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Antithrombotic therapy in non-valvular AF patients

Rohan Subasinghe. Antithrombotic therapy in non-valvular AF patients. Why is it important?. Non valvular aF increases with age from 0.5 % at age 50-59 to 9 % at age 80-89 AF is an independent Risk factor for CVA Patients with AF have a 5 fold mean increase in Stroke due to atrial thrombosis.

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Antithrombotic therapy in non-valvular AF patients

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  1. Rohan Subasinghe Antithrombotic therapy in non-valvular AF patients

  2. Why is it important? • Non valvular aF increases with age from 0.5 % at age 50-59 to 9 % at age 80-89 • AF is an independent Risk factor for CVA • Patients with AF have a 5 fold mean increase in Stroke due to atrial thrombosis. • Stroke mortality is higher in aptients with AF

  3. What are the agents? • Aspirin - irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation • Warfarin - Warfarin inhibits the vitamin K-dependent synthesis of biologically active forms of the calcium-dependent clotting factors II, VII, IX and X • ximelagatran - direct thrombin inhibitor – less monitoring required but increased ALT levels

  4. What are the issues? • Risk stratification of patients –aspirin or warfarin? • Possibility of intra and extra cranial haemorrhages. • Interaction with other medications • Disability, cognitive impairment, and problems with compliance are common in the elderly patients with AF • Inconvenience of monitoring in warfarin therapy and impact on quality of life

  5. Current NICE Guideline • http://www.nice.org.uk/nicemedia/pdf/CG036quickrefguide.pdf

  6. What is the evidence? • Numerous RCTs support tnromboprophylaxis in non valvular AF patients • Meta-analysis: Antithrombotic Therapy to Prevent Stroke in Patients Who Have Nonvalvular Atrial Fibrillation Robert G. Hart, MD; Lesly A. Pearce, MS; and Maria I. Aguilar, MD

  7. aims • To characterize the efficacy and safety of antithrombotic agents for stroke prevention in patients who have atrial fibrillation • Adding 13 recent randomized trials to a previous meta-analysis.

  8. Study selection • Double Blind Randomised trials • Mean follow-up of 3 months or longer that tested • Antithrombotic agents in patients who have nonvalvular atrial fibrillation. • Data Extraction: Two coauthors independently extracted information regarding interventions; participants; and occurrences of ischemic and hemorrhagic stroke, major extracranial bleeding, and death.

  9. Results • Twenty-nine trials included 28 044 participants • Mean age, 71 years; mean follow-up, 1.5 years). • Compared with the control, adjusted-dose warfarin (6 trials, 2900 participants) reduced stroke by 64% (95% CI, 49% to 74%) NNT 37 primary 12 secondary prev • Antiplatelet agents (8 trials, 4876 participants) reduced stroke by 22% (CI, 6% to 35%). NNT 125 / 40 • Adjusted-dose warfarin was substantially more efficacious than antiplatelet therapy (relative risk reduction, 39% [CI, 22% to 52%]) (12 trials, 12 963 participants). Heterogeneous NNT not calculable (estimated at 24)

  10. Harms • Other randomized comparisons were inconclusive. • Absolute increases in major extracranial haemorrhage were small (0.3% per year) on the basis of metaanalysis. • NNH for major haemorrhage 250 • NNT for mortality benefit 200

  11. Comment BMJ 1992 305 p1460-5 Sordercoat et al

  12. Comment – Meta-analysis • Bearing in mind that AF prevalence increases with age – is a mean age of 71 in the trials representative of patients we see?

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