hemorrhage

Importance: Data from randomized clinical trials on a long-term anticoagulation strategy for patients after catheter-based ablation for atrial fibrillation (AF) are lacking.

Objective: To evaluate whether discontinuing oral anticoagulant therapy provides superior clinical outcomes compared with continuing oral anticoagulant therapy in patients without documented atrial arrhythmia recurrence after catheter ablation for AF.

Design, setting, and participants: A randomized clinical trial including 840 adult patients (aged 19-80 years) who were enrolled and randomized from July 28, 2020, to March 9, 2023, at 18 hospitals in South Korea. Enrolled patients had at least 1 non-sex-related stroke risk factor (determined using the CHA2DS2-VASc score [range, 0-9]) and no documented recurrence of atrial arrhythmia for at least 1 year after catheter ablation for AF. The CHA2DS2-VASc score is used as an assessment of stroke risk among patients with AF (calculated using point values for congestive heart failure, hypertension, ≥75 years of age, diabetes, stroke or transient ischemic attack, vascular disease, between 65 and 74 years of age, and sex category). The date of final follow-up was June 4, 2025.

Interventions: The patients were randomly assigned in a 1:1 ratio to discontinue oral anticoagulant therapy (n = 417) or continue oral anticoagulant therapy (with direct oral anticoagulants; n = 423).

Main outcomes and measures: The primary outcome was the first occurrence of a composite of stroke, systemic embolism, and major bleeding at 2 years. Individual components of the primary outcome (such as ischemic stroke and major bleeding) were assessed as secondary outcomes.

Results: Of the 840 adults randomized, the mean age was 64 (SD, 8) years, 24.9% were women, the mean CHA2DS2-VASc score was 2.1 (SD, 1.0), and 67.6% had paroxysmal AF. At 2 years, the primary outcome occurred in 1 patient (0.3%) in the discontinue oral anticoagulant therapy group vs 8 patients (2.2%) in the continue oral anticoagulant therapy group (absolute difference, -1.9 percentage points [95% CI, -3.5 to -0.3]; P = .02). The 2-year cumulative incidence of ischemic stroke was 0.3% in the discontinue oral anticoagulant therapy group vs 0.8% in the continue oral anticoagulant therapy group (absolute difference, -0.5 percentage points [95% CI, -1.6 to 0.6]). Major bleeding occurred in 0 patients in the discontinue oral anticoagulant therapy group vs 5 patients (1.4%) in the continue oral anticoagulant therapy group (absolute difference, -1.4 percentage points [95% CI, -2.6 to -0.2]).

Conclusions and relevance: Among patients without documented atrial arrhythmia recurrence after catheter ablation for AF, discontinuing oral anticoagulant therapy resulted in a lower risk for the composite outcome of stroke, systemic embolism, and major bleeding vs continuing direct oral anticoagulant therapy.

Trial registration: ClinicalTrials.gov Identifier: NCT04432220.

Author/s:

Daehoon Kim, MD, Jaemin Shim, MD, Eue-Keun Choi, MD

Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation

Megan George — Tue, 02 Sep 2025 13:36:10 +0000

Date Added:

September 2, 2025

Journal/Publication:

New England Journal of Medicine

Publication Date:

August 30, 2025

URL:

Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa2507532

Keywords

Chronic Coronary Syndrome

Oral Anticoagulation

aspirin

atherothrombotic risk

stent implantation

PMID (1):

40888725

MeSH

aspirin

Fibrinolytic Agents

follow-up studies

Clinical Trials Data Monitoring Committees

Confidence Intervals

random allocation

myocardial infarction

coronary artery disease

In patients with high-risk CAD already on an anticoagulant, the addition of aspirin increases the risk of adverse events. James W. Mold, MD, MPH

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Background: The appropriate antithrombotic regimen for patients with chronic coronary syndrome who are at high atherothrombotic risk and receiving long-term oral anticoagulation remains unknown.

Methods: We conducted a multicenter, double-blind, randomized, placebo-controlled trial in France involving patients with chronic coronary syndrome who had undergone a previous stent implantation (>6 months before enrollment) and were at high atherothrombotic risk and currently receiving long-term oral anticoagulation. The patients were randomly assigned in a 1:1 ratio to receive aspirin (100 mg once daily) or placebo; all the patients continued to receive their current oral anticoagulation therapy. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia. The key safety outcome was major bleeding.

