|Year : 2020 | Volume
| Issue : 1 | Page : 13-18
Incidence, predictors, and mortality of in-hospital stroke after acute coronary syndrome in the Middle East
Wadhha AlSaeed1, Ibrahim Al-Zakwani2, Prashanth Panduranga3, Mohammad Zubaid4, Wafa Rashed4, Peter A Brady5
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 Submission||10-Apr-2020|
|Date of Decision||15-Apr-2020|
|Date of Acceptance||16-Apr-2020|
|Date of Web Publication||16-Jun-2020|
Dr. Wadhha AlSaeed
Department of Cardiology, Sabah Al Ahmad Cardiac Center, Al Amiri Hospital, Kuwait City, Kuwait. 32001.
Source of Support: None, Conflict of Interest: None
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|| |
Stroke is the second-most common cause of death and disability worldwide. Although an uncommon (0.7%–2%) in-hospital event after acute myocardial infarction (AMI), stroke has been associated with significant morbidity and mortality.,, Previous studies have reported on the AMI and in-hospital acute stroke.,, 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,,, coexisting cerebral atherosclerosis, or changes in platelet function and coagulation during anticoagulation and newer antiplatelets use., The type of revascularization therapy in the setting of AMI, such as thrombolysis versus primary angioplasty, may also influence the development of stroke., However, data are lacking regarding the incidence and risk factors associated with stroke in ACS patients and specifically in the Middle East. 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|| |
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. 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., 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.
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. 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. 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|| |
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 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).
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.
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|
Click here to view
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|
Click here to view
| Discussion|| |
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. 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.,,, 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.,,,,, 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.
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.,, 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.,,,,, Furthermore, unlike in the current study, STEMI has been associated with increased stroke risk that has led to blood stasis and thromboembolism.,, 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. 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.,, 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. 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. 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. Several studies, 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.,, 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,,, 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|| |
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
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dutta M, Hanna E, Das P, Steinhubl SR. Incidence and prevention of ischemic stroke following myocardial infarction: Review of current literature. Cerebrovasc Dis 2006;22:331-9.
Albaker O, Zubaid M, Alsheikh-Ali AA, Rashed W, Alanbaei M, Almahmeed W, et al
. Early stroke following acute myocardial infarction: Incidence, predictors and outcome in six Middle-Eastern countries. Cerebrovasc Dis 2011;32:471-82.
Guenancia C, Hachet O, Stamboul K, Béjot Y, Leclercq T, Garnier F, et al
. Incremental predictive value of mean platelet volume/platelet count ratio in in-hospital stroke after acute myocardial infarction. Platelets 2017;28:54-9.
Saczynski JS, Spencer FA, Gore JM, Gurwitz JH, Yarzebski J, Lessard D, et al.
Twenty-year trends in the incidence of stroke complicating acute myocardial infarction: Worcester Heart Attack Study. Arch Intern Med 2008;168:2104-10.
Kajermo U, Ulvenstam A, Modica A, Jernberg T, Mooe T. Incidence, trends, and predictors of ischemic stroke 30 days after an acute myocardial infarction. Stroke 2014;45:1324-30.
Mooe T, Olofsson BO, Stegmayr B, Eriksson P. Ischemic stroke. Impact of a recent myocardial infarction. Stroke 1999;30:997-1001.
Olsen FJ, Pedersen S, Jensen JS, Biering-Sørensen T. Global longitudinal strain predicts incident atrial fibrillation and stroke occurrence after acute myocardial infarction. Medicine (Baltimore) 2016;95:e5338.
Al Suwaidi J, Al Habib K, Asaad N, Singh R, Hersi A, Al Falaeh H, et al
. Immediate and one-year outcome of patients presenting with acute coronary syndrome complicated by stroke: Findings from the 2nd
Gulf Registry of Acute Coronary Events (Gulf RACE-2). BMC Cardiovasc Disord 2012;12:64.
Sampson UK, Pfeffer MA, McMurray JJ, Lokhnygina Y, White HD, Solomon SD, et al
. Predictors of stroke in high-risk patients after acute myocardial infarction: Insights from the VALIANT Trial. Eur Heart J 2007;28:685-91.
Zubaid M, Thani KB, Rashed W, Alsheikh-Ali A, Alrawahi N, Ridha M, et al
. Design and rationale of gulf locals with acute coronary syndrome events (Gulf Coast) registry. Open Cardiovasc Med J 2014;8:88-93.
Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, et al
. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur J Heart Fail 2008;10:933-89.
