Drug and Therapeutics Bulletin
A commentary on the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) highlights that intensive antiplatelet therapy with three drugs should not be used in routine clinical practice to prevent recurrent events in patients with acute cerebral ischaemia.
JAMA Internal Medicine
Study (n=39,622) found testosterone therapy was associated with an increase in short-term risk for VTE among men with (OR 2.32; 95% CI, 1.97-2.74) and without (2.02; 1.47-2.77) hypogonadism, with some evidence that the association was more pronounced among younger men.
JAMA Cardiology
Article notes adjunctive antithrombotic therapy used to mitigate thrombotic risks in this population must be balanced against bleeding complications. Evidence for its use remains scarce and no risk prediction models have been established to guide antithrombotic therapy.
Biospace Inc.
Feedback from regulatory authorities, and from recent study site inspections indicated that additional clinical data would be required for approval. As a result, Actelion has decided to withdraw ongoing worldwide submissions based on phase 2 MERIT-1 study.
The above records have been identified by UKMi and feature in the NICE Medicines Awareness Service. Further details on this service can be found at:
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The Lancet Haematology
RCT (n=500) reports fewer symptomatic recurrent venous thromboembolism rates with rivaroxaban: 1% of 335 children receiving weight-adjusted rivaroxaban vs 3% of 165 receiving standard anticoagulants (HR 0.40, 95% CI 0.11–1.41), with similar rates of bleeding in both groups.
The above records have been identified by UKMi and feature in the NICE Medicines Awareness Service. Further details on this service can be found at:
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Journal of the American Medical Association
RCT of 735 adults who underwent CABG surgery and developed significant bleeding and hypofibrinogenemia post surgery showed similar number of blood components transfused within 24hrs with both fibrinogen concentrate group and cryoprecipitate group (p<0.01 for non-inferiority).
Annals of Internal Medicine
Recommendations for patients receiving anticoagulation or antiplatelet therapy have been updated. PPI therapy is recommended to prevent UGIB in patients with previous ulcer bleeding who are receiving single- or dual-antiplatelet or anticoagulant therapy.
Prevalence and Knowledge of Potential Interactions Between Over‐the‐Counter Products and Apixaban
Journal of the American Geriatrics Society
Survey (n=791,California) found significant number of patients take OTC meds (particularly dietary supplements) with potentially serious interactions (SIs) with apixaban (33% took ≥1 and 6.7% multiple interacting OTC meds) and they appear to lack knowledge about potentially SIs.
European Heart Journal
Review (4 RCTs; n= 10 234) reported lower major or clinically relevant non-major bleeding with double vs. triple antithrombotic therapy (RR 0.66, 95% CI 0.56–0.78; P < 0.0001; I2 = 69%) but at higher risk of stent thrombosis (RR 1.59, 95% CI 1.01–2.50; P = 0.04; I2 = 0%).
NIHR Signal: Significant risk of another thrombosis remains if anticoagulation is stopped
NIHR Dissemination Centre
This expert commentary of a meta-analysis (18 studies, n= 7,515) states clinical decisions to cease anticoagulation should remain tailored to each patient's circumstances and balanced against risk of bleeding.
European Medicines Agency
PRAC has concluded that tofacitinib could increase risk of blood clots in the lungs and deep veins in patients who are already at high risk. Also, patients older than 65 years of age should be treated with tofacitinib only when there is no alternative treatment.
The above records have been identified by UKMi and feature in the NICE Medicines Awareness Service. Further details on this service can be found at:
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Annals of Internal Medicine
In this RCT of 190 APS patients, after 3years 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] prespecified noninferiority margin for RR was 1.40).
The Lancet
RCT of 9202 patients treated within 3hrs of injury reports lower risk of head injury-related death at 28days with tranexamic acid (18.5%) vs placebo (19.8%; RR 0.94 [95% CI 0.86–1.02]), and this was statistically significant in those with mild-moderate injury (RR 0.78, 0.64–0.95).
Biospace Inc.
