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ISSN: Print -2349-0977, Online - 2349-4387


 
 Table of Contents  
ORIGINAL CONTRIBUTION: CURRENT APPROACHES IN STROKE MEDICINE
Year : 2015  |  Volume : 2  |  Issue : 1  |  Page : 12-15

Significance of statins and antiplatelet molecules in hyperacute acute ischemic stroke outcome


1 Department of Neurology, University of Massachusetts, Worcester, MA, USA
2 Department of Neuro-Critical Care, Massachusetts General Hospital, Boston, MA, USA
3 Department of Biostatistics, University of Massachusetts, Worcester, MA, USA

Date of Web Publication26-Oct-2015

Correspondence Address:
Prof. Majaz Moonis
Director, Stroke Services, UMass Memorial Medical Center, Worcester, Massachusetts 01655
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2349-0977.168246

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  Abstract 

Introduction: Ischemic stroke is a major cause of morbidity and mortality. However, the interface of various premorbid medical conditions, vascular risk factors prior, prior antithrombotic or statins medication use, and in-hospital complications in effecting outcomes is not clearly established. We attempt establishing factors associated with improved outcomes after an acute ischemic stroke (AIS). Materials and Methods: Using the prospectively collected database, University Health Consortium from 1999 to 2004, a national USA database, multivariate step-wise backward regression analysis was performed and we were able to define premorbid characteristics, and medications that affect the outcome of AIS. Results: Initial stroke severity and poststroke in-hospital complications were associated with a poor outcome, while prior antiplatelet drug use was associated with an improved outcome. Statin use demonstrated a trend toward an improved outcome.

Keywords: Acute ischemic stroke, antiplatelet agents, mortality, outcome, statins


How to cite this article:
Mayasi Y, Knobel M, Izzy S, Kane K, Moonis M. Significance of statins and antiplatelet molecules in hyperacute acute ischemic stroke outcome. Astrocyte 2015;2:12-5

How to cite this URL:
Mayasi Y, Knobel M, Izzy S, Kane K, Moonis M. Significance of statins and antiplatelet molecules in hyperacute acute ischemic stroke outcome. Astrocyte [serial online] 2015 [cited 2022 Jul 3];2:12-5. Available from: http://www.astrocyte.in/text.asp?2015/2/1/12/168246


  Introduction Top


Stroke is a major cause of morbidity and mortality in the general population, affecting around 1 million persons per year worldwide.[1] Stroke risk factors are well established including hypertension, diabetes, dyslipidemia, smoking, and atrial fibrillation.[2] Effectiveness of risk factor modification in preventing strokes has been extensively studied along with efficacy of secondary prevention.[3]

To date, not much is known whether these factors, especially prestroke medications, impact subsequent inpatient mortality after an acute ischemic stroke (AIS). It is known that lipid-lowering medications (LLA) and antihypertensive medications reduce recurrence [4] and that LLA may improve outcomes among survivors,[5] but their effect on influencing inpatient mortality after AIS is not entirely established.

There are conflicting reports regarding 3-hydroxy-3-methylglutaryl-coenzyme (HMG CoA) reductase inhibitors' (statins) use in hyperacute AIS. On the one hand, it has been shown that statins started within 72 h of an AIS reduce the inpatient as well as 3 months mortality and morbidity.[6] On the other hand, postulated risks include hemorrhagic transformation.[7],[8],[9] A large part of statin neuroprotective effects were thought to be due to its "anti-inflammatory actions", yet a recent study by Karlinski et al. revealed that elevated inflammatory markers are not independent factors altering the outcome.[10]

Health care-associated infections (HCI) are a major cause of prolonging hospital stay and increased rate of mortality. It is estimated that a third of stroke patients suffer an inpatient infection. A Japanese analysis of 36 hospitals reported a strong association between inpatient mortality after AIS and HCI.[11]

Multiple other preexisting factors are known to be related to adverse outcomes after sustaining an acute ischemic event, which includes the extent of preexisting white matter disease,[12] poor collateral circulation,[13] alcohol abuse,[14] and elevated admission blood sugar levels [15] in addition to atrial fibrillation in women and prior stroke in men.[16] To determine whether these factors additionally contribute to an in-hospital outcome in AIS, we performed a retrospective analysis of a combined large database, the University Health Consortium (UHC) from 1999 to 2004. This database incorporates prespecified information across the United States.


