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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 2  |  Issue : 1  |  Page : 13-18

Incidence, predictors, and mortality of in-hospital stroke after acute coronary syndrome in the Middle East


1 Department of cardiology, Sabah Al Ahmad Cardiac Center, Al Amiri hospital, Kuwait City, Kuwait
2 Department of Pharmacology & Clinical Pharmacy, College of Medicine & Health Sciences, Sultan Qaboos University; Gulf Health Research, Muscat, Oman
3 Department of Cardiology, Royal Hospital, Muscat, Sultanate of Oman
4 Department of internal medicine with the subspecialty of cardiology, Mubarak hospital, Kuwait City, Kuwait
5 Department of Cardiology, Illinois Masonic Medical Center, Chicago, IL, USA

Date of Submission10-Apr-2020
Date of Decision15-Apr-2020
Date of Acceptance16-Apr-2020
Date of Web Publication16-Jun-2020

Correspondence Address:
Dr. Wadhha AlSaeed
Department of Cardiology, Sabah Al Ahmad Cardiac Center, Al Amiri Hospital, Kuwait City, Kuwait. 32001.
Kuwait
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ACCJ.ACCJ_4_20

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  Abstract 


Background and Objectives: The aim of this study is to determine the incidence, predictors, and outcomes of patients that developed in-hospital stroke in acute coronary syndrome (ACS) in the Middle East region. Methods: Data were analyzed from 4044 patients with a diagnosis of ACS admitted to 29 hospitals in 4 Arabian Gulf countries (Bahrain, Kuwait, Oman, and United Arab Emirates) from January 2012 to January 2013. Stroke was defined as a loss of neurological function caused by an ischemic or hemorrhagic event with residual symptoms at least 24 h after onset or leading to death. Analyses were performed using univariate and multivariate statistics. Results: Mean age of the cohort was 60 ± 13 years and 66% (n = 2686) were male. A total of 0.89% (n = 36) developed acute stroke during the index hospital admission. Of these, 25 (69%) were diagnosed with thrombotic, 9 (25%) hemorrhagic, and 2 (6%) unknown. Those patients that developed in-hospital stroke were more likely to suffer in-hospital death (31 vs. 4.0%; P < 0.001), cardiogenic shock (25 vs. 5.1%; P < 0.001), major bleeding (8.3 vs. 1.6%; P = 0.022), heart failure (39 vs. 13%; P < 0.001), and cardiac arrest (17 vs. 3.2%; P < 0.001). At 1 year, the cumulative all-cause mortality was 53% (n = 19) in those that developed in-hospital stroke. In hospital stroke was also associated with more prolonged hospital stay (7.5 vs. 4.0 days; P < 0.001). Adjusting for other factors in the model, the multivariate logistic regression model demonstrated that prior stroke (adjusted odds ratio [aOR], 4.61; 95% confidence interval [CI]: 1.97–10.8; P < 0.001) and left ventricular ejection fraction (LVEF) of <40% (aOR, 2.26; 95% CI: 1.05–4.87; P = 0.038) were associated with the development of in-hospital stroke. Conclusions: The incidence of in-hospital stroke in patients with ACS in the Middle East is low, but, when it occurs is associated with high all-cause in-hospital and 1-year mortality. Prior stroke and LVEF <40% were associated with the development of in-hospital stroke in this population.

Keywords: Acute coronary syndrome, Arab, Middle East, stroke


How to cite this article:
AlSaeed W, Al-Zakwani I, Panduranga P, Zubaid M, Rashed W, Brady PA. Incidence, predictors, and mortality of in-hospital stroke after acute coronary syndrome in the Middle East. Ann Clin Cardiol 2020;2:13-8

How to cite this URL:
AlSaeed W, Al-Zakwani I, Panduranga P, Zubaid M, Rashed W, Brady PA. Incidence, predictors, and mortality of in-hospital stroke after acute coronary syndrome in the Middle East. Ann Clin Cardiol [serial online] 2020 [cited 2020 Nov 28];2:13-8. Available from: http://www.onlineacc.org/text.asp?2020/2/1/13/286473




