Melanie R. F. Greenway, MD
@MRFGreenwayMD

Dearborn-Tomazos JL, Hu X, Bravata DM, Phadke MA, Baye FM, Myers LJ, Concato J, Zillich AJ, Reeves MJ, Sico JJ. Deintensification or No Statin Treatment Is Associated with Higher Mortality in Patients With Ischemic Stroke or Transient Ischemic Attack. Stroke. 2021.

Optimizing statin therapy in patients after stroke or TIA is an important component of secondary stroke prevention. High-intensity statin and LDL-C goal <70 mg/dL are the two main targets for secondary stroke prevention based on SPARCL1 and TST.2 The recent “2021 Guideline for the Prevention of Stroke in Patients with Stroke and Transient Ischemic Attack”3 recommends atorvastatin 80mg daily in patients with ischemic stroke, no known coronary artery disease, no major cardiac source of embolism, and LDL-C > 100mg/dL. In those with ischemic stroke or TIA who have evidence of atherosclerotic disease, LDL-C lowering to <70mg/dL is recommended with statin and, if needed, ezetimibe, though a specific dose or intensity of statin is not specified. 

This study looked at 10,871 patients with a primary diagnosis of acute ischemic stroke or TIA who presented to the ER or were admitted during the fiscal year of 2011 at 134 VA centers across the United States. After excluding those who were transferred out of the VA system, died during hospitalization, left against medical advice, were discharged to hospice, or allergic to statins, 9,380 patients were left for review. Their cohort of patients was 96.3% male, 71.1% White, and 34.9% smokers. The mean age was 68.7.

Using the databases available, they looked at the statin prescribed within the 120 days before the stroke or TIA and the statin prescribed up to 7 days after discharge for stroke or TIA. Statins were categorized based on potency, and moderate-high intensity statins were considered “at goal.” 

With this in mind, they divided their patients into 6 practical groups based on the pre-hospitalization statin and post-hospitalization statin. The groups were described as goal-to-goal, low-to-goal, deintensification, none-to-none, none-to-low, and low-to-low. 

At the time of admission, half of patients were not on any statin. After hospitalization, 34.1% remained off of statin, 6.7% were on low-intensity statin, 39.3% were on moderate-intensity statin, and 19.9% were on high-intensity statin. In 14% of patients, the statin dose was deintensified during their admission for stroke or TIA. 

The main outcomes were 30-day and 1-year all-cause mortality. Both no statin at discharge and deintensification of statin at discharge were associated with higher odds of both 30-day and 1-year all-cause mortality, after adjusting for covariates. 

This study did not evaluate the reasons for statin deintensification or reasons why no statin was prescribed, and it did not include specific cause of death. The authors also did not specifically evaluate the LDL level before and after the index stroke, which would help understand why a specific statin intensity was chosen and provide insight into whether high-intensity statin or an LDL target approach has an effect on all-cause mortality. These next steps could help determine if deintensification of statin has a causal relationship with mortality or not. 

These results are a timely addition to the literature on appropriate statin use after ischemic stroke or TIA for secondary stroke prevention. While it was initially somewhat surprising to see that one-third of patients in their sample remained off statins at the time of discharge, the patient sample studied in this article was from the fiscal year of 2011 — 10 years ago. With growing evidence and recommendations for statin use in patients with ischemic stroke and TIA, it would be interesting to evaluate how the statin prescribing practice has changed within this type of system. 

Overall, the study demonstrates that deintensification of statin or not starting a statin after stroke or TIA is associated with an increase in mortality, and therefore, maintaining moderate-to-high-intensity statin may be the best approach for patients after acute ischemic stroke or TIA. 

References:

1.     Amarenco P, Bogousslavsky J, Callahan A, Goldstein LB, Hennerici M, Rudolph AE, Sillesen H, Simunovic L, Szarek M, Welch KMA, Zivin JA, Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N. Engl. J. Med. 2006;355:549–559.

2.     Amarenco P, Kim JS, Labreuche J, Charles H, Abtan J, Béjot Y, Cabrejo L, Cha J-K, Ducrocq G, Giroud M, Guidoux C, Hobeanu C, Kim Y-J, Lapergue B, Lavallée PC, Lee B-C, Lee K-B, Leys D, Mahagne M-H, Meseguer E, Nighoghossian N, Pico F, Samson Y, Sibon I, Steg PG, Sung S-M, Touboul P-J, Touzé E, Varenne O, Vicaut E, Yelles N, Bruckert E. A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke. N. Engl. J. Med. 2019;382:9–19.

3.     Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, Kamel H, Kernan WN, Kittner SJ, Leira EC, Lennon O, Meschia JF, Nguyen TN, Pollak PM, Santangeli P, Sharrief AZ, Smith SC, Turan TN, Williams LS. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke. 0:STR.0000000000000375.