODS: Key COMPASS selection criteria were applied to identify a COMPASS-eligible population (n = 16,875) from the REACH (REduction of Atherothrombosis for Continued Health) Registry of stable atherothrombotic patients. Ischemic outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Bleeding outcome was serious bleeding (hemorrhagic stroke, hospitalization for bleeding, transfusion). RESULTS: Patients were categorized according to the enrichment criteria: age >65 years (81.5%), diabetes (41.0%), moderate renal failure (40.2%), peripheral artery disease (33.7%), current smoker (13.8%), heart failure (13.3%), ischemic stroke (11.1%), and asymptomatic carotid stenosis (8.7%). Each criterion was associated with a consistent increase in ischemic and bleeding events, but no individual subgroup derived a more favorable trade-off. Patients with multiple criteria had a dramatic increase in ischemic risk (7.0% [95% confidence interval (CI): 5.6% to 8.7%], 12.5% [95% CI: 11.1% to 14.1%], 16.6% [95% CI: 14.7% to 18.6%], and 21.8% [95% CI: 19.9% to 23.9%] with 1, 2, 3, and ≥4 enrichment criteria, respectively), but a more modest absolute increase in bleeding risk (1.5% [95% CI: 0.9% to 2.1%], 1.8% [95% CI: 1.3% to 2.2%], 2.0% [95% CI: 1.5% to 2.6%], 3.2% [95% CI: 2.6% to 3.9%]). CONCLUSIONS: In a population of stable vascular patients at high risk of atherothrombotic events, the subset with multiple enrichment criteria had a greater absolute increase in ischemic than in bleeding risk and may be good candidates for low-dose rivaroxaban in addition to aspirin.

Dual Pathway Inhibition with Low-Dose Direct Factor Xa Inhibition after Acute Coronary Syndromes-Why Is It Not Used in Clinical Practice?

The optimal anti-thrombotic therapy for secondary prevention after an acute coronary syndrome is still a matter of debate. While current guidelines recommend dual anti-platelet therapy with aspirin and a P2Y12 inhibitor over 12 months especially in patients with stent implantation, the value of prolonged anticoagulation is still controversial. In the ATLAS-TIMI 52 trial, a low-dose direct factor Xa inhibition with rivaroxaban compared with placebo reduced the combined primary endpoint of cardiovascular mortality, myocardial infraction and stroke with an increase in major bleeding complications. This article discusses the value and problems of adding low-dose rivaroxaban to anti-platelet therapy as secondary prevention measure after an acute myocardial infarction. It will describe the pros and cons of intensified anti-platelet therapy versus dual pathway inhibition and give recommendations for different patient groups in clinical practice.

Protocol for an economic evaluation of the randomised controlled trial of culprit lesion only PCI versus immediate multivessel PCI in acute myocardial infarction complicated by cardiogenic shock: CULPRIT-SHOCK trial.

INTRODUCTION: Emergency percutaneous coronary intervention (PCI) of the culprit lesion for patients with acute myocardial infarctions is an accepted practice. A majority of patients present with multivessel disease with additional relevant stenoses apart from the culprit lesion. In haemodynamically stable patients, there is increasing evidence from randomised trials to support the practice of immediate complete revascularisation. However, in the presence of cardiogenic shock, the optimal management strategy for additional non-culprit lesions is unknown. A multicentre randomised controlled trial, CULPRIT-SHOCK, is examining whether culprit vessel only PCI with potentially subsequent staged revascularisation is more effective than immediate multivessel PCI. This paper describes the intended economic evaluation of the trial. METHODS AND ANALYSIS: The economic evaluation will be conducted using a pre-trial decision model and within-trial analysis. The modelling-based analysis will provide expected costs and health outcomes, and incremental cost-effectiveness ratio over the lifetime for the cohort of patients included in the trial. The within-trial analysis will provide estimates of cost per life saved at 30 days and in 1 year, and estimates of health-related quality of life. Bootstrapping and cost-effectiveness acceptability curves will be used to address any uncertainty around these estimates. Different types of regression models within a generalised estimating equation framework will be used to examine how the total cost and quality-adjusted life years are explained by patients' characteristics, revascularisation strategy, country and centre. The cost-effectiveness analysis will be from the perspective of each country's national health services, where costs will be expressed in euros adjusted for purchasing power parity. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the local Ethics Committee at each recruiting centre. The economic evaluation analyses will be published in peer-reviewed journals of the concerned literature and communicated through the profiles of the authors at www.twitter.com and www.researchgate.net. TRIAL REGISTRATION NUMBER: NCT01927549; Pre-results.

Cardiovascular benefits of acarbose in impaired glucose tolerance and type 2 diabetes.

Impaired glucose metabolism is associated with an increased risk of cardiovascular events and cardiovascular-associated mortality. Postprandial hyperglycaemia is one of the earliest identifiable indicators of impaired glucose control. It contributes to the progression from impaired glucose tolerance to overt type 2 diabetes and exacerbates chronic hyperglycaemia in established diabetes. It is also an independent risk factor for cardiovascular disease in patients with impaired glucose tolerance and type 2 diabetes. Thus, an important strategy to reduce cardiovascular risk in patients with impaired glucose metabolism is to reduce postprandial glucose excursions. Acarbose, an alpha (alpha)-glucosidase inhibitor, reduces postprandial hyperglycaemia by delaying carbohydrate absorption from the small intestine. This mechanism of action provides glycaemic control without increasing insulin levels and exacerbating coexisting cardiovascular risk factors. The Study to Prevent Non-Insulin Dependent Diabetes Mellitus (STOP-NIDDM) assessed the ability of acarbose to reduce cardiovascular risk. In this study of 1429 individuals with impaired glucose tolerance, acarbose therapy reduced the risk of any cardiovascular event by 49% (P=0.03), of an acute myocardial infarction by 91% (P=0.02) and of developing hypertension by 34% (P=0.006). Furthermore, a retrospective meta-analysis of randomised studies of acarbose in type 2 diabetes patients showed that acarbose therapy reduced the risk of any cardiovascular event by 35% (P=0.006) and the risk of a myocardial infarction by 64% (P=0.012). These results suggest that acarbose is useful in reducing the risk of cardiovascular events in patients with impaired glucose metabolism.

Effect of acarbose treatment on the risk of silent myocardial infarctions in patients with impaired glucose tolerance: results of the randomised STOP-NIDDM trial electrocardiography substudy.

BACKGROUND: The moderate increase in postprandial plasma glucose in subjects with impaired glucose tolerance has been shown to be a predictor of cardiovascular disease. In the randomised STOP-NIDDM trial, we could demonstrate that lowering postprandial plasma glucose with acarbose in subjects with impaired oral glucose tolerance could reduce the risk of diabetes. METHODS: The current report focuses on the effect of acarbose on silent ischaemic events evaluated in the electrocardiographic substudy, using the Minnesota code classification. RESULTS: A total of 1181 patients were included in the ECG substudy. From these 72 patients had significant changes between the baseline and end of treatment ECG, 33 in the acarbose and 39 in the placebo group. Higher rates of myocardial infarctions occurred in the placebo group (P=0.07 with Fisher's Exact test and P=0.023 with Chi-square test), while there were no differences between the two groups with ECG changes classified under the other Minnesota codes. CONCLUSIONS: In this prospective intervention study we could show that acarbose, by decreasing postprandial hyperglycaemia, can reduce the incidence of silent myocardial infarctions in subjects with impaired glucose tolerance. This approach should therefore be evaluated in other higher risk populations.