COMPARISON WITH THROMBECTOMY IN ISCHEMIC STROKE
A Dissertation Submitted to
THE TAMIL NADU DR. M.G.R. MEDICAL UNIVERSITY CHENNAI - 600032
In partial fulfillment of the requirements for the award of the Degree of MASTER OF PHARMACY
IN
PHARMACY PRACTICE
Submitted by MOHANAPRIYA. R
261740609
Under the guidance of
DR.SHALINI SIVADASAN, M.Pharm., Ph.D Department of Pharmacy Practice
KMCH COLLEGE OF PHARMACY KOVAI ESTATE, KALAPPATTI ROAD
COIMBATORE - 641048
NOVEMBER 2019
KMCH College of Pharmacy, Kovai Estate, Kalappatti Road, Coimbatore - 641048
CERTIFICATE
This is to certify that the dissertation work entitled “SAFETY AND EFFICACY OF TENECTEPLASE IN COMPARISON WITH THROMBECTOMY IN ISCHEMIC STROKE” was carried out by Ms. MOHANAPRIYA .R(Reg No.261740609). The work mentioned in the dissertation was carried out at the Department of Pharmacy Practice, KMCH College of Pharmacy, Coimbatore, Tamil Nadu, under the guidance of DR.SHALINI SIVADASAN, M. Pharm., Ph.D. for the partial fulfilment for the Degree of Master of Pharmacy during the academic year 2018-2019.
Date: DR. A. RAJASEKARAN, M.Pharm., Ph.D., Place: Coimbatore PRINCIPAL
KMCH College of Pharmacy, Kovai Estate, Kalapatti Road, Coimbatore - 641048
CERTIFICATE
This is to certify that the research work entitled “SAFETY AND EFFICACY OF TENECTEPLASE IN COMPARISON WITH THROMBECTOMY IN ISCHEMIC STROKE” was carried out by Ms. MOHANAPRIYA .R (Reg No.261740609). The work mentioned in the dissertation was carried out at the Department of Pharmacy Practice, KMCH College of Pharmacy, Coimbatore, Tamil Nadu, under my supervision and guidance for the partial fulfilment for the Degree of Master of Pharmacy during the academic year 2018-2019.
Date:
Place: Coimbatore DR.SHALINI SIVADASAN, M. Pharm., Ph.D.
Department of Neurology,
Kovai Medical Center and Hospital Coimbatore - 641014
CERTIFICATE
This is to certify that the research work entitled “SAFETY AND EFFICACY OF TENECTEPLASE IN COMPARISON WITH THROMBECTOMY IN ISCHEMIC STROKE” was carried out by Ms.MOHANAPRIYA.R (Reg No.261740609). The work mentioned in the dissertation was carried out at the Department of Neurology, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, under my supervision and guidance for the partial fulfilment for the Degree of Master of Pharmacy during the academic year 2018-2019.
Dr. V. ARUL SELVAN, MD., DM(Neuro.), MRCP (UK), FRCP (London & Edin)
Date:
Place: Coimbatore
DECLARATION
I hereby declare that the dissertation work entitled “SAFETY AND EFFICACY OF TENECTEPLASE IN COMPARISON WITH THROMBECTOMY IN ISCHEMIC STROKE” submitted to The Tamil Nadu Dr. M.G.R. Medical University, Chennai, in partial fulfillment for the Degree of Master of Pharmacy in Pharmacy Practice was carried out under the guidance of DR. SHALINI SIVADASAN, M.Pharm., Ph.D. at the Department of Pharmacy Practice, KMCH College of Pharmacy, Coimbatore, Tamil Nadu during the academic year 2018-2019.
This research work either in part or full does not constitute any of other thesis / dissertation.
Date:
Place: Coimbatore Ms. MOHANAPRIYA .R (261740609)
EVALUATION CERTIFICATE
This is to certify that the research work entitled “SAFETY AND EFFICACY OF TENECTEPLASE IN COMPARISON WITH THROMBECTOMY IN ISCHEMIC STROKE” submitted by Ms. MOHANAPRIYA .R (Reg No.261740609) to the Tamil Nadu Dr. M.G.R. Medical University, Chennai, in the partial fulfilment for the Degree of Master of Pharmacy at the Department of Pharmacy Practice, is a bonafide work carried out by the candidate at KMCH College of Pharmacy, Coimbatore, Tamil Nadu during the academic year 2018-2019 and the same was evaluated.
Examination Centre: KMCH College of Pharmacy, Coimbatore
Date:
Internal Examiner External Examiner
Convener of Examination
To acknowledge is known gratitude and gratitude is a valuable duty which ought to paid to valuable people in a lifetime
First and foremost I pay obeisance to the almighty for blessing me with all the confidence, courage, inspiration and curiosity to complete this project
I take this opportunity to express my deep sense of gratitude and faithfulness to my esteemed teacher and guide, DR. SHALINI SIVADASAN, M.Pharm., Ph.D., Professor, Department of Pharmacy Practice, for her remarkable guidance, patience, constant encouragement and constructive comment for the successful completion for this work.
Words are not enough to express my deep gratitude to my esteemed clinical guide Dr. V. ARUL SELVAN, MD., DM(Neuro), MRCP (UK), FRCP (London &
Edin), Consultant Neurologist, Kovai Medical Center and Hospital, Coimbatore, for his keen interest, timely help and valuable suggestions from very beginning till the completion of the study.
I extend my sincere thanks and gratitude to my Principal, DR. A. RAJESEKARAN, M.Pharm., PhD., for providing me with co-operative and
creative environment which enabled me to the work assiduously.
I extend my sincere thanks to Dr. NALLA G. PALANISAMY, M.D., AB
(USA), Chairman of Kovai Medical Center and Hospital and Madam Trustee, Dr. THAVAMANI D. PALANISAMY, M.D., AB (USA), for providing me with
outstanding infrastructure, resourced and the opportunity to work in a clinical setting.
always, for their invaluable affection, concern, encouragement and for the prayers they have offered for the successful completion of my project. It also gives me great pleasure to dedicate my work to such adorable and affectionate parents and expose without whom I wouldn’t have been able to reach this stage.
Last but not the least; I owe my thanks and gratefulness to my ever loving friends Charumathi, Suganthi, Sathish Kumar, Arya, Reshma, Pavithra and Bharathi for their memorable support and for making my days cheerful and marvellous. My special and heart full thanks to my beloved friends, Palanichami, Nithyakala, Vivek, Remo, Akshaya and Rathika for supporting me, encouraging me, listening to me and helping me all times for the successful completion of my project work.
My heartfelt sincere thanks to all those who directly and indirectly contributed to the successful completion of my work.
Above all, I bow my work in feet of Almighty who let me to the actualization of this research work.