Radford MJ, Arnold JM, Bennett SJ, Cinquegrani MP, Cleland JG, Havranek EP, et al
. ACC/AHA key data elements and definitions for measuring the clinical management and outcomes of patients with chronic heart failure: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Heart Failure Clinical Data Standards): Developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart Failure Society of America. Circulation 2005;112:1888-916.
Lemeshow S, Hosmer DW Jr. A review of goodness of fit statistics for use in the development of logistic regression models. Am J Epidemiol 1982;115:92-106.
Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982;143:29-36.
Ulvenstam A, Kajermo U, Modica A, Jernberg T, Söderström L, Mooe T. Incidence, trends, and predictors of ischemic stroke 1 year after an acute myocardial infarction. Stroke 2014;45:3263-8.
Kontny F, Dale J, Abildgaard U, Pedersen TR. Randomized trial of low molecular weight heparin (dalteparin) in prevention of left ventricular thrombus formation and arterial embolism after acute anterior myocardial infarction: The Fragmin in Acute Myocardial Infarction (FRAMI) Study. J Am Coll Cardiol 1997;30:962-9.
Turpie AG, Robinson JG, Doyle DJ, Mulji AS, Mishkel GJ, Sealey BJ, et al
. Comparison of high-dose with low-dose subcutaneous heparin to prevent left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction. N
Engl J Med 1989;320:352-7.
Van de Graaff E, Dutta M, Das P, Shry EA, Frederick PD, Blaney M, et al
. Early coronary revascularization diminishes the risk of ischemic stroke with acute myocardial infarction. Stroke 2006;37:2546-51.
Van de Werf F, Barron HV, Armstrong PW, Granger CB, Berioli S, Barbash G, et al
. Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents: A comparison of TNK-tPA and rt-PA. Eur Heart J 2001;22:2253-61.
Khafaji HA. Fibrinolysis in acute myocardial infarction; State of the art. Ann Cardiovasc Surg 2018;1:1015.
Yaghi S, Pilot M, Song C, Blum CA, Yakhkind A, Silver B, et al
. Ischemic stroke risk after acute coronary syndrome. J Am Heart Assoc 2016;5. pii: e002590.
Hachet O, Guenancia C, Stamboul K, Daubail B, Richard C, Béjot Y, et al
. Frequency and predictors of stroke after acute myocardial infarction: Specific aspects of in-hospital and postdischarge events. Stroke 2014;45:3514-20.
Allen NB, Holford TR, Bracken MB, Goldstein LB, Howard G, Wang Y, et al
. Geographic variation in one-year recurrent ischemic stroke rates for elderly Medicare beneficiaries in the USA. Neuroepidemiology 2010;34:123-9.
Budaj A, Flasinska K, Gore JM, Anderson FA Jr., Dabbous OH, Spencer FA, et al
. GRACE Investigators. Magnitude of and risk factors for in-hospital and postdischarge stroke in patients with acute coronary syndromes: Findings from a Global Registry of Acute Coronary Events. Circulation 2005;111:3242-7.
O'Neal WT, Qureshi WT, Judd SE, Meschia JF, Howard VJ, Howard G, et al
. Heart rate and ischemic stroke: The reasons for geographic and racial differences in stroke (REGARDS) study. Int J Stroke 2015;10:1229-35.
Lee TC, Goodman SG, Yan RT, Grondin FR, Welsh RC, Rose B, et al
. Disparities in management patterns and outcomes of patients with non-ST-elevation acute coronary syndrome with and without a history of cerebrovascular disease. Am J Cardiol 2010;105:1083-9.
Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet 1988;2:349-60.
Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, et al
. Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: The MIRACL study: A randomized controlled trial. JAMA 2001;285:1711-8.
Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, et al
. CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N
Engl J Med 2005;352:1179-89.
Puletti M, Morocutti C, Tronca M, Fattapposta F, Borgia C, Curione M, et al
. Cerebrovascular accidents in acute myocardial infarction. Ital J Neurol Sci 1987;8:245-8.
Dundar Y, Hill R, Dickson R, Walley T. Comparative efficacy of thrombolytics in acute myocardial infarction: A systematic review. QJM 2003;96:103-13.
Apsangikar P, Chaudhry S, Naik M, Deoghare S, Joseph J. Multicentric, randomized, double-blind, comparative study in STEMI patients to establish clinical biosimilarity of biosimilar tenecteplase with reference product. Ann Clin Cardiol 2019;1:8-14. [Full text]
[Table 1], [Table 2], [Table 3], [Table 4]