Approval is based on data from the phase III MAGELLAN and MARINER trials. MAGELLAN met its co-primary endpoints, demonstrating non-inferiority to enoxaparin in short-term (10 days) and superiority in long-term (35 days) use, while MARINER demonstrated reduction in symptomatic VTE.
The above records have been identified by UKMi and feature in the NICE Medicines Awareness Service. Further details on this service can be found at:
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National Institute for Health Research
Expert commentary is provided on a network meta-analysis (17 RCTs, n= 46,864) which showed standard 12-month treatment increased the risk of any bleeding compared with 6 month short-term treatment (OR 1.39, 95% CI 1.01 to 1.92).
Heart
Study (n=36,652) found adherence & persistence to direct oral anticoagulants are low at 1 yr with heterogeneity across drugs and over time at individual and system levels. Authors state better understanding of contributory factors will inform interventions to improve adherence.
British Medical Journal
Analysis (20 RCTs;n=4083) found moderate evidence to support dual antiplatelet use [aspirin(AS)+ticagrelor; OR 0.50,95% CI 0.31-0.79, NNT 10 or AS+clopidogrel; 0.60;0.42-0.86, 19] to reduce saphenous vein graft failure vs aspirin, with no significant differences in major bleeding.
Comparison of Events Across Bleeding Scales in the ENGAGE AF-TIMI 48 Trial
Circulation
In this study of edoxaban vs warfarin (n=21,105; and 10,311 total bleeding events), there was ~4-fold difference in frequency of most severe bleeding events across commonly used bleeding scales (ISTH, TIMI, GUSTO, and BARC) among patients with AF at risk for stroke.
JAMA Cardiology
Study found new-onset post op AF (POAF) was linked to a similar long-term risk of thromboembolism as nonvalvular AF (crude incidence rates 21.9 and 17.7 events/1000 person-years respectively), highlighting need for further studies addressing anticoagulation in POAF population.
Revised SPC: Plavix (clopidogrel) tablets
electronic Medicines compendium
SPC now details that co-administration of opioids has the potential to delay and reduce the absorption of clopidogrel due to delayed gastric emptying. The use of parenteral antiplatelet agent in ACS should be considered where opioid co-administration is required.
Journal of Thrombosis and Haemastasis
Review of 28 studies reports that low‐dose direct oral anticoagulant prophylaxis reduces the rate of overall venous thromboembolism in high‐risk cancer patients starting systemic chemotherapy but may increase the risk of bleeding.
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Journal of the American Medical Association
Review of 3 RCTs (n=368) found that protocol-based general anaesthesia was associated with less disability at 3 months vs procedural sedation (difference = +0.43 on modified Rankin Scale score, OR 1.58, 95% CI 1.09-2.29).
Compression stockings to prevent post-thrombotic syndrome in adults, a Bayesian meta-analysis
Thrombosis Reasearch
Review of 4 studies found that compression stockings reduced post thrombotic syndrome (PTS) vs. control in acute DVT, but that the difference was not statistically significant (OR = 0.57, 95% CI: 0.21-1.20).
Circulation
Japanese RCT (n=3,009) found 1-month therapy reduced major bleeding vs. 12-months (0.41% vs. 2.71%, HR 0.15, 95% CI 0.03-0.65, p=0.01); without any increase in CV events (3.48% vs. 5.98%, absolute difference -2.50%, 95% CI -5.06% to 0.06%, HR 0.57, 95% CI 0.32-1.03, p=0.06).
The above records have been identified by UKMi and feature in the NICE Medicines Awareness Service. Further details on this service can be found at:
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Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Asians With Atrial Fibrillation
Stroke
Review, based on subanalyses of 5 RCTs and 21 observational cohorts, found use of NOACs is noninferior vs warfarin with respect to risk of stroke or systemic embolism, all-cause mortality, major bleeding and intracranial bleeding, irrespective of the NOAC type and dose.
BMJ Open
Database study (n=30 467; 2011-2016) reported 76.9% of patients starting NOACs were prescribed an appropriate dose. Underdosing more frequent in apixaban vs dabigatran and rivaroxaban cohorts. Overdosing more frequent in dabigatran vs rivaroxaban or apixaban cohorts.