Results: A total of 872 patients underwent randomization; 433 were assigned to the aspirin group, and 439 to the placebo group. The trial was stopped early at the advice of the independent data and safety monitoring board after a median follow-up of 2.2 years because of an excess of deaths from any cause in the aspirin group. A primary efficacy outcome event occurred in 73 patients (16.9%) in the aspirin group and in 53 patients (12.1%) in the placebo group (adjusted hazard ratio, 1.53; 95% confidence interval [CI], 1.07 to 2.18; P = 0.02). Death from any cause occurred in 58 patients (13.4%) in the aspirin group and in 37 (8.4%) in the placebo group (adjusted hazard ratio, 1.72; 95% CI, 1.14 to 2.58; P = 0.01). Major bleeding occurred in 44 patients (10.2%) in the aspirin group and in 15 patients (3.4%) in the placebo group (adjusted hazard ratio, 3.35; 95% CI, 1.87 to 6.00; P<0.001). A total of 467 and 395 serious adverse events were reported in the aspirin group and placebo group, respectively.

Conclusions: Among patients with chronic coronary syndrome at high atherothrombotic risk who were receiving an oral anticoagulant, the addition of aspirin led to a higher risk of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia than placebo, as well as higher risks of death from any cause and major bleeding. (Funded by the French Ministry of Health and Bayer Healthcare; ClinicalTrials.gov number, NCT04217447.).

Author/s:

Gilles Lemesle, M.D., Ph.D., Romain Didier, M.D., Ph.D., Philippe Gabriel Steg, M.D., Tabassome Simon, M.D., Ph.D., Gilles Montalescot, M.D., Ph.D., Nicolas Danchin, M.D., Christophe Bauters, M.D., Ph.D.

Adrenal Insufficiency in Adults: A Review

Megan George — Thu, 28 Aug 2025 18:23:08 +0000

Date Added:

August 28, 2025

Journal/Publication:

JAMA

Publication Date:

August 26, 2025

Issue:

334

Volume:

Pages:

714-725

URL:

Adrenal Insufficiency in Adults: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.5485

Keywords

PMID (1):

40522647

A review of what we know about adrenal insufficiency in adults. James W. Mold, MD, MPH

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Importance: Adrenal insufficiency is a syndrome of cortisol deficiency and is categorized as primary, secondary, or glucocorticoid induced. Although primary and secondary adrenal insufficiency are rare, affecting less than 279 per 1 million individuals, glucocorticoid-induced adrenal insufficiency is common.

Observations: Primary adrenal insufficiency, which involves deficiency of all adrenocortical hormones, is caused by autoimmune destruction, congenital adrenal hyperplasia, pharmacological inhibition (eg, high doses of azole antifungal therapy), infection (eg, tuberculosis, fungal infections), or surgical removal of adrenal cortical tissue. Secondary adrenal insufficiency is caused by disorders affecting the pituitary gland, such as tumors, hemorrhage, inflammatory or infiltrative conditions (eg, hypophysitis, sarcoidosis, hemochromatosis), surgery, radiation therapy, or medications that suppress corticotropin production, such as opioids. Glucocorticoid-induced adrenal insufficiency is caused by administration of supraphysiological doses of glucocorticoids. Patients with adrenal insufficiency typically present with nonspecific symptoms, including fatigue (50%-95%), nausea and vomiting (20%-62%), and anorexia and weight loss (43%-73%). Glucocorticoid-induced adrenal insufficiency should be suspected in patients who have recently tapered or discontinued a supraphysiological dose of glucocorticoids. Early-morning (approximately 8 am) measurements of serum cortisol, corticotropin, and dehydroepiandrosterone sulfate (DHEAS) are used to diagnose adrenal insufficiency. Primary adrenal insufficiency is typically characterized by low morning cortisol levels (<5 µg/dL), high corticotropin levels, and low DHEAS levels. Patients with secondary and glucocorticoid-induced adrenal insufficiency typically have low or intermediate morning cortisol levels (5-10 µg/dL) and low or low-normal corticotropin and DHEAS levels. Patients with intermediate early-morning cortisol levels should undergo repeat early-morning cortisol testing or corticotropin stimulation testing (measurement of cortisol before and 60 minutes after administration of cosyntropin, 250 µg). Treatment of adrenal insufficiency involves supplemental glucocorticoids (eg, hydrocortisone, 15-25 mg daily, or prednisone, 3-5 mg daily). Mineralocorticoids (eg, fludrocortisone, 0.05-0.3 mg daily) should be added for patients with primary adrenal insufficiency. Adrenal crisis, a syndrome that can cause hypotension and shock, hyponatremia, altered mental status, and death if untreated, can occur in patients with adrenal insufficiency who have inadequate glucocorticoid therapy, acute illness, and physical stress. Therefore, all patients with adrenal insufficiency should be instructed how to increase glucocorticoids during acute illness and prescribed injectable glucocorticoids (eg, hydrocortisone, 100 mg intramuscular injection) to prevent or treat adrenal crisis.