Dedicated to Almighty, My Beloved Parents,
Respected Teachers
&
Friends
AHA - American Heart Association
AIS - Acute Ischemic Stroke
ASPECTS - Aberta Stroke Program Early CT Score
BBB - Blood Brain Barrier
BP - Blood Pressure
CNS - Central Nervous system
CT - Computed Tomography
CVS - Cerebrovascular Accident
dMTE - Direct Mechanical Thrombectomy
DNT - Door to Needle Time
DSA - Digital Subtraction Angiography
DVT - Deep vein Thrombosis
ET - Endovascular Thrombectomy
GCS - Glasgow Coma Scale
GI - Gastrointestinal
AHA - American Heart Association
HTN - Hypertension
IA - Intra- arterial
ICH - Intracerebral Hemorrhage
ICP - Intracranial Pressure
IV - Intravenous
LMWH - Low Molecular Weight Heparin
LVO - Large vessel Occlusion
MCA - Middle Cerebral Artery
MI - Myocardial Infarction
MRI - Magnetic Resonance Imaging
MRS - Modified Rankin Scale
MTE - Mechanical Thrombectomy
NADPH - Nicotinamide Adenine Dinucleotide Phosphate
NECT - Noncontrast Head Computed Tomography
NIHSS - National Institutes of Health Stroke Scale NINDS - National Institute of Neurological Disorders rt-PA - Recombinant Tissue Plasminogen Activators SPSS - Statistical Package for the Social Science
SD - Standard Deviation
TIA - Transient Ischemic Stoke
WHO - World Health Organization
S.NO CONTENTS
PAGE NO
1 INTRODUCTION 1-18
2 REVIEW OF LITERATURE 19-27
3 AIM AND OBJECTIVES 28
4 PLAN OF STUDY 29
5 METHODOLOGY 30-32
6 TABLES AND GRAPHS 33-44
7 RESULTS 45-46
8 DISCUSSION 47-49
9 CONCLUSION 50
10 STUDY LIMITATIONS 51
11 REFERENCES 52-57
12
ANNEXURES
ANNEXURE I: ETHICAL COMMITTEE APPROVAL LETTER ANNEXURE II: DATA COLLECTION FORM
ANNEXURE III: NIHSS SCALE ANNEXURE IV: MRS SCALE
Department of Pharmacy Practice 1
INTRODUCTION
Stroke is the leading cause of death in world and a leading cause of adult disability. According to the World Health Organization (WHO), stroke is the seconding leading cause of death and people above the age of 60 years, and the fifth leading cause in people aged 15 to 59 years. Each year, nearly six million people worldwide die from stroke. Stroke is a brain attack or brain injury caused by a sudden interruption in the blood supply of the brain. Approximately two million brain cells destroy every minute during a stroke. In which increases the risk of brain damage, disability, and death (1).
Ischemic stroke syndromes have a multitude of possible causes, characterized by a rule of quarters: 25% cardio embolic, 25% artero embolic (large artery disease), 25%
lacunar (small-vessel disease) and 25% due to other causes, with global variation in proportions by population (2).
Epidemiological studies have shown that stroke is more common in men than women, and that become more severely ill after suffering a stroke. The mismatch between the genders is much greater than that described previously. In the present study as well, more men than women were affected by acute ischemic stroke, and the condition of the men was worse than that of the women, even after tissue plasminogen activator (rt-PA) treatment. The unmodified risk factors for stroke are age, gender, prior stroke, race and family history. Almost three quarters of stroke occur in individuals over 65 years of age. The modifiable risk factors are hypertension, diabetes, high cholesterol levels, coronary heart disease, cocaine use, obesity and heavy alcohol use(3).
Department of Pharmacy Practice 2 ISCHEMIC STROKE
The majority of strokes occur the blood vessels to the brain become narrowed or clogged with fatty deposits are called plaque. This cuts off blood flow to brain cells.
A stroke caused by lack of blood reaching part of the brain called an ischemic stroke.
High blood pressure is a leading risk factor for ischemic stroke. An acute occlusion of an intracranial vessel causes reduction in blood flow the region it supplies. A fall in cerebral blood flow to zero causes death of brain tissues within 4 to 10 minutes, values is 16-18 ml/100 gm tissues per minute an infraction unless prolonged for several hours or days (4).
Tissue surrounding the core region of infarction is ischemia but reversibly dysfunctional and is referred to as ischemic pneumbra. Even after many studies have proven the safety and efficacy of thrombolytic therapy using rt-PA and treat the patients, several reasons explain the situation, an excessive fear of hemorrhagic complications because, rt-PA is the only drug licensed for treatment of acute ischemic stroke. Thrombotic stroke are caused by a blood clot (thrombus) in an artery going to the brain. The clot blocks blood flow to part of the brain. Formation of blood clots in the arteries damaged by plaque. Embolic stroke are caused by wandering clot (embolus) that’s formed elsewhere (usually in the heart or neck arteries). Clots are carried in the bloodstream and block a blood vessel or damage to the brain (5).
HEMORRAGIC STROKE
Strokes mainly cause the breakage or “blowout” of a blood vessel in the brain are called hemorrhagic strokes. Hemorrhages can be caused by a number of disorders which damage the blood vessels, including long-standing high blood pressure and
Department of Pharmacy Practice 3 cerebral aneurysms. An aneurysm is a weak or thin spot on the blood vessel wall. These weak spots are usually present at birth itself. Aneurysms develop over a number of years and usually does not cause any detectable problems until they break.
There are two types of hemorrhagic stroke: In intracerebral hemorrhage, bleeding occurs from vessels within the brain itself. Hypertension (high blood pressure) is the primary cause of this type of hemorrhage. In a subarachnoid hemorrhage, an aneurysm bursts in a large artery or near the thin, delicate membrane surrounding to the brain. Blood spills into the area around whole brain, which is filled with some protective fluid, cause the brain after surrounded by the blood-contaminated fluid (6).
Other forms of stroke
In addition to major causes of stroke described above, there are a number of other causes, including the two most common ones: cardiac arrest and hematomas adjacent to the brain. In cardiac arrest, the heart stops pumping the blood or does not pump effectively, and the brain is deprived of both the oxygen and glucose. Even though entire brain is affected, certain areas are more vulnerable. Hematoma accumulations of blood that are the result of the hemorrhage sometimes occur in the outermost covering of the brain, the subdural or epidural layers. These are usually caused by the injury especially in the elderly people. In this type of stroke, surgery can usually correct the problem by removing the clot, and may be lifesaving (7).
