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. 2022 Sep 6;12(10):e2752. doi: 10.1002/brb3.2752

Antithrombotics prescription and adherence among stroke survivors: A systematic review and meta‐analysis

Min Yang 1,#, Hang Cheng 1,#, Xia Wang 2,#, Menglu Ouyang 2, Sultana Shajahan 2, Cheryl Carcel 2,3, Craig Anderson 2,3,4, Espen Saxhaug Kristoffersen 5,6, Yapeng Lin 1,7, Else Charlotte Sandset 8,9, Xiaoyun Wang 10,#,✉, Jie Yang 11,#,✉
PMCID: PMC9575604  PMID: 36067030

Abstract

Objectives

We aimed to investigate the prescription of antithrombotic drugs (including anticoagulants and antiplatelets) and medication adherence after stroke.

Methods

We performed a systematic literature search across MEDLINE and Embase, from January 1, 2015, to February 17, 2022, to identify studies reporting antithrombotic medications (anticoagulants and antiplatelets) post stroke. Two people independently identified reports to include, extracted data, and assessed the quality of included studies according to the Newcastle–Ottawa scale. Where possible, data were pooled using random‐effects meta‐analysis.

Results

We included 453,625 stroke patients from 46 studies. The pooled proportion of prescribed antiplatelets and anticoagulants among patients with atrial fibrillation (AF) was 62% (95% CI: 57%–68%), and 68% (95% CI: 58%–79%), respectively. The pooled proportion of patients who were treated according to the recommendation of guidelines of antithrombotic medications from four studies was 67% (95% CI: 41%–93%). It was reported that 11% (95% CI: 2%–19%) of patients did not receive antithrombotic medications. Good adherence to antiplatelet, anticoagulant, and antithrombotic medications was 78% (95% CI: 67%–89%), 71% (95% CI: 57%–84%), and 73% (95% CI: 59%–86%), respectively.

Conclusion

In conclusion, we found that less than 70% of patients were prescribed and treated according to the recommended guidelines of antithrombotic medications, and good adherence to antithrombotic medications is only 73%. Prescription rate and good adherence to antithrombotic medications still need to be improved among stroke survivors.

Keywords: anticoagulant, antiplatelet, antithrombotic, secondary prevention, stroke, systematic review

Graphical Abstract

 

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1. INTRODUCTION

Recurrent strokes account for approximately 20% of all strokes (Benjamin et al., 2018). The cause of stroke recurrence includes nonadherence to antithrombotic treatment (Broderick et al., 2011). Antithrombotic agents (anticoagulants and antiplatelets) are among important factors to prevent short‐ and long‐term recurrence of ischemic stroke (Del Brutto et al., 2019). Patients with stroke with high medication adherence have lower incidence of adverse outcomes compared to those with low medication adherence (Kim et al., 2017; Perreault et al., 2012; Rijkmans et al., 2018). Despite this, the secondary prevention measures after stroke have shown significant gaps in specialist care, monitoring, and treatment programs (Broderick et al., 2011; Webb et al., 2019; Weimar et al., 2013). The European Stroke Action Plan (ESAP) for the years 2018–2030 outlined targets for the development of stroke care, one of which is secondary prevention and organized follow‐up (Norrving et al., 2018).

To summarize the prescription rate and patient medication adherence of antithrombotics after stroke, we conducted this systematic review and meta‐analysis synthesizing the evidence on the optimal antithrombotic treatment and adherence according to guidelines for the secondary prevention of stroke.

2. MATERIALS AND METHODS

The systematic review was reported following Meta‐analysis Of Observational Studies in Epidemiology (MOOSE) guidelines (Stroup et al., 2000). We reviewed only previously published data, and ethics committee approval and all subjects informed consent were not required.

2.1. Search strategy

A comprehensive search strategy (the Appendix), which was developed in consultation with a university librarian, neurologists, and epidemiologists, was used to address the unique features and indexing of each of the two electronic databases (Medline and Embase) that were searched from January 1, 2015, to February 17, 2022. As well as searching for original studies, the reference lists of any relevant reviews appearing in their reports were examined.

2.2. Selection criteria

Any studies reporting antithrombotic medications (anticoagulants and antiplatelets) after stroke (ischemic or hemorrhagic) or transient ischemic attack (TIA) were included. Patients aged 18 years and over, of any race with a clinical or imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) diagnosis of stroke, were included. There were no language restrictions.

2.3. Data extraction and quality assessment

MY and HC independently screened the titles and abstracts, excluded irrelevant references, and reviewed abstracts of potential relevance to identify reports for review in full text. MY and HC extracted data independently from the included studies. MO and SS assessed the quality of included studies according to the Newcastle–Ottawa scale (NOS) (Stang, 2010). Any disagreements were resolved by a third author (XW or JY).

2.4. Outcomes

The main outcomes were the proportion of patients prescribed and using (adherence) antithrombotic medication after stroke. Medication adherence refers to the extent to which patients act in accordance with the prescribed interval and dose of the medication regimen. Medication persistence was defined as the duration of time from initiation to discontinuation of therapy (Cramer et al., 2008). Good adherence to the medications was defined by continuation of medications (Ullberg et al., 2017) or prescription refill, for example, Continuous Measure of Medication Acquisition (CMA) (Hess et al., 2006), the proportion of days covered (PDC) (Yeo et al., 2020), or the 4‐item Morisky Medication Adherence Scale (MMAS‐4) (Morisky et al., 1986).

2.5. Statistical analysis

The data were pooled using random‐effects models where data were available. An I 2 statistic was considered to reflect low likelihood (0%−25%), moderate likelihood (26%−75%), and high likelihood (76%−100%) of differences beyond chance, as was a P value of less than or equal to 0.05 for heterogeneity (Rothman et al., 2008). Statistical analysis was performed with Stata, version 16.

3. RESULTS

Of 54,407 references identified through the databases, 109 remained after screening titles and abstracts for relevance (Figure S1). Forty‐six studies (453,625 patients) that satisfied the eligibility criteria were included in the review (Table 1). Of the 46 studies, 31 studies reported prescription of antiplatelets, and 11 reported anticoagulation among patients with atrial fibrillation (AF). Two studies were defined as low quality (scores < 5) on the NOS (Table 2).

TABLE 1.