Conclusions and relevance: Although primary and secondary adrenal insufficiency are rare, glucocorticoid-induced adrenal insufficiency is a common condition. Diagnosis of adrenal insufficiency involves early-morning measurement of cortisol, corticotropin, and DHEAS. All patients with adrenal insufficiency should be treated with glucocorticoids and instructed how to prevent and treat adrenal crisis.

Author/s:

Anand Vaidya, James Findling, Irina Bancos

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

Adverse Events Associated With the Addition of Aspirin to Direct Oral Anticoagulant Therapy Without a Clear Indication

Saige Blanchard — Tue, 08 Jun 2021 05:00:00 +0000

Date Added:

June 8, 2021

Journal/Publication:

Journal of the American Medical Association

Publisher:

American Medical Association

Publication Date:

June 1, 2021

Issue:

Volume:

181

Pages:

817-824

URL:

Adverse Events Associated With the Addition of Aspirin to Direct Oral Anticoagulant Therapy Without a Clear Indication

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamainternmed.2021.1197

Keywords

aspirin

anticoagulant therapy

treatment

heart-valve replacement

thrombosis

PMID (1):

33871544

MeSH

Patients at risk for thrombotic events almost never require the combination of a DOAC and low-dose aspirin. Those taking both are at significantly increased risk of bleeding and no reduction in thrombosis. James W. Mold, MD, MPH

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Importance: It is unclear how many patients treated with a direct oral anticoagulant (DOAC) are using concomitant acetylsalicylic acid (ASA, or aspirin) and how this affects clinical outcomes.

Objective: To evaluate the frequency and outcomes of prescription of concomitant ASA and DOAC therapy for patients with atrial fibrillation (AF) or venous thromboembolic disease (VTE).

Design, setting, and participants: This registry-based cohort study took place at 4 anticoagulation clinics in Michigan from January 2015 to December 2019. Eligible participants were adults undergoing treatment with a DOAC for AF or VTE, without a recent myocardial infarction (MI) or history of heart valve replacement, with at least 3 months of follow-up.

Exposures: Use of ASA concomitant with DOAC therapy.

Main outcomes and measures: Rates of bleeding (any, nonmajor, major), rates of thrombosis (stroke, VTE, MI), emergency department visits, hospitalizations, and death.

Results: Of the study cohort of 3280 patients (1673 [51.0%] men; mean [SD] age 68.2 [13.3] years), 1107 (33.8%) patients without a clear indication for ASA were being treated with DOACs and ASA. Two propensity score-matched cohorts, each with 1047 patients, were analyzed (DOAC plus ASA and DOAC only). Patients were followed up for a mean (SD) of 20.9 (19.0) months. Patients taking DOAC and ASA experienced more bleeding events compared with DOAC monotherapy (26.0 bleeds vs 31.6 bleeds per 100 patient years, P = .01). Specifically, patients undergoing combination therapy had significantly higher rates of nonmajor bleeding (26.1 bleeds vs 21.7 bleeds per 100 patient years, P = .02) compared with DOAC monotherapy. Major bleeding rates were similar between the 2 cohorts. Thrombotic event rates were also similar between the cohorts (2.5 events vs 2.3 events per 100 patient years for patients treated with DOAC and ASA compared with DOAC monotherapy, P = .80). Patients were more often hospitalized while undergoing combination therapy (9.1 vs 6.5 admissions per 100 patient years, P = .02).