Department of Pharmacy Practice 4 PATHOPHYSIOLOGY (8)
Superoxide NO- Glutamate
release
Myocardial dysfunction
Excitotoxicity Caspases BBB Disruption
↑ permeability NADPH
oxidase (leukocyte &
glia)
Xanthine
oxidase ATP
depletion
Cytotoxic and vasogenic edema
Neuronal depolarization Na+ influx K+ exflux
↑ cytosolic Ca2+
ISCHEMIC STROKE
Inflammation Ischemia reperfusion Oxygen and glucose deprivation
INFARCT SIZE
Neurological morbidity and mortality Apoptosis Cytotoxic and
vasogenic edema
↑ ICP ↓cerebral blood flow
Necrosis Autophagy y
Activation of proteases,
phospholipases &
endonucleases OXIDATIVE STRESS
Peroxynitrite
Attack to biomolecules
Department of Pharmacy Practice 5 Causes of ischemic stroke (4)(5)
Atherosclerosis
Small vessel disease
Heart conditions
Atrial fibrillation
Patent foramen ovale (PFO)
Arterial dissection Symptoms
Arm or leg (especially on one side of the body), sudden numbness or weakness of the face, confusion, trouble speaking or understanding of the speech, trouble walking, dizziness, loss of balance and coordination with unknown cause.
It is important to treat strokes as quickly as possible. Blood thinners may be used during the stroke to stop the further complications while it happening by quickly dissolving the blood clot. Post-stroke rehabilitation may help the people overcome the disabilities and caused by stroke damage (9).
Emergency evaluation and diagnosis of acute ischemic stroke
The initial treatment and evaluation of patients with the stroke should be performed efficiently. Because, the time is critical, a limited number of essential diagnostic tests are recommended for guidelines. Stroke protocols and the pathways should be clearly defined which test must be performed during the acute treatment decisions and which may be performed subsequent to acute stroke therapies (10).
Department of Pharmacy Practice 6 DIAGNOSIS OF ACUTE ISCHEMIC STROKE
Brain and vascular imaging and head CT
Non-contrast head CT (NECT) is excellent in discriminating the presence of an intracranial hemorrhage which will preclude patients from thrombolytics.
Detection of the early ischemic changes on NECT is variable, but structured scales such as aspects may assist.
Presence of the hyperdense of MCA sign have seen in roughly 1/3 of cases but correlates to the large vessel occlusion.
Presence of the extensive early ischemic changes on NECT correlates to an 8- fold risk of symptomatic hemorrhage with intravenous t-PA.
MRI Brain
Diffusion weighted imaging is highly specific and very sensitive in detecting ischemia.
The GRE sequence may assist in detecting thrombus with higher sensitivity compared to NECT
MR is sensitive at detecting acute hemorrhage and comparable to NECT and reasonable to use for early imaging.
Limitation of MR is patient movement, pacemakers, metal implants or claustrophobia.
Department of Pharmacy Practice 7 CT Angiography
The accuracy of the CTA for evaluation of large-vessel intracranial stenosis or occlusion tested. Because CTA provides a static image of the vascular anatomy and it is inferior to DSA for the demonstration of flow rates and direction
Direct comparisons of the CT angiography source images (CTA-SI) or MRI have demonstrated very similar sensitivity of these two techniques for detecting ischemic regions of the brain.
Transcranial Doppler
TCD accuracy is less compared to CTA and MRA for steno-occlusive disease, with a sensitivity and specificity of TCD ranging from 55-90% and 90-95%, respectively.
TCD usefulness is limited in patients with poor bony windows, and its overall accuracy is dependent on the experience of the technician, interpreter, and the patients vascular anatomy.
Conventional angiography
DSA remains the gold standar for the detectionof many types of cerebrovascular lesions and disease.
DSA is invasive test but it cause some serious complications such as stroke and death
The largest series of the cases to date reported stroke or death of less than 0.2%
A MRA may obviate the need for catheter angiography (11)
Department of Pharmacy Practice 8 TREATMENT
SUPPORTIVE CARE
Stroke is a primary failure of focal tissue oxygenation and energy supply.
Systemic hypoxemia and hypotension should be avoided if present, corrected to limit further cellular damage of the brain. Supplemental oxygen does not recommended in non hypoxic patients with acute ischemic stroke.
ANTIPLATELET TREATMENT
Aspirin is the oral anti platelet agent that has been evaluated for acute ischemic stroke. Aspirin after the stroke reduced the major risk for the recurrent ischemic stroke by 30%. Aspirin showed reduction in death or disability when treatment with aspirin was initiated within 48 hours of stroke and a small increase in bleeding complication was noted. The combination therapy of aspirin with clopidogrel synergistically inhibits platelet aggregation and such dual therapy reduces the risk of recurrent ischemic events.
ANTICOAGULANT TREATMENT
Anticoagulants are often prescribed to patients with stroke to prevent early recurrent stroke and to improve neurological outcome. Bleeding complication increases with early administration of heparin / low molecular weight heparin (LMWH). These medications increase the risk of symptomatic hemorrhagic transformation of ischemic strokes, especially among patients with severe events.
These anticoagulants are also associated with a risk of serious bleeding in other parts of body. Early administration of anticoagulants does not lessen the risk of neurological worsening (12).
Department of Pharmacy Practice 9 THROMBOLYTIC TREATMENT
Thrombolytic treatment is the most promising treatments for acute ischemic stroke. Blockage of an artery in the brain by a blood clot is referred as ischemic stroke. Initiation of treatment within the window period with clot dissolving drug can restore the normal blood flow. The only approved therapy for acute ischemic stroke is intravenous administration of tissue plasminogen activator (t-PA). The drug works by splitting plasminogen into plasmin, leading to fibrin degradation at the site of occlusion.
Intravenous administration of rt-PA showed outcome in wide spectrum of patients who can be treated within 3 hours of stroke onset. Treatment within 90 minutes may be more likely to result in favourable outcome than the patient treated at 90-180 minutes. Disability improvement is three times greater than any antiplatelet, anticoagulant or any neuroprotector. Bleeding complications can be prevented by careful selection of patients and scrupulous ancillary care, close observation and monitoring of patient with early treatment of arterial hypertension. There are thrombolytics like alteplase, tenecteplase, streptokinase and urokinase (13).
THROMBOLYSIS
Thrombolysis is mainly caused by a class of drugs called fibrinolytic drugs, these class of drugs break the thrombi by catalyzing the formation of serine protease plasmin from its precursors zymogens, plasminogen. These drugs cause lysis of clot when administered intravenously. Thus the both protective haemostatic thrombi and target thrombo emboli are broken down in arteries. Plasminogen can also be activated
Department of Pharmacy Practice 10 by tissue plasminogen activator. They activate the plasminogen that is bound to the fibrin which causes fibrinolysis of the formed thrombus. Finally avoids the systemic activation. Efficacy of thrombolytic drugs depends on a few important factors:
The age of the clot can reduce the efficacy of the thrombolytic, and older clots tend to have more fibrin cross linking and are more resistant to thrombolytics.
The specificity of the lytic for fibrin will determine its activity, and other determinants of efficacy include half-life and the presence of any neutralizing antibodies (14).