Included studies

Author Country Study design Subtype Number of subjects Age (mean, SD) Sex (female, %)
Bergstrom 2017 (Bergstrom et al., 2017) Sweden Population‐based study/national registry Ischemic stroke 196765 76 (11.4) 50
Mechtouff 2018 (Mechtouff et al., 2018) France Single‐center hospital‐based study Ischemic stroke or tia 373 <60 (24.9%) 43
Faure 2020 (Faure et al., 2020) Canada Population‐based study/national registry Ischemic stroke 5587 <65 (17.3%) 50
Jithin 2016 (Jithin et al., 2016) India Single‐center hospital‐based study Ischemic stroke 295 <60 (42.0%) 39
Eriksson 2017 (Eriksson, 2017) Sweden Single‐center hospital‐based study Stroke 549 70 48
Rijkmans 2018 (Rijkmans et al., 2018) The Netherlands Single‐center hospital‐based study Ischemic stroke 286 70 48
Desmaele 2016 (Desmaele et al., 2016) International Multi‐center hospital‐based study Stroke 247 68.6 (60.0‐75.4) 47
Zhang 2017 (Zhang et al., 2017) China Multi‐center hospital‐based study Ischemic stroke & AF 1014 70.3 (10.8) 54
Lim 2015 (Lim et al., 2015) Korea Multi‐center hospital‐based study Tia 500 64.4 (11.8) 42
Park 2017 (Park et al., 2017) Korea Multi‐center hospital‐based study Ischemic stroke or tia 9506 65.9 (12.7) 39
Ullberg 2017 (Ullberg et al., 2017) Sweden Population‐based study/national registry Ischemic stroke 5602 73 47
Sarfo 2016 (Sarfo et al., 2017) Ghana Single‐center hospital‐based study Stroke 418 60 50
Sluggett 2015 (Sluggett et al., 2015) Australia Population‐based study/national registry Ischemic stroke or tia 1541 85 51
Jiang 2017 (Jiang et al., 2017) China Population‐based study/national registry Ischemic stroke or tia 18344 64 (56‐73) 36
Brewer 2015 (Brewer et al., 2015) United Kingdom Multi‐center hospital‐based study Ischemic stroke 302 > = 65 (66%) 43
Haeusler 2015 (Haeusler et al., 2015) Germany Population‐based study/national registry Ischemic stroke or tia & af 896 71.3 (9.6) 43
Yeo 2020 (Yeo et al., 2020) Singapore Population‐based study/national registry Ischemic stroke 1215 65.3 (13.4) 38
Mazurek 2017 (Mazurek et al., 2016) United Kingdom Population‐based study/national registry Stroke & AF 428 79.6 (9.6) 45
Abdo 2019 (Abdo et al., 2019) Lebanon Multi‐center hospital‐based study Ischemic stroke or TIA 173 69.8 (12.7) 40
Magwood 2017 (Magwood et al., 2017) United States Population‐based study/national registry Stroke 125 39.6 (7.7) 54
Akijian 2017 (Akijian et al., 2017) United Kingdom Population‐based study/national registry TIA 172 71 (12.2) 51
Akijian 2017 United Kingdom Population‐based study/national registry Ischemic stroke 412 71.4 (13.4) 49
Sauer 2015 (Sauer et al., 2015) Germany Single‐center hospital‐based study Ischemic stroke & AF 284 78.1 (9.5) 51
Xian 2015 (Xian et al., 2015) United States Population‐based study/national registry Ischemic stroke & AF 12552 80.5 (7.6) 60
Shah 2016 (Shah et al., 2016) Canada Multi‐center hospital‐based study Ischemic stroke or TIA & AF 5781 – 46
Guidoux 2019 (Guidoux et al., 2019) France Multi‐center hospital‐based study Stroke & AF 400 78.7 (11.0) 52
Xu 2017 (Xu et al., 2016) China Single‐center hospital‐based study Ischemic stroke 878 63.2 (13.1) 35
Jurjans 2019 (Jurjans et al., 2019) Latvia Single‐center hospital‐based study Ischemic stroke & AF 682 80 (75‐85) 69
Saade 2021 (Saade et al., 2021) Lebanon Multi‐center hospital‐based study Ischemic stroke 100 74.0 (10) 43
Gynnild 2021 (Gynnild et al., 2021) Norway Multi‐center hospital‐based study Ischemic stroke 664 72.9 (11.5) 43
Dalli 2020 (Dalli et al., 2021) Australia Population‐based study/national registry Stroke or TIA 9817 74.2 (63.3, 82.5) 45
Yeo 2020 (Yeo et al., 2020) Singapore Population‐based study/national registry Ischemic stroke 3469 – 44
Shankari 2020 (Shankari et al., 2020) Singapore Single‐center hospital‐based study Ischemic stroke or TIA 199 62.9 (11.9) 36
Malaeb 2020 (Malaeb et al., 2020) Lebanon Multi‐center hospital‐based study Ischemic stroke 204 65.4 (11.9) 33.3
MacDonald 2020 (MacDonald et al., 2020) United States Multi‐center hospital‐based study Stroke 107 56.0 (11.2) 42.1
Gronemann 2020 (Gronemann et al., 2020) Germany Population‐based study/national registry Ischemic stroke & AF 1512 76.7 (9.6) 53.3
Flach 2020 (Flach et al., 2020) United Kingdom Population‐based study/national registry Stroke 6052 <65 (34%) 49
Chang 2020 (Chang et al., 2020) United States Population‐based study/national registry Stroke & AF 64228 84 (78‐89) 63
Abanto 2020 (Abanto et al., 2020) Peru Population‐based study/national registry Stroke 150 66.3 (12.6) 38
Chen 2019 (Chen et al., 2019) Canada Multi‐center hospital‐based study Ischemic stroke or TIA 408 68 (13) 47.5
Chen 2019 Canada Multi‐center hospital‐based study Ischemic stroke or TIA 392 70 (11) 43.1
Dalli 2021 (Dalli et al., 2021) Australia Multi‐center hospital‐based study Stroke or tia 8363 ≥75 (44%) 44
Kim 2021 (Kim et al., 2021) South Korea Population‐based study/national registry Ischemic stroke 4621 66.4 (12.3) 43.8
Kothagundla 2021 (Kothagundla et al., 2021) India Single‐center hospital‐based study Stroke 150 60 (1) 37
Preinreich 2021 (Preinreich et al., 2021) Austria Population‐based study/national registry Stroke 76354 – –
Rodríguez‐Bernal 2021 (Rodríguez‐Bernal et al., 2021) Spain Population‐based study/national registry Ischemic stroke or TIA & AF 10986 78.8 (9.3) 53.3
Sheehan 2021 (Sheehan et al., 2021) United States Population‐based study/national registry Ischemic stroke 172 75.0 (7.3) –
Tiili 2021 (Tiili et al., 2021) Finland Population‐based study/national registry Ischemic stroke & AF 396 75.0 (70−80) 43
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AF: atrial fibrillation; IS: ischemic stroke; TIA: transient ischemic stroke.

TABLE 2.

Quality assessment for the included studies

Study Study type Selection_1 Selection_2 Selection_3 Selection_4 Comparability Outcome_1 Outcome_2 Outcome_3 Total scale
Abdo, 2019 Cohort 1 1 0 1 0 0 0 1 4
Akijian, 2017 Cohort 1 1 1 1 2 1 0 1 8
Bergstrom, 2017 Cohort 1 1 1 1 2 1 1 1 9
Brewer, 2015 Cohort 1 1 1 1 0 1 1 0 6
Chen, 2019 Cohort 1 1 1 1 2 1 1 0 8
Dalli, 2021 Cohort 1 1 1 1 2 1 1 0 8
Desmaele, 2016 Cohort 1 1 1 1 0 0 1 0 5
Eriksson, 2017 Cohort 0 1 1 1 0 1 1 1 6
Kim, 2021 Cohort 1 1 1 1 2 1 1 1 9
Faure, 2020 Cohort 1 1 1 1 2 1 1 1 9
Jiang, 2017 Cohort 1 1 1 1 2 0 1 1 8
Jithin, 2016 cross‐sectional 1 1 1 1 0 1 0 NA 5
Jurjans, 2019 Cohort 0 1 1 1 0 0 1 1 5
Lim, 2015 Cohort 1 1 1 1 2 1 1 1 9
Magwood, 2017 Cross‐sectional 1 0 0 0 1 1 1 NA 4
Kothagundla, 2021 Cohort 1 1 1 1 2 0 1 0 7
Mechtouff, 2018 Cross‐sectional 1 0 0 2 2 1 1 NA 7
Park, 2017 Cohort 1 1 1 1 2 0 1 1 8
Rijkmans, 2018 Cohort 0 1 1 1 1 1 1 1 7
Sarfo, 2016 Cohort 1 1 1 1 2 0 1 0 7
Sluggett, 2015 Cohort 1 1 1 1 2 0 1 1 8
Ullberg, 2017 Cohort 1 1 1 1 1 0 1 0 6
Yeo, 2020 Cohort 1 1 1 1 2 1 1 1 9
Preinreich, 2021 Cohort 1 1 1 1 2 1 1 0 8
Rodríguez‐Bernal, 2021 Cohort 1 1 1 1 2 1 1 0 8
Sheehan, 2021 Cohort 1 1 1 1 2 1 1 0 8
Tiili, 2021 Cohort 1 1 1 1 2 1 1 1 9
Guidoux, 2019 Cohort 0 1 1 1 2 0 1 1 7
Haeusler, 2015 Cross‐sectional 1 0 1 0 2 1 1 NA 6
Mazurek, 2017 Cohort 1 1 1 1 2 0 1 1 8
Sauer, 2015 Cohort 0 1 1 1 2 0 1 1 7
Shah, 2016 Cohort 1 1 1 1 2 1 1 1 9
Xian, 2015 Cohort 1 1 1 1 2 0 1 1 8
Xu, 2017 Cohort 0 1 1 1 2 1 1 0 7
Abanto, 2020 Cross‐sectional 1 0 0 2 2 2 1 NA 8
Chang, 2020 Cohort 1 1 1 1 2 1 1 1 9
Dalli, 2020 Cohort 1 1 1 1 2 0 1 1 8
Zhang, 2017 Cross‐sectional 1 1 0 2 2 2 1 NA 9
Flach, 2020 Cohort 1 1 1 1 2 1 1 1 9
Gronemann, 2020 Cohort 1 1 1 1 2 1 1 1 9
Gynnild, 2020 Cohort 1 1 1 1 2 1 1 1 9
MacDonald, 2020 Cross‐sectional 1 0 0 1 1 2 1 NA 6
Malaeb, 2020 Cross‐sectional 1 0 0 1 0 2 1 NA 5
Saade, 2021 Cross‐sectional 1 0 0 2 0 1 1 NA 5
Shankari, 2020 Cross‐sectional 1 0 0 2 2 1 1 NA 7
Yeo, 2020 Cross‐sectional 1 0 1 2 2 2 1 NA 9
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3.1. Antiplatelet medications

