Randomized Controlled Trial of Early Versus Delayed Statin Therapy in Patients With Acute Ischemic Stroke

ASSORT Trial (Administration of Statin on Acute Ischemic Stroke Patient)

Shinichi Yoshimura, MD, PhD; Kazutaka Uchida, MD; Takashi Daimon, PhD; Ryuzo Takashima, BA; Kazuhiro Kimura, PhD; Takeshi Morimoto, MD, PhD, MPH

Disclosures

Stroke. 2017;48(11):3057-3063.

Conclusions

Our RCT involving patients with acute ischemic stroke and dyslipidemia did not show any superiority of early statin therapy administered within 24 hours of admission versus delayed administration until the seventh day of admission to alleviate the degree of disability at 90 days after admission.

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Acknowledgments
We are indebted to Yukari Matsunaga, Yoko Kai, and Michiyo Horie for their data management and Kunimi Takashima and Noriko Fujita for their project management.

Sources of Funding
This study was supported by Shionogi Co, Ltd and the representative of Shionogi participated into the design and the drafting the article, but the operation, data collection, and statistical analyses were solely conducted by the academic authors (Drs Yoshimura, Uchida, Daimon, and Morimoto).

Clinical Trial Registration:
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02549846.

Table 1. Patients' Characteristics
Variables	Early Statin Group (n=131)	Delayed Statin Group (n=126)
Age, y, mean (SD)	70 (13)	70 (11)
Age ≥70 y, n (%)	76 (58)	68 (54)
Sex male, n (%)	86 (66)	81 (64)
History of smoking, n (%)	69 (53)	70 (56)
History of hypertension, n (%)	103 (79)	93 (74)
History of diabetes mellitus, n (%)	38 (29)	44 (35)
History of dyslipidemia, n (%)	64 (49)	59 (47)
History of stroke, n (%)	41 (31)	48 (38)
Statin use before admission, n (%)	23 (18)	16 (13)
Systolic blood pressure, mm Hg, mean (SD)	160 (24)	160 (26)
Diastolic blood pressure, mm Hg, mean (SD)	87 (15)	89 (16)
Body weight, kg, mean (SD)	64 (14)	63 (13)
NIHSS on admission, median (IQR)	3 (1–5)	3 (1–5)
Stroke classification
Lacunar, n (%)	56 (43)	56 (44)
Atherothrombotic, n (%)	55 (42)	54 (43)
Cardioembolic, n (%)	5 (4)	9 (7)
Others*, n (%)	15 (11)	7 (6)
Intravenous thrombolysis, n (%)	11 (8.4)	10 (7.9)
ASPECTS, median (IQR)	9 (9–10)	9 (9–10)
ASPECTS on DWI, median (IQR)	9 (8–9)	9 (9–9)
pc-ASPECTS on DWI, median (IQR)	8 (8–9)	8 (8–9)
Laboratories
LDL cholesterol, mmol/L, mean (SD); [mg/dL, mean (SD)]	3.52 (0.78); [136 (30)]	3.52 (0.85); [136 (33)]
HDL cholesterol, mmol/L, mean (SD); [mg/dL, mean (SD)]	1.37 (0.36); [53 (14)]	1.32 (0.44); [51 (17)]
Total cholesterol, mmol/L, mean (SD); [mg/dL, mean (SD)]	5.54 (0.91); [214 (35)]	5.44 (0.93); [210 (36)]
Triglycerides, mmol/L, median (IQR); [mg/dL, median (IQR)]	3.16 (2.07–4.09); [122 (80–158)]	3.11 (2.23–4.56); [120 (86–176)]
HbA1c, % (NGSP), median (IQR)	6.0 (5.6–6.6)	6.0 (5.6–7.0)
CRP, mg/dL, median (IQR)	0.11 (0.05–0.28)	0.11 (0.05–0.29)

ASPECTS indicates Alberta Stroke Program Early CT Score; CRP, C-reactive protein; DWI, diffusion-weighted imaging; HDL, high-density lipoprotein; IQR, interquartile range; LDL, low-density lipoprotein; NGSP, National Glycohemoglobin Standardization Program; NIHSS, National Institute of Health Stroke Scale; and pc-ASPECTS, posterior circulation-Alberta Stroke Program Early CT Score.
*Abnormality of coagulation, arterial dissection, vasculitis, or undetermined.

Table 2. Secondary Outcomes
Secondary Outcomes	Early Statin Group (n=131)	Delayed Statin Group (n=126)	P Values
Change in NIHSS from baseline through seventh day, median (IQR)	−1 (−2 to 0)	−1 (−2 to 0)	0.40
Change in LDL-C from baseline through 21st day or discharge, mmol/L, mean (SD); [mg/dL, mean (SD)]	−1.68 (0.79); [−65.0 (30.6)]	−1.32 (0.76); [−51.0 (29.2)]	0.001
Acute myocardial infarction, n (%)	0 (0)	1 (0.8)	0.49
Unstable angina, n (%)	0 (0)	0 (0)	1
New acute ischemic stroke, n (%)	9 (6.9)	5 (4.0)	0.41
Nontraumatic cerebral hemorrhage, n (%)	1 (0.7)	0 (0)	1
Nontraumatic subarachnoid hemorrhage, n (%)	1 (0.7)	0 (0)	1
Large vessel or peripheral artery disease requiring treatment, n (%)	0 (0)	1 (0.8)	0.49

IQR indicates interquartile range; LDL-C, low-density lipoprotein cholesterol; and NIHSS, National Institutes of Health Stroke Scale.

Table 3. Safety Outcomes
Outcomes	Early Statin Group (n=134)	Delayed Statin Group (n=129)
Death*	2 (1.5)	1 (0.8)
Any adverse event, n (%)	32 (23.9)	22 (17.1)
Progression of symptom†, n (%)	15 (11.2)	10 (8.5)
Musculoskeletal adverse events‡, n (%)	4 (3.0)	2 (1.6)
Liver dysfunction, n (%)	3 (2.2)	1 (0.8)
Gastrointestinal symptoms, n (%)	4 (3.0)	2 (1.6)
Renal dysfunction, n (%)	1 (0.7)	1 (0.8)
Incidental malignancy, n (%)	4 (3.0)	2 (1.6)
Incidental infection, n (%)	7 (5.2)	4 (3.1)
Incidental bleeding, n (%)	3 (2.2)	2 (1.6)
Eczema or skin lesion, n (%)	2 (1.5)	3 (2.3)
Metal disorders, n (%)	2 (1.5)	1 (0.8)
Others§, n (%)	2 (1.5)	3 (2.3)
Laboratory changes
CK ≥3×ULN, n (%)	11 (9.5)	20 (17.5)
AST ≥3×ULN, n (%)	0 (0)	1 (0.8)
ALT ≥3×ULN, n (%)	2 (1.7)	1 (0.8)

ALT indicates alanine aminotransferase; AST, aspartate transaminase; CK, creatine kinase; and ULN, upper limit of normal range.
*Gallbladder cancer, pancreatic cancer, and gastric cancer.
†Clinically worsened stroke or deterioration of NIHSS score of ≥4 points.
‡Low back pain, lower extremity myalgia, ankle sprain, knee arthrosis, and shoulder subluxation.
§Asthma, left atrial myxoma, dehydration, hypokalemia, and hypertrophic obstructive cardiomyopathy.