Mar 26, 2014

Newsletter - New Anticoagulants - March 2014

RECENT RELEVANT FACTS ABOUT NEW TARGET-SPECIFIC ORAL ANTICOAGULANTS

GUIDELINE
Stroke prevention in nonvalvular atrial fibrillation, according to the American Academy of Neurology
Main practice recommendations:
  • “To reduce the risk of stroke or subsequent stroke in patients with NVAF judged to require oral anticoagulants, clinicians should choose one of the following options…
    • Warfarin, target INR 2.0–3.0
    • Dabigatran 150 mg twice daily (if creatinine clearance [CrCl] >30 mL/min)
    • Rivaroxaban 15 mg/d (if CrCl 30–49 mL/min) or 20 mg/d
    • Apixaban 5 mg twice daily (if serum creatinine <1.5 mg/dL) or 2.5 mg twice daily (if serum creatinine >1.5 and <2.5 mg/dL, and body weight <60 kg or age at least 80 years [or both])
    • Triflusal 600 mg plus acenocoumarol...”
  • “Clinicians might recommend that patients taking warfarin whose condition is well-controlled continue warfarin treatment rather than switch to treatment with a new oral anticoagulant.”
  • “Clinicians should administer dabigatran, rivaroxaban, or apixaban to patients who have NVAF requiring anticoagulant medication and are at higher risk of intracranial bleeding.”
  • “Clinicians might offer apixaban to patients with NVAF and GI bleeding risk who require anticoagulant medication.”

Feb 17, 2014

Newsletter - New Anticoagulants - February 2014

RECENT RELEVANT FACTS ABOUT NEW TARGET-SPECIFIC ORAL ANTICOAGULANTS

MAGELLAN SUBSTUDY
D-dimer concentration may refine benefit of extended anticoagulant prophylaxis in acutely ill, hospitalized medical patients
“Elevated baseline D-dimer concentrations may identify acutely ill, hospitalized medical patients at high venous thromboembolism (VTE) risk for whom extended anticoagulant prophylaxis may provide greater benefit than those with low D-dimer concentrations.” That is the conclusion of this MAGELLAN subanalysis.
MAGELLAN was a multicenter, randomized, controlled trial, involving patients 40 years of age or older who were hospitalized for an acute medical illness. Subjects received subcutaneous enoxaparin 40 mg once daily for 10±4 days then placebo up to Day 35, or oral rivaroxaban 10 mg once daily for 35±4 days. Main results of the original trial published in the New England Journal of Medicine last year:
  • rivaroxaban was noninferior to enoxaparin for standard-duration thromboprophylaxis;
  • extended-duration rivaroxaban reduced the risk of VTE;
  • rivaroxaban was associated with an increased risk of bleeding.

Feb 3, 2014

Rivaroxaban: MAGELLAN substudy

Rivaroxaban and prevention of venous thromboembolism in acutely ill medical patients.

 MAGELLAN was funded by Bayer HealthCare Pharmaceuticals and Janssen Research and Development

MAGELLAN substudy: D-dimer concentration may refine benefit of extended anticoagulant prophylaxis in acutely ill, hospitalized medical patients
In hospitalized patients due to an acute medical illness, at risk of venous thromboembolism (VTE), is it possible to identify a subgroup of high risk individuals for whom extended-duration anticoagulant prophylaxis should be indicated?
This MAGELLAN subanalysis may help answer this question. The authors identified that “VTE frequency was 3.5-fold greater in patients with high D-dimer concentrations”. “In the high D-dimer group, rivaroxaban was non-inferior to enoxaparin at Day 10, and, unlike the low D-dimer group, superior to placebo at Day 35 (P<0.001) and Days 11-35 (P<0.001).” However, as in the original publication, rivaroxaban was associated with an increased risk of bleeding, regardless of the D-dimer group.
The authors conclude that “elevated baseline D-dimer concentrations may identify acutely ill, hospitalized medical patients at high VTE risk for whom extended anticoagulant prophylaxis may provide greater benefit than those with low D-dimer concentrations.”

Reference:
Cohen AT, Spiro TE, Spyropoulos AC, et al. D-dimer as a predictor of venous thromboembolism in acutely ill, hospitalized patients: a subanalysis of the randomized controlled MAGELLAN trial. J Thromb Haemost. 2014 Jan 27. [Epub ahead of print]. Abstract.

Jan 24, 2014

Newsletter - New Anticoagulants - January 2014

RECENT RELEVANT FACTS ABOUT NEW TARGET-SPECIFIC ORAL ANTICOAGULANTS

 Landmark clinical trials and substudies 

RE-COVER II and pooled analysis: dabigatran as efficacious as and safer than warfarin for the treatment of acute venous thromboembolism
RECOVER II was undertaken to expand the findings of RECOVER trial, when dabigatran was shown to be as effective and safe as warfarin for the treatment of acute venous thromboembolism (VTE). Dabigatran met the primary endpoint of non-inferiority to warfarin for recurrent, symptomatic, objectively-confirmed deep vein thrombosis and/or pulmonary embolism and related deaths during 6 months of therapy. The risk of any bleeding was lower with dabigatran, compared with warfarin.
A pooled analysis of RECOVER and RECOVER II trials showed similar results.
See more details of this study here.

Reference:
Schulman S, Kakkar AK, Goldhaber SZ, et al. Treatment of Acute Venous Thromboembolism with Dabigatran or Warfarin and Pooled Analysis. Circulation. 2013 Dec 16. [Epub ahead of print]. Abstract.
Editorial. Verhamme P, Bounameaux H. Direct Oral Anticoagulants for Acute Venous Thromboembolism: Closing the Circle? Circulation. 2013 Dec 16. [Epub ahead of print]. Abstract.

Jan 22, 2014

New target-specific oral anticoagulants in patients with kidney disease: review articles


Prescribing new target-specific oral anticoagulants to patients with chronic kidney disease (CKD) is always challenging due to several factors:
  • renal impairment increases both the thromboembolic and the bleeding risks;
  • there is limited experience with these new drugs in patients with CKD and most, if not all, trials excluded subjects with severe renal impairment;
  • all drugs are eliminated by the kidneys by some degree (dabigatran is eliminated primarily in the urine, whereas rivaroxaban, apixaban, and edoxaban are eliminated in urine and feces).

 RELEVANT REVIEWS  on new oral anticoagulants in chronic kidney disease (CKD), in reverse chronological order of appearance in PubMed.

Preventing stroke and systemic embolism in renal patients with atrial fibrillation
The authors conclude that  "there is a need for large randomised control trials in patients with renal insufficiency and on haemodialysis to provide a bank of high-quality scientific data on which clinicians can base their management decisions. Until then, we must adopt a pragmatic approach which involves careful consideration of the relative risk of stroke and bleeding in each individual patient.”

Reference:
Ahmad Y, Lip GY. Preventing stroke and systemic embolism in renal patients with atrial fibrillation: focus on anticoagulation. Contrib Nephrol. 2013;179:81-91. Epub 2013 May 3. Abstract.