3.1.1. Prescription rate of antiplatelet medications

The pooled proportion of prescribed antiplatelet medication is 62% (95% CI: 57%−68%) (Figure 1), with 62% (95% CI: 54%−70%), 71% (95% CI: 58%−85%), 55% (95% CI: 37%−72%), and 70% (95% CI: 55%−85%) at discharge, 1–6 months, 1–4 years, and 5 years post index stroke, respectively (Figure 1).

FIGURE 1.

FIGURE 1

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Forest plot of prescribed antiplatelet medications

3.1.2. Medication adherence

Definitions for adherence are heterogeneous between studies (Table 3). Good adherence to antiplatelet is 78% (95% CI: 67%−89%) (Figure 2). The adherence rate is 79% (95% CI: 64%−95%), 72% (95% CI: 39%−106%), and 82% (95% CI: 80%−84%) for ≤1, 1–4, and ≥5 years post index stroke, respectively (Figure S2). Adherence reported by high‐income countries (HICs) (77%, 95% CI: 63%−91%) was lower than that in the low‐and‐middle‐income countries (LMICs) (81%, 95% CI: 64%−98%) (Figure S2).

TABLE 3.

Adherence to antithrombotics medications

Study Population Time post index stroke Definition Findings
Mechtouff, 2018 IS or TIA 3 years and 6 years post index stroke Continuous Measure of Medication Acquisition (CMA) was defined as medication adherence. CMA≥80% Adherence to any antithrombotic drugs was 82% and 72%, at 3 years and 6 years, respectively.
Adherence to anticoagulant was 60% and 52%, at 3 years and 6 years, respectively.
Adherence to the antiplatelet drug was 91% and 84%, at 3 years and 6 years, respectively.
Xu, 2017 IS 5 years Discontinuation of antiplatelet therapy 165 Discontinued during follow up
Yeo, 2020 IS Unkown Adherence was defined using PDC: high (≥75%), intermediate (50%−74%), low (25%−49%), and very low (< 25%). 29%, 18%, 20%, and 34% had high, intermediate, low, and very low adherence to antithrombotic medications, respectively.
Ullberg, 2017 IS 4 months Primary drug adherence was defined as filling the first drug prescription within 120 days after stroke. Drug adherence rates 4 months post‐stroke were 96% for antiplatelet drugs, and 90% for warfarin.
Ullberg, 2017 IS 14 months Drug persistence at 14 months was defined as filling a prescription between 10 and 14 months after stroke. Drug adherence rates 14 months post‐stroke were 85% for antiplatelet drugs, and 69% for warfarin.
Sarfo, 2016 Stroke 1 year Persistence was defined as the continuation of medications. Persistent rate was 95% for antiplatelets, and 50% for anticoagulants.
Jiang, 2017 IS or TIA 3 months Three‐month persistence was defined as continuation of all secondary preventive medications prescribed at discharge. Persistence at 3 months after discharge was 66.35% for antiplatelets, and 63.16% for warfarin.
Mazurek, 2017 Stroke & AF 1 year Persistence was defined as the continuation of medications. 56% were adherent to antithrombotic treatment
Gynnild, 2021 Ischemic stroke 3 months MMAS‐4 = 4 (high adherence) 469/474 (99%)
Gynnild, 2021 Ischemic stroke 18 months MMAS‐4 = 4 (high adherence) 464/474 (98%)
Dalli, 2020 stroke or TIA 1 year Discontinuation was assessed among medication users and defined as having no medication supply for ≥90 days in the year postdischarge. 2426/7112 (34.1)
Dalli, 2021 stroke or TIA 1 year Adherence to each medication group was estimated using the proportion of days covered (PDC) method from hospital discharge until the 1‐year landmark date. 3218/4845 (66.4)
Malaeb, 2020 IS Post discharge Post discharge prescription medications. 149/204 (73%)
Kim, 2021 IS 6 months Discontinuation was defined as when the antiplatelet agents were discontinued without refills throughout the rest of the observation period. Prevalence of premature discontinuation of antiplatelets within 6 months was 25.3%
Kim, 2021 IS 12 months Discontinuation was defined as when the antiplatelet agents were discontinued without refills throughout the rest of the observation period. Prevalence of premature discontinuation of antiplatelets within 12 months was 35.5%
Kim, 2021 IS 24 months Discontinuation was defined as when the antiplatelet agents were discontinued without refills throughout the rest of the observation period. Prevalence of premature discontinuation of antiplatelets within 24 months was 58.5%
Rijkmans, 2018 IS 5.5 years Discontinuation of medication was considered nonpersistent. Persistent rate was 90% for aspirin, 72% for dipyridamole, and 53% for anticoagulants.
Sheehan, 2021 IS 10 months Medication persistence was defined as the continuation of medication classes prescribed at hospital discharge. Persistent rate was 87% for antithrombotics
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AF: atrial fibrillation; IS: ischemic stroke; TIA: transient ischemic stroke.

FIGURE 2.

FIGURE 2

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Forest plot of medication adherence

3.2. Anticoagulant medications

3.2.1. Prescription rate of anticoagulant medications

The pooled proportion of prescribed anticoagulants among patients with AF is 68% (95% CI: 58%−79%) (Figure 3), with 62% (95% CI: 45%−78%), 77% (95% CI: 69%−85%), 78% (95% CI: 51%−105%), and 76% (95% CI: 73%−79%) at discharge, 1–6 months, 1–2 years, and 5 years post index stroke, respectively (Figure 3).

FIGURE 3.

FIGURE 3

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Forest plot of prescribed anticoagulants among patients with AF

3.2.2. Medication adherence

Good adherence to anticoagulant is 71% (95% CI: 57%−84%) (Figure 2). The adherence rate is 76% (95% CI: 51%−102%), 64% (95% CI: 61%−67%), and 73% (95% CI: 33%−113%) for ≤1, 1–4, and ≥5 years post index stroke, respectively (Figure S3). Adherence reported by HICs (73%, 95% CI: 57%−88%) was higher than that in the LMICs (63%, 95% CI: 57%−74%) (Figure S3).

3.3. Adherence to antithrombotic medications

Good adherence to antithrombotic medications is 73% (95% CI: 59%−86%) (Figure 2). Studies that defined adherence using prescription refill had higher adherence rate of 74% (95% CI: 55%−93%) than studies that used medication continuation: 70% (95% CI: 60%−81%) (Figure S4). The adherence rate is 75% (95% CI: 57%−93%), 90% (95% CI: 74%−106%), and 72% (95% CI: 64%−79%) for ≤1, 1–4, and ≥5 years post index stroke, respectively (Figure S4). Adherence reported by HICs (73%, 95% CI: 58%−87%) was approximate to that in the LMICs (73%, 95% CI: 67%−79%) (Figure S4).

