rivaroxaban

Importance: Superficial vein thrombosis (SuVT) is characterized by thrombus in the superficial veins, typically in the lower or upper extremities, and has an estimated annual incidence of 64 to 131 per 100 000 person-years. Approximately 10% of patients with SuVT progress to deep vein thrombosis (DVT) or pulmonary embolism (PE).

Observations: Endothelial injury (caused by infection or intravenous devices), venous stasis (such as from chronic venous insufficiency or prolonged immobility), and hypercoagulability (due to cancer or pregnancy) are pathophysiologic factors associated with SuVT. Clinical risk factors for lower extremity SuVT are similar to those of DVT and PE and include pregnancy, varicose veins, and active cancer. The incidence of SuVT is greater in females than males (78-167 compared with 49-116 per 100 000 person-years). In contrast with lower extremity SuVT, upper extremity SuVT is primarily caused by indwelling intravenous catheters. Patients typically present with a tender, red, palpable cord under the skin in the upper or lower extremity. D-dimer testing has a sensitivity of approximately 48% to 74.3% and, therefore, is not reliable for excluding SuVT. Approximately 25% of patients with lower extremity SuVT present with concomitant DVT, likely because risk factors for SuVT and DVT are similar and because SuVT can extend into deep veins. In people without classic symptoms and signs of SuVT, ultrasonography can establish the presence and extent of the thrombus. Management may include elastic compression stockings and nonsteroidal anti-inflammatory drugs. For patients with SuVTs that are at least 5 cm long or those with persistent or worsening symptoms despite several days of conservative therapy, treatment includes anticoagulation with fondaparinux 2.5 mg. Alternative anticoagulation treatment includes rivaroxaban 10 mg once daily and low-molecular-weight heparins (eg, enoxaparin 40 mg once daily), which may reduce subsequent venous thromboembolic events. SuVT located within 3 cm of a deep vein should be treated with therapeutic doses of anticoagulation such as direct oral anticoagulants.

Conclusions and relevance: SuVT typically presents as a tender, painful, palpable cord under the skin. Management may include elastic compression stockings, nonsteroidal anti-inflammatory drugs, and systemic anticoagulation with fondaparinux 2.5 mg or rivaroxaban 10 mg. SuVTs within 3 cm of a deep vein should be treated with therapeutic dose anticoagulation.

Author/s:

Gregory Piazza, Darsiya Krishnathasan, Nada Hamade

Perioperative Management of Patients Taking Direct Oral Anticoagulants

Alex Haga — Tue, 20 Aug 2024 19:58:18 +0000

Date Added:

August 20, 2024

Journal/Publication:

JAMA

Publication Date:

August 12, 2024

URL:

Perioperative Management of Patients Taking Direct Oral Anticoagulants

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.12708

Keywords

Perioperative

oral

anticoagulants

PMID (1):

39133476

MeSH

Venous Thromboembolism

hemorrhage

A review of the perioperative management of patients on oral anticoagulants. James W. Mold, MD, MPH

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Importance: Direct oral anticoagulants (DOACs), comprising apixaban, rivaroxaban, edoxaban, and dabigatran, are commonly used medications to treat patients with atrial fibrillation and venous thromboembolism. Decisions about how to manage DOACs in patients undergoing a surgical or nonsurgical procedure are important to decrease the risks of bleeding and thromboembolism.

Observations: For elective surgical or nonsurgical procedures, a standardized approach to perioperative DOAC management involves classifying the risk of procedure-related bleeding as minimal (eg, minor dental or skin procedures), low to moderate (eg, cholecystectomy, inguinal hernia repair), or high risk (eg, major cancer or joint replacement procedures). For patients undergoing minimal bleeding risk procedures, DOACs may be continued, or if there is concern about excessive bleeding, DOACs may be discontinued on the day of the procedure. Patients undergoing a low to moderate bleeding risk procedure should typically discontinue DOACs 1 day before the operation and restart DOACs 1 day after. Patients undergoing a high bleeding risk procedure should stop DOACs 2 days prior to the operation and restart DOACs 2 days after. With this perioperative DOAC management strategy, rates of thromboembolism (0.2%-0.4%) and major bleeding (1%-2%) are low and delays or cancellations of surgical and nonsurgical procedures are infrequent. Patients taking DOACs who need emergent (<6 hours after presentation) or urgent surgical procedures (6-24 hours after presentation) experience bleeding rates up to 23% and thromboembolism as high as 11%. Laboratory testing to measure preoperative DOAC levels may be useful to determine whether patients should receive a DOAC reversal agent (eg, prothrombin complex concentrates, idarucizumab, or andexanet-α) prior to an emergent or urgent procedure.