  Materials and Methods Top


Prospectively collected data from the UHC for the years 1999, 2001, and 2005 were pooled and analyzed. Information for each patient in the dataset included demographic factors (gender, age), stroke type and severity, complication comorbidities, and medications used prior to discharge.

Outcome measures

Primary outcome was death from all causes during initial hospitalization. Survival was defined as being discharged from the hospital to home, rehabilitation, or long-term care.

Statistical analysis

Each factor was individually analyzed using univariate analysis (t-test for continuous variables) and Fisher's exact test (FET; χ2-test used for greater than 2 × 2 contingency) for discrete variables. Univariate significant variables (P < 0.1) were then included in the multivariate analysis. Stepwise logistic regression was used to determine the independent predictors of mortality.


  Results Top


A total of 3522 cases offirst time AIS were included in our sample of which 201 (5.7%) died during the initial hospitalization. Univariate analyses revealed that stroke-related factors of severity (χ2 = 187.2; P < 0.001) and complications (FET; P < 0.001) were significant. Patients with more severe strokes and/or complications were more likely to die during their admission. Moreover, prior use of aspirin (FET, P < 0.001) or other antiplatelet agents (FET, P < 0.001) had a significant protective effect. There was also a trend in the univariate analyses for the protective effect of lipid-lowering medication (FET, P = 0.085). These factors were included in the multivariate model. All univariate analyses are presented in [Table 1].
Table 1: Demographics, Vascular Risk Factors, Medications and Co-Morbid Conditions Effecting Outcome

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In the multivariate stepwise logistic regression analysis, stroke severity (P = 0.133 for moderate vs. mild; odds ratio [OR] = 1.39; confidence interval [CI] = [0.90, 2.14]; P < 0.001 for severe vs. mild; OR = 4.98, CI = [3.39, 7.32]) and poststroke complications (P < 0.001; OR = 22.22, CI = (12.34, 40.00)) were independent significant predictors. Likewise, aspirin (P = 0.007; OR = 0.65, CI = [0.47, 0.89]) and other antiplatelet medication use (P = 0.012; OR = 0.62, CI = [0.42, 0.90]) were also independent significant predictors, while statins demonstrated a trend toward significance.


  Discussion Top


Statin therapy has been well established to improve the outcome after an AIS in both animal models and clinical studies.[6],[7],[17] Most of the studies done this far assess the outcome at 1 and 3 months.[17],[18],[19] Our study, on the other hand, focuses on the effect of statin use and other factors on the risk of in-hospital mortality. Our results indicate that statin use prior to AIS has a trend toward improved outcomes. This result is explained by the underlying mechanism of action of statins. Statins are known to decrease stroke-associated parenchymal infiltration of immune cells.[20] Decreased inflammatory cells in the setting of stroke is known to be beneficial to alter outcomes, as intrinsic glial cell and neuronal release of cytokines as a result of ischemic injury, is sufficient to propagate the inflammatory cascade with its detrimental sequelae. In addition, there are reports that the pleotropic protective effects of statins are most pronounced in the first 72 h.[21],[22] Most patients with severe stroke are placed nothing per os for safety. As there is no other route of administration, LLA are not given in the initial phases of the stroke, hence eliminating the protective effects at critical times. Statin therapy has been shown to promote collateral circulation formation,[23] which might entail a smaller stroke burden and lower National Institutes of Health Stroke Scale, hence categorizing these patients at a lower stroke severity scale.

