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Table of Contents    
BRIEF REPORT
Year : 2021  |  Volume : 69  |  Issue : 6  |  Page : 1743-1746

Recurrent Ischemic Strokes: “Discontinuation of Antiplatelet Drugs Appears to be an Important Preventable Cause”


Department of Neurology, St. John's Medical College Hospital, Sarjapura Road, Bengaluru, Karnataka, India

Date of Submission06-Dec-2019
Date of Decision15-Jun-2020
Date of Acceptance10-Jul-2020
Date of Web Publication23-Dec-2021

Correspondence Address:
Dr. Thomas Mathew
Professor and Head, Department of Neurology, St. John's Medical College Hospital, Sarjapura Road, Bengaluru - 560 034, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.333533

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 » Abstract 


Background: Antiplatelet therapy (APT) is an integral part of secondary stroke prevention. Noncompliance to APT is an important factor in stroke recurrence. In this study, we have evaluated the reasons for noncompliance to APT.
Objective: The aim of this study was to identify the various causes of nonadherence to APT in recurrent stroke patients.
Material and Methods: The study was conducted in a tertiary care hospital in south India with a huge stroke burden. The study period was from October 2017 to September 2018. A total of 60 consecutive patients of recurrent stroke who were nonadherent to antiplatelet therapy were evaluated for various factors that prevented compliance.
Results: During the 12-month study period among 604 ischemic stroke patients, 128 (21%) had recurrent strokes. Of this 128, 60 (46.8%) were due to discontinuation of APT. The main factor for nonadherence to APT was lack of awareness about the need for lifelong medication (41/60; 68.3%). 10 patients (16.7%) stopped treatment as they opted for alternative therapy and 4 (6.7%) discontinued antiplatelets due to side effects. A small proportion of the patients (3.3%) cited financial constraints and forgetfulness as the issue, while 1.7% had difficulty in finding assistance to administer medicine. 27 (45%) patients had recurrent stroke within 2-15 days of stopping APT.
Conclusions: The main reason for nonadherence to antiplatelet therapy is lack of awareness about the need for lifelong antiplatelet therapy. Stroke patients should be educated about the importance of lifelong antiplatelet therapy to prevent recurrent strokes.


Keywords: Antiplatelet therapy, lack of awareness, noncompliance, recurrent strokes
Key Message: Discontinuation of antiplatelet therapy is one of the commonest causes for recurrent ischemic strokes and is well preventable with adequate patient education. All patients with ischemic strokes should be advised not to stop the antiplatelets even for few days as it may cause stroke recurrence.


How to cite this article:
Mathew T, John SK, Souza DD, Nadig R, Badachi S, K Sarma G R. Recurrent Ischemic Strokes: “Discontinuation of Antiplatelet Drugs Appears to be an Important Preventable Cause”. Neurol India 2021;69:1743-6

How to cite this URL:
Mathew T, John SK, Souza DD, Nadig R, Badachi S, K Sarma G R. Recurrent Ischemic Strokes: “Discontinuation of Antiplatelet Drugs Appears to be an Important Preventable Cause”. Neurol India [serial online] 2021 [cited 2022 Jan 26];69:1743-6. Available from: https://www.neurologyindia.com/text.asp?2021/69/6/1743/333533




Every year, stroke claims the lives of millions of people worldwide. In many countries, it is the second most common cause of morbidity and mortality after ischemic heart disease.[1] Survivors of stroke are at increased risk of suffering from a recurrent stroke. Recurrent strokes are associated with increased morbidity and mortality. Antiplatelet therapy is pivotal in reducing the risk of another ischemic episode.[2] Noncompliance to APT is an important but not so commonly recognized factor in stroke recurrence. The objective of this study was to analyze the reasons for noncompliance, in patients with recurrent strokes due to antiplatelet noncompliance.


 » Methods Top


We analyzed the cause of stroke recurrence in a cohort of 604 ischemic stroke patients at a tertiary care hospital in south India with a huge stroke burden, between October 2017 to September 2018. Both male and female in the age group of 18–84 years were included in this study. Subjects who had recurrent stroke due to cardio-embolism and prothrombotic states were excluded from the study. Patients who had embolic strokes were also excluded from the study. Patients with significant carotid artery disease as a cause of stroke were excluded from this study.