Conclusion and relevance: Nearly one-third of patients with AF and/or VTE who were treated with a DOAC received ASA without a clear indication. Compared with DOAC monotherapy, concurrent DOAC and ASA use was associated with increased bleeding and hospitalizations but similar observed thrombosis rate. Future research should identify and deprescribe ASA for patients when the risk exceeds the anticipated benefit.

Author/s:

Schaefer, J. K., Errickson, J., Li, Y., Kong, X., Alexandris-Souphis, T., Ali, M. A., Decamillo, D., Haymart, B., Kaatz, S., Kline-Rogers, E., Kozlowski, J. H., Krol, G. D., Shankar, S, R., Sood, S. L., Froehlich, J. B., Barnes, G. D.

Mild bleeding disorders in adults

Devin Evans — Mon, 08 Mar 2021 06:00:00 +0000

Date Added:

March 8, 2021

Journal/Publication:

Canadian Medical Association Journal

Publication Date:

March 8, 2021

Issue:

Volume:

193

URL:

Mild bleeding disorders in adults

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

https://doi.org/10.1503/cmaj.201182

Keywords

von Willebrand Diseases

Blood Platelet Disorders

Hemorrhagic Disorders

hemorrhage

MeSH

von Willebrand Diseases

Blood Platelet Disorders

Hemorrhagic Disorders

hemorrhage

A concise summary of how to evaluate adults with mild bleeding disorders. James W. Mold, MD, MPH

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About 11% of patients in primary care reported bleeding symptoms in a 2010 Canadian study.1 Mild bleeding disorders should be considered in patients with disproportionate bleeding (i.e., excessive postsurgical bleeding from multiple sites or bleeding that requires blood or iron transfusion).2 Mild bleeding disorders can be inherited or acquired; common diagnoses include mild von Willebrand disease, platelet dysfunction and mild–moderate factor deficiencies.2 Unlike severe inherited bleeding disorders that are often diagnosed in early life, mild inherited bleeding disorders can present in adulthood.

Author/s:

Sun, Dongmei, Phua, Chai W.

Aspirin for Primary Atherosclerotic Cardiovascular Disease Prevention as Baseline Risk Increases: A Meta-Regression Analysis

John Bayhi — Thu, 21 May 2020 16:39:36 +0000

Date Added:

May 21, 2020

Journal/Publication:

The American Journal of Medicine

Publisher:

Elsevier Inc

Publication Date:

May 20, 2020

Volume:

Article in Press

URL:

Aspirin for Primary Atherosclerotic Cardiovascular Disease Prevention as Baseline Risk Increases: A Meta-Regression Analysis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/j.amjmed.2020.04.028

Keywords

aspirin

primary prevention

Atherosclerotic Cardiovascular Disease

myocardial infarction

MeSH

cardiovascular diseases

Brain Ischemia

follow-up studies

myocardial infarction

This analysis of 12 RCTs involving almost 1 million patients found that low-dose aspirin prevents major cardiovascular events (RRReduction 14%; ARR/1000 patient years 0.06%) but increases major bleeding events (RRIncrease 40%; ARR/1000 patient years 0.1%) across all levels of baseline risk. The researchers concluded that the absolute risk reduction and the risk: benefit ratio suggest that we should probably not prescribe low-dose aspirin for primary prevention even if the baseline risk of CV events is high and the risk of bleeding is low. James W. Mold, MD, MPH

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Background

Aspirin is often prescribed for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) however, recent randomized trials (RCTs) have challenged this practice. Despite this, aspirin is commonly recommended for high risk primary prevention. We tested the hypothesis that aspirin is more efficacious for the primary prevention of ASCVD, as the baseline risk increases.

Methods

RCTs that compared aspirin to control for primary prevention and evaluated ASCVD (composite of myocardial infarction and ischemic stroke) and major bleeding were included. Rate ratios (RR) and 95% confidence intervals (CI) were calculated. A regression analysis was performed using the ASCVD event rate in the control arm of each RCT as the moderator.