Being a prospective cohort trial has several advantages including avoiding selection bias and allowing us to directly estimate the relative risk. A particular strength of this study is that given the relatively short duration of hospitalization, there was no loss to follow-up. Some weaknesses of our study relate to the specifics of the lipid-lowering medications and their usage. Though we assume that the majority of patients on lipid-lowering medications were using statins, we cannot confirm the specific proportion. Lastly, when dealing with stroke and mortality, there is potential for bias due to the small proportion of patients who do not survive to admission and are thus not represented in our sample.

Our analysis was similar to other observations in that pre-admission antiplatelet use is an independent factor resulting in a decreased rate of inpatient mortality after AIS.[24] In addition, we reiterate the notion of stroke burden and risk of death in the acute setting. As previously described, severe strokes are more likely to result in mortality compared to mild and moderate strokes.[25] We also show that complications, especially pneumonia, increase the likelihood of mortality after AIS, in-line with prior reports. A meta-analysis in 2011 revealed that infections complicate AIS patients in about 30% of cases, with pneumonia and urinary tract infections being the most common. Pneumonia was associated with higher mortality rates.[26] This sheds light onto the importance of preventive measures to decrease the risk of infections, such as elevation of the head of the bed, dysphagia screen, and removal of indwelling catheters when possible.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Krishnamurthi RV, Feigin VL, Forouzanfar MH, Mensah GA, Connor M, Bennett DA, et al. Global and regional burden offirst-ever ischaemic and haemorrhagic stroke during 1990-2010: Findings from the global burden of disease study 2010. Lancet Glob Health 2013;1:e259-81.  Back to cited text no. 1
    
2.
Pollack A, Harrison C, Henderson J, Miller G. Stroke. Aust Fam Physician 2014;43:93.  Back to cited text no. 2
    
3.
Eissa A, Krass I, Bajorek BV. Use of medications for secondary prevention in stroke patients at hospital discharge in Australia. Int J Clin Pharm 2014;36:384-93.  Back to cited text no. 3
    
4.
Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014;45:2160-236.  Back to cited text no. 4
[PUBMED]    
5.
Laloux P. Risk and benefit of statins in stroke secondary prevention. Curr Vasc Pharmacol 2013;11:812-6.  Back to cited text no. 5
    
6.
Al-Khaled M, Matthis C, Eggers J. Statin treatment in patients with acute ischemic stroke. Int J Stroke 2014;9:597-601.  Back to cited text no. 6
    
7.
Collins R, Armitage J, Parish S, Sleight P, Peto R; Heart Protection Study Collaborative Group. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet 2004;363:757-67.  Back to cited text no. 7
[PUBMED]    
8.
Gonzalez-Castellon MA, Marshall RS. Statin use and brain hemorrhage: Real risk or unfounded fear? JAMA Neurol 2014;71:1353-4.  Back to cited text no. 8
    
9.
Goldstein LB, Amarenco P, Szarek M, Callahan A III, Hennerici M, Sillesen H, et al. Hemorrhagic stroke in the stroke prevention by aggressive reduction in cholesterol levels study. Neurology 2008;70 (24 Pt 2):2364-70.  Back to cited text no. 9
    
10.
Karlinski M, Bembenek J, Grabska K, Kobayashi A, Baranowska A, Litwin T, et al. Routine serum C-reactive protein and stroke outcome after intravenous thrombolysis. Acta Neurol Scand 2014;130:305-11.  Back to cited text no. 10
    
11.
Lee J, Imanaka Y, Sekimoto M, Ikai H, Otsubo T. Healthcare-associated infections in acute ischaemic stroke patients from 36 Japanese hospitals: Risk-adjusted economic and clinical outcomes. Int J Stroke 2011;6:16-24.  Back to cited text no. 11
    
12.
Henninger N, Khan MA, Zhang J, Moonis M, Goddeau RP Jr. Leukoaraiosis predicts cortical infarct volume after distal middle cerebral artery occlusion. Stroke 2014;45:689-95.  Back to cited text no. 12
    