Diagnosis of cerebral infarction was confirmed by history, clinical signs and symptoms and magnetic resonance imaging (MRI Brain and MR Angiogram) in all patients. The study protocol was approved by the Institutional Review Board of the Hospital. Written informed consent was obtained from the patients or their caregivers for contributing their data to the study. Data was entered and analyzed on SPSS software. A comparative analysis in an age- and sex-matched cohort, who did not have stroke recurrence was done using Pearson's Chi-squared test, to check for anti-platelet compliance.


 » Results Top


Over the study period of 1 year, 604 stroke patients were admitted to our stroke center. Among these, 128 (21%) admissions were due to recurrent stroke, of which 60 (46.8%) had recurrence due to noncompliance to APT. The mean age of participants was 56 years (SD ± 13.21), and 73% were male gender. The common risk factors observed in the study group were hypertension 93.3%, diabetes 56.6%, dyslipidemia 31.67%, and smoking 8.3%. Demographic and risk factor profile are summarized in [Table 1]. The stroke subtypes according to TOAST classification were, large artery atherosclerosis 60%, small vessel disease 35%, and stroke of undetermined cause 5%. Stroke due to cardioembolism was excluded from the study. 24-hour Holter done in all patients with recurrent strokes did not reveal atrial fibrillation or any other cardiac arrhythmia.
Table 1: Demographic and risk factor profile

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The comparative analysis in an age- and sex-matched cohort, who did not have stroke recurrence showed that the proportion of patients with hypertension and diabetes were comparable between the two groups. In the comparative group only 18.6% were nonadherent to antiplatelet therapy (p < 0.001).

The cohort of patients who had recurrence of strokes due to antiplatelet noncompliance had all their modifiable risk factors well controlled. Only 5 of 60 subjects were smokers and all of them had stopped smoking after the first stroke. The blood pressure, blood sugar, and lipids were in the recommended target ranges. They were compliant with the risk factor modifying drugs. 60% of the patients were on single antiplatelet agent and 40% were on dual antiplatelet agents. 90% of patients who were on single antiplatelet agent were taking aspirin (80% on 150 mg and 20% on 75 mg) and those on clopidogrel were taking 75 mg. The patients who were noncompliant had taken APT from a period ranging from 3 months to 15 years (Mean 1.97 years, SD ± 1.69) before stopping the antiplatelet drugs.

In the subgroup of patients who had stopped APT, we evaluated the reasons for discontinuation. The main factor for nonadherence to APT was lack of awareness about the need for lifelong medication (41/60; 68.3%). The second most common cause found was alternative therapy such as Ayurveda, Homeopathy, and Acupuncture (10/60; 16.7%). All the factors for noncompliance are listed in [Table 2]. Most of the stroke recurrence occurred between 2-90 days after APT discontinuation. 75% of patients had stroke recurrence within 2 -30 days [Table 3]. It was also observed that the recurrent stroke patients were adequately compliant with their risk factor modifying drugs for hypertension, diabetes, and dyslipidemia but not to APT. They were aware about the importance of continuing antihypertensive, antidiabetic, and lipid-lowering medications but were ignorant of the importance of long-term APT.
Table 2: Reason for non-compliance to anti-platelet therapy(APT)

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Table 3: Time to stroke recurrence after discontinuation of anti-platelet therapy(APT)

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 » Discussion Top


Recurrent strokes have become a major public health issue worldwide, with high mortality and morbidity.[3] In the Perth Community Stroke Study, for 10 years, it was found that the risk of recurrent stroke is six times greater than the risk of initial stroke among the general population.[4] Half of those who had a stroke remained disabled, with 15% requiring institutional care.[4] As per the international guidelines on stroke prevention, lifelong use of antiplatelets is recommended to prevent a second thrombotic event.[5] However today there is an increasing incidence of recurrent strokes which can be attributed to noncompliance to APT. Discontinuation of aspirin (ASA) has recently been reported to increase the risk of stroke and transient ischemic attack by 40%.[6]

Our study revealed that “lack of knowledge” about the importance of compliance to APT as the most common barrier for continuation of APT. Majority of stroke victims and their care givers were unaware of the real-time risk of stroke recurrence, if they missed medications even for 2-3 days. Optimal medication adherence in stroke survivors is very important for preventing recurrences. Antiplatelet therapy has shown their effectiveness on stroke recurrence.[7],[8] The National Stroke Association (NSA) guidelines also recommend the use of antiplatelet agents to prevent secondary stroke after noncardio embolic TIA.[9]

