Treatment of Acute Ischemic Stroke – A new possibilityDr. Samiran Adhikari, MD

Age adjusted prevalence per 100,000

• Kashmir (1986) - 244North

• Kolkata (1998-99) - 334East

• Mumbai (1985) - 424West

• Vellore (1969-71) – 84South

Banerjee TK and Das SK. Neurology Asia 2006;11:1-4.

Stroke Related Mortality & Types in India Limited data

available Only 13.5% of all

deaths in India were medically certified in 1994

1.2% of the total deaths in the country

in the oldest group stroke contributed 2.4% of all deaths

Banerjee TK et al. Neuroepidemiology 2001;20:201-7.Anand Ket al. Neuroepidemiology 2001;20:208-11.

Time is brain

N Engl J Med 2007;357:572-9.

Ischemic Penumbra Infarct Core

Progression over Time of the Infarct Core, with Irreversible Damage at the Expense of the Ischemic Penumbra

STROKE Management

SECONDARY PREVENTIONPRIMARY

PREVENTION

ACUTE CARE

COMPREHENSIVE REHABILITATION

Treatment Puzzle:Integrated approach to improve Stroke Management

Acute stroke: What do we have in store?

Another patient

suffers a stroke

every 2nd sec

Leading cause of

adult disability

Vast majority

(85%) due to an Acute

Ischemic Stroke

Few treatment

options

A massive disease burden with few treatment options

Disease

Drugs

Few treatment optionsThrombolytics

Antiplatelet Agents

Anticoagulants

Vasodilators

Surgical Interventions

Neuroprotective Agents

Thrombolytics : Two sides of a coin

STRENGTH Approved by US FDA

WEAKNESS Negative results of

some trials Symptomatic brain

hemorrhage- 6.4 % of the patients

Stroke 2007;38;1655-1711

t-PA: demonstrate and protect – selected option

t-PA is contraindicated in hemorrhagic stroke

t-PA: Short therapeutic window - Selected option

Short therapeutic window or reperfusion window is a serious limitation and implementation of intravenous therapy may not always be easy and safe

t-PA is effective if treatment is initiated within 3 hours

Antiplatelet Agents

The oral administration of aspirin (initial dose is 325 mg) within 24 to 48 hours after stroke onset is recommended for treatment of most patients

The administration of clopidogrel alone or in combination with aspirin is not recommended for the treatment of acute ischemic stroke

Stroke 2007;38;1655-1711

Anticoagulants The results of the recent trials show that

early administration of either heparin or a LMW heparin/danaparoid is associated with an increased risk of bleeding complications.

Initiation of anticoagulant therapy within 24 hours of treatment with intravenously administered rtPA is not recommended

Stroke 2007;38;1655-1711

Vasodilators in Acute Ischemic Stroke

The administration of medications such as pentoxifylline is not recommended for treatment of patients with acute ischemic stroke

The trial by Huber et al in 1993 included 30 patientsafter pentoxifylline treatment and found no difference in latecase fatality

Stroke 2007;38;1655-1711

Surgical Interventions: CEA

Data on the safety and effectiveness of carotid endarterectomy and other operations for treatment of patients with acute ischemic stroke are not sufficient to permit a recommendation

increase the development of brain edema

lead to hemorrhagic transformation

Stroke 2007;38;1655-1711

Structural lesion

Impairment of function (‘penumbra’)

Hours

Days and weeks

Minutes

Preventing the progression of Ischemic stroke - the goal of neuroprotection

PENUMBRA

PENUMBRANEURON

CORENEURON

CLOT

CORE

The ischemic penumbra is considered to be the area of constrained blood flow with partially preserved energy metabolism around the ischemic core.

Neuroprotective Agents – Step in and Step out

Although piracetam may be effective in some patients with ischemic stroke, there may be a trend for increased risk of death among patients treated with piracetam

NXY 059 – unfulfilled promise

Data are not sufficiently clear to draw a conclusion about the utility of Piracetam

1. Cerebrovasc Dis. 2001;11(suppl 1):60 –70.2. Cochrane Database Syst Rev. 2002;(4):CD000419.3. Stroke 2007;38;1655-1711

Primary Outcome at 90 Days According tothe Score on the Modified Rankin ScaleSAINT I - PROMISE 1699 subjects The administration of NXY-059 within

six hours after the onset of acute ischemic stroke significantly improved the primary outcome (reduced disability at 90 days)

Additional research is needed to confirm

SAINT II – PROBLEM 3195 patients NXY-059 is safe but ineffective

for the treatment of acute ischemic stroke within 6 hours after the onset of symptoms

Shuaib A et al. N Engl J Med 2007;357:562-71.Kennedy R et al. N Engl J Med 2006;354:588-600.

Neuroprotective Agents – Kept promises

Meta analysis reported that patients with moderate to severe stroke might be helped if citicoline was started within 24 hours of onset of symptoms1

Clinical trials found that edaravone might improve outcomes2,3

Seizes the moment of neuroprotective window before it slips away

√ 1. Stroke. 2002;33:2850 –28572. Stroke 2007;38;1655-17113. Cerebrovasc Dis. 2003;15:222–229.

Thank YouQuestions