Prophylactic Rivaroxaban Therapy for Left Ventricular Thrombus After Anterior ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: The aim of this study was to investigate the effects of rivaroxaban on left ventricle thromboprophylaxis in patients with anterior ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Anterior STEMI is associated with an increased risk of left ventricular thrombus (LVT) formation. The contemporary role of prophylactic rivaroxaban therapy remains unclear. METHODS: We randomly assigned 279 patients with anterior STEMI who had undergone primary percutaneous coronary intervention to receive, in a 1:1 ratio, low-dose rivaroxaban (2.5 mg twice daily for 30 days) and dual antiplatelet therapy (DAPT) or only DAPT. The primary efficacy outcome was the LVT formation within 30 days. Net clinical adverse events were assessed at 30 days and 180 days, including all-cause mortality, LVT, systemic embolism, rehospitalization for cardiovascular events, and bleeding. RESULTS: The addition of low-dose rivaroxaban to DAPT reduced LVT formation within 30 days compared with only DAPT (0.7% vs 8.6%; HR: 0.08; 95% CI: 0.01-0.62; P = 0.015; P < 0.001 for superiority). Net clinical adverse events were lower within 30 days in the rivaroxaban group versus those in the only DAPT group and remained relatively low throughout the follow-up period. There were no significant differences in bleeding events between the 2 groups in 30 days and 180 days. However, 1 case of intracranial hemorrhage (major bleeding) occurred in the rivaroxaban group within 30 days. CONCLUSIONS: Our results supported that the short-duration addition of low-dose rivaroxaban to DAPT could prevent LVT formation in patients with anterior STEMI following primary percutaneous coronary intervention. A larger multiple-institution study is necessary to determine the generalizability.

Reduced Rivaroxaban Dose Versus Dual Antiplatelet Therapy After Left Atrial Appendage Closure: ADRIFT a Randomized Pilot Study.

BACKGROUND: Percutaneous left atrial appendage closure (LAAC) exposes to the risk of device thrombosis in patients with atrial fibrillation who frequently have a contraindication to full anticoagulation. Thereby, dual antiplatelet therapy (DAPT) is usually preferred. No randomized study has evaluated nonvitamin K antagonist oral anticoagulant after LAAC, and we decided to evaluate the efficacy and safety of reduced doses of rivaroxaban after LAAC. METHODS: ADRIFT (Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban in Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure) is a multicenter, phase IIb study, which randomized 105 patients after successful LAAC to either rivaroxaban 10 mg (R10, n=37), rivaroxaban 15 mg (R15, n=35), or DAPT with aspirin 75 mg and clopidogrel 75 mg (n=33). The primary end point was thrombin generation (prothrombin fragments 1+2) measured 2 to 4 hours after drug intake, 10 days after treatment initiation. Thrombin-antithrombin complex, D-dimers, rivaroxaban concentrations were also measured at 10 days and 3 months. Clinical end points were evaluated at 3-month follow-up. RESULTS: The primary end point was reduced with R10 (179 pmol/L [interquartile range (IQR), 129-273], P<0.0001) and R15 (163 pmol/L [IQR, 112-231], P<0.0001) as compared with DAPT (322 pmol/L [IQR, 218-528]). We observed no significant reduction of the primary end point between R10 and R15 while rivaroxaban concentrations increased significantly from 184 ng/mL (IQR, 127-290) with R10 to 274 ng/mL (IQR, 192-377) with R15, P<0.0001. Thrombin-antithrombin complex and D-dimers were numerically lower with both rivaroxaban doses than with DAPT. These findings were all confirmed at 3 months. The clinical end points were not different between groups. A device thrombosis was noted in 2 patients assigned to DAPT. CONCLUSIONS: Thrombin generation measured after LAAC was lower in patients treated by reduced rivaroxaban doses than DAPT, supporting an alternative to the antithrombotic regimens currently used after LAAC and deserves further evaluation in larger studies. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03273322.

New Horizons in Pharmacologic Therapy for Secondary Stroke Prevention.

Importance: Even with currently available therapies and lifestyle modifications following an ischemic stroke, there remains a substantial residual lifetime risk of stroke recurrence and cardiovascular morbidity. This review summarizes emerging novel therapeutic approaches that have demonstrated signals of efficacy for prevention of noncardioembolic stroke from phase II and phase III randomized clinical trials (RCTs) and provides an overview of drug regimens that have had promising results in primary stroke prevention and could be considered for further evaluation. Observations: After a minor acute ischemic stroke or transient ischemic attack, patients bear a high cardiovascular risk that is insufficiently addressed by long-term antiplatelet treatment. The potent combination of low-dose rivaroxaban with aspirin as an antithrombotic option for the secondary prevention in patients with clinical atherosclerosis and a history of previous stroke warrants further study. Two international RCTs are currently evaluating the utility of oral factor XI inhibitors combined with antiplatelets for secondary, noncardioembolic ischemic stroke prevention. Aggressive lipid management with statins has been shown to ameliorate ischemic stroke recurrence and total cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 inhibitors are drug regimens that researchers have suggested confer additional protection against stroke recurrence, while antisense oligonucleotide therapies targeting lipoprotein(a) have been reported to hold great promise as a future therapeutic strategy to decrease the residual cardiovascular risk mediated through lipoprotein(a). Glucagon-like peptide-1 receptor agonists are newer antidiabetic medications, recently highlighted because of their consistently greater benefit on stroke reduction compared with other cardiovascular outcomes. Conclusions and Relevance: There are currently several exciting emerging opportunities in secondary stroke prevention, with RCTs investigating novel antithrombotic, hypolipidemic, anti-inflammatory, and antidiabetic agents with novel mechanisms that are likely to reduce the future burden of recurrent stroke.

