Transcript of Pharmacologic Prevention of Stroke Jonathan Raser-Schramm, MD, PhD Medical Director, Stroke Program...
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- Pharmacologic Prevention of Stroke Jonathan Raser-Schramm, MD,
PhD Medical Director, Stroke Program Christiana Care Health System
March 21, 2014
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- Disclosures No financial relationships Will discuss off-label
use of a number of antithrombotic agents
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- What is a stroke? sudden onset neurological deficit
attributable to a vascular cause
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- What is a stroke? ICHSAHinfarction
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- What is a stroke? ICHSAHinfarction 80% 15% 5%
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- Modifiable stroke risk factors ICHSAHinfarction hypertension
tobacco abuse
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- Modifiable stroke risk factors infarction
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- Atherothrombosis VASCULAR NEUROLOGY Lammie et al. Stroke (1999)
thrombus atheromatous plaque
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- Thromboembolism Lammie et al. Stroke (1999) thrombus
atheromatous plaque
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- Modifiable stroke risk factors infarction diabetes mellitus
dyslipidemia
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- Outline antihypertensives antilipid agents antithrombotics
other pharmacologic approaches
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- Two phases of stroke treatment acute stroke secondary
prevention
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- Two phases of stroke treatment acute stroke secondary
prevention weeks to months
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- Hypertension and stroke
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- Who should be treated? All patients after stroke? All
hypertensive patients after stroke? What about patients with non-
atherosclerotic causes of stroke? Could some patients be harmed by
lowering blood pressure?
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- Causes of cerebral infarction small vessel disease atrial
fibrillation cryptogenic large vessel disease other
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- Who should be treated? All patients after stroke? Across
numerous randomized studies, there has not been any subset of
patients that does not clearly benefit from blood pressure
reduction in stroke prevention. Yes
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- Who should be treated? All hypertensive patients after stroke?
Stroke prevention occurs with treatment in patients regardless of
baseline blood pressure.
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- Who should be treated? What about non-atherosclerotic causes of
stroke? There is an argument that patients who are normotensive
(120/70) and have specific causes of stroke such as atrial
fibrillation, DVT with PFO, endocarditis, or hypercoagulable states
may not benefit from treatment. This question is not
well-studied.
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- Who should be treated? Who might be harmed? large vessel
disease concern for cerebral hypoperfusion
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- Who should be treated? Who might be harmed? For patients with
large vessel stenosis >50% (especially >70%), there is a risk
of recurrent stroke with aggressive treatment. However, some
studies suggest benefit with long-term, stepwise aggressive
lowering of blood pressure.
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- How much to lower?
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- How much to lower? Some support for all these answers!! the
lower, the less risk of stroke
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- Which agents to choose? Diuretics Beta blockers ACE inhibitors
Angiotension receptor blockers Calcium channel blockers Alpha
blockers
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- Which agents to choose? Diuretics Beta blockers ACE inhibitors
Angiotension receptor blockers Calcium channel blockers Alpha
blockers Ultimately, achieving reduction in blood pressure is
likely more important than specific agent required.
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- Which agents to choose? Diuretics Beta blockers ACE inhibitors
Angiotension receptor blockers Calcium channel blockers Alpha
blockers All these agents have safety/efficacy after stroke.
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- Which agents to choose? Diuretics Beta blockers ACE inhibitors
Angiotension receptor blockers Calcium channel blockers Alpha
blockers Though traditionally first-line agents, in one trial HCTZ
was inferior to CaCB; indapamide and chlorthalidone may have better
support.
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- Which agents to choose? Diuretics Beta blockers ACE inhibitors
Angiotension receptor blockers Calcium channel blockers Alpha
blockers Concerns about blood pressure variability and central vs
peripheral effects make beta blockers not the initial preferred
agents after stroke.
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- Which agents to choose? Diuretics Beta blockers ACE inhibitors
Angiotension receptor blockers Calcium channel blockers Alpha
blockers These agents may increase the risk of stroke, despite
being effective in lowering blood pressure.
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- Which agents to choose? Diuretics Beta blockers ACE inhibitors
Angiotension receptor blockers Calcium channel blockers Alpha
blockers Ultimately, achieving reduction in blood pressure is
likely more important than specific agent required.
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- Antilipid therapies
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- Cholesterol and stroke Relationship between high cholesterol
(high LDL) and stroke is less strong than for coronary heart
disease Low cholesterol has been associated with intracerebral
hemorrhage However, similar mechanism from CAD strongly implied for
many causes of stroke, and similar benefit expected
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- Trial X stroke (vascular event) hemorrhage death treatment A
treatment B 15% 10% 5% 10% 10% 10% patients enrolled
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- SPARCL (2006) cerebral infarction* ICH* death atorvastatin 80
mg placebo 9% 2% 9% 12% 1% 9% stroke/TIA (LDL>100) *p
- Reasons to avoid high-intensity Characteristics predisposing
individuals to statin adverse effects include, but are not limited
to: Multiple or serious comorbidities, including impaired renal or
hepatic function. History of previous statin intolerance or muscle
disorders. Unexplained ALT elevations >3 times ULN. Patient
characteristics or concomitant use of drugs affecting statin
metabolism. >75 years of age. Additional characteristics that
may modify the decision to use higher statin intensities may
include, but are not limited to: History of hemorrhagic stroke.
Asian ancestry.
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- What about other agents? Niacin-ER did not lower risk of
cardiovascular events compared with placebo though it is effective
in increasing HDL and lowering triglycerides Ezetimibe has not been
shown to have any clinical benefit though it can lower LDL Omega-3
fatty acids have not been shown to benefit in stroke
prevention
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- Antithrombotic therapies thrombus atheromatous plaque aspirin
clopidogrel prasugrel warfarin dabigatran dipyridamole rivaroxaban
apixaban ticagrelor
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- Antithrombotic therapies thrombus atheromatous plaque aspirin
COX-inhibitor
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- Antithrombotic therapies thrombus atheromatous plaque
clopidogrel prasugrel P2Y 12 (ADP-R) inhibitor ticagrelor
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- Antithrombotic therapies thrombus atheromatous plaque
dipyridamole PDE-inhibitor
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- Antithrombotic therapies thrombus atheromatous plaque warfarin
vit K antagonist fII, fVII, fIX, fX
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- Antithrombotic therapies thrombus atheromatous plaque
rivaroxaban apixaban factor Xa inhibitor
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- Antithrombotic therapies thrombus atheromatous plaque
dabigatran direct thrombin inhibitor
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- Antithrombotic therapies ANTIPLATELET - aspirin - clopidogrel -
Aggrenox DUAL ANTIPLATELET - aspirin + clopidogrel ANTICOAGULANT -
warfarin - dabigatran - apixaban - rivaroxaban - enoxaparin
etc.
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- How do we pick the right one? Stroke mechanism Patient
preference Cost Ease of compliance Failure of prior agent
Tolerability and side effects
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- Causes of cerebral infarction small vessel disease atrial
fibrillation/ cardioembolism cryptogenic large vessel disease
other
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- Atrial fibrillation
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- Meta-analysis (2002) Meta-analysis (2002) stroke* major
hemorrhage* death warfarinaspirin 2% 2% 5% 5% 1% 5% afib *p