A patient who has suffered ischemic stroke is at a higher risk of getting strokes in future. This is called recurrent stroke. The current presentation looks at the factors responsible for stroke recurrence, and discusses strategies to reduce the risk of stroke recurrence.

1. SECONDARY PREVENTION OF
ISCHEMIC STROKE
DR SUDHIR KUMAR MD DM
CONSULTANT NEUROLOGIST
APOLLO HOSPITALS, HYDERABAD

2. This talk would cover
• Antiplatelet therapy,
• Anticoagulant therapy,
• Statins in stroke prevention,
• Control of risk factors- diabetes mellitus,
hypertension, hyperhomocystinemia- in
patients with ischemic stroke

3. STROKE-EPIDEMIOLOGY
• Stroke is common
• 3rd leading cause of death and disability (after
heart attacks and cancer) in the world,
• One in six people develop stroke in their lifetime
• Incidence and prevalence of stroke are increasing
due to 1. an increase in the number of older
people (older people have a higher stroke risk); 2.
Increase in the incidence of DM/HTN

4. STROKE MANAGEMENT
• Acute stroke treatments- IV thrombolysis and
mechanical thrombectomy- are available and are being
increasingly used.
• Still, only about 10% of patients with acute ischemic
stroke (AIS) are thrombolysed, even in the best centers.
• For the remaining patients, preventive treatments for
stroke and risk factor modification are the only
management options (besides physiotherapy, speech
therapy and neuro-rehabilitation),
• Those who are thrombolysed also need treatment to
prevent stroke recurrence.

5. RECURRENT ISCHEMIC STROKE
• Most strokes are ischemic (70-80% of all
strokes),
• Strokes can recur in about 30% (3 out of 10
patients),
• 14% of patients with a new ischemic stroke
would develop a recurrence of stroke within
one year,

6. FACTORS ASSOCIATED WITH STROKE
RECURRENCE
• Diabetes mellitus,
• Hypertension,
• Absence of statin use,
• Atrial fibrillation,
• Leukoaraiosis on MRI,
• Presence of old infarct in the territory of
stenotic artery,
• Presence of >80% stenosis of affected artery,

7. ANTIPLATELET AGENTS
• Aspirin
• Clopidogrel
• Aspirin plus dipyridamole
• Aspirin plus clopidogrel

8. ASPIRIN
• Aspirin reduces the rates of all vascular events by
19%, and ischemic strokes by 13%,
• Rapid onset of action within one hour of
administration,
• Dose ranging 75-1300 mg daily are effective
(equal efficacy),
• However, adverse events may increase with
increasing dose,
• In India, 150 mg OD is the most preferred dose.
• Needs to be given lifelong after the 1st stroke.

9. ASPIRIN RESISTANCE
• Exclude noncompliance first (leading to
pseudo resistance),
• “real” resistance to aspirin is unknown (may
range from 15-25%),
• Resistance is higher with lower doses of
aspirin and enteric-coated aspirin,
• Treatment options include: 1. Increase the
dose of aspirin, 2. Switch to clopidogrel, or 3.
Add clopidogrel to aspirin

10. CLOPIDOGREL
• Widely used in stroke prevention,
• 75 mg once daily is the standard dose,
• It may take 4-5 days for the antiplatelet activity of
clopidogrel to show full effects,
• A loading dose of 300 mg of clopidogrel may be given
at the time of starting it,
• 12% people may not respond to clopidogrel therapy
due to the presence of CYP2C19*2 genotype,
• Concomitant administration of PPIs reduces the effects
of clopidogrel.

