SECONDARY PREVENTION OF ISCHEMIC STROKE

DR SUDHIR KUMAR MD DMCONSULTANT NEUROLOGIST

APOLLO HOSPITALS, HYDERABAD

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

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

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.

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,

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,

ANTIPLATELET AGENTS

• Aspirin• Clopidogrel• Aspirin plus dipyridamole• Aspirin plus clopidogrel

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.

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

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.

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,

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

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.

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.

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.

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

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

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.

DIABETES MANAGEMENT

• About 9% of recurrent strokes are attributable to diabetes,

• To prevent stroke recurrence, the target HbA1C <7%

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)

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.

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

THANKSEmail: drsudhirkumar@yahoo.comFacebook: http://www.facebook.com/bestneurologist/