New treatments for peripheral artery disease.

The stenosis or occlusion of extremities defining peripheral artery disease (PAD) is a risk factor for adverse cardiovascular events and adverse limb events including amputation. PAD is common, can occur without symptoms or with claudication, and is easily diagnosed. Proper diagnosis and adherence to guideline-directed therapy can reduce the morbidity and potential mortality associated with PAD.

[Antithrombotic therapy after acute coronary syndromes: is it possible to identify the PEGASUS and COMPASS patient?] / Terapia antitrombotica dopo sindrome coronarica acuta: come identificare il paziente PEGASUS ed il paziente COMPASS.

Although having different rationales and purposes, the PEGASUS-TIMI 54 and COMPASS trials present various points of contact and, especially after the first recommended year of dual antiplatelet therapy (DAPT) from an acute coronary syndrome, pose the clinical question of whether DAPT should be prolonged (PEGASUS strategy) or aspirin should be maintained by combining rivaroxaban 2.5 mg bid (COMPASS strategy). In this review, we try to trace the PEGASUS and COMPASS patient's profile by analyzing the design of each study with their inclusion/exclusion criteria, the main subanalyses and the real-world studies recently published in this setting.

Rationale and design of "Can Very Low Dose Rivaroxaban (VLDR) in addition to dual antiplatelet therapy improve thrombotic status in acute coronary syndrome (VaLiDate-R)" study : A randomised trial modulating endogenous fibrinolysis in patients with acute coronary syndrome.

Impaired endogenous fibrinolysis is novel biomarker that can identify patients with ACS at increased cardiovascular risk. The addition of Very Low Dose Rivaroxaban (VLDR) to dual antiplatelet therapy has been shown to reduce cardiovascular events but at a cost of increased bleeding and is therefore not suitable for all-comers. Targeted additional pharmacotherapy with VLDR to improve endogenous fibrinolysis may improve outcomes in high-risk patients, whilst avoiding unnecessary bleeding in low-risk individuals. The VaLiDate-R study (ClinicalTrials.gov Identifier: NCT03775746, EudraCT: 2018-003299-11) is an investigator-initiated, randomised, open-label, single centre trial comparing the effect of 3 antithrombotic regimens on endogenous fibrinolysis in 150 patients with ACS. Subjects whose screening blood test shows impaired fibrinolytic status (lysis time > 2000s), will be randomised to one of 3 treatment arms in a 1:1:1 ratio: clopidogrel 75 mg daily (Group 1); clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily (Group 2); ticagrelor 90 mg twice daily (Group 3), in addition to aspirin 75 mg daily. Rivaroxaban will be given for 30 days. Fibrinolytic status will be assessed during admission and at 2, 4 and 8 weeks. The primary outcome measure is the change in fibrinolysis time from admission to 4 weeks follow-up, using the Global Thrombosis Test. If VLDR can improve endogenous fibrinolysis in ACS, future large-scale studies would be required to assess whether targeted use of VLDR in patients with ACS and impaired fibrinolysis can translate into improved clinical outcomes, with reduction in major adverse cardiovascular events in this high-risk cohort.

Antithrombotic regimen for patients with cardiac indication for dual antiplatelet therapy and anticoagulation: a meta-analysis of randomized trials.

OBJECTIVES: The optimal antithrombotic strategy for patients with a long-term indication for anticoagulation and acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remains controversial. This meta-analysis aims to compare randomised trials' outcomes of these patients, focussing on dual versus triple antithrombotic and non vitamin K oral anticoagulants (NOACs) versus vitamin K oral anticoagulants regimens. METHODS: Medline, Embase and Cochrane databases were searched from January 1980 to March 2019 yielding 309 articles, and after careful screening, five randomized trials totalling 10 643 patients were included for analysis. RESULTS: Dual antithrombotic regimens were associated with significantly less thrombolysis in myocardial infarction (TIMI) major and minor bleeding [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.40-0.71], with no significant difference in major adverse cardiovascular events (OR 0.93, 95% CI 0.72-1.22) or all-cause mortality (OR 0.89, 95% CI 0.61-1.19). NOAC regimens had significantly lower TIMI major and minor bleeding (OR 0.58, 95% CI 0.43-0.78) and intracranial bleeding (OR 0.33, 95% CI 0.16-0.66), with similar rates of major adverse cardiovascular events (OR 1.00, 95% CI 0.86-1.16) and all-cause mortality (OR 1.01, 95% CI 0.81-1.26). CONCLUSION: Dual antithrombotic and NOAC regimens have reduced bleeding without compromising the risk of cardiovascular events or mortality, and should be preferred for patients with ACS or PCI also needing long-term anticoagulation.