3.4. Optimal treatment

The recommendations from major guidelines are summarized in table S1 (Coutts et al., 2014; Kleindorfer et al., 2021; Klijn et al., 2019; Liu et al., 2020; Ringleb et al., 2008;). The proportion of patients who were treated according to the recommendation of guidelines of antithrombotic medications is 67% (95% CI: 41%−93%) (Figure 4). 11% (95% CI: 2%−19%) of patients did not receive any antithrombotic medications as recommended (Figure 5). Faure et al. (2020) reported that 36% of patients received ≥2 antiplatelets or a combination of antiplatelet and anticoagulant. Such combinations are not recommended because of the potential increased risk of bleeding (Table S1).

FIGURE 4.

FIGURE 4

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Forest plot of guideline antithrombotics

FIGURE 5.

FIGURE 5

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Forest plot of not receive any antithrombotic medications as recommended

4. DISCUSSION

In this systematic review and meta‐analysis, we summarized the proportions of antithrombotic medication prescription and adherence in patients with stroke. We found that less than 70% of patients were prescribed and treated according to the recommended guidelines of antithrombotic medications. Good adherence to antiplatelet, anticoagulant, and antithrombotic medications was 78% (95% CI: 67%−89%), 71% (95% CI: 57%−84%), and 73% (95% CI: 59%−86%), respectively. It was reported that 11% (95% CI: 2%−19%) of patients did not receive antithrombotic medications.

We found the lowest rates of anticoagulant prescription in Asia, compared with Europe and Americas (Figure S5), which is in line with a previous study (Kozieł et al., 2021). Moreover, our results show that prescription for antiplatelet medication is highest in Asia (Figure S6). This may be because large artery atherosclerosis was the leading ischemic stroke etiology in Asians and less anticoagulants were prescribed for Asian stroke patients with AF (Ornello et al., 2018).

In our results, the prescribing rate (68%) of anticoagulants for patients with AF has increased, compared to 45% in the past decade (Hsu et al., 2016). There are around only 50% of patients still taking anticoagulants therapy by 2 years in the past 5–10 years studies (Collings et al., 2017; Deitelzweig et al., 2013; Wang et al., 2016), whereas our statistical analysis showed that the good adherence rate is 64% for 1–4 years post index stroke. This may be due to promotion of the AF management guidelines, along with the improvement of educational and economic standards.

Although our prescription rate has increased from the previous decade, it is still less than 70%. We suspect that the insufficient prescription rate may still exist for the following reasons: uncertainty about clinical benefits and risks, knowledge and experience deficit, competing medical issues, and medication cost (Gross et al., 2003; Kirley et al., 2016). There may be potential ways to increase antithrombotic drug prescription rates, for example, increasing physicians' awareness of under‐treatment, emphasizing accurate assessment of bleeding risk (Hsu et al., 2016), and addressing drug high cost in some areas.

We also found lower adherence rate with anticoagulant in low‐ and middle‐income countries compared with that in high‐income countries, which may be related to different educational levels and cultural concepts. We found lower adherence rate with antiplatelet in high‐income countries compared with that in low‐ and middle‐income countries. This may be due to the fact that Asians are more afraid of the risk of bleeding from anticoagulants, so they prefer antiplatelet drugs, while patients in developed countries are the opposite (Lowres et al., 2019). Given the association of nonadherence with increased morbidity and mortality (Viswanathan et al., 2012), adequate measures taken to improve medication adherence should receive much more attention in stroke patients. These strategies can be: (1) medical insurance or medication cost was associated with medication adherence (Kronish et al., 2013; Wang et al., 2006) as reducing drug costs or increasing health insurance coverage may increase medication adherence; 2) large‐scale, national public health campaigns to focus on groups of medications effective for secondary prevention in stroke may make patients or caregivers take notice; and 3) patient education regarding medications to improve adherence. Then regular follow‐up visits and direct asking about medication adherence could be efficient.

There are several limitations in this meta‐analysis. First, there is no common gold standard method for evaluating medication adherence, which may introduce measurement bias in our results. Second, the pooling data were highly heterogeneous; this was not explained by differences in patient characteristics. We conducted subgroup analyses to pool the same definitions, study design, country, and timepoint; however, residual heterogeneity persisted.

5. CONCLUSION

In conclusion, we found that less than 70% of patients were prescribed and treated according to the recommended guidelines of antithrombotic medications, and good adherence to antithrombotic medications is only 73%. Prescription rate and good adherence to antithrombotic medications still need to be improved among stroke survivors.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

PEER REVIEW

The peer review history for this article is available at https://publons.com/publon/10.1002/brb3.2752

Supporting information

Appendix Search strategy

Click here for additional data file. (23KB, docx)

Figure S1. Flow chart of the systematic review and meta‐analysis

Figure S2. Forest plot of Subgroup analyses of antiplatelet medication adherence

Figure S3. Forest plot of Subgroup analyses of anticoagulants adherence among patients with AF

Figure S4. Forest plot of Subgroup analyses of antithrombotic adherence

Figure S5. Forest plot of Subgroup analyses of prescribed anticoagulants among patients with AFSfigure 6. Forest plot of Subgroup analyses of prescribed antiplatelet medications

Click here for additional data file. (384.4KB, pdf)

Table S1. Recommendations for secondary stroke prevention according to major guidelines

Click here for additional data file. (27.5KB, docx)

ACKNOWLEDGMENTS

Xia Wang, Jie Yang, and Else Charlotte Sandset conceived the study. Min Yang, Hang Cheng, and Xia Wang screened the studies and extracted data. Menglu Ouyang and Sultana Shajahan did the quality assessment. Min Yang and Xiaoyun Wang did the statistical analysis and wrote the first draft of the manuscript; all authors revised this draft. All authors read and approved the final version. This study was supported by grants from the National Natural Science Foundation of China (81870940, 82171295), Science & Technology Department of Sichuan Province (2021YFS0376) and from Chengdu Science and Technology Bureau (2020‐GH02‐00057‐HZ).

Yang, M. , Cheng, H. , Wang, X. , Ouyang, M. , Shajahan, S. , Carcel, C. , Anderson, C. , Kristoffersen, E. S. , Lin, Y. , Sandset, E. C. , Wang, X. , & Yang, J. (2022). Antithrombotics prescription and adherence among stroke survivors: A systematic review and meta‐analysis. Brain and Behavior, 12, e2752. 10.1002/brb3.2752

Contributor Information

Xiaoyun Wang, Email: 331043821@qq.com.

Jie Yang, Email: yangjie1126@163.com.

DATA AVAILABILITY STATEMENT

All data included in this study are available upon request by contact with the corresponding author.