  Introduction Top


Stroke is the second-most common cause of death and disability worldwide.[1] Although an uncommon (0.7%–2%) in-hospital event after acute myocardial infarction (AMI), stroke has been associated with significant morbidity and mortality.[2],[3],[4] Previous studies have reported on the AMI and in-hospital acute stroke.[1],[5],[6] However, recently, there is a major shift in the management of acute coronary syndrome (ACS) with the introduction of primary angioplasty as the first revascularization strategy, less frequent use of fibrinolysis and increased use of newer anticoagulants and antiplatelet agents. Given these changes, we do not know how they have affected the incidence of stroke in the current era. Several potential mechanisms could contribute to post ACS stroke, including thrombolysis, atrial fibrillation, left ventricular mural thrombus formation,[5],[6],[7] coexisting cerebral atherosclerosis,[1] or changes in platelet function and coagulation during anticoagulation and newer antiplatelets use.[1],[8] The type of revascularization therapy in the setting of AMI, such as thrombolysis versus primary angioplasty, may also influence the development of stroke.[1],[9] However, data are lacking regarding the incidence and risk factors associated with stroke in ACS patients and specifically in the Middle East.[3] Therefore, the aim of this study was to examine the incidence, predictors, and outcome of in-hospital stroke in patients admitted with ACS in the Middle East.


  Methods Top


Data were derived from the Gulf with ACS events (Gulf COAST) registry. Consecutive residents in this region hospitalized in 29 participating hospitals in 4 Arabian Gulf countries with the final diagnosis of ACS between January 2012 and January 2013 were included. The registry is a prospective, observational cohort-based survey. Details of the registry's design and methodology have been previously published.[10] The registry's protocol was designed by a steering committee from regional experts and approved by ethical committees in the participating countries. Patients ≥18 years with a diagnosis of ACS were enrolled after obtaining written informed consent. Data were prospectively collected in a standardized case report form All data were then entered online. Follow-up data were obtained at the time of clinic visit or telephone interview, at 1, 6, and 12 months.

Outcomes of patients with early stroke versus no stroke after ACS were compared. Stroke was defined as a loss of neurological function caused by an ischemic or hemorrhagic event with residual symptoms at least 24 h after onset or leading to death.[11],[12] Stroke type was diagnosed mostly by brain computed tomography (CT) scan or magnetic resonance imaging to detect either infarction or hemorrhage (intracerebral, subdural, or subarachnoid). Further evidence of hemorrhagic stroke was obtained from lumbar puncture, neurosurgery, or autopsy. If neither scans nor procedures were carried out, then stroke type was classified as unknown. In-hospital stroke was defined as a stroke occurring during the index admission for ACS and before discharge from the hospital. Disability at discharge from stroke was classified as (1) none to minor if the patient had mild or no disability and was completely self-dependent; (2) moderate to severe, if the patient had moderate-to-severe limitation of functional status and needed help for self-care and daily activities. If the patient died from complications of stroke, the case was classified as death.

Statistical analysis

Descriptive statistics were used to summarize the data. For categorical variables, frequencies and percentages were reported. Differences between groups were analyzed using Pearson's χ2 test. For continuous variables, mean and standard deviation were used to summarize the data while analysis was performed using Student's t-test.

The association between various predictors and the development stroke was analyzed using multivariable logistic regression model utilizing the step-wise method. The goodness-of-fit of the multivariable logistic model was examined using the Hosmer and Lemeshow goodness-of-fit statistic.[13] The Hosmer and Lemeshow statistical analyses actual versus the predicted responses; theoretically, the observed and expected counts should be close. Based on the χ2 distribution, a Hosmer and Lemeshow statistic with a P > 0.05 is considered a good fit. The discriminatory power of the logistic model was assessed by the area under the receiver operating characteristics (ROC) curve, also known as C-index.[14] A model with perfect discriminative ability has a C-index of 1.0; an index of 0.5 provides no better discrimination than chance. Models with the area under the ROC curve of >0.7 are preferred. An a priori two-tailed level of statistical significance was set at P ≤ 0.05. Statistical analyses were performed using STATA version 13.1 (STATA Corporation, College Station, TX, USA).