Various studies have shown that the main reasons for poor compliance to APT among stroke survivors are lack of knowledge about the gravity of their illness and importance of secondary prophylaxis, lack of motivation to take medications, patients concern about safety of medications and a perceived discrimination in society and by the health system.[10],[11] This study has also brought to light an interesting disparity between the adherence to long term medications for co-morbidities such as, hypertension or diabetes as compared to adherence to antiplatelet medications for secondary prevention of stroke. This may be due to the fact that over last few decades people were made aware and have been educated regarding these co-morbidities and the importance of long-term medications. However, this education was lacking when it came to stroke and medications involved in secondary prevention of stroke. Along with lack of awareness, the strong beliefs in various complementary and alternative medicines also act as a significant hindrance to APT compliance. Patients usually opt for alternative treatments when their deficits are not improving with medications. An Australian survey showed 50% of stroke survivors had insufficient knowledge based on a stroke knowledge score. Furthermore, stroke survivors were not more knowledgeable about the disease than nonstroke survivors.[12]

The main initiative required to prevent recurrent strokes is that all the medical personnel, including the stroke team should educate the stroke patients and their caregivers about the need for continuation of APT and the increased risk of thrombosis and recurrent stroke on discontinuation of treatment.[13] For this, we need a dedicated team of doctors, nurses, and medical social workers who will educate and motivate the patients to take their medications regularly. Patient's false perception that these medications are for disability improvement should be addressed appropriately and the fact that they are for future prevention of stroke should be stressed while they are counseled. In this way a significant number of recurrent strokes can be prevented.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but complete anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Mathers CD, Ma Fat D, Boerma JT. The Global Burden of Disease: 2004 Update. Geneva: World Health Organization; 2008.  Back to cited text no. 1
    
2.
Weimar C, Cotton D, Sha N, Sacco RL, Bath PM, Weber R, et al. Discontinuation of anti-platelet study medication and risk of recurrent stroke and cardiovascular events: Results from the PRoFESS study. Cerebrovasc Dis 2013;35:538-43.  Back to cited text no. 2
    
3.
Kocaman G, Dürüyen H, Koçer A, Asil T. Recurrent ischemic stroke characteristics and assessment of sufficiency of secondary stroke prevention. Noro Psikiyatr Ars 2015;52:139-44.  Back to cited text no. 3
    
4.
Hardie K, Hankey GJ, Jamrozik K, Broadhurst RJ, Anderson C. Ten-year risk of first recurrent stroke and disability after first-ever stroke in the Perth Community Stroke Study. Stroke 2004;35:731-5.  Back to cited text no. 4
    
5.
Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, Fagan SC, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:227-76.  Back to cited text no. 5
    
6.
Garcia Rodriguez LA, Cea Soriano L, Hill C, Johansson S. Increased risk of stroke after discontinuation of acetylsalicylic acid: A UK primary care study. Neurology 2011;76:740-6.  Back to cited text no. 6
    
7.
Kirshner HS. Prevention of secondary stroke and transient ischaemic attack with anti-platelet therapy: The role of the primary care physician. Int J Clin Pract 2007;61:1739-48.  Back to cited text no. 7
    
8.
Davis SM, Donnan GA. Secondary prevention after ischemic stroke or transient ischemic attack. N Engl J Med 2012;366:1914-22.  Back to cited text no. 8
    
9.
Johnston SC, Nguyen-Huynh MN, Schwarz ME, Fuller K, Williams CE, Josephson SA, et al. National Stroke Association Guidelines for the management of transient ischemic attacks. Ann Neurol 2006;60:301-13.  Back to cited text no. 9
    
10.
Karttunen V, Alfthan G, Hiltunen L, Rasi V, Kervinen K, Kesaniemi YA, et al. Risk factors for cryptogenic ischemic stroke. Eur J Neurol 2002;9:625-32.  Back to cited text no. 10
    
11.
Kronish IM, Diefenbach MA, Edmondson DE, Phillips LA, Fei K, Horowitz CR. Key barriers to medication adherence in survivors of strokes and transient ischemic attacks. J Gen Intern Med 2013;28:675-82.  Back to cited text no. 11
    
12.
Sullivan K, White K, Young R, Chang A, Roos C, Scott C. The nature and predictors of stroke knowledge amongst at risk elderly persons in Brisbane, Australia. Disabil Rehabil 2006;28:1339-48.  Back to cited text no. 12
    
13.
Jamison J, Graffy J, Mullis R, Mant J, Sutton S. Barriers to medication adherence for the secondary prevention of stroke: A qualitative interview study in primary care. Br J Gen Pract 2016;66:e568-76.  Back to cited text no. 13
    



 
 
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  [Table 1], [Table 2], [Table 3]



 

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