Clinical Pharmacy Note RE: Stroke

Mar 6/17 1330h Clinical Pharmacy Note RE: Secondary Stroke Prevention

ID: 41 yo male admitted with stroke
(Mar 6 Head CT showed established infarct in L side with no signs of hemorrhage)

S/O: v/s: T 36.5, BP 125/65, HR 76, RR 9

  • RASS -1 to 0, aphasia but still able to answer yes/no questions
  • Aspirin 325mg PR load given at 1720 hr on Mar 5, 17 but 80mg daily is held by neurology until infective endocarditis (IE) can be ruled out with negative BCx
  • Due to previous IVDU (on methadone daily, urine + cannabis, opioids, amphetamines), suspecting septic emboli from IE
    • ECHO for IE w/u pending (currently empirically txed with pip/taz and vanco)
    • BCx prelim, results (Mar 5): G+ cocci likely streptococcus or enterococcus
  • Hgb (Mar 6): 78 (stable)

A:

  • Maintenance aspirin is necessary to help ↓ the risk of early and future recurrent ischemic stroke and ↓ the risk of mortality
  • There are no contraindications to use of aspirin with IE. No suspected intracranial hemorhage
  • Patient has no previous history of CVA or TIA, therefore currently no strong need for clopidogrel
  • No significant drug interactions with ASA (low risk of increased bleeding with escitalopram)

P: Suggest

  • Start ASA 80mg daily (life long). Continue Dalteparin SC (VTE Px dose)
  • Monitor for s/s of ischemic stroke: one-sided weakness, numbness, trouble speaking, trouble seeing, severe headache, confusion
  • Monitor for SEs of ASA: bleeding (tarry stools, hematuria), GI upset, hemorrhagic stroke (severe headache, bizarre behaviour), daily CBCs
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MATCH

Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial (2004)

Managment of ATherothrombosis with Clopidogrel in High-risk patients

Design: Randomised, double-blind, placebo-controlled trial (Dec 2000 – April 2002)

  • 507 centres (stroke units and neurology departments) in 28 countries
P  N = 7599
High risk patients with recent ischemic stroke or TIA and at least one additional vascular risk factor who were already receiving clopidogrel 75mg dailyInclusion:

  • ischemic stroke or transient ischemic attack in the previous 3 months
    • categorised ischemic stroke with the TOAST classification
  • 1 or more of 5 additional risk factors – previous ischemic stroke, previous myocardial infarction, angina pectoris, diabetes mellitus or symptomatic peripheral arterial disease within the previous 3 years

Exclusion:

  • age < 40 yo
  • severe comorbid conditions
  • increased risk of bleeding (clinical evience of severe hepatic insufficiency, current peptic ulceration, history of systemic bleeding or other history of bleeding diathesis or coagulopathy)
  • scheduled for major surgery or vascular surgery
  • contraindications for aspirin or clopidogrel

Patient characteristics – fairly well balanced between treatment arms

  • Mean age ~ 66 yo
  • 37% female
  • Qualifying event – 21% TIA, 79% ischemic stroke
    • TOAST classification:
      • 34% large artery atherosclerosis
      • 53% small vessel occlusion
      • 2-3% cardioembolism
  • 50% 7 days to 1 month from qualifying event
  • 74% none to slight disability (Modified Rankin scale)
  • 26% ischemic stroke history
  • 19% tia history
  • 5% MI history
  • 78% hypertension
  • 68% diabetes
  • 57% hypercholestermia
  • 48% past or current smoker
  • 80% on aspirin at baseline
I Aspirin 75mg daily (+ Clopidogrel 75mg daily)
Duration of treatment + f/u: 18 months
C Placebo daily (+ Clopidogrel 75mg daily)
Duration of treatment + f/u: 18 months
O Primary endpoint: composite of ischemic stroke, myocardial infarction, vascular death (including haemorrhagic death of any origin) or rehospitalization for acute ischemia (including rehospitalization for TIA, angina pectoris or worsening of peripheral arterial disease requiring therapeutic iintervention or urgent revascularization or transient ischemic attack)

Secondary endpoints:

  • individual and various combinations of the primary endpoint
  • any death
  • any stroke

Safety:

  • incidence of life-threatening bleeding (any fatal bleeding event, a drop in hgb of >50g/L, significant hypotension with need for inotropes (haemorrhagic shock), symptomatic intracranial haemorrhage or transfusion of >4 units of RBC or equivalent amount of whole blood) and major bleeding (defined as significant disabling (with persistent sequalae)), intra-ocular bleeding leading to significant loss of vision or transfusion of <3 units of RBC or equivalent amount of whole blood

Analysis: Intention to treat (irrespective of compliance to protocol)
Power: 80% power, N = 7600 – to detect a 14% relative risk reduction
Funding: Sanofi Synthelabo – undertake site monitoring and data management, and provide input into the study by putting employee into the steering committee

Results:

Efficacy:

  • Primary composite endpoint:
    • RRR: 9.5% (CI: -2 to 19.6%)
  • All stroke NSS
  • Ischemic stroke NSS
  • All-cause mortality NSS

Safety:

  • Life-threatening bleeding:
    • ARR: 1.26% (0.64-1.88) p < 0.0001
    • No early increase in life-threatening bleeding and primary intracranial haemorrhage)
    • No report of haemorrhagic transformations of ischemic stroke
  • GI bleeds
    • Life-threatening: 1.4% vs. 0.6%
    • Major: 1.12% vs 0.29%
  • Fatal bleeds: NSS
  • Symptomatic intracranial haemorrhage:
    • ARR: 0.40% (0.04-0.76)
  • Minor bleeding:
    • ARR: 2.16% (1.51-2.81) p < 0.0001
  • symptomatic intracranial haemorrhage was  more frequent in the aspirin group than in patients allocated placebo; however, in both treatment arms, no haemorrhageic transformations of ischemic stroke were reported as life-threatening bleeding (1.4% vs. 0.6% and 1.12% vs. 0.29%

Take-home points:

  • Aspirin ADDED to clopidogrel (not clopidogrel ADDED to aspirin) resulted in signigifantly higher bleeding with no significant efficacy benefit
  • Patient population are “select high-risk patients”

Academic Day Seminar – Nov 18

✔ Stroke

Anna and Julia did a wonderful job covering ischemic stroke! I haven’t really had much opportunity to encounter stroke in my rotations – so this was a great overview to have! My notes can be found here: stroke

Ways I will apply this:

  • BP management
    • Identify if patient is or is not a candidate for tPA
      – Not on tPA: 15% reduction if >220/120
      – on TPA: target 180/105
      – Choice of BP meds not well-established
      *If on BB PTA, avoid discontinuing or holding to prevent rapid afib or rapid tachycardia – may consider lowering dose of BB if needed*
      – 9/10 of the times, it is hard to control BP in 1st wk after stroke (acute)
    • Keep in mind the pros and cons of lowering BP
    • If patient needs regular BP meds and administration is impeded by swallong difficulities, assess need for NG tube (But avoid NG tube insertion in 1st 24 hours)
  • Assess for VTE prophylaxis
    • evidence for hemorrhagic stroke is low
    • SC LMWH or UFH within 48 hrs of stroke or 24 hrs after thrombolytic admin for ischemic stroke
      – may consider IPC but monitor for skin breaks
  • Differentiating ischemic and hemorrhagic stroke:
    • s/s that are associated with hemorrhagic stroke: coma, neck stiffness, seizures, elevated BP, vomiting and extremely severe headache

Other trials to review: SOCRATES, FASTER