Conclusions and relevance: When patients who are taking a DOAC require an elective surgical or nonsurgical procedure, standardized management protocols can be applied that do not require testing DOAC levels or heparin bridging. When patients taking a DOAC require an emergent, urgent, or semiurgent surgical procedure, anticoagulant reversal agents may be appropriate when DOAC levels are elevated or not available.

Author/s:

James D Douketis, Alex C Spyropoulos

Rivaroxaban Versus Vitamin K Antagonist in Antiphospholipid Syndrome: A Randomized Noninferiority Trial

Brian Desmarais — Thu, 17 Oct 2019 14:29:29 +0000

Date Added:

October 17, 2019

Journal/Publication:

Annals of Internal Medicine

Publication Date:

October 15, 2019

URL:

Rivaroxaban Versus Vitamin K Antagonist in Antiphospholipid Syndrome: A Randomized Noninferiority Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.7326/M19-0291

Keywords

MeSH

International Normalized Ratio

Antiphospholipid Syndrome

Rivaroxaban apparently doesn’t work as well as warfarin at preventing recurrent venous thrombosis in patients with antiphospholipid syndrome. That suggests to me that patients should be tested for that condition before recommending a non-warfarin option. James W. Mold, MD, MPH

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BACKGROUND:

The potential role of new oral anticoagulants in antiphospholipid antibody syndrome (APS) remains uncertain.

OBJECTIVE:

To determine whether rivaroxaban is noninferior to dose-adjusted vitamin K antagonists (VKAs) for thrombotic APS.

DESIGN:

3-year, open-label, randomized noninferiority trial. (EU Clinical Trials Register: EUDRA [European Union Drug Regulatory Authorities] code 2010-019764-36).

SETTING:

6 university hospitals in Spain.

PARTICIPANTS:

190 adults (aged 18 to 75 years) with thrombotic APS.

INTERVENTION:

Rivaroxaban (20 mg/d or 15 mg/d, according to renal function) versus dose-adjusted VKAs (target international normalized ratio, 2.0 to 3.0, or 3.1 to 4.0 in patients with a history of recurrent thrombosis).

MEASUREMENTS:

The primary efficacy outcome was the proportion of patients with new thrombotic events; the primary safety outcome was major bleeding. The prespecified noninferiority margin for risk ratio (RR) was 1.40. Secondary outcomes included time to thrombosis, type of thrombosis, changes in biomarker levels, cardiovascular death, and nonmajor bleeding.

RESULTS:

After 3 years of follow-up, recurrent thrombosis occurred in 11 patients (11.6%) in the rivaroxaban group and 6 (6.3%) in the VKA group (RR in the rivaroxaban group, 1.83 [95% CI, 0.71 to 4.76]). Stroke occurred more commonly in patients receiving rivaroxaban (9 events) than in those receiving VKAs (0 events) (corrected RR, 19.00 [CI, 1.12 to 321.9]). Major bleeding occurred in 6 patients (6.3%) in the rivaroxaban group and 7 (7.4%) in the VKA group (RR, 0.86 [CI, 0.30 to 2.46]). Post hoc analysis suggested an increased risk for recurrent thrombosis in rivaroxaban-treated patients with previous arterial thrombosis, livedo racemosa, or APS-related cardiac valvular disease.

LIMITATION:

Anticoagulation intensity was not measured in the rivaroxaban group.

CONCLUSION:

Rivaroxaban did not show noninferiority to dose-adjusted VKAs for thrombotic APS and, in fact, showed a non-statistically significant near doubling of the risk for recurrent thrombosis.

PRIMARY FUNDING SOURCE:

Bayer Hispania.

Author/s:

Ordi-Ros, J, Sáez-Comet, L., Pérez-Conesa, M., Vidal, X., Riera-Mestre, A., Castro-Salomó, A., Cuquet-Pedragosa, J., Ortiz-Santamaria, V., Mauri-Plana, M., Solé, C., Cortés-Hernández, J.

Association of Oral Anticoagulants and Proton Pump Inhibitor Cotherapy With Hospitalization for Upper Gastrointestinal Tract Bleeding.

Jeffrey Wilson — Mon, 17 Dec 2018 14:59:18 +0000

Date Added:

December 21, 2018

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

December 4, 2018

Issue:

Volume:

320

Pages:

2221-2230

URL:

Association of Oral Anticoagulants and Proton Pump Inhibitor Cotherapy With Hospitalization for Upper Gastrointestinal Tract Bleeding.

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jama.2018.17242

Keywords

proton pump inhibitor

upper gastrointestinal tract

anticoagulants

atrial fibrillation

PMID (1):

30512099

MeSH

proton pump inhibitors

atrial fibrillation

anticoagulants

upper gastrointestinal tract

This study suggests that Medicare patients on anticoagulants are least likely to be hospitalized for UGI bleeding if they are taking apixaban vs. other anticoagulants, and co-treatment with a PPI reduces the rate by one-third. However, the percentage of patients hospitalized for UGI bleeding was only about 1% so the differences between drugs and between no PPI vs. PPI were small (see table below). Gastroenterologists are likely to begin recommending PPIs for all patients on oral anticoagulants based upon this study. You will have to decide whether or not the potential side effects of PPIs outweigh the very small absolute risk reduction in individual patients.