REFERENCES

  1. Benjamin, E. J. , Virani, S. S. , Callaway, C. W. , Chamberlain, A. M. , Chang, A. R. , Cheng, S. , Chiuve, S. E. , Cushman, M. , Delling, F. N. , Deo, R. , De Ferranti, S. D. , Ferguson, J. F. , Fornage, M. , Gillespie, C. , Isasi, C. R. , Jim‐Nez, M. C. , Jordan, L. C. , Judd, S. E. , Lackland, D. , …, Muntner, P. (2018). Heart disease and stroke statistics—2018 update: A report From the American Heart Association. Circulation, 137(12), e67–e492. 10.1161/CIR.0000000000000558 [DOI] [PubMed] [Google Scholar]
  2. Broderick, J. P. , Bonomo, J. B. , Kissela, B. M. , Khoury, J. C. , Moomaw, C. J. , Alwell, K. , Woo, D. , Flaherty, M. L. , Khatri, P. , Adeoye, O. , Ferioli, S. , & Kleindorfer, D. O. (2011). Withdrawal of antithrombotic agents and its impact on ischemic stroke occurrence. Stroke, 42(9), 2509–2514. 10.1161/STROKEAHA.110.611905 [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Del Brutto, V. J. , Chaturvedi, S. , Diener, H.‐C. , Romano, J. G. , & Sacco, R. L. (2019). Antithrombotic therapy to prevent recurrent strokes in ischemic cerebrovascular disease. J Am Coll Cardiol, 74(6), 786–803. 10.1016/j.jacc.2019.06.039 [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Kim, J. , Lee, H. S. , Nam, C. M. O. , & Heo, Ji. H. (2017). Effects of statin intensity and adherence on the long‐term prognosis after acute ischemic stroke. Stroke, 48(10), 2723–2730. 10.1161/STROKEAHA.117.018140 [DOI] [PubMed] [Google Scholar]
  5. Perreault, S. , Yu, A. Y. X. , Cote, R. , Dragomir, A. , White‐Guay, B. , & Dumas, S. (2012). Adherence to antihypertensive agents after ischemic stroke and risk of cardiovascular outcomes. Neurology, 79(20), 2037–2043. 10.1212/WNL.0b013e3182749e56 [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Rijkmans, M. , De Jong, G. , & Van Den Berg, J. S. P. (2018). Non‐persistence in ischaemic stroke: Risk of recurrent vascular events. Acta Neurol Scand, 137(3), 288–292. 10.1111/ane.12813 [DOI] [PubMed] [Google Scholar]
  7. Webb, A. , Heldner, M. R. , Aguiar De Sousa, D. , Sandset, E. C. , Randall, G. , Bejot, Y. , Van Der Worp, B. , Caso, V. , & Fischer, U. (2019). Availability of secondary prevention services after stroke in Europe: An ESO/SAFE survey of national scientific societies and stroke experts. Eur Stroke J, 4(2), 110–118. 10.1177/2396987318816136 [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Weimar, C. , Cotton, D. , Sha, N. , Sacco, R. L. , Bath, P. M. W. , Weber, R. , & Diener, H. C. (2013). Discontinuation of antiplatelet study medication and risk of recurrent stroke and cardiovascular events: Results from the PRoFESS study. Cerebrovasc Dis, 35(6), 538–543. 10.1159/000351144 [DOI] [PubMed] [Google Scholar]
  9. Norrving, B. O. , Barrick, J. , Davalos, A. , Dichgans, M. , Cordonnier, C. , Guekht, A. , Kutluk, K. , Mikulik, R. , Wardlaw, J. , Richard, E. , Nabavi, D. , Molina, C. , Bath, P. M. , Stibrant Sunnerhagen, K. , Rudd, A. , Drummond, A. , Planas, A. , & Caso, V. (2018). Action plan for stroke in Europe 2018–2030. Eur Stroke J, 3(4), 309–336. 10.1177/2396987318808719 [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Stroup, D. F. (2000). Meta‐analysis of observational studies in epidemiology: A proposal for reporting. JAMA, 283(15), 2008–2012. 10.1001/jama.283.15.2008 [DOI] [PubMed] [Google Scholar]
  11. Stang, A. (2010). Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta‐analyses. European Journal of Epidemiology, 25(9), 603–605. 10.1007/s10654-010-9491-z [DOI] [PubMed] [Google Scholar]
  12. Cramer, J. A. , Roy, A. , Burrell, A. , Fairchild, C. J. , Fuldeore, M. J. , Ollendorf, D. A. , & Wong, P. K. (2008). Medication compliance and persistence: Terminology and definitions. Value Health, 11(1), 44–47. 10.1111/j.1524-4733.2007.00213.x [DOI] [PubMed] [Google Scholar]
  13. Ullberg, T. , Glader, E.‐L. , Zia, E. , Petersson, J. , Eriksson, M. , & Norrving, B. O. (2017). Associations between ischemic stroke follow‐up, socioeconomic status, and adherence to secondary preventive drugs in Southern Sweden: Observations from the Swedish Stroke Register (Riksstroke). Neuroepidemiology, 48(1–2), 32–38. 10.1159/000456618 [DOI] [PubMed] [Google Scholar]
  14. Hess, L. M. , Raebel, M. A. , Conner, D. A. , & Malone, D. C. (2006). Measurement of adherence in pharmacy administrative databases: A proposal for standard definitions and preferred measures. Ann Pharmacother, 40(7–8), 1280–1288. 10.1345/aph.1H018 [DOI] [PubMed] [Google Scholar]
  15. Yeo, S.‐H. , Toh, M. P. H. S. , Lee, S. H. , Seet, R. C. S. , Wong, L. Y. , & Yau, W.‐P. (2020). Impact of medication nonadherence on stroke recurrence and mortality in patients after first‐ever ischemic stroke: Insights from registry data in Singapore. Pharmacoepidemiol Drug Saf, 29(5), 538–549. 10.1002/pds.4981 [DOI] [PubMed] [Google Scholar]
  16. Morisky, D. E. , Green, L. W. , & Levine, D. M. (1986). Concurrent and predictive validity of a self‐reported measure of medication adherence. Med Care, 24(1), 67–74. 10.1097/00005650-198601000-00007 [DOI] [PubMed] [Google Scholar]
  17. Rothman, K. J. , Greenland, S. , & Lash, T. L. (2008). Modern epidemiology 3Ed. Lippincott Williams & Wilkins.
  18. Faure, M. , Castilloux, A.‐M. , Lillo‐Le‐Louet, A. S. , BaGaud, B. , & Moride, Y. (2020). Secondary stroke prevention: A population‐based cohort study on anticoagulation and antiplatelet treatments, and the risk of death or recurrence. Clinical Pharmacology and Therapeutics, 107(2), 443–451. 10.1002/cpt.1625 [DOI] [PubMed] [Google Scholar]
  19. Kozieå, M. , Teutsch, C. , Bayer, V. , Lu, S. , Gurusamy, V. K. , Halperin, J. L. , Rothman, K. J. , Diener, H.‐C. , Ma, C.‐S. , Huisman, M. V. , & Lip, G. Y. H. (2021). Changes in anticoagulant prescription patterns over time for patients with atrial fibrillation around the world. J Arrhythm, 37(4), 990–1006. 10.1002/joa3.12588 [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ornello, R. , Degan, D. , Tiseo, C. , Di Carmine, C. , Perciballi, L. , Pistoia, F. , Carolei, A. , & Sacco, S. (2018). Distribution and temporal trends from 1993 to 2015 of ischemic stroke subtypes. Stroke., 49(4), 814–819. 10.1161/STROKEAHA.117.020031 [DOI] [PubMed] [Google Scholar]
  21. Hsu, J. C. , Maddox, T. M. , Kennedy, K. F. , Katz, D. F. , Marzec, L. N. , Lubitz, S. A. , Gehi, A. K. , Turakhia, M. P. , & Marcus, G. M. (2016). Oral anticoagulant therapy prescription in patients with atrial fibrillation across the spectrum of stroke risk. JAMA Cardiol, 1(1), 55–62. 10.1001/jamacardio.2015.0374 [DOI] [PubMed] [Google Scholar]
