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


Stroke. 2017;48(11):3057-3063. 

In This Article


Patient Population

Two hundred seventy patients were enrolled from 11 Japanese hospitals from September 2015 until August 2016: 135 were assigned to the early statin group and 135 to the delayed statin group (Figure 1). The patients' mean age (SD) was 70.0 years (11.9 years), and 65% were men. Thirty percent had an ischemic stroke history, and 15% received statins before admission. Lacunar stroke (44%) and atherothrombotic infarction (42%) were the most common. There were 14 (5%) cardioembolic infarctions in patients not diagnosed as cardioembolic at enrollment. Demographic and clinical characteristics were similar in both groups (Table 1). The median (interquartile ranges) length of hospital stay in early and delayed statin group were 18 (13–30) and 15 (12–21), respectively. The poor compliance rates (taking statins <75% of prescribed) at 90th day were 6% (7/123) and 1% (1/118) in the early and delayed statin groups, respectively.

Figure 1.

Trial profile. FAS indicates full analyses set; mRS, modified Rankin Scale; and SAS, safety analyses set.

Primary and Secondary Outcomes

Ninety days after stroke, the mRS score distribution did not differ between groups (P=0.7), and adjusted common OR of the early statin group was 0.84 (95% CI, 0.53–1.3) compared with the delayed statin group. The results were confirmed by the Wilcoxon–Mann–Whitney generalized OR of 1.1 (95% CI, 0.79–1.4). About 70% of all patients had improved mRS disability status ranging from 0 to 2 (Figure 2). The OR of the early statin group for excellent outcome (mRS score of 0 or 1) was 1.59 (95% CI, 0.90–2.85) compared with the delayed statin group.

Figure 2.

Primary outcome. mRS indicates modified Rankin Scale.

Prespecified subgroup analyses indicated no significant effect of early statin treatment on mRS at 90 days in any subgroups (Figure 3). The interaction P values were not significant for any subgroup factors.

Figure 3.

Subgroup analyses. CI indicates confidence interval; LDL-C, low-density lipoprotein cholesterol; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; and tPA, tissue-type plasminogen activator.

Secondary outcomes also did not differ between groups except for the change in LDL-C (Table 2). There were only small changes in NIHSS (median-1) in both groups (P=0.4), but the change in LDL-C in the early statin group was significantly larger than that in the delayed statin group (-65.0 versus -51.0; P=0.001). Major adverse cardiovascular or cerebrovascular events were infrequent, except that new acute ischemic stroke occurred in 6.9% and 4.0% of the early and delayed statin patients, respectively.


The 90-day safety profile was similar between groups (Table 3). There were 2 deaths from malignancy in the early statin group and 1 in the delayed group. Including minor symptoms, there were 32 (23.9%) adverse events in the early statin group and 22 (17.1%) in the delayed statin group, and half were symptom progression necessitating hospital admission. Infrequent musculoskeletal adverse events (myalgia or orthostatic symptoms but no rhabdomyolysis or myositis) were observed in both groups. Creatine kinase, aspartate transaminase, and alanine aminotransferase laboratory changes were also similar between groups. There were 11 (9.5%) and 20 (17.5%) patients with creatine kinase elevated to ≥3× the upper normal limit in the early and delayed statin groups, respectively. The locations of stroke regressed until 21 days after onset or discharge in both groups (Table in the online-only Data Supplement).