13.
Seeta Ramaiah S, Churilov L, Mitchell P, Dowling R, Yan B. The impact of arterial collateralization on outcome after intra-arterial therapy for acute ischemic stroke. AJNR Am J Neuroradiol 2014;35:667-72.  Back to cited text no. 13
    
14.
Sacco RL, Shi T, Zamanillo MC, Kargman DE. Predictors of mortality and recurrence after hospitalized cerebral infarction in an urban community: The Northern Manhattan Stroke Study. Neurology 1994;44:626-34.  Back to cited text no. 14
    
15.
Carlberg B, Asplund K, Hägg E. The prognostic value of admission blood pressure in patients with acute stroke. Stroke 1993;24:1372-5.  Back to cited text no. 15
    
16.
Heuschmann PU, Kolominsky-Rabas PL, Misselwitz B, Hermanek P, Leffmann C, Janzen RW, et al. Predictors of in-hospital mortality and attributable risks of death after ischemic stroke: The German Stroke Registers Study Group. Arch Intern Med 2004;164:1761-8.  Back to cited text no. 16
    
17.
Aslanyan S, Weir CJ, McInnes GT, Reid JL, Walters MR, Lees KR. Statin administration prior to ischaemic stroke onset and survival: Exploratory evidence from matched treatment-control study. Eur J Neurol 2005;12:493-8.  Back to cited text no. 17
    
18.
Elkind MS, Flint AC, Sciacca RR, Sacco RL. Lipid-lowering agent use at ischemic stroke onset is associated with decreased mortality. Neurology 2005;65:253-8.  Back to cited text no. 18
    
19.
Moonis M, Kane K, Schwiderski U, Sandage BW, Fisher M. HMG-CoA reductase inhibitors improve acute ischemic stroke outcome. Stroke 2005;36:1298-300.  Back to cited text no. 19
    
20.
Kawashima S, Yamashita T, Miwa Y, Ozaki M, Namiki M, Hirase T, et al. HMG-CoA reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats. Stroke 2003;34:157-63.  Back to cited text no. 20
    
21.
Gertz K, Laufs U, Lindauer U, Nickenig G, Böhm M, Dirnagl U, et al. Withdrawal of statin treatment abrogates stroke protection in mice. Stroke 2003;34:551-7.  Back to cited text no. 21
    
22.
Blanco M, Nombela F, Castellanos M, Rodriguez-Yáñez M, García-Gil M, Leira R, et al. Statin treatment withdrawal in ischemic stroke: A controlled randomized study. Neurology 2007;69:904-10.  Back to cited text no. 22
    
23.
Ovbiagele B, Saver JL, Starkman S, Kim D, Ali LK, Jahan R, et al. Statin enhancement of collateralization in acute stroke. Neurology 2007;68:2129-31.  Back to cited text no. 23
    
24.
Dowlatshahi D, Hakim A, Fang J, Sharma M; Investigators of the Registry of the Canadian Stroke Network. Pre admission antithrombotics are associated with improved outcomes following ischaemic stroke: A cohort from the Registry of the Canadian Stroke Network. Int J Stroke 2009;4:328-34.  Back to cited text no. 24
    
25.
Mogensen UB, Olsen TS, Andersen KK, Gerds TA. Cause-specific mortality after stroke: Relation to age, sex, stroke severity, and risk factors in a 10-year follow-up study. J Stroke Cerebrovasc Dis 2013;22:e59-65.  Back to cited text no. 25
    
26.
Westendorp WF, Nederkoorn PJ, Vermeij JD, Dijkgraaf MG, van de Beek D. Post-stroke infection: A systematic review and meta-analysis. BMC Neurol 2011;11:110.  Back to cited text no. 26
    



 
 
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  [Table 1]


This article has been cited by
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Journal of Stroke and Cerebrovascular Diseases. 2016;
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