  22. Collings, S.‐L. I. , Lef‐Vre, C. , Johnson, M. E. , Evans, D. , Hack, G. , Stynes, G. , & Maguire, A. (2017). Oral anticoagulant persistence in patients with non‐valvular atrial fibrillation: A cohort study using primary care data in Germany. PLoS One, 12(10), e0185642. 10.1371/journal.pone.0185642 [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Deitelzweig, S. B. , Buysman, E. , Pinsky, B. , Lacey, M. , Jing, Y. , Wiederkehr, D. , & Graham, J. (2013). Warfarin use and stroke risk among patients with nonvalvular atrial fibrillation in a large managed care population. Clin Ther, 35(8), 1201–1210. 10.1016/j.clinthera.2013.06.005 [DOI] [PubMed] [Google Scholar]
  24. Wang, Z.‐Z. , Du, X. , Wang, W. , Tang, R. I.‐B. O. , Luo, J.‐G. , Li, C. , Chang, S.‐S. , Liu, X.‐H. , Sang, C.‐H. , Yu, R.‐H. , Long, D. e.‐Y. , Wu, J.‐H. , Bai, R. , Liu, N. , Ruan, Y.‐F. , Dong, J.‐Z. , & Ma, C.‐S. (2016). Long‐term persistence of newly initiated warfarin therapy in chinese patients with nonvalvular atrial fibrillation. Circ Cardiovasc Qual Outcomes, 9(4), 380–387. 10.1161/CIRCOUTCOMES.115.002337 [DOI] [PubMed] [Google Scholar]
  25. Gross, C. P. , Vogel, E. W. , Dhond, A. J. , Marple, C. B. , Edwards, R. A. , Hauch, O. , Demers, E. A. , & Ezekowitz, M. (2003). Factors influencing physicians' reported use of anticoagulation therapy in nonvalvular atrial fibrillation: A cross‐sectional survey. Clin Ther, 25(6), 1750–1764. 10.1016/S0149-2918(03)80167-4 [DOI] [PubMed] [Google Scholar]
  26. Kirley, K. , Goutham, R. , Bauer, V. , & Masi, C. (2016). The role of NOACs in atrial fibrillation management: A qualitative study. J Atr Fibrillation, 9(1), 1416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lowres, N. , Giskes, K. , Hespe, C. , & Freedman, B. (2019). Reducing stroke risk in atrial fibrillation: Adherence to guidelines has improved, but patient persistence with anticoagulant therapy remains suboptimal. Korean Circ J, 49(10), 883–907. 10.4070/kcj.2019.0234 [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Viswanathan, M. , Golin, C. E. , Jones, C. D. , Ashok, M. , Blalock, S. J. , Wines, R. C. M. , Coker‐Schwimmer, E. J. L. , Rosen, D. L. , Sista, P. , & Lohr, K. N. (2012). Interventions to improve adherence to self‐administered medications for chronic diseases in the United States. Ann Intern Med, 157(11), 785–795. 10.7326/0003-4819-157-11-201212040-00538 [DOI] [PubMed] [Google Scholar]
  29. Kronish, I. M. , Diefenbach, M. A. , Edmondson, D. E. , Phillips, L. A. , Fei, K. , & Horowitz, C. R. (2013). Key barriers to medication adherence in survivors of strokes and transient ischemic attacks. J Gen Intern Med, 28(5), 675–682. 10.1007/s11606-012-2308-x [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wang, Y. , Wu, D. I. , Wang, Y. , Ma, R. , Wang, C. , & Zhao, W. (2006). A survey on adherence to secondary ischemic stroke prevention. Neurol Res, 28(1), 16–20. 10.1179/016164106X91816 [DOI] [PubMed] [Google Scholar]
  31. Bergstrãm, L. , Irewall, A.‐L. , Söderström, L. , Ögren, J. , Laurell, K. , & Mooe, T. (2017). One‐year incidence, time trends, and predictors of recurrent ischemic stroke in Sweden from 1998 to 2010. Stroke, 48(8), 2046–2051. 10.1161/STROKEAHA.117.016815 [DOI] [PubMed] [Google Scholar]
  32. Mechtouff, L. , Haesebaert, J. , Viprey, M. , Tainturier, V. R. , Termoz, A. , Porthault‐Chatard, S. , David, J.‐S. P. , Derex, L. , Nighoghossian, N. , & Schott, A.‐M. (2018). Secondary prevention three and six years after stroke using the french national insurance healthcare system database. European neurology, 79(5–6), 272–280. 10.1159/000488450 [DOI] [PubMed] [Google Scholar]
  33. Jithin, K. C. , Arya, G. , Nair, L. P. , & Lakshmi, R. (2016). A study on pattern of prescribing medications used in secondary prevention of stroke. Asian Journal of Pharmaceutical and Clinical Research, 9(3), 328–330. [Google Scholar]
  34. Eriksson, S.‐E. (2017). Secondary prophylactic treatment and long‐term prognosis after TIA and different subtypes of stroke. A 25‐year follow‐up hospital‐based observational study. Brain and Behavior, 7(1), e00603. 10.1002/brb3.603 [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rijkmans, M. , De Jong, G. , & Van Den Berg, J. S. P. (2018). Non‐persistence in ischaemic stroke: Risk of recurrent vascular events. Acta Neurologica Scandinavica, 137(3), 288–292. 10.1111/ane.12813 [DOI] [PubMed] [Google Scholar]
  36. Desmaele, S. , Putman, K. , De Wit, L. , Dejaeger, E. , Gantenbein, A. R. , Schupp, W. , Steurbaut, S. , Dupont, A. G. , & De Paepe, K. (2016). A comparative study of medication use after stroke in four countries. Clinical Neurology and Neurosurgery, 148, 96–104. 10.1016/j.clineuro.2016.07.007 [DOI] [PubMed] [Google Scholar]
  37. Zhang, J. , Yang, X. I.‐A. I. , Zhang, Y. I. , Wei, J.‐Y. A. , Yang, F. , Gao, H. , Jiao, W.‐W. , Sun, X.‐L. , Gao, Q. , & Jiang, W. (2017). Oral anticoagulant use in atrial fibrillation‐associated ischemic stroke: A retrospective, multicenter survey in Northwestern China. Journal of Stroke and Cerebrovascular Diseases : The Official Journal of National Stroke Association, 26(1), 125–131. 10.1016/j.jstrokecerebrovasdis.2016.08.042 [DOI] [PubMed] [Google Scholar]
  38. Lim, J.‐S. , Hong, K.‐S. , Kim, G.‐M. , Bang, O. H. Y. , Bae, H.‐J. , Kwon, H.‐M. , Park, J.‐M. , Lee, S.‐H. , Rha, J.‐H. O. , Koo, J. , Yu, K.‐H. O. , Seo, W.‐K. , Lee, K. B. , & Lee, Y.‐S. (2015). Cerebral microbleeds and early recurrent stroke after transient ischemic attack. JAMA Neurology, 72(3), 301–308. 10.1001/jamaneurol.2014.3958 [DOI] [PubMed] [Google Scholar]
  39. Park, H.‐K. , Kim, B. J. , Han, M.‐K. , Park, J.‐M. , Kang, K. , & Lee, S. J. (2017). One‐year outcomes after minor stroke or high‐risk transient ischemic attack: korean multicenter stroke registry analysis. Stroke, 48(11), 2991–2998. [DOI] [PubMed] [Google Scholar]
  40. Sarfo, F. S. , Ovbiagele, B. , Akassi, J. , & Kyem, G. (2017). Baseline prescription and one‐year persistence of secondary prevention drugs after an index stroke in Central Ghana. eNeurologicalSci, 6, 68–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Sluggett, J. K. , Caughey, G. E. , Ward, M. B. , & Gilbert, A. L. (2015). Medicines taken by older Australians after transient ischaemic attack or ischaemic stroke: A retrospective database study. International Journal of Clinical Pharmacy, 37(5), 782–789. [DOI] [PubMed] [Google Scholar]
  42. Jiang, Y. , Yang, X. , Li, Z. , Pan, Y. , Wang, Y. , Wang, Y. , Ji, R. , & Wang, C. (2017). Persistence of secondary prevention medication and related factors for acute ischemic stroke and transient ischemic attack in China. Neurological Research, 39(6), 492–497. 10.1080/01616412.2017.1312792 [DOI] [PubMed] [Google Scholar]