  Results Top


A total of 4044 patients with ACS were included in the analysis. Of these, 36 patients (0.89%) developed acute stroke during the index hospital admission. Of these, 25 (69%) were diagnosed with thrombotic, 9 (25%) hemorrhagic, and 2 (6%) unknown (CT not done). The overall incidence of in-hospital stroke was 0.9% (36/4044). The incidence of in-hospital stroke in patients with ST-elevation myocardial infarction (STEMI) population was 1.4% (14/1033). In comparison, in those patients with non-STEMI (NSTEMI), the incidence was 0.8% (16/1906).

Baseline characteristics

Baseline characteristics are summarized in [Table 1]. Patients who developed in-hospital stroke were older (66 vs. 60 years; P = 0.006), and more likely to have history of hypertension (86% vs. 65%; P = 0.007), peripheral vascular disease (11% vs. 3.2%; P = 0.028), and prior stroke (33% vs. 5.9%; P < 0.001). Patients in the stroke group were also more likely to have left ventricular ejection fraction (LVEF) of ≤40% (46% vs. 22%; P = 0.002), higher heart rate (92 vs. 85 beats/min; P = 0.039), higher serum creatinine levels on admission (109 vs. 85 μmol/L; P < 0.001), and higher Killip classes > (42% vs. 21%; P = 0.003).
Table 1: Baseline demographic clinical characteristics of the cohort

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In-hospital treatment patterns

As shown in [Table 2], apart from beta blockers which were less likely to be prescribed to those that had developed in-hospital stroke (64% vs. 78%; P = 0.038), there were no significant differences in the administration of fibrinolytic therapy, antiplatelet drugs (aspirin, clopidogrel), anticoagulant medications, glycoprotein IIb/IIIa inhibitors, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and statins between the stroke and no stroke groups.
Table 2: Inpatient treatment of the cohort within 24 hours of admission

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In-hospital and 1-year outcomes of patients with stroke

Acute in-hospital stroke was associated with higher in-hospital death (31 vs. 4.0%; P < 0.001) and greater likelihood to develop in-hospital cardiogenic shock (25 vs. 5.1%; P < 0.001), major bleeding (8.3 vs. 1.6%; P = 0.022), heart failure (39 vs. 13%; P < 0.001), and cardiac arrest (17 vs. 3.2%; P < 0.001) [Table 3]. Length of hospital stay was significantly longer for those that developed acute in-hospital stroke (7.5 vs. 4.0 days; P < 0.001) compared to those that did not develop stroke. In addition, those that developed stroke had significantly higher 1-year all-cause cumulative mortality (53 vs. 12%; P < 0.001).
Table 3: In-hospital outcomes and cumulative all-cause mortality of the cohort

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Multivariate predictors of in-hospital stroke

Adjusting for other factors in the model [Table 4], the multivariate logistic regression utilizing the stepwise method with a probability of 0.2 for inclusion, demonstrated that factors associated with in-hospital development of stroke were prior stroke (adjusted odds ratio [aOR], 4.61; 95% confidence interval [CI]: 1.97–10.8; P < 0.001) and ejection fraction of < 40% (aOR, 2.26; 95% CI: 1.05–4.87; P = 0.038).
Table 4: Predictors of in-hospital stroke in patients admitted with acute coronary syndrome

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  Discussion Top


In this prospective observational study, we found a low prevalence of in-hospital stroke in ACS patients in the Middle East but, when present, was associated with high all-cause mortality, not only during hospital admission but also during 1-year follow-up. Moreover, multivariable logistic regression demonstrated that prior stroke and LVEF < 40% were associated with the development of in-hospital stroke in this population.

