risk of ischaemic stroke (CVA) increases with age but varies depending on risk factors
risk factor
annual risk of stroke untreated
AF with mitral stenosis or prosthetic valves
15-20%
non-valvular AF
2-18%
PH TIA
5-7%
PH stroke
4-5%
hypertension
2-3%
smoking, diabetes or CVS disease
1-2%
Valvular AF
patients with prosthetic heart valves or mitral stenosis have the highest risk of thromboembolism and should have life long anticoagulation with warfarin unless C/I
target INR 2.5-3.5 for mechanical prosthetic heart valves
Non-valvular AF
most patients with chronic or intermittent AF should be on an anti-thrombotic agent, although those with lower risk or in whom these are C/I should be considered for aspirin
aspirin is ~half as effective as warfarin for preventing stroke in AF and for most has half the risk of major bleeding.
aspirin with clopidogrel is not safer or more effective than warfarin in Rx of AF.
the DOACs / NOACs, in particular, apixaban, have largely replaced warfarin as the antithrombotic agent of choice
a trial of apixaban showed that it reduced stroke risk by more than 50% when compared to aspirin alone (3.4% per year on aspirin, 1.6% per year on apixaban), whilst increasing risk of major bleeding from 1.2% per year on aspirin to 1.4% per year on apixaban 5mg bd 1).
the ARISTOTLE trial compared apixaban with warfarin and showed it was 21% better at reducing stroke, had 30% lower incidence of major bleeding, and reduced all-cause mortality by 11%
apixaban was approved on PBS for use in non-valvular AF in Sept 2013.
absolute risk of major bleeding with warfarin is 0.5-1% per year and is greatest in the 1st few months of Rx
in moderate bleed risk patients with a 5% pa major bleed rate, if their annual stroke risk rate is 15% without warfarin , then for treating 100 such patients, each year, 5 will have a major bleed but stroke will be prevented in 9.
the risk of major bleeds with aspirin Rx in the elderly > 80yrs may be similar to risk of bleed from Rx with warfarin
aspirin alone has a limited role in preventing stroke in patients with AF and perhaps should only be used if anticoagulation is C/I and combination Rx of aspirin with clopidogrel is also C/I
non-inferiority RE-LY trial showed dabigatran 110 mg and warfarin did not differ in terms of stroke prevention however dabigatran was associated with lower rates of bleeding.
150 mg of dabigatran produced lower rates of stroke and similar rates of bleeding as warfarin.
new AMI and non-valvular AF
for patients who have an AMI and are in AF:
patients who have recently had a myocardial infarction receive antiplatelet therapy, in particular the combination of aspirin and a potent P2Y12 inhibitor, to reduce their risk of another ischemic event
HOWEVER, avoid using prasugrel or ticagrelor with a DOAC (the experimental arm in this study) as the 2026 EPIDAURUS trial comparing this with DOAC plus clopidogrel with in-hospital aspirin control group for a 1 month duration post AMI was terminated early as there was no evidence of benefit of the experimental arm and a 3.5x risk of significant bleeding2)
warfarin Rx for the elderly
NB. in general a DOAC is preferred over warfarin for most patients with non-valvular AF
age > 80 yrs - 13% have a major bleed in their 1st year of Rx
age > 75yrs with non-valvular AF study (Mant et al. Lancet 2007; 370:493-503) has shown:
annual rate of stroke and systemic embolism was 1.8% on warfarin vs 3.8% on aspirin
annual rate of major extracranial bleeding was 1.4% on warfarin vs 1.6% on aspirin
thus older age and propensity for falls do not preclude use of warfarin unless bleed risk is too high for that patient
do not use high loading doses in the elderly, start with 5mg or less
older patients should have a lower INR target eg. 2-2.5 but targeting a lower INR of 1.5-2.0 does not appear to reduce risk of bleeding on warfarin, and is less likely to prevent stroke and thus not generally advocated.
warfarin should not be used in people with:
bleeding disorders
PH GIT bleeding
haemorrhagic retinopathy
intracerebral aneurysm or haemorrhage
bacterial endocarditis
uncontrolled hypertension
heavy alcohol intake
liver disease
unsupervised dementia
potential non-compliance with Rx or anticoagulation monitoring
patients who don't have AF but have PH stroke or TIA due to presumed arterial disease
using antiplatelet Rx in these patients will over 3 years prevent 25 strokes per 1000 patients treated at a risk of 1-2 additional bleeds per year.
aspirin:
usual Rx is aspirin 100-300mg daily as soon as possible after an ischaemic stroke or TIA
aspirin with dipyridamole sustained release
an option for those who have recurrent stroke or TIA whilst on aspirin
whilst it does reduce relative risk of non-fatal stroke by 23% (95% CI 11-33%) compared with aspirin alone, it does not prevent more vascaular deaths than aspirin alone and is often not tolerated due to headache.
clopidogrel:
has similar efficacy to aspirin with dipyridamole in preventing recurrent stroke, and a comparable risk of bleeding but is more expensive than aspirin with only marginal additional benefit.
who have recurrent ischaemic episodes whilst on aspirin
who also have ischaemic heart disease for which adding dipyridamole to aspirin has not been shown to be as helpful for the heart disease as using clopidogrel alone
clopidogrel should only be used with aspirin in those patients with acute coronary syndromes or where there are coronary stents as the combination does not further reduce risk of stroke but does increase risk of major bleeding.