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The influence of statin withdrawal and adherence on stroke outcomes

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Abstract

Introduction

With multiple proven benefits, statin therapy has become the most critical advance in stroke prevention. We aimed to evaluate the risk factors and the effect of poor adherence or statin interruption on the clinical outcomes of ischemic stroke.

Methods

This prospective cohort study included patients admitted with acute ischemic stroke between 2014 and 2018. Consecutive patients were distinguished into subgroups according to the adherence and withdrawal of statin. All participants were followed for 24 months. The outcomes included stroke recurrence, major cardiovascular events, all-cause mortality, and functional performance. Functional outcome was assessed using the modified Rankin Scale at 7 days, 30 days, 6 months, and 2 years after hospital admission for ischemic stroke. In a secondary analysis, outcome variables were compared with statin-naïve patients.

Results

We included 479 patients with acute ischemic stroke. The mean age was 58.3, and 55.0% were male. There were 96 (21.8%) patients who received no statin, 150 (34.9%) patients with poor adherence, 40 (9.1%) patients with intermediate adherence, and 154 (35.0%) patients with good adherence. There were 54 (15.7%) cases of withdrawal of treatment. Patients with hypertension, previous stroke, and large-artery atherosclerosis were associated with poor adherence (p < 0.05). Those with poor adherence were significantly associated with worse functional outcomes and a higher incidence of stroke recurrence (p < 0.05). Significant functional recovery was just seen in patients with satisfactory adherence.

Conclusion

The suboptimal use of statins is associated with significantly worse clinical outcomes in stroke patients.

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References

  1. Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL, Parag V (2009) Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol 8(4):355–369. https://doi.org/10.1016/S1474-4422(09)70025-0

    Article  PubMed  Google Scholar 

  2. Amarenco P, Labreuche J (2009) Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol 8(5):453–463. https://doi.org/10.1016/S1474-4422(09)70058-4

    Article  CAS  PubMed  Google Scholar 

  3. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL, American Heart Association Stroke Council (2018) 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 49(3):e46–e110. https://doi.org/10.1161/STR.0000000000000158

    Article  PubMed  Google Scholar 

  4. Castilla-Guerra L, del Fernandez-Moreno M, C, Leon-Jimenez D, Rico-Corral MA (2019) Statins in ischemic stroke prevention: what have we learned in the post-SPARCL (The Stroke Prevention by Aggressive Reduction in Cholesterol Levels) decade? Curr Treat Options Neurol 21(5):22. https://doi.org/10.1007/s11940-019-0563-4

  5. Vitturi BK, Gagliardi RJ (2020) The influence of statins on the risk of post-stroke epilepsy. Neurol Sci 41:1851–1857. https://doi.org/10.1007/s10072-020-04298-5

    Article  PubMed  Google Scholar 

  6. Chung PW, Yoon BW, Lee YB, Shin BS, Kim HY, Park JH, Kim BK, Yoo BG, Shin WC, Kim EG, Do JK, Park KP, Jung Y, Seo WK, Han MK, Kim J, Kim Y, Bang OY, Hwang YH, Cha JH, Kim YJ (2018) Medication adherence of statin users after acute ischemic stroke. Eur Neurol 80(1–2):106–114. https://doi.org/10.1159/000493530

    Article  PubMed  Google Scholar 

  7. Morisky DE, Green LW, Levine DM (1986) Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care 24(1):67–74. https://doi.org/10.1097/00005650-198601000-00007

    Article  CAS  PubMed  Google Scholar 

  8. Kusznir Vitturi B, José GR (2020) Use of CHADS2 and CHA2DS2-VASc scores to predict prognosis after stroke. Rev Neurol (Paris) 176(1–2):85–91. https://doi.org/10.1016/j.neurol.2019.05.001

    Article  CAS  Google Scholar 

  9. Thomas M, Mann J (1998) Increased thrombotic vascular events after change of statin. Lancet. 352(9143):1830–1831. https://doi.org/10.1016/S0140-6736(05)79893-7

    Article  CAS  PubMed  Google Scholar 

  10. Heeschen C, Hamm CW, Laufs U, Snapinn S, Böhm M, White HD (2002) Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation. 105(12):1446–1452. https://doi.org/10.1161/01.CIR.0000012530.68333.C8

    Article  CAS  PubMed  Google Scholar 

  11. Gertz K, Laufs U, Lindauer U, Nickenig G, Böhm M, Dirnagl U, Endres M (2003) Withdrawal of statin treatment abrogates stroke protection in mice. Stroke. 34(2):551–557. https://doi.org/10.1161/01.STR.0000054055.28435.BF

    Article  CAS  PubMed  Google Scholar 

  12. Perreault S, Ellia L, Dragomir A, Côté R, Blais L, Bérard A, Lalonde L (2009) Effect of statin adherence on cerebrovascular disease in primary prevention. Am J Med 122(7):647–655. https://doi.org/10.1016/j.amjmed.2009.01.032

    Article  CAS  PubMed  Google Scholar 

  13. Lee M, Saver JL, Wu YL et al (2017) Utilization of statins beyond the initial period after stroke and 1-year risk of recurrent stroke. J Am Heart Assoc 6(8):e005658. https://doi.org/10.1161/JAHA.117.005658

    Article  PubMed  PubMed Central  Google Scholar 

  14. Endres M, Laufs U (2006) Discontinuation of statin treatment in stroke patients. Stroke. 37(10):2640–2643. https://doi.org/10.1161/01.STR.0000240690.69406.28