The incidence of in-hospital stroke complicating ACS appears to have decreased in recent years.[5] The present findings provide data on the incidence of ischemic stroke risk in the Middle East and identify risk factors that are associated with the development of acute stroke in this population after an ACS event. Our finding of a low prevalence of in-hospital stroke is consistent with previous studies in both the Middle East region and worldwide.[2],[6],[8],[9] Possible reasons for the decline in rates of stroke after ACS may include the application of international guidelines leading to early diagnosis and treatment which reduce the formation of intracardiac thrombus, reduced occurrence of atrial fibrillation/atrial dysfunction, and most importantly application of early antiplatelet therapy, high dose statin, weight-adjusted use of fibrin-specific thrombolytics and weight-adjusted anticoagulants.[15],[16],[17],[18],[19],[20] Ulvenstam et al. indicated that reperfusion treatment with fibrinolysis and percutaneous coronary intervention (PCI) and treatment with aspirin, P2Y12-inhibitors, and statins predicted a reduced risk of stroke which was also seen in this study with high usage of these treatment modalities. The implementation of weight-adjusted fibrin specific thrombolysis and primary PCI has resulted in a significant reduction in stroke risk from 5% in the 1970s to 1% in the current era.[8]

This study also demonstrated that prior stroke and LVEF <40% were predictors of in-hospital stroke following an ACS event. Previous studies have shown similar associations.[2],[8],[21] Of note, we did not find an association between stroke after ACS and other risk factors, including diabetes mellitus, dyslipidemia, and atrial fibrillation, as has been reported in some studies.[5],[7],[8],[9],[22],[23] Furthermore, unlike in the current study, STEMI has been associated with increased stroke risk that has led to blood stasis and thromboembolism.[14],[21],[24] The nonsignificant findings could be due to the relatively small number of acute in-hospital stroke cases in this study. In the REGARDS study, high resting heart rates were associated with an increased risk of ischemic stroke compared with low heart rates.[25] However, this trend was not seen in this study.

The overall majority of patients received evidence-based therapy according to current international guidelines. Besides beta-blocker use, there were no differences in the use of evidence-based therapy in stroke patients compared to nonstroke patients in our study. Previously published studies have shown that an association between under treatment of ACS patients with evidence-based therapy and the development of in-hospital stroke.[4],[8],[26] We hypothesize that the high proportion of patients receiving aspirin and statins could have resulted in the low incidence of in-hospital stroke in the current study. In the Second International Study of Infarct Survival 2, aspirin reduced the risk of stroke.[27] In the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering study, high dose atorvastatin was shown to reduce the risk of nonfatal stroke in patients with AMI.[28] Furthermore, in the Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28 trial, there was a nonsignificant trend toward a reduced stroke risk which was the antiplatelet mostly used in the current study.[29] Several studies[30],[31] have reported that thrombolytic therapy may prevent acute stroke in AMI patients; by reducing the occurrence of LV thrombus, and this was noted in this study where overall 65% of patients with STEMI received thrombolytic therapy.

Although stroke numbers were very low to come to any statistical conclusions with regard to mortality, we did find high early and 1-year mortality (31% and 53%, respectively). It is noted that in strokes following AMI, the neurological deficit is more extensive, the clinical course more unfavorable, and the mortality higher compared with stroke in patients without a recent myocardial infarction.[2],[4],[32] In addition, stroke patients in this study had a more cardiogenic shock, cardiac arrest, and major bleeding, which may have contributed to increasing in-hospital mortality. Most of the studies have shown that high mortality in early stroke patients with AMI,[2],[8],[9] in agreement with similar findings in our study.

A major strength of our study is a large number of consecutive patients with a uniform prospective data collection derived from 29 participating hospitals from 4 Arabian Gulf countries. Thus, our findings are generalizable to the wider population of patients presenting with AMI. However, since this was an observational study that did not control for unmeasured confounders, its ability to assess causal relationships is limited. Since this study relied only on patients admitted with a diagnosis of ACS, the results should not be generalized to all ACS population, including those that were not hospitalized. Furthermore, the number of in-hospital strokes was low, limiting the statistical power of the multivariable logistic regression model. As this study only captured all-cause mortality (in-hospital and at 1-year follow-up), if available, cardiovascular mortality would have been more appropriate.


  Conclusions Top


The incidence of in-hospital stroke in ACS patients in the Middle East is low. However, in-hospital stroke is associated with high all-cause mortality during index-hospitalization and at 1 year. In-hospital stroke was associated with a higher prevalence of cardiogenic shock, major bleeding, heart failure, and cardiac arrest. Prior stroke and LVEF <40% were predictors of in-hospital stroke in patients presenting with ACS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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