Thrombosis Reasearch
Retrospective US study of 2890 matched pairs of morbidly obese VTE patients reported similar recurrent VTE risk (OR: 0.99; 95% CI: 0.85–1.14) and major bleeding (0.75: 0.47–1.19) with rivaroxaban vs warfarin. Hospitalizations and outpatient visits were lower with rivaroxaban.
Oral Anticoagulation in patients with non-valvular atrial fibrillation and a CHA2DS2-VASc score of 1
European Heart Journal
This report outlines the currently available evidence in this field and provides a risk stratification of the individual thromboembolic risk in patients with AF and a CHA2DS2-VASc score of 1 to guide clinicians on whether to anticoagulate or not.
Revised SPC: Brilique (ticagrelor) film coated tablets – all strengths
electronic Medicines compendium
The SPC has been updated to warn of potential for ticagrelor to interfere with platelet function tests to diagnose heparin induced thrombocytopenia (HIT).
Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery
Cochrane Database of Systematic Reviews
Updated review of 7 RCTs (n=1728) concludes prolonged thromboprophylaxis (14 days) with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications or mortality.
JAMA Neurology
Pooled analysis of data from 251 patients with mild-deficit emergency large-vessel occlusion stroke concludes mechanical thrombectomy has a similar efficacy and safety profile vs best medical management, and a separate systematic review confirms this finding.
Circulation
Study (n=4,614) shows regimen of apixaban + P2Y12 inhibitor without aspirin provides superior safety & similar efficacy in atrial fibrillation patients who have ACS (managed medically or with PCI), or those undergoing elective PCI; vs. regimens with VKAs, aspirin, or both.
Heart
Study (n=159,222) found the female/male ischaemic stroke risk ratio varied with age. Only women aged >75 years had a higher risk, whereas women aged <65 years had a lower risk vs. men. Authors state findings challenge the 'sex category' of the CHA2DS2-VASc score.
Ticagrelor with or without Aspirin in High-Risk Patients after PCI
New England Journal of Medicine
RCT (n=7,119) found ticagrelor monotherapy was associated with lower incidence of clinically relevant bleeding vs. ticagrelor + aspirin (1.0% vs. 2.0%; HR 0.49; 95% CI, 0.33 to 0.74), with no higher risk of death, myocardial infarction, or stroke.
The above records have been identified by UKMi and feature in the NICE Medicines Awareness Service. Further details on this service can be found at:
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Stroke and thromboembolism prevention in atrial fibrillation
Heart
Review discusses this association, medical/non-medical therapy for stroke prevention, guideline recommendations for prevention, electrical and pharmacological cardioversion, ablation therapy and antithrombotic medication management, as well as key outstanding research questions.
Annals of Internal Medicine
This study, based on an analysis of 245,028 persons (43.6% women) aged 30-79yrs without established CVD who had their CVD risk assessed suggests a model that provides a personalised prediction of the benefits and bleeding harms from aspirin when used for primary prevention of CVD.
Head injury: assessment and early management – updated guideline [CG176]
National Institute for Health and Care Excellence
Updates have been made to the recommendations on head CT scans in people on anticoagulant treatment, diagnosis and management of post head injury hypopituitarism, and management of indirect brain injuries.
The above records have been identified by UKMi and feature in the NICE Medicines Awareness Service. Further details on this service can be found at:
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Bleeding and New Cancer Diagnosis in Patients with Atherosclerosis
Circulation
Study (n=27,395) found that in patients with atherosclerosis treated with antithrombotic drugs, any GI bleeding was linked to new GI cancer diagnosis (HR 20.6, 95% CI, 15.2 to 27.8); likewise for genitourinary(GU) bleeding and new GU cancer diagnosis (32.5; 24.7 to 42.9).
Thrombosis and Haemostasis
Review of 9 RCTs (n=7,656) found that rivaroxaban reduced VTE vs aspirin (1.3% vs 3.5%, RR 0.36, 95% CI 0.26-0.48), but increased non-major bleeding (11.5% vs 7.5%, 1.28, 1.13-1.44). There was no difference in all-cause mortality and major bleeding.