Results

Twelve RCTs were identified with 963,829 patient years of follow-up. Aspirin was associated with a reduction in ASCVD (4.7 versus 5.3 events per 1,000 patient years; RR 0.86; 95% CI 0.79-0.92). There was increased major bleeding among aspirin users (2.5 versus 1.8 events per 1000 patient years, RR 1.41 95% CI, 1.29-1.54). Regression analysis found no relationship between the log rate ratio of ASCVD or major bleeding and incidence of ASCVD in the control arm of each RCT.

Conclusion

Aspirin is associated with a reduction in ASCVD when used for primary prevention; however, it is unlikely to be clinically significant given the increase in bleeding. More importantly, aspirin's treatment effect does not increase as ASCVD risk increases as many hypothesize. There is no suggestion from this data that use of aspirin for higher risk primary prevention patients is beneficial.

Author/s:

Nudy, M, Cooper, J, Ghahramani, M, Ruzieh, M, Mandrola, J, Foy, AJ

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation

John Bayhi — Fri, 28 Feb 2020 14:21:39 +0000

Date Added:

February 28, 2020

Journal/Publication:

JAMA Network Open

Publisher:

American Medical Association

Publication Date:

February 5, 2020

Issue:

Volume:

Pages:

e200107

URL:

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamanetworkopen.2020.0107

Keywords

PMID (1):

32101311

MeSH

acute coronary syndrome

coronary artery disease

Platelet Aggregation Inhibitors

stroke

hemorrhage

Registries

The results of this cohort study suggest that for patients with atrial fibrillation, adding an antiplatelet agent to an oral anticoagulant results in more strokes and bleeding and does not protect them from MI. James W. Mold, MD, MPH

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IMPORTANCE:

Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy.

OBJECTIVE:

To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone.

DESIGN, SETTING, AND PARTICIPANTS:

Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019.

EXPOSURE:

Participants received either OAC plus AP or OAC alone.

MAIN OUTCOMES AND MEASURES:

Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications.

RESULTS:

A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months).

CONCLUSIONS AND RELEVANCE:

This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation.

Author/s:

Fox, KAA, Velentgas, P, Camm, AJ, Bassand, JP, Fitzmaurice, DA, Gersh, BJ, Goldhaber, SZ, Goto, S, Haas, S, Misselwitz, F, Pieper, KS, Turpie, AGG, Verhegut, FWA, Dabrowski, E, Luo, K, Gibbs, L, Kakkar, AK, GARFIELD-AF Investigators

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.

Periprocedural Bridging in Patients with Venous Thromboembolism: A Systematic Review

Brian Desmarais — Wed, 19 Jun 2019 20:00:05 +0000

Date Added:

June 19, 2019

Journal/Publication:

The American Journal of Medicine

Publication Date:

June 16, 2019

Issue:

Volume:

132

Pages:

722-732.e7

URL:

Periprocedural Bridging in Patients with Venous Thromboembolism: A Systematic Review.

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/j.amjmed.2019.01.004

Keywords

MeSH

Venous Thromboembolism

This systematic review of 28 cohort studies suggests that anticoagulation bridging in patients on warfarin for procedures is probably both unwise (increased bleeding) and unnecessary (no reduction in thromboembolic risk) .

James W. Mold, MD, MPH

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Abstract

BACKGROUND:

Vitamin K antagonists (VKA) are the most widely used anticoagulants, and bridging is commonly administered during periprocedural VKA interruption. Given the unclear benefits and risks of periprocedural bridging in patients with previous venousthromboembolism, we aimed to assess recurrent venous thromboembolism and bleeding outcomes with and without bridging in this population.

METHODS:

We performed a systematic review searching the PubMed and Embase databases from inception to December 7, 2017 for randomized and nonrandomized studies that included adults with previous venous thromboembolism requiring VKA interruption to undergo an elective procedure, and that reported venous thromboembolism or bleeding outcomes. Quality of evidence was graded by consensus.