The three clinically relevant recombinant thrombolytic peptides are
Alteplase
Reteplase
Tenecteplase
Department of Pharmacy Practice 11 GENERAL MECHANISM OF THROMBOLYTIC AGENTS (15)
Tissue plasminogen
Activator (tPA) PLASMINOGEN
Plasminogen activator Inhibitor 1 & 2 PLASMIN
Recombinant t-PA
(Alteplase,Tnk,Reteplase)
Fibrinogen FIBRIN Fibrin degradation products
Thrombin Thrombin- activatable fibrinolysis inhibitor ALTEPLASE
Alteplase is used to dissolve blood clots that have formed in the blood vessels.
It is used reduce the risk and also used after symptoms of a stroke and to treat blood clots pulmonary embolism. Alteplase is used to dissolve the blood clots in tubes (catheters) that are placed in large blood vessels to reduce the major problems. Acute ischemic stroke and understood the potential for these to be reduced through the thrombolytic action of alteplase. For the successful stroke management, prompt Factors 11a, 12 a kallikrein
α2-anti-plasmin, α2- macroglobulin
Department of Pharmacy Practice 12 assessment, supportive care and careful monitoring in stroke units is crucial. While acknowledging the potential role of a thrombolytic treatment in resolving a stroke episode, the awareness of its time-dependent efficacy and of the safety concerns around the use of alteplase is essential, this is mainly related to the incidence of potentially fatal intracranial haemorrhage. It was very expensive. Adverse drug reactions include bleeding, hypersensitivity and anaphylactic reactions (16).
RETEPLASE
Reteplase is similar to the recombinant human tissue plasminogen activator (alteplase), but the modification of reteplase is the longer half-life of 13-16 minutes.
Reteplase also binds with fibrin it has lower affinity than alteplase, improving its ability to penetrate into clots. It is produced in the bacterium Escherichia coli.
Adverse effects are reperfusion arrhythmias, hypotension, dizziness, fever, severe headache, anemia, cholesterol embolization, GI/GU bleeding, intracranial hemorrhage. Its pharmacokinetics includes half-life of 13-16 minutes; Onset of Coronary thrombolysis occurs in 30 minutes, reaches peak response at 30-90 minutes.
It is metabolized or inactivated by blood components C₁ inactivator, α₁-antitrypsin, α₂- antiplasmin and is excreted in urine and feces (16)(17).
TENECTEPLASE (TNK)
TNK is a structurally modified form of native t-PA (performed to increase its half-life and fibrin specificity), which has undergone pre-clinical and clinical study in ischemic stroke. Due to the modified structure, TNK has a longer half- life. Already approved for myocardial infarction (MI), the drug also boasted an improved safety
Department of Pharmacy Practice 13 profile with lower systemic bleeding complications in MI. in addition to the longer half- life, TNK is 14 times more fibrin specific and is more resistant to degradation from plasminogen activator-1 compared with rt-PA. human t-PA is manufactured as TENECTEPLASE by means of recombinant DNA technology.
DRUG PROFILE (17)
INDIAN BRAND NAME : Elaxim, metalyse, velix
MECHANISM : Tenecteplase is a biosynthetic form of the enzyme human tissue- type plasminogen activator (t-PA). it is a fibrin specific thrombolytic, converts plasminogen to plasmin, a proteolytic enzyme that has fibrinolytic effects.
PHARMACOLOGICAL CATEGORY : Thrombolytic agent PHARMACOKINETICS & PHARMACODYNAMICS:
DISTRIBUTION: Tenecteplase having terminal half-life of 90-130 minutes.
METABOLISM: Mainly cleared by hepatic metabolism
ADVERSE DRUG REACTIONS : Haemorrhage, fever, nausea, vomiting, allergic reactions, hypotention
DOSAGE : 30-50 mg as a single bolus dose over 5-10 second as soon as possible after the onset of symptoms. The dose is based on body weight. Maximum dose is 50mg.
INDICATION
Preventing death from acute myocardial infarction (sudden heart attack)
Department of Pharmacy Practice 14
It helps in over production of plasmin of plasmin in the body to dissolve unwanted blood clots.
SIDE EFFECT
BLOOD : Bleeding episodes such as gartrointestinal bleeding, nose bleed, blood vomiting, and pain at injection site.
HEART : Shock, abnormal heart rhythm, lung swelling, heart failure, heart attack, back flow of blood, heart arrest,and electromechanical dissociation.
MISCELLANEOUS : Nausea and / or vomiting, low blood pressure and fever.
ADVERSE REACTIONS
Hypersensitivity
Bleeding
Cardiogenic shock
Arrhythmias
Atrioventricular block
Pulmonary edema
Heart failure (18)
THROMBECTOMY
Timely restoration of cerebral blood flow using reperfusion therapy is the most effective maneuver or salvaging ischemic brain tissue that is not already
Department of Pharmacy Practice 15 infaracted. There is a narrow time window during which this can be accomplished, since the benefit of blood clot decreases over the time.
For the eligible patients with acute ischemic stroke, intravenous recombinant tissue plasminogen activator (tPA) is first- line therapy for providing treatment is initiated within 4.5 hours of clearly defined symptom onset. Because the benefit or rt- PA is time dependent, it is critical to treat patients as quickly as possible. Eligible patients should receive intravenous rt-PA without delay even if mechanical thrombectomy is being considered (19).
How to select patients
The decision to proceed with the mechanical thrombectomy should be made by a physician trained in the diagnosis and treatment of stroke, in conjunction with a neuro interventionist who has the relevant brain and arterial imaging. Necessary expert clinical assessment for stroke diagnosis, localization, severity stratification (NIHSS) and assessment of pre-stroke functional status (modified Rankin score) and co-morbidities and adequate brain and vascular imaging acquisition (typically CT and CT angiography) and interpretation. It is very important for discussion and teamwork between stroke physician and neuro interventionist to make what are often complex and time- sensitive decisions.
Extracranial vessel imaging (easily obtained with the same CT angiogram) is essential for determining the feasibility of access to the target artery occlusion. The selection criteria applied in practice should parallel those of the successful trails, including the following:
Department of Pharmacy Practice 16
Documented large vessel anterior circulation occlusion (middle cerebral artery or internal carotid artery)
Significant clinical deficit at the time of treatment (this might be NIHSS>5 or a lower score that is functionally significant for the patient)
Lack of expensive early ischemic change (those with ASPECTS more than 5 on plain CT clearly benefit)
Pre- stroke functional status and lack of serious co-morbidities indicating potential to benefit from treatment(note that age>80 years alone is NOT a contraindication to treatment)
Treatment with intravenous thrombolysis within 4.5 hours (although patients ineligible for intravenous thrombolysis dur to bleeding risk were also included in some of the trials and might also reasonably be offered treatment)
Thrombectomy can be performed within 6 hours
Good collateral circulation(though benefit in patients with poor collaterals remains uncertain).
