Rohan Subasinghe

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

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

• 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

http://www.nice.org.uk/nicemedia/pdf/CG036quickrefguide.pdf

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

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.

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.

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)

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

Comment BMJ 1992 305 p1460-5 Sordercoat et al

CVA AF Non-AF

30-day Mortality

23% 8%

30-day recurrent CVA

1% 4%

Annual recurrent CVA

11% 8.2%

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?