RESULTS:

We included 28 cohort studies (20 being single-arm cohorts) with, overall, 6915 procedures for analysis. In 27 studies reporting perioperative venous thromboembolism outcomes, the pooled incidence of recurrent venous thromboembolism with bridging was 0.7% (95% confidence interval [CI], 0.4%-1.2%) and 0.5% (95% CI, 0.3%-0.8%) without bridging. Eighteen studies reported major or nonmajor bleeding outcomes. The pooled incidence of any bleeding was 3.9% (95% CI, 2.0%-7.4%) with bridging and 0.4% (95% CI, 0.1%-1.7%) without bridging. In bridged patients at high thromboembolic risk, the pooled incidence for venous thromboembolism was 0.8% (95% CI, 0.3%-2.5%) and 7.5% (95% CI, 3.1%-17.4%) for any bleeding. Quality of available evidence was very low, primarily due to a high risk of bias of included studies.

CONCLUSIONS:

Periprocedural bridging increases the risk of bleeding compared with VKA interruption without bridging, without a significant difference in periprocedural venous thromboembolism rates.

KEYWORDS:

Anticoagulants; Bleeding; Bridging; PROSPERO; Periprocedural; Venous thromboembolism; registration number CRD42017074710

Author/s:

Baumgartner, C., de Kouchkovsky, I., Whitaker, E., Fang, M.C.

Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis

Tracy Ashby — Mon, 11 Feb 2019 06:00:00 +0000

Date Added:

February 11, 2019

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

January 22, 2019

Issue:

Volume:

321

Pages:

277-287

URL:

Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2018.20578 Free full text

Keywords

aspirin

bleeding events

cardiovascular events

PMID (1):

30667501

MeSH

aspirin

primary prevention

hemorrhage

cardiovascular diseases

Consistent with the findings of the USPSTF, in adults with no history of cardiovascular disease, aspirin reduces the incidence of adverse cardiovascular events and increases the rate of major bleeding episodes. It has little or no effect on mortality.

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IMPORTANCE:

The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk.

OBJECTIVE:

To assess the association of aspirin use for primary prevention with cardiovascular events and bleeding.

DATA SOURCES:

PubMed and Embase were searched on Cochrane Library Central Register of Controlled Trials from the earliest available date through November 1, 2018.

STUDY SELECTION:

Randomized clinical trials enrolling at least 1000 participants with no known cardiovascular disease and a follow-up of at least 12 months were included. Included studies compared aspirin use with no aspirin (placebo or no treatment).

DATA EXTRACTION AND SYNTHESIS:

Data were screened and extracted independently by both investigators. Bayesian and frequentist meta-analyses were performed.

MAIN OUTCOMES AND MEASURES:

The primary cardiovascular outcome was a composite of cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke. The primary bleeding outcome was any major bleeding (defined by the individual studies).

RESULTS:

A total of 13 trials randomizing 164 225 participants with 1 050 511 participant-years of follow-up were included. The median age of trial participants was 62 years (range, 53-74), 77 501 (47%) were men, 30 361 (19%) had diabetes, and the median baseline risk of the primary cardiovascular outcome was 9.2% (range, 2.6%-15.9%). Aspirin use was associated with significant reductions in the composite cardiovascular outcome compared with no aspirin (57.1 per 10 000 participant-years with aspirin and 61.4 per 10 000 participant-years with no aspirin) (hazard ratio [HR], 0.89 [95% credible interval, 0.84-0.95]; absolute risk reduction, 0.38% [95% CI, 0.20%-0.55%]; number needed to treat, 265). Aspirin use was associated with an increased risk of major bleeding events compared with no aspirin (23.1 per 10 000 participant-years with aspirin and 16.4 per 10 000 participant-years with no aspirin) (HR, 1.43 [95% credible interval, 1.30-1.56]; absolute risk increase, 0.47% [95% CI, 0.34%-0.62%]; number needed to harm, 210).

CONCLUSIONS AND RELEVANCE:

The use of aspirin in individuals without cardiovascular disease was associated with a lower risk of cardiovascular events and an increased risk of major bleeding. This information may inform discussions with patients about aspirin for primary prevention of cardiovascular events and bleeding.

Author/s:

Zheng, Sean L., Roddick, Alistair J.