11. ASPIRIN VERSUS CLOPIDOGREL
• Aspirin more widely available, lesser cost
• Similar efficacy (CAPRIE trial, 1999)
• Clopidogrel more beneficial in patients with
concomitant peripheral artery disease,
diabetes and in those with past history of
CABG,
• Nonfatal primary ICH and fatal hemorrhage
are less common with clopidogrel (0.39%)
than with aspirin (0.53%) treatment,

12. DUAL ANTIPLATELET THERAPY-
aspirin+clopidogrel (1)
• MATCH trial- combination of aspirin and
clopidogrel tested against clopidogrel alone,
• Similar efficacy,
• Higher risk of bleeding (threefold increased
risk of life-threatening bleeding and 2-fold
increased risk of major bleeding) with the
combination

13. DUAL ANTIPLATELET THERAPY-
aspirin+clopidogrel (2)
Aspirin + clopidogrel combination is likely to be effective
in multiple settings:
• High risk cases of TIA and minor stroke,
• Severe, symptomatic intracranial artery stenosis,
• Symptomatic extracranial and intracranial artery
stenosis causing artery-to-artery embolism,
• Strokes attributable to aortic arch plaques,
• High-risk AF not suitable for oral anticoagulation,
• Ischemic stroke with acute coronary artery syndrome,
• Intracranial and extracranial stent implantation.

14. Aspirin + Dipyridamole
• ESPS-2 trial- aspirin 25 mg BD, or Extended
release dipyridamole (ER-DP) 200 mg BD or
their combination were used,
• Combination of aspirin with ER-DP was twice
as more effective than either agent alone in
stroke prevention,
• The most common side effect with
dipyridamole is headache. Bleeding is lesser
than with aspirin.

15. ANTICOAGULANT THERAPY (1)
Anticoagulant therapy indicated in patients with:
• Atrial fibrillation,
• Prosthetic heart valves,
• LA/LV clot,
• Severe LV dysfunction,
• Arterial dissection (carotid or vertebro-basilar)
• Significant arterial stenosis with crescendo TIAs
or progressive stroke,
• Hypercoagulable states.

16. ANTICOAGULANT THERAPY (2)
• Warfarin is commonly used (heparin injections
are used during the first few days)
• Need to adjust the dose with periodic PT/INR
monitoring (Target INR: 2-4),
• Alternative- dabigatran 150 mg bd (110 mg bd
in patients with severe renal impairment)
• No need of INR monitoring

17. HYPERTENSION MANAGEMENT (1)
• BP should not be lowered in the first 24 hours
after acute ischemic stroke (risk of worsening of
infarction due to reduced cerebral perfusion
pressure),
• Post the initial 24 hours, BP should be lowered
with appropriate antihypertensive agents,
• Target BP in patients without comorbid illness:
<140/90 mmHg
• Target BP in patients with diabetes, CKD, recent
lacunar stroke<130/90 mmHg

18. HYPERTENSION MANAGEMENT (2)
• ACE inhibitors or ARBs are usually preferred,
• AHA/ASA guideline recommends using a
combination of diuretic and ACE inhibitor,
• PROGRESS study- combination of perindopril
(ADE inhibitor) and indapamide (diuretic) found
to be effective in stroke prevention,
• Beta blockers may have lesser ability to prevent
stroke, and can cause side effects such as weight
gain, dyslipidemia and diabetes- so, avoid beta
blockers.

19. DIABETES MANAGEMENT
• About 9% of recurrent strokes are attributable
to diabetes,
• To prevent stroke recurrence, the target
HbA1C <7%

20. STATINS
• Needed for all patients with stroke,
• Atorvastatin or rosuvastatin are commonly used.
• Atorvastatin 80 mg OD safe and effective in
preventing stroke recurrence (SPARCL study),
• Especially important in diabetics and older
people,
• Should be administered even if total cholesterol
and LDL levels are within normal limits
(pleiotropic effects)

21. HYPERHOMOCYSTINEMIA
• Controversy still exists on its role in causing stroke
recurrence,
• 30% of stroke patients have elevated homocysteine
levels,
• High homocysteine as a risk factor is more important in
younger people, males, smokers, pure vegetarians and
those with high LDL and cholesterol levels.
• Optimum level is 10-12, those with >15 have a higher
risk of stroke,
• HOPE 2 study: Folic acid 2.5 mg, pyridoxine 50 mg and
vitamin B12 lowered homocysteine and reduced stroke
recurrence.

22. OTHER STRATEGIES
• Moderate physical activity: 30 minutes per
day, at least five days a week,
• Smoking cessation,
• Reduction of obesity and overweight,
• Moderation of alcohol consumption

23. THANKS
Email: drsudhirkumar@yahoo.com
Facebook:
http://www.facebook.com/bestneurologist/