Anticoagulant

Percent Hospitalized Per Year for UGI Bleeding Not on PPI

Percent hospitalized Per Year for UGI Bleeding On PPI

Warfarin

1.13%

0.73%

Apixaban

0.73%

0.48%

Dabigatran

1.2%

0.59%

Rivaroxaban

1.44%

1.08%

Any of Above

1.15%

0.76%

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IMPORTANCE:

Anticoagulant choice and proton pump inhibitor (PPI) cotherapy could affect the risk of upper gastrointestinal tract bleeding, a frequent and potentially serious complication of oral anticoagulant treatment.

OBJECTIVES:

To compare the incidence of hospitalization for upper gastrointestinal tract bleeding in patients using individual anticoagulants with and without PPI cotherapy, and to determine variation according to underlying gastrointestinal bleeding risk.

DESIGN, SETTING, AND PARTICIPANTS:

Retrospective cohort study in Medicare beneficiaries between January 1, 2011, and September 30, 2015.

EXPOSURES:

Apixaban, dabigatran, rivaroxaban, or warfarin with or without PPI cotherapy.

MAIN OUTCOMES AND MEASURES:

Hospitalizations for upper gastrointestinal tract bleeding: adjusted incidence and risk difference (RD) per 10 000 person-years of anticoagulant treatment, incidence rate ratios (IRRs).

RESULTS:

There were 1 643 123 patients with 1 713 183 new episodes of oral anticoagulant treatment included in the cohort (mean [SD] age, 76.4 [2.4] years, 651 427 person-years of follow-up [56.1%] were for women, and the indication was atrial fibrillation for 870 330 person-years [74.9%]). During 754 389 treatment person-years without PPI cotherapy, the adjusted incidence of hospitalization for upper gastrointestinal tract bleeding (n = 7119) was 115 per 10 000 person-years (95% CI, 112-118). The incidence for rivaroxaban (n = 1278) was 144 per 10 000 person-years (95% CI, 136-152), which was significantly greater than the incidence of hospitalizations for apixaban (n = 279; 73 per 10 000 person-years; IRR, 1.97 [95% CI, 1.73-2.25]; RD, 70.9 [95% CI, 59.1-82.7]), dabigatran (n = 629; 120 per 10 000 person-years; IRR, 1.19 [95% CI, 1.08-1.32]; RD, 23.4 [95% CI, 10.6-36.2]), and warfarin (n = 4933; 113 per 10 000 person-years; IRR, 1.27 [95% CI, 1.19-1.35]; RD, 30.4 [95% CI, 20.3-40.6]). The incidence for apixaban was significantly lower than that for dabigatran (IRR, 0.61 [95% CI, 0.52-0.70]; RD, -47.5 [95% CI,-60.6 to -34.3]) and warfarin (IRR, 0.64 [95% CI, 0.57-0.73]; RD, -40.5 [95% CI, -50.0 to -31.0]). When anticoagulant treatment with PPI cotherapy (264 447 person-years; 76 per 10 000 person-years) was compared with treatment without PPI cotherapy, risk of upper gastrointestinal tract bleeding hospitalizations (n = 2245) was lower overall (IRR, 0.66 [95% CI, 0.62-0.69]) and for apixaban (IRR, 0.66 [95% CI, 0.52-0.85]; RD, -24 [95% CI, -38 to -11]), dabigatran (IRR, 0.49 [95% CI, 0.41-0.59]; RD, -61.1 [95% CI, -74.8 to -47.4]), rivaroxaban (IRR, 0.75 [95% CI, 0.68-0.84]; RD, -35.5 [95% CI, -48.6 to -22.4]), and warfarin (IRR, 0.65 [95% CI, 0.62-0.69]; RD, -39.3 [95% CI, -44.5 to -34.2]).

CONCLUSIONS AND RELEVANCE:

Among patients initiating oral anticoagulant treatment, incidence of hospitalization for upper gastrointestinal tract bleeding was the highest in patients prescribed rivaroxaban, and the lowest for patients prescribed apixaban. For each anticoagulant, the incidence of hospitalization for upper gastrointestinal tract bleeding was lower among patients who were receiving PPI cotherapy. These findings may inform assessment of risks and benefits when choosing anticoagulant agents.

Author/s:

Ray, Wayne A., Chung, Cecilia P., Murray, Katherine T., Smalley, Walter E., Daugherty, James R., Dupont, William D.