Intravenous fibrinolytic therapy at the cerebral circulation dose within the first 3 hours of ischemic stroke onset offers substantial net benefits for virtually all the patients with potentially disabling deficits.
Intravenous fibrinolytic therapy at the cerebral circulation dose within 3-4.5 hours offers substantial net benefits when applied to all patients with potentially disabling deficits.
Department of Pharmacy Practice 17
MRI of the extent of the infarct core (already irreversibly injured tissue) and the penumbra (tissue at risk but still salvageable) can likely increase the therapeutic yield of lytic therapy, especially in the 3-9 hour window.
Intra-arterial fibrinolytic therapy in the 3-6 hour window offers moderate net benefits when applied to all patients with potentially disabling deficits and large artery cerebral thrombotic occlusions.
Mechanical thrombectomy is a highly successful, safe and cost-effective treatment for patients with large artery occlusive stroke (20).
NEED OF THE STUDY
Intravenous alteplase (recombinant tissue plasminogen activator) as reperfusion therapy that has caused a dramatic change in the way acute ischemic stroke is approached. Alteplase is administered in a dose of 0.9 mg/kg body weight as a IV bolus (10% of total dose) followed by the remaining dose as an infusion over 1 hour. However, because the risk of major bleeding also particularly in the brain cells, patients need to be carefully selecting the basis of eligibility criteria, which have been largely, adopted from the inclusion and exclusion criteria. Alteplase was high cost and within 3 hours only it should be administered. But tenecteplase having more fibrin specificity and longer half life and cost wise it is low. There are very few studies conducted in South India that studied the safety and efficacy of tenecteplase in comparison with thrombectomy.
RESEARCH HYPOTHESIS
Department of Pharmacy Practice 18
Alteplase is the mostly prescribed drug for the treatment of stroke however, this may induce the intracerebral hemorrhage.but this will not happen with the use of Tenecteplase.
Tenecteplase is also most widely used drug for patients with ischemic stroke, where it does not cause intra cerebral hemorrhage, there is a need to compare the safety and efficacy of Tenecteplase.
This study will focus on comparing the patients who are treated with Tenecteplase alone, thrombectomy alone and Tenecteplase with thrombectomy.
RESEARCH QUESTIONS
For adults with large vessel occlusion-related acute ischemic stroke within 6 hours of symptom onset, does mechanical thrombectomy plus medical management or medical management alone improve functional outcome?
How should thrombectomy be delivered and is mechanical thrombectomy cost effective?
Department of Pharmacy Practice 19
REVIEW OF LITERATURE
Alawieh et al., (2019) (21) conducted a study to evaluate the impact of procedure time on outcome and complications. It was a multicenter study, 1359 patients were involved using MRS scale used. Patients undergoing endovascular thrombectomy with a Stent Retriever (SR) or a direct aspiration at first pass technique at 7 centers in 5 years were reviewed from prospectively maintained databases that included baseline variables and technical and clinical outcomes. Multivariate analyses were used to assess the impact of Physical Therapy (PT) on 90-day Modified Rankin scores, successful re-canalization post-procedural symptomatic intracranial hemorrhage (sICH), and complications. When PT extended beyond 30 min (p<0.01) successful re-canalization was achieved faster with the direct aspiration at first pass technique than in SR. The direct aspiration technique was more sensitive to PT than SR, and posterior stroke was more sensitive to PT than anterior stroke. Longer ET procedures lead to lower rates of functional independence and higher rates of ICH and complications.
Owais et al., (2018) (22) conducted a study on acute ischemic stroke thrombolysis with tenecteplase: an institutional experience from South India. It was a prospective observational study among 14 patients who underwent IV stroke thrombolysis with tenecteplase. Primary clinical efficacy outcome was defined as an improvement in the National Institute of Health Stroke Scale (NIHSS) score of > 4 points at 24 hour. Secondary clinical efficacy outcome was the favorable outcome on modified rankin scale at 90 days. This study confirms the efficacy and safety of tenecteplase for stroke thrombolysis in clinical settings. The athors reported that
Department of Pharmacy Practice 20 tenecteplase appeared to be a suitable option for stroke thrombolysis in resource- limited settings, considering its cost-effectiveness and ease of administration.
Sun et al., (2018) (23) conducted a study on effects of mechanical thrombectomy for acute stroke patients with etiology of large artery atherosclerosis.
About 649 patients were involved in the study who were treated with mechanical thrombectomy. Successful revascularization was defined as modified Thrombolysis in Cerebral Infarction (mTICI) grade > 2b. Favorable outcome was defined as modified Rankin Scale (mRS) score < 2 at 90 days. There was no significant difference in the rate of successful post procedural mTICI between groups (84.5% versus 83.2%, P=0.671). Rates of symptomatic intracranial hemorrhage (20.0% versus 11.7%, p=0.004) and mortality (31.8% versus 18.8%, p<0.001) within 3 months were notably higher in the cardio embolism group than that in the Left Arterial Abnormality (LAA) group. Mechanical thrombectomy may be more efficacious in treating acute ischemic stroke of LAA etiology than that of cardio embolism.
Almallouhi et al., (2018) (24) conducted to assess the long-term functional outcome of stroke in patients treated with mechanical thrombectomy (MT) performed during work hours (on-hours) versus after-hours, weekends and official holidays (off- hours). It was a prospective study of 2 years with 90-day modified Rankin Scale (mRS) monitored. They estimated logistic regression to assess the relationship between off-hours treatment and favourable patient outcomes. During the study period, 80 (41%) patients underwent thrombectomy during on-hours. The authors reported that there is a higher probability of a good functional outcome in acute ischemic stroke patients who receive mechanical thrombectomy when performed during regular work hours.
Department of Pharmacy Practice 21 Ramakrishnan et al., (2018) (25) conducted a prospective study to assess the efficacy and safety of intravenous tenecteplase bolus in acute ischemic stroke: results of two open-label, multicenter trials. About 67 patients who were given with the two doses of TNK-tPA (0.1 and 0.2 mg/kg) compared with TNK-tPA 0.2 mg/kg. Two studies were conducted: Study I was an open-label, randomized study in which two doses of TNK-tPA (0.1 and 0.2 mg/kg) were compared; and Study II was an open- label study in which TNK-tPA 0.2 mg/kg bolus was compared with historical controls. The primary endpoint for study I and study II was an improvement of C 8 points or a score of 0 on the National Institutes of Health Stroke Scale (NIHSS) [major neurological improvement (MNI)] at 24 h. Secondary endpoints for both studies were neurological improvement as assessed using the NIHSS score, modified Rankin Scale (mRS) score and the Barthel Index (BI) on days 7, 30 and 90. Minimal disability was defined as an mRS score of 0 or 1 and good functional recovery as a BI score of 50–90. Safety was assessed by the proportion of patients having symptomatic intracranial hemorrhage (sICH) within 36 h and asymptomatic intracranial hemorrhage at 48 h after treatment.