    Article  CAS  PubMed  Google Scholar 

  15. Blanco M, Nombela F, Castellanos M, Rodriguez-Yanez M, Garcia-Gil M, Leira R, Lizasoain I, Serena J, Vivancos J, Moro MA, Davalos A, Castillo J (2007) Statin treatment withdrawal in ischemic stroke: a controlled randomized study. Neurology. 69(9):904–910. https://doi.org/10.1212/01.wnl.0000269789.09277.47

    Article  CAS  PubMed  Google Scholar 

  16. Lavikainen P, Helin-Salmivaara A, Eerola M, Fang G, Hartikainen J, Huupponen R, Korhonen MJ (2016) Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence. BMJ Open 6(6):e011306. https://doi.org/10.1136/bmjopen-2016-011306

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kim J, Lee HS, Nam CM, Heo JH (2017) Effects of statin intensity and adherence on the long-term prognosis after acute ischemic stroke. Stroke. 48(10):2723–2730. https://doi.org/10.1161/STROKEAHA.117.018140

    Article  CAS  PubMed  Google Scholar 

  18. Flint AC, Kamel H, Navi BB, Rao VA, Faigeles BS, Conell C, Klingman JG, Sidney S, Hills NK, Sorel M, Cullen SP, Johnston SC (2012) Statin use during ischemic stroke hospitalization is strongly associated with improved poststroke survival. Stroke. 43(1):147–154. https://doi.org/10.1161/STROKEAHA.111.627729

    Article  CAS  PubMed  Google Scholar 

  19. Flint AC, Kamel H, Navi BB, Rao VA, Faigeles BS, Conell C, Klingman JG, Hills NK, Nguyen-Huynh M, Cullen SP, Sidney S, Johnston SC (2012) Inpatient statin use predicts improved ischemic stroke discharge disposition. Neurology. 78(21):1678–1683. https://doi.org/10.1212/WNL.0b013e3182575142

    Article  CAS  PubMed  Google Scholar 

  20. Hong KS, Lee JS (2015) Statins in acute ischemic stroke: a systematic review. J Stroke 17(3):282–301. https://doi.org/10.5853/jos.2015.17.3.282

    Article  PubMed  PubMed Central  Google Scholar 

  21. Prinz V, Endres M (2011) Statins and stroke: prevention and beyond. Curr Opin Neurol 24(1):75–80. https://doi.org/10.1097/WCO.0b013e3283424c53

    Article  CAS  PubMed  Google Scholar 

  22. Kusznir Vitturi B, José GR (2020) The role of statins in cardioembolic stroke. J Clin Neurosci 72:174–179. https://doi.org/10.1016/j.jocn.2019.12.028

    Article  CAS  PubMed  Google Scholar 

  23. Laufs U, Gertz K, Huang P, Nickenig G, Böhm M, Dirnagl U, Endres M (2000) Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice. Stroke. 31(10):2442–2449. https://doi.org/10.1161/01.STR.31.10.2442

    Article  CAS  PubMed  Google Scholar 

  24. Colivicchi F, Bassi A, Santini M, Caltagirone C (2007) Discontinuation of statin therapy and clinical outcome after ischemic stroke. Stroke. 38(10):2652–2657. https://doi.org/10.1161/STROKEAHA.107.487017

    Article  CAS  PubMed  Google Scholar 

  25. Lingsma HF, Steyerberg EW (2010) Scholte Op Reimer WJM, Van Domburg R, Dippel DWJ. Statin treatment after a recent TIA or stroke: is effectiveness shown in randomized clinical trials also observed in everyday clinical practice? Acta Neurol Scand 122(1):15–20. https://doi.org/10.1111/j.1600-0404.2009.01247.x

    Article  CAS  PubMed  Google Scholar 

  26. Vitturi BK, Gagliardi RJ (2020) Effects of statin therapy on outcomes of ischemic stroke: a real-world experience in Brazil. Arq Neuropsiquiatr 78:461–467. https://doi.org/10.1590/0004-282x20200027

    Article  PubMed  Google Scholar 

  27. Chapman RH, Benner JS, Petrilla AA, Tierce JC, Collins SR, Battleman DS, Schwartz JS (2005) Predictors of adherence with antihypertensive and lipid-lowering therapy. Arch Intern Med 165(10):1147–1152. https://doi.org/10.1001/archinte.165.10.1147

    Article  PubMed  Google Scholar 

  28. Ofori-Asenso R, Jakhu A, Curtis AJ, Zomer E, Gambhir M, Jaana Korhonen M, Nelson M, Tonkin A, Liew D, Zoungas S (2018) A systematic review and meta-analysis of the factors associated with nonadherence and discontinuation of statins among people aged ≥65 years. J Gerontol - Ser A Biol Sci Med Sci 73(6):798–805. https://doi.org/10.1093/gerona/glx256

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Santa Casa de São Paulo School of Medical Sciences, Dr. Cesário Motta Júnior Street 112, São Paulo, 01221-020, Brazil

    Bruno Kusznir Vitturi & Rubens José Gagliardi

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  1. Bruno Kusznir Vitturi
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  2. Rubens José Gagliardi
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Correspondence to Bruno Kusznir Vitturi.

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Vitturi, B.K., Gagliardi, R.J. The influence of statin withdrawal and adherence on stroke outcomes. Neurol Sci 42, 2317–2323 (2021). https://doi.org/10.1007/s10072-020-04790-y

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