  43. Brewer, L. , Mellon, L. , Hall, P. , Dolan, E. , Horgan, F. , Shelley, E. , Hickey, A. , & Williams, D. (2015). Secondary prevention after ischaemic stroke: The ASPIRE‐S study. BMC neurology, 15, 216. 10.1186/s12883-015-0466-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Haeusler, K. G. , Gerth, A. , Limbourg, T. , Tebbe, U. , Oeff, M. , Wegscheider, K. , Treszl, A. S. , Ravens, U. , Meinertz, T. , Kirchhof, P. , Breithardt, G. , Steinbeck, G. , & Nabauer, M. (2015). Use of vitamin K antagonists for secondary stroke prevention depends on the treating healthcare provider in Germany—Results from the German AFNET registry. BMC neurology, 15, 129. 10.1186/s12883-015-0371-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Yeo, S. H. , Toh, M. , Lee, S. H. , Seet, R. C. S. , Wong, L. Y. , & Yau, W. P. (2020). Impact of medication nonadherence on stroke recurrence and mortality in patients after first‐ever ischemic stroke: Insights from registry data in Singapore. Pharmacoepidemiology and Drug Safety, 29(5), 538–549. [DOI] [PubMed] [Google Scholar]
  46. Mazurek, M. , Shantsila, E. , Lane, D. , Wolff, A. , Proietti, M. , & Lip, G. Y. (2016). Secondary versus primary stroke prevention in atrial fibrillation—Insights from the community‐based darlington atrial fibrillation registry. European Heart Journal, 37(1), 845. [DOI] [PubMed] [Google Scholar]
  47. Abdo, R. , Hosseini, H. , Salameh, P. , & Abboud, H. (2019). Acute ischemic stroke management in Lebanon: Obstacles and solutions. Functional Neurology, 34(3), 167–176. [PubMed] [Google Scholar]
  48. Magwood, G. S. , White, B. M. , & Ellis, C. (2017). Stroke‐related disease comorbidity and secondary stroke prevention practices among young stroke survivors. The Journal of Neuroscience Nursing: Journal of the American Association of Neuroscience Nurses, 49(5), 296–301. [DOI] [PubMed] [Google Scholar]
  49. Akijian, L. , Ni Chroinin, D. , Callaly, E. , Hannon, N. , Marnane, M. , Merwick, A. I. , Sheehan, A. R. , Hayden, D. , Horgan, G. , Duggan, J. , Kyne, L. , O‐Rourke, K. , Murphy, S. , Dolan, E. , Williams, D. , & Kelly, P. J. (2017). Why do transient ischemic attack patients have higher early stroke recurrence risk than those with ischemic stroke? Influence of patient behavior and other risk factors in the North Dublin Population Stroke Study. International journal of stroke : official journal of the International Stroke Society, 12(1), 96–104. 10.1177/1747493016669851 [DOI] [PubMed] [Google Scholar]
  50. Sauer, R. , Sauer, E.‐M. , Bobinger, T. , Blinzler, C. , Huttner, H. B. , Schwab, S. , & KaHrmann, M. (2015). Adherence to oral anticoagulation in secondary stroke prevention‐the first year of direct oral anticoagulants. Journal of Stroke and Cerebrovascular Diseases: The Official Journal of National Stroke Association, 24(1), 78–82. 10.1016/j.jstrokecerebrovasdis.2014.07.032 [DOI] [PubMed] [Google Scholar]
  51. Xian, Y. , Wu, J. , O'Brien, E. C. , Fonarow, G. C. , Olson, D. M. , & Schwamm, L. H. (2015). Real world effectiveness of warfarin among ischemic stroke patients with atrial fibrillation: Observational analysis from Patient‐Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study. BMJ (Clinical Research ed), 351, h3786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Shah, R. , Li, S. , Stamplecoski, M. , & Kapral, M. K. (2016). Low use of oral anticoagulant prescribing for secondary stroke prevention. Med Care, 54(10), 907–912. 10.1097/MLR.0000000000000589 [DOI] [PubMed] [Google Scholar]
  53. Guidoux, C. , Meseguer, E. , Ong, E. , Lavallae, P. C. , Hobeanu, C. , Monteiro‐Tavares, L. , Charles, H. , Cabrejo, L. , Martin‐Bechet, A. , Rigual, R. , Nighoghossian, N. , & Amarenco, P. (2019). Twelve‐month outcome in patients with stroke and atrial fibrillation not suitable to oral anticoagulant strategy: The WATCH‐AF registry. Open Heart, 6(2), e001187. 10.1136/openhrt-2019-001187 [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Xu, J. , Liu, Y. I. , Tao, Y. , Xie, X. , Gu, H. , Pan, Y. , Zhao, X. , Wang, Y. , Yan, A. , & Wang, Y. (2016). The design, rationale, and baseline characteristics of a nationwide cohort registry in China: Blood pressure and clinical outcome in TIA or ischemic stroke. Patient Preference and Adherence, 10, 2419–2427. 10.2147/PPA.S119825 [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Jurjans, K. , Vikmane, B. , Vetra, J. , Miglane, E. , Kalejs, O. , & Priede, Z. (2019). Is anticoagulation necessary for severely disabled cardioembolic stroke survivors? Medicina (Kaunas, Lithuania), 55(9),. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Saade, S. , Kobeissy, R. , Sandakli, S. , Malaeb, D. , Lahoud, N. , Hallit, S. , Hosseini, H. , & Salameh, P. (2021). Medication adherence for secondary stroke prevention and its barriers among Lebanese survivors: A cross‐sectional study. Clinical Epidemiology and Global Health, 9, 338–346. 10.1016/j.cegh.2020.10.007 [DOI] [Google Scholar]
  57. Gynnild, M. N. , Aakerã¸Y, R. , Spigset, O. , Askim, T. , Beyer, M. K. , Ihle‐Hansen, H. , Munthe‐Kaas, R. , Knapskog, A. B. , Lydersen, S. , Nass, H. , RaSstad, T. G. , Seljeseth, Y. M. , Thingstad, P. , Saltvedt, I. , & Ellekjã¦R, H. (2021). Vascular risk factor control and adherence to secondary preventive medication after ischaemic stroke. J Intern Med, 289(3), 355–368. 10.1111/joim.13161 [DOI] [PubMed] [Google Scholar]
  58. Dalli, L. L. , Kim, J. , Thrift, A. G. , Andrew, N. E. , Sanfilippo, F. M. , Lopez, D. , Grimley, R. , Lannin, N. A. , Wong, L. , Lindley, R. I. , Campbell, B. C. V. , Anderson, C. S. , Cadilhac, D. A. , & Kilkenny, M. F. (2021). Patterns of use and discontinuation of secondary prevention medications after stroke. Neurology, 96(1), e30–e41. 10.1212/WNL.0000000000011083 [DOI] [PubMed] [Google Scholar]
  59. Yeo, S.‐H. , Toh, M. P. H. s. , Lee, S. H. , Seet, R. C. s. , Wong, L. Y. , & Yau, W.‐P. (2020). Temporal trends and patient characteristics associated with drug utilisation after first‐ever stroke: Insights from chronic disease registry data in Singapore. Ann Acad Med Singap, 49(3), 137–154. 10.47102/annals-acadmedsg.2019196 [DOI] [PubMed] [Google Scholar]
  60. Shankari, G. , Ng, S. C. , Goh, S. i. Y. , Woon, F. P. , Doshi, K. , Wong, P. S. , Fan, Q. , Tan, I. l. F. , Narasimhalu, K. , & De Silva, D. A. (2020). Modifiable factors associated with non‐adherence to secondary ischaemic stroke prevention strategies. J Stroke Cerebrovasc Dis, 29(12), 105395. 10.1016/j.jstrokecerebrovasdis.2020.105395 [DOI] [PubMed] [Google Scholar]
  61. Malaeb, D. , Cherri, S. , Hallit, S. , Saade, S. , Hosseini, H. , & Salameh, P. (2020). Assessment of post discharge medication prescription among Lebanese patients with cerebral infarction: Results of a cross‐sectional study. Clin Neurol Neurosurg, 191, 105674. [DOI] [PubMed] [Google Scholar]
  62. MacDonald, M. R. , Zarriello, S. , Swanson, J. , Ayoubi, N. , Mhaskar, R. , & Mirza, A. S. (2020). Secondary prevention among uninsured stroke patients: A free clinic study. SAGE Open Med, 8, 2050312120965325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Gronemann, C. , Hause, S. , Assmann, A. , Neumann, J. , Schreiber, S. , Heinze, H.‐J. , & Goertler, M. (2020). Modification of in‐hospital recommendation and prescription of anticoagulants for secondary prevention of stroke after launch of direct oral anticoagulants and change of national guidelines. Cerebrovasc Dis, 49(4), 412–418. 10.1159/000509416 [DOI] [PubMed] [Google Scholar]