Shelagh et al., (2015) (17) conducted a study on Tenecteplase-tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion.
This study was a multicenter, prospective, uncontrolled, TNK-tissue-type plasminogen activator dose-escalation, safety and feasibility. Patients with a National Institute of Health stroke Scale (NIHSS) 5 within 12 hours of symptom onset, intracranial arterial occlusion on computed tomographic angiography and absence of well-evolved infarction were eligible about 50 patients were enrolled; 25 patients at a dose of 0.1 mg/kg and 25 patients at 0.25 mg/kg. Primary outcome was to assess the
Department of Pharmacy Practice 22 rate of drug-related serious adverse events and the secondary outcomes included recanalization and 90-day neurological outcome. Median baseline NIHSS was 2.5 and median age was 71 years. There were no drug-related serious adverse events in 1group and 2nd group. In group 2, there was 1 symptomatic intracranial hemorrhage.
Stroke progression occurred in 6% of cases. Overall, 66% had excellent functional outcome at 90 days. Complete re-canalization was significantly related to excellent functional outcome. The safety and feasibility of thrombolysis using TNK-tPA for the acute treatment of minor ischemic stroke or transient ischemic attack. The authors concluded that administration of tenecteplase is both feasible and safe however; a larger randomized controlled trial is needed to prove that this treatment is efficacious.
Chu et al., (2017) (26) conducted a study on endovascular thrombectomy for acute ischemic stroke: to evaluate its efficiency and safety in Asian population from a single center of Taiwan. Patients who experienced AIS and received endovascular thrombectomy during the study period were included in the study. About 65 patients received endovascular thrombectomy, including 33 who received intravenous thrombolysis before the endovascular treatment. Successful revascularization was achieved in 41 patients. Two patients had symptomatic hemorrhagic transformation.
At 90 days, 25 patients achieved favourable outcome. The authors reported that a shorter time from onset to puncture and successful re-canalization were independent predictors of favorable outcome.
Kathirvela et al., (2017) (27) conducted a study on Tenecteplase versus streptokinase thrombolytic therapy in patients with mitral PVT diagnosed by clinical data, trans-thoracic echocardiography, trans-esophageal echocardiography. This study compared the thrombolytic therapy with tenecteplase (tnk) and streptokinase (SK)
Department of Pharmacy Practice 23 head to head in patients with mitral PVT. After excluding patients with contraindications for thrombolysis, they were randomly assigned to receive either SK or TNK regimen. Patients were monitored for success or failure of TT and for any complications. Among 52 episodes of mechanical mitral PVT, 40 patients were thrombolysed with SK and 12 patients were thrombolysed with TNK. Complete success rate was 77.5% in SK group and 75% in TNK group (p=0.88). Within 12 hours of therapy, TNK showed complete success in 33.3% of patients compared to 15% in SK group. Minor bleeding was more common in TNK group. Slow infusion of TNK is equally efficacious but more effective than SK in the management of mitral mechanical PVT. About 75% to 77.5% of PVT patients were completely recovered from thrombolytic therapy.
Cerejo et al., (2016) (28) conducted a retrospective study on treatment of patients with mild acute ischemic stroke and associated large vessel occlusion about 2636 patients were included in the study. Acute ischemic stroke patients with mild presenting symptoms and associated large vessel occlusion have an unfavorable response. This study specifically evaluated rapid treatment in AIS patients with associated LVO. Favourable outcomes were 4.5 times higher in treated (78.3%) versus untreated (53.8%) patients. None of the treated patients had symptomatic hemorrhage. Although the actual treatment effect cannot be directly addressed due to the non-randomized nature of our study, they observed better outcome in patients who received early therapeutic intervention rather than conservative management. They reported that detection of LVO, even with mild clinical symptoms, may prompt early treatment considerations rather than conservative management.
Department of Pharmacy Practice 24 Belkouch et al., (2015) (29) conducted a study on thrombolysis for acute ischemic stroke by tenecteplase in the emergency department of a hospital. They conducted an open prospective study among all patients who were treated with tenecteplase for an open AIS admitted to emergency department. Tenecteplase was administered intravenously at a dose of 0.4 mg/kg as single bolus. The primary outcome was to measure the proportion of patients achieving significant early neurological recovery defined as an improvement of 4 or more points on the NIHSS score at admission which was found to be 14.3 and 24 hour after was at 9.1. The right middle cerebral artery was involved in 69% of cases. The mean time to the first medical contact after the onset of symptoms was 3 hour 30 min. The authors concluded that tenecteplase is a more interesting thrombolytic than alteplase, which has proven itself in the thrombolysis.
Logallo N et al., (2015) (30) conducted a study to assess the therapeutic potential of tenecteplase in the management of acute ischemic stroke. Alteplase has been the only approved thrombolytic agent for almost two decades, there has been intense interest in more potent and safer agents over the last few years. Tenecteplase is a bioengineered mutation of alteplase with advantageous pharmacodynamics and pharmacokinetics. In patients with acute ischemic stroke, tenecteplase has shown promise in randomized phase. It was concluded that its potential activity was higher than other rt-PA.
Adeoye et al., (2011) (31) conducted a study on efficiency of enrollment in a successful phase II acute stroke clinical trial. It was a population-based study, in which they determined the eligibility and actual enrollment for a successful study.
Acute ischemic stroke (AIS) cases were identified in 17 local hospitals as part of an
Department of Pharmacy Practice 25 epidemiologic study involving 1175 patients. The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue Plasminogen Activator (CLEAR) trial assessed the safety of this combination in AIS patients within 3 hours of symptom onset. Although the CLEAR trial was successful in meeting its delineated recruitment goals, findings suggest enrollment could have been more efficient. Three out of 4 patients approached for enrollment participated in the trial. Eligible patients who were not approached and those treated with recombinant tissue plasminogen activator but not enrolled represent targets for improving enrollment rates.
Blakeley et al., (2007) (32) conducted a study on thrombolytic therapy for acute ischemic stroke to assess the treatment of acute stroke changed dramatically since the publication of the National Institute of Neurological Disorders & Stroke (NINDS) trial for IV rt-PA for acute stroke. Subsequently there has been an explosion in acute treatment modalities since the NINDS trial showed that acute stroke treatment is feasible. The authors also discussed that the new pharmacotherapies and mechanical devices will hopefully expand the treatment window and make thrombolysis safer and more effective. The authors reported that the most effective treatment for stroke is the control of hypertension, anticoagulation for atrial fibrillation and hypercholesterolemia and education of the people at risk for ischemic stroke.