Annals of Internal Medicine
Meta-analysis of registry data from 5 countries concludes prevalence of hemophilia is higher than previously estimated: prevalence (per 100,000 males) is 17.1 cases for all severities of haemophilia A, and 3.8 cases for all severities of haemophilia B.
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JAMA Neurology
RCT (n=120) found no recurrent VTEs and one major bleeding event with dabigatran and two with warfarin. Authors conclude that both may be effective for recurrent VTE prevention in patients with central venous thrombosis.
Journal of the American Medical Association
RCT (n=1,650) failed to establish non-inferiority of an INR goal of 1.8 vs 2.5 for VTE prevention post hip or knee arthroplasty (rate of VTE or death was 5.1% for INR target of 1.8 vs 3.8% for INR target 2.5, difference 1.3%, p=0.06 for non-inferiority).
A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI
New England Journal of Medicine
Open label RCT (n=2,488) found a similar efficacy outcome (composite of stent thrombosis, mortality and myocardial infarction) for a CYP2C19 genotype–guided strategy vs standard ticagrelor or prasugrel, but minor bleeding rates were lower (9.8% vs 12.5% p=0.04).
The Lancet
RCT (n=1,506) found that edoxaban was non-inferior to a vitamin K antagonist (VKA) for bleeding events (annualised rate of 20.7% for edoxaban vs 25.6% for VKAs, HR 0.83, 95% CI 0.65-1.05, non-inferiority margin HR = 1.20, p=0.001 for non-inferiority).
British Journal of Clinical Pharmacology
This review gives background information on critical factors for the formulary uptake process of LMWHs. It introduces a straightforward instrument to enhance formulary policy making in a transparent, rational way (the System of Objectified Judgment Analysis/Infomatrix model).
The Lancet Oncology
This guidance is based on a systematic review of the literature. Results from head to head trials comparing DOACs with LMWHs are included for information in the guidance along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.
Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease
New England Journal of Medicine
Study of 2236 AF patients reports rivaroxaban monotherapy is non-inferior to combination therapy with antiplatelet+rivaroxaban for the primary efficacy end point (composite of stroke, systemic embolism, MI, unstable angina requiring revascularization, or death from any cause).
European Heart Journal
Predicted individual gain in life expectancy free of stroke or MI from added low-dose rivaroxaban had a median of 16 months (range 1–48 months), while predicted individualized lifetime lost in terms of major bleeding had a median of 2 months (range 0–20 months).
Ticagrelor in Patients with Stable Coronary Disease and Diabetes
New England Journal of Medicine
RCT (n=19,220; median follow-up 39.9 months) reported lower incidence of ischaemic cardiovascular events with ticagrelor + aspirin vs aspirin (7.7 vs. 8.5%; HR, 0.90; 95% CI, 0.81 to 0.99; P=0.04) but higher incidence of major bleeding (2.2 vs. 1.0%; 2.32; 1.82 to 2.94; P<0.001).
Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes
New England Journal of Medicine
Open-label RCT (n=4018) reported incidence of death, MI, or stroke was significantly lower in the prasugrel group vs ticagrelor group (6.9% vs 9.3%; HR, 1.36; 95% CI, 1.09 to 1.70; P=0.006) with no difference in major bleeding (4.8% vs 5.4%; 1.12; 0.83 to 1.51; P=0.46).
The Lancet
Sub-group analysis (n=11,154) reported that addition of ticagrelor to aspirin reduced cardiovascular death, MI, and stroke vs placebo for a median of 3.3 years (7.3 vs 8.6% in the PCI group; HR 0.85; 95% CI 0.74–0.97; p=0.013), although with increased risk of major bleeding.
European Heart Journal
These guidelines, an update of the 2014 guidelines, outline the optimal diagnosis, assessment, and treatment of patients with pulmonary embolism.
The above records have been identified by UKMi and feature in the NICE Medicines Awareness Service. Further details on this service can be found at:
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