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stroke_antithromboticrx

antithrombotic Rx for prevention of stroke

introduction

  • 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 warfarin with target INR 2.0-3.0, although those with lower risk or in whom warfarin is 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.
  • a new oral antithrombotic, rivaroxaban, is currently being trialled in AF patients and if successful, may eventually replace warfarin in this role.
  • a trial of the new oral factor Xa inhibitor, 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). Apixaban was approved on PBS for use in non-valvular AF in Sept 2013.
  • a tool for determining risk in patients with non-valvular AF is the CHADS2 criteria:
criteria score
PH stroke or TIA 2
age > 74 years 1
hypertension 1
diabetes 1
heart failure 1
  • sum the scores and recommended Rx is given by:
stroke risk recommended Rx
high risk (score 2-6) warfarin (INR 2-3)
moderate (score 1) warfarin or aspirin
low (score 0) aspirin 100-300mg daily

balance the stroke prevention benefits with risk of major bleeding

  • 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.

warfarin Rx for the elderly

  • 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.
  • may be useful for those:
    • who cannot tolerate aspirin (eg. hypersensitivity to aspirin or non-steroidal anti-inflammatory drugs (NSAIDs), unacceptable risk of GIT bleeding)
    • 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.

references and resources

1)
NEJM 364:9 March 3, 2011 p806-817
stroke_antithromboticrx.txt · Last modified: 2014/04/04 17:11 (external edit)