  64. Flach, C. , Muruet, W. , Wolfe, C. D. A. , Bhalla, A. , & Douiri, A. (2020). Risk and secondary prevention of stroke recurrence: A population‐base cohort study. Stroke., 51(8), 2435–2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Chang, K.‐W. , Xian, Y. , Zhao, X. , Mi, X. , Matsouaka, R. , Schwamm, L. H. , Shah, S. , Lytle, B. L. , Smith, E. E. , Bhatt, D. L. , Fonarow, G. C. , & Hsu, J. C. (2020). Antiplatelet patterns and outcomes in patients with atrial fibrillation not prescribed an anticoagulant after stroke. Int J Cardiol, 321, 88–94. 10.1016/j.ijcard.2020.08.011 [DOI] [PubMed] [Google Scholar]
  66. Abanto, C. , Ulrich, A. K. , Valencia, A. , Dues, V. ­C. , Montano, S. , Tirschwell, D. , & Zunt, J. (2020). Adherence to american heart association/american stroke association clinical performance measures in a peruvian neurological reference institute. Journal of Stroke and Cerebrovascular Diseases, 29(11), 10.1016/j.jstrokecerebrovasdis.2020.105285 [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Chen, B. Y. U. , Perkins, H. , Ehrensperger, E. , Minuk, J. , Vieira, L. , Wein, T. , & Cat, R. (2019). Adherence to guidelines at a stroke prevention clinic: A follow‐up study. Canadian Journal of Neurological Sciences, 46(1), 57–63. 10.1017/cjn.2018.352 [DOI] [PubMed] [Google Scholar]
  68. Dalli, L. L. , Kim, J. , Cadilhac, D. A. , Greenland, M. , Sanfilippo, F. M. , Andrew, N. E. , Thrift, A. G. , Grimley, R. , Lindley, R. I. , Sundararajan, V. , Crompton, D. E. , Lannin, N. A. , Anderson, C. S. , Whiley, L. , & Kilkenny, M. F. (2021). Greater adherence to secondary prevention medications improves survival after stroke or transient ischemic attack: A linked registry study. Stroke, 3569–577. 10.1161/STROKEAHA.120.033133 [DOI] [PubMed] [Google Scholar]
  69. Kim, S. J. , Kwon, O. D. , Choi, H. C. , Lee, E. J. , Cho, B. L. , & Yoon, D. H. (2021). Prevalence and associated factors of premature discontinuation of antiplatelet therapy after ischemic stroke: A nationwide population‐based study. BMC Neurology, 21(1), . [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Kothagundla, P. , Radhika, K. , Nemmani, K. V. S. , & Chandana, M. S. (2021). Assessment of prescribing patterns and health‐related quality of life in cerebral stroke patients. International Journal of Pharmaceutical Sciences Review and Research, 69(1), 209–215. [Google Scholar]
  71. Preinreich, J. , Sheikh Rezaei, S. , Mittlböck, M. , Greisenegger, S. , Reichardt, B. , & Wolzt, M. (2021). Oral anticoagulant therapy and outcome in patients with stroke. A retrospective nation‐wide cohort study in Austria 2012–2017. Pharmacoepidemiology and Drug Safety, 30(10), 1332–1338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Rodríguez‐Bernal, C. L. , Sanchez‐Saez, F. , Bejarano‐Quisoboni, D. , Riera‐Arnau, J. , Sanfélix‐Gimeno, G. , & Hurtado, I. (2021). Real‐world management and clinical outcomes of stroke survivors with atrial fibrillation: A population‐based cohort in Spain. Frontiers in Pharmacology, 12, . [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Sheehan, O. C. , Dhamoon, M. S. , Bettger, J. P. , Huang, J. , Liu, C. , Rhodes, J. D. , Clay, O. J. , & Roth, D. L. (2021). Racial differences in persistence to secondary prevention medication regimens after ischemic stroke. Ethn Health, 1–13. 10.1080/13557858.2021.1943321 [DOI] [PubMed] [Google Scholar]
  74. Tiili, P. , Leventis, I. , Kinnunen, J. , Svedjeback, I. , Lehto, M. , Karagkiozi, E. , Sagris, D. , Ntaios, G. , & Putaala, J. (2021). Adherence to oral anticoagulation in ischemic stroke patients with atrial fibrillation. Ann Med, 53(1), 1613–1620. 10.1080/07853890.2021.1968031 [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Coutts, S. B. , Wein, T. H. , Lindsay, M. P. , Buck, B. , Cote, R. , Ellis, P. , Foley, N. , Hill, M. D. , Jaspers, S. , Jin, A. Y. , Kwiatkowski, B. , Macphail, C. , Mcnamara‐Morse, D. , Mcmurtry, M. S. , Mysak, T. , Pipe, A. , Silver, K. , Smith, E. E. , & Gubitz, G. (2014). Canadian stroke best practice recommendations: Secondary prevention of stroke guidelines. Update 2014. Int J Stroke, 10(3), 282–291. 10.1111/ijs.12439 [DOI] [PubMed] [Google Scholar]
  76. Kleindorfer, D. O. , Towfighi, A. , Chaturvedi, S. , Cockroft, K. M. , Gutierrez, J. , Lombardi‐Hill, D. , Kamel, H. , Kernan, W. N. , Kittner, S. J. , Leira, E. C. , Lennon, O. , Meschia, J. F. , Nguyen, T. N. , Pollak, P. M. , Santangeli, P. , Sharrief, A. Z. , Smith, S. C. , Turan, T. N. , & Williams, L. S. (2021). 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: A guideline from the American heart association/American stroke association. Stroke., 52(7), e364–e467. 10.1161/STR.0000000000000375 [DOI] [PubMed] [Google Scholar]
  77. Ringleb, P. A. , Bousser, M. G. , Ford, G. , Bath, P. , Brainin, M. , & Caso, V. (2008). Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis, 25(5), 457–507. [DOI] [PubMed] [Google Scholar]
  78. Liu, L. , Chen, W. , Zhou, H. , Duan, W. , Li, S. , & Huo, X. (2020). Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: Executive summary and 2019 update of clinical management of ischaemic cerebrovascular diseases. Stroke Vasc Neurol, 5(2), 159–176. 10.1136/svn-2020-000378 [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Klijn, C. J. , Paciaroni, M. , Berge, E. , Korompoki, E. , Kõrv, J. , & Lal, A. (2019). Antithrombotic treatment for secondary prevention of stroke and other thromboembolic events in patients with stroke or transient ischemic attack and non‐valvular atrial fibrillation: A European Stroke Organisation guideline. European Stroke Journal, 4(3), 198–223. 10.1177/2396987319841187 [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Appendix Search strategy

Click here for additional data file. (23KB, docx)

Figure S1. Flow chart of the systematic review and meta‐analysis

Figure S2. Forest plot of Subgroup analyses of antiplatelet medication adherence

Figure S3. Forest plot of Subgroup analyses of anticoagulants adherence among patients with AF

Figure S4. Forest plot of Subgroup analyses of antithrombotic adherence

Figure S5. Forest plot of Subgroup analyses of prescribed anticoagulants among patients with AFSfigure 6. Forest plot of Subgroup analyses of prescribed antiplatelet medications

Click here for additional data file. (384.4KB, pdf)

Table S1. Recommendations for secondary stroke prevention according to major guidelines

Click here for additional data file. (27.5KB, docx)

Data Availability Statement

All data included in this study are available upon request by contact with the corresponding author.

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