Nordt et al., (2003) (33) conducted study on thrombolysis, newer thrombolytic agents and their role in clinical medicine. In the study thrombolytic agents used in reperfusion therapy was compared. Comparison with alteplase and its accelerated dose (over 90 minutes) the plasminogen activators, reteplase and tenecteplase equal in their efficacy but the mortality range after 30 days and superior
Department of Pharmacy Practice 26 in their application (reteplase as a double bolus, tenecteplase as a single bolus). The authors concluded that the safety and efficacy of tenecteplase was more than other thrombolytic agents.
Ringleb et al., (2002) (34) conducted a study on thrombolytic therapy within 3 to 6 h after onset of ischemic stroke to individualize and qualify the time window based on the findings of each patient’s imaging results rather than the use of therapeutic time window which is strictly time defined. The authors suggested that thrombolytic therapy based on therapeutic time window should be done only as part of their respected institutional protocols after obtaining complete information regarding their symptoms before they reach the hospital from the patient or patient’s relatives and better methods for patient selection is required, newer MRI techniques, such as diffusion and perfusion weighted imaging plays a key role. From the authors point of view they concluded that it appears unjustified to limit thrombolytic therapy to 3 hours.
Kwiatkowski et al., (1999) (35) conducted a study on effects of tissue plasminogen activator for acute ischemic stroke at one year to evaluate the patients functional ability and patients’ condition. They included patients who can be treated with 3 hours after the onset of acute ischemic stroke symptoms. They used 3 types of scales (modified rankin scale, barthel scale, Glasgow outcome scale) for the outcome measurement during the admission and discharge. From the output they came to know that t-PA showed minimal or no disability over the three months after the stroke and this improvement can be seen only if it is administered before 3 hour after the onset of symptoms.
Department of Pharmacy Practice 27 Martin et al., (1998) (36) conducted a study on early intravenous thrombolysis for acute ischemic stroke in a community-based approach. They included 453 patients among them 100 patients were thrombolysed. After 3 months, 53 patients recovered fully with independent function. NIHSS was used scale for clinical assessment after 24 hours and after 90 days. Daily activities were measured by barthel index and mRS for overall functions. The authors concluded that thrombolysis with recombinant tissue plasminogen activator is effective in routine management for stroke patients both in disability improvement wise and cost wise.
Department of Pharmacy Practice 28
AIM AND OBJECTIVES
AIM:
This study was carried out to assess the safety and efficacy of tenecteplase in acute ischemic stroke patients.
OBJECTIVES:
To compare the safety and efficacy of tenecteplase with thrombectomy and tenecteplase plus thrombectomy treatment in ischemic stroke.
To evaluate the neurological outcome after 3 months using NIHSS (National Institute of Health stroke scale) (Annexure-lll).
To measure the degree of disability among ischemic stroke patients using Modified Rankin scale (Annexure-IV).
Department of Pharmacy Practice 29
PLAN OF STUDY
Literature search and topic selection
Obtaining ethical approval for the study
Preparing data collection form &
patient enrollment based on inclusion criteria
Data collection through emergency department and medication form
Follow up of the patient for 3 months using NIHSS &
mRS scale
Statistical analysis to determine the score of patients
Submission of Report
Department of Pharmacy Practice 30
METHODOLOGY
STUDY TYPE
A prospective observational study STUDY SITE
This study was carried out in the Department of Neurology, Kovai Medical Center and Hospital, a multispecialty hospital, Coimbatore.
STUDY POPULATION WITH SAMPLE
A total of 24 patient’s viz., 12 in tenecteplase and 12 in mechanical thrombectomy.
SAMPLE SIZE
Confidence level = 95% z score = 1.96 Confidence interval (e) = 0.05
Standard deviation (p) = 0.5 Population size (N) = 18 n= sample size
Formula
n
=1.962 X 0.5 (1-0.5) / 0.052
1 + [1.962 * 0.5 (1-0.5) / 0.05218)]
384.96 22.34 Sample size (n) = 17
17
Department of Pharmacy Practice 31 STUDY PERIOD
The study was carried out from June 2019 to October 2019 after the KMCH ethics committee approval, Ref. No: EC/AP/716/06/2019 (Annexure-I) at Kovai Medical Center and Hospital, Coimbatore.
STUDY POPULATION
Patients attending neurological department or emergency department due to ischemic stroke
Inclusion criteria:
All patients with ischemic stroke
Patients with age ≥ 18 years
Diagnosis of ischemic stroke causing measurable neurological outcomes.
Onset of symptoms less than 4.5 hours before beginning the treatment.
CT showing no evidence of bleed
Diagnosis of ischemic stroke causing measurable neurological outcomes.
Exclusion criteria:
Patients with unconscious state
Hemorrhagic stroke patients SOURCES OF DATA
A data collection form (Annexure-ll) was designed to collect patient information including demographic data (age, sex, in patient number, weight, height) and medical data (past history, initiation of treatment, tenecteplase dose, route of administration, risk and thrombectomy dose, etc.,)
Department of Pharmacy Practice 32
NIHSS (Annexure-lll) was used to assess the safety and efficacy of tenecteplase in comparison with thrombectomy in ischemic stroke patients.
mRS scale (Annexure-IV) was used to assess the mortality and morbidity.
STUDY PROCEDURE
The patients meeting the inclusion criteria were considered for further analysis. A total 24 patients were considered for the study in two different groups:
one was tenecteplase and another one was mechanical thrombectomy group.
Quick neurological assessments were done to patients who were brought to the emergency department. The details of demographics, medication prescribed, dose of drugs, duration and other details as per the NIHSS and MRS scale for the assessment of ischemic stroke. Thrombectomy and Tenecteplase treatment was compared and assessed for the safety and efficacy of ischemic stroke patients.
STATISTICAL ANALYSIS
IBM SPSS statistical software version 20 was used for the statistical analysis.
Tenecteplase and thrombectomy groups were compared by the independent t-test.
