\
J Stroke Search

CLOSE


J Stroke > Volume 19(3); 2017 > Article
Jeong, Kim, Yang, Han, and Bae: Early Statins after Intravenous or Endovascular Recanalization Is Beneficial Regardless of Timing, Intensity, and Stroke Mechanism

Dear Sir:

In the modern era of ischemic stroke treatment, stroke physicians have highly effective tools to recanalize occluded major cerebral arteries. After hyperacute treatments, deleterious effects of reperfusion into the ischemic brain, including oxidative injuries, extravasation of intravascular blood, and recurrent infarctions should be managed appropriately. Statins may be a feasible and effective therapeutic option because of their pleiotropic effects, such as the stabilization of endothelial activation, augmentation of cerebral blood flow, and anti-oxidative and anti-inflammatory effects protecting against ischemic-reperfusion injuries [1-3]. Several studies have attempted to evaluate therapeutic potential of statins to address this issue, but the majority of such studies analyzed the effect of statin medication before stroke or statin withdrawal after stroke [4]. Considering the early development of oxidative and inflammatory injuries after recanalization treatment, it may be better to initiate statins earlier to obtain the best effects. Previously, we reported on the efficacy of early statin use after recanalization treatment [5]. In this current study, we aimed to update the analysis with recent data on recanalization treatment and to determine the subgroups that benefit from early statin initiation (≤72 hours).
A total of 857 acute ischemic stroke patients treated with intravenous or endovascular recanalization between July 2007 and December 2015 were identified from a prospective clinical registry from a single center. We retrospectively obtained data on the timing and dose of statins from an electronic barcode medication administration system. Favorable shifts on the modified Rankin Scale score at 3 months and symptomatic hemorrhagic transformation were analyzed, and clustering effects by treatment year were considered. Early statins were used in 67% (n=574) of the patients, with 33% (n=191) receiving them within 12 hours. High-intensity statins (atorvastatin 40–80 mg or rosuvastatin 20 mg) were used in 73% (n=418) of patients, and low-to-moderate intensity statins were used in 27% (n=156) of patients (Supplementary Tables 1 and 2). Adjusted multivariable analyses revealed that early statin initiation within 72 hours was associated with a favorable modified Rankin Scale score shift (adjusted odds ratio 1.52; 95% confidence interval 1.13–2.03) compared with no statin therapy (Figure 1). Early statins were also associated with decreased odds of having symptomatic hemorrhagic transformation (adjusted odds ratio 0.44; 95% confidence interval 0.24–0.83). Early statins showed no substantial exposure-response relationship with time of initiation or intensity. The beneficial effects of early statin initiation maintained in subgroup analyses regarding the mode of recanalization, stroke mechanism, and statin use before the index stroke. The clinical profiles in the exposure-response and subgroup analyses are provided in Supplementary Tables 37. The full models of multivariable logistic regression analyses are presented in Supplementary Table 8.
This study shows that early initiation of statins may confer improved functional recovery and decrease hemorrhagic transformation after recanalization treatment for acute ischemic stroke, regardless of treatment modalities, stroke mechanisms, and pre-stroke statin use. Several studies have reported the efficacy of early statin use after recanalization treatment, but they included only intravenous thrombolysis cases [6] or were mostly performed before stent-retrievers were used in a majority of patients [5,7]. In addition, the post-treatment National Institute of Health Stroke Scale score was incorporated into all models in our study as a covariate, which resulted in more accurate assessment of the effect of early statins following recanalization treatment [8].

Conflicts of Interest

The authors have no financial conflicts of interest.

Acknowledgments

This study was supported by grant 02-2015-023 from the SNUBH Research Fund.