Department of Pharmacy Practice 33
TABLES AND GRAPHS
Table 1. GENDERWISE DISTRIBUTION OF PATIENTS (n=24) Tenecteplase (n=12) Thrombectomy (n=12) Gender Frequency Percentage
(%) p-value Frequency Percentage
(%) p-value
Male 9 75
0.223
6 50
0.223
Female 3 25 6 50
Total 12 100 12 100
Graph 1. FREQUENCY OF GENDERWISE DISTRIBUTION OF PATIENTS (n=24)
9
3
6 6
0 1 2 3 4 5 6 7 8 9 10
Male Female
No.of patients
Gender
Tenecteplase Thrombectomy
Department of Pharmacy Practice 34 Table 2. AGEWISE DISTRIBUTION OF PATIENTS IN TENECTEPLASE
AND THROMBECTOMY GROUP (n=24)
Tenecteplase (n=12) Thrombectomy (n=12) Age Frequency Percentage
(%) p-value Frequency Percentage
(%) p-value
41-50 3 25
0.409
4 33.3
0.411
51-60 4 33.3 2 16.7
61-70 4 33.3 3 25.0
71-80 1 8.3 1 8.3
81-90 0 0 2 16.7
Total 12 100 12 100
Graph 2. FREQUENCY OF AGEWISE DISTRIBUTION TO TENECTEPLASE AND THROMBECTOMY GROUP (n=24)
3
4 4
1
0 4
2
3
1
2
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5
41-50 51-60 61-70 71-80 81-90
No .of pa tie nts
Age
Agewise distribution in both group of patients
Tenecteplase Thrombectomy
Department of Pharmacy Practice 35 Table 3. DISTRIBUTION OF TENECTEPLASE GROUP PATIENTS BASED
ON SOCIAL HABITS (n=12)
Graph 3. DISTRIBUTION OF TENECTEPLASE GROUP PATIENTS BASED ON SOCIAL HABITS (n=12)
8.3
91.7
8.3
91.7
0 10 20 30 40 50 60 70 80 90 100
Yes No
Percentage of patients
TENECTEPLASE
SMOKER ALCOHOLIC
Smoker (n=12) Alcoholic (n=12) Frequency Percentage
(%) p-value Frequency Percentage
(%) p-value
Yes 1 8.3
0.557
1 8.3
0.558
No 11 91.7 11 91.7
Total 12 100 12 100
Department of Pharmacy Practice 36 Table 4. PERCENTAGE DISTRIBUTION OF THROMBECTOMY GROUP
PATIENTS BASED ON SOCIAL HABITS (n=12)
Graph 4. PERCENTAGE DISTRIBUTION OF THROMBECTOMY GROUP PATIENTS BASED ON SOCIAL HABITS (n=12)
16.7
83.3
0
100
0 20 40 60 80 100 120
Yes No
Percentage of patients
THROMBECTOMY
SMOKER ALCOHOLIC
Smoker (n=12) Alcoholic (n=12) Frequency Percentage
(%) p-value Frequency Percentage
(%) p-value
Yes 2 16.7
0.328
0 0
0.339
No 10 83.3 12 100
Total 12 100 12 100
Department of Pharmacy Practice 37 Table 5. DISTRIBUTION OF PATIENTS BASED ON GCS SCORE IN
TENECTEPLASE GROUP AND THROMBECTOMY GROUP (n=12 in each group)
Graph 5. DISTRIBUTION OF PATIENTS BASED ON GCS SCORE IN TENECTEPLASE GROUP AND THROMBECTOMY GROUP
(n=12 in each group)
Tenecteplase (n=12) Thrombectomy (n=12) GCS
score Frequency Percentage (%)
p-
value Frequency Percentage
(%) p-value
0-5/15 1 8.3
0.167
0 0
0.169 6-
10/15
3 25.0 9 75
11- 15/15
8 66.7 3 25
Total 12 100 12 100
Department of Pharmacy Practice 38 Table 6. INITIATION OF TREATMENT IN TENECTEPLASE GROUP AND
THROMBECTOMY GROUP (n=12 in each group)
Graph 6. INITIATION OF TREATMENT IN TENECTEPLASE GROUP AND THROMBECTOMY GROUP (n=12 in each group)
Treatment initiation
Tenecteplase (n=12)
Percentage (%)
p- value
Thrombectomy (n=12)
Percentage
(%) p-value
1-2 hours 3 25.5
0.167
2 16.7
0.169
2-3 hours 3 25.5 1 8.3
3-4 hours 4 42.3 3 25.5
4-5 hours 2 16.7 5 41.7
Above 5 hours 0 0 0 0
Department of Pharmacy Practice 39 Table 7. PAST HISTORY OF PATIENTS IN TENECTEPLASE GROUP AND
THROMBECTOMY GROUP (n=12 each group)
Tenecteplase (n=12) Thrombectomy (n=12) Past history Frequency Percentage
(%) p-value Frequency Percentage
(%) p-value
No history 4 33.3
0.564
5 41.7
0.564
Hypertension 1 8.3 4 33.3
Diabetes Mellitus
2 16.7 0 0
HT+DM 2 16.7 1 8.3
IHD 1 8.3 0 0
Asthma 1 8.3 0 0
IHD+HT 1 8.3 0 0
HT+DM+CAD 0 0 1 8.3
Acute pulmo edema
0 0 1 8.3
Total 12 100 12 100
Department of Pharmacy Practice 40 Graph 7. PAST HISTORY OF PATIENTS IN TENECTEPLASE GROUP AND
THROMBECTOMY GROUP (n=12 each group)
33.3
8.3
16.7 16.7
8.3 8.3 8.3
0 0
41.7
33.3
0
8.3
0 0 0
8.3 8.3
0 5 10 15 20 25 30 35 40 45
Percentage of patients
Initiation of treatment
Tenecteplase
Department of Pharmacy Practice 41 DISTRIBUTION OF PATIENTS BASED ON NIHSS SCALE FOR
TENECTEPLASE PLUS THROMBECTOMY
Table 8. DISTRIBUTION OF TENECTEPLASE GROUP PATIENTS (n=12)
Score 12 h Percentage (%)
p-
value 15 days Percentage (%)
p- value
3 months
Percentage (%)
p- value
0 0
0.152
1 8.3
0.294
8 66.7
0.731
1-4 0 0 0 0 4 33.3
5-15 0 0 9 75 0 0
16-20 9 75 2 16.7 0 0
21-42 3 25 0 0 0 0
Graph 8. DISTRIBUTION OF TENECTEPLASE GROUP PATIENTS (n=12)
0 0 0
75
25
8.3
0
75
16.7
0 66.7
33.3
0 0 0
0 10 20 30 40 50 60 70 80
0 1 - 4 5 - 15 16 - 20 21 - 42
Percentage of Patients
Tenecteplase
12 hours 15 days 3 months
Department of Pharmacy Practice 42 Table 9. DISTRIBUTION OF THROMBECTOMY GROUP PATIENTS (n=12)
Score 12 h Percentage (%)
p- value
15 days
Percentage (%)
p- value
3 months
Percentage (%)
p- value
0 0 0
0.152
0 0
0.294
2 16.7
0.731
1-4 0 0 0 0 8 66.7
5-15 0 0 8 66.7 2 16.7
16-20 5 41.7 4 33.3 0 0
21-42 7 58.3 0 0 0 0
Graph 9. DISTRIBUTION OF THROMBECTOMY GROUP PATIENTS (n=12)
0 0 0
41.7
58.3
0 0
66.7
33.3
0 16.7
66.7
16.7
0 0
0 10 20 30 40 50 60 70 80
0 1-4 5-15 16-20 21-42
Percentage of patients
Thrombectomy
12 hours 15 days 3 months