Supplementary Material

Supplementary materials related to this article can be found online at https://doi.org/10.5853/jos.2017.00836.
Supplementary Table 1.
Clinical characteristics of study patients by early statin use and the timing of statin administration
jos-2017-00836-suppl1.pdf
Supplementary Table 2.
Statin agent, dose, and time of early statin administration
jos-2017-00836-suppl2.pdf
Supplementary Table 3.
Clinical characteristics of study patients by timing of early statin administration
jos-2017-00836-suppl3.pdf
Supplementary Table 4.
Clinical profiles by statin intensity
jos-2017-00836-suppl4.pdf
Supplementary Table 5.
Clinical profiles of subgroups divided by recanalization modalities
jos-2017-00836-suppl5.pdf
Supplementary Table 6.
Clinical profiles of subgroups by stroke mechanism
jos-2017-00836-suppl6.pdf
Supplementary Table 7.
Clinical profiles of subgroups by pre-stroke statin use
jos-2017-00836-suppl7.pdf
Supplementary Table 8.
Full models of multivariable analyses
jos-2017-00836-suppl8.pdf

Figure 1.
The effects of early statins on functional outcome after recanalization treatment. All models (except symptomatic hemorrhagic transformation) are commonly adjusted with age, sex, premorbid mRS, NIHSS score at arrival, NIHSS score after recanalization treatment, recanalization modalities, stroke mechanism, hypertension, hyperlipidemia, atrial fibrillation, regular smoking, prestroke antithrombotics, prestroke stain, hemoglobin, HbA1c, triglycerides, low density lipoprotein-cholesterol. mRS at 3 mo, modified Rankin Scale at 3 months after stroke; OR, odds ratio; CI, confidence interval; IV, intravenous; LAA, large artery atherosclerosis; CE, cardioembolism NIHSS, National Institute of Health Stroke Scale.
jos-2017-00836f1.tif

References

1. Tsunekawa T, Hayashi T, Kano H, Sumi D, Matsui-Hirai H, Thakur NK, et al. Cerivastatin, a hydroxymethylglutaryl coenzyme a reductase inhibitor, improves endothelial function in elderly diabetic patients within 3 days. Circulation 2001;104:376–379.
crossref pmid
2. Ovbiagele B, Saver JL, Starkman S, Kim D, Ali LK, Jahan R, et al. Statin enhancement of collateralization in acute stroke. Neurology 2007;68:2129–2131.
crossref pmid
3. Walter DH, Fichtlscherer S, Britten MB, Rosin P, Auch-Schwelk W, Schächinger V, et al. Statin therapy, inflammation and recurrent coronary events in patients following coronary stent implantation. J Am Coll Cardiol 2001;38:2006–2012.
crossref pmid
4. Hong KS, Lee JS. Statins in acute ischemic stroke: a systematic review. J Stroke 2015;17:282–301.
crossref pmid pmc pdf
5. Kang J, Kim N, Park TH, Bang OY, Lee JS, Lee J, et al. Early statin use in ischemic stroke patients treated with recanalization therapy: retrospective observational study. BMC Neurol 2015;15:122.
crossref pmid pmc pdf
6. Cappellari M, Bovi P, Moretto G, Zini A, Nencini P, Sessa M, et al. The THRombolysis and STatins (THRaST) study. Neurology 2013;80:655–661.
crossref pmid pmc
7. Restrepo L, Bang OY, Ovbiagele B, Ali L, Kim D, Liebeskind DS, et al. Impact of hyperlipidemia and statins on ischemic stroke outcomes after intra-arterial fibrinolysis and percutaneous mechanical embolectomy. Cerebrovasc Dis 2009;28:384–390.
crossref pmid pmc
8. Sajobi TT, Menon BK, Wang M, Lawal O, Shuaib A, Williams D, et al. Early trajectory of stroke severity predicts long-term functional outcomes in ischemic stroke subjects: results from the ESCAPE Trial (endovascular treatment for small core and anterior circulation proximal occlusion with emphasis on minimizing CT to recanalization times). Stroke 2017;48:105–110.
crossref pmid


ABOUT JoS
AUTHOR INFORMATION
ARTICLE CATEGORY

Browse all articles >

BROWSE ARTICLES
Editorial Office
Department of Neurology, Asan Medical Center,Ulsan University College of Medicine
88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
Submission, status and progress, etc ⟫ E-mail: editor@j-stroke.org
Website and system ⟫ E-mail: journal@m2community.co.kr
Publishing company ⟫ E-mail: jin@ijpnc.com
Developed in M2community
Copyright © 2017 by Korean Stroke Society. All rights reserved.
Close layer
prev next