The Japan Statin Treatment Against Recurrent Stroke (J-STARS): A Multicenter, Randomized, Open-label, Parallel-group Study

Abstract

BackgroundAlthough statin therapy is beneficial for the prevention of initial stroke, the benefit for recurrent stroke and its subtypes remains to be determined in Asian, in whom stroke profiles are different from Caucasian. This study examined whether treatment with low-dose pravastatin prevents stroke recurrence in ischemic stroke patients.MethodsThis is a multicenter, randomized, open-label, blinded-endpoint, parallel-group study of patients who experienced non-cardioembolic ischemic stroke. All patients had a total cholesterol level between 4.65 and 6.21 mmol/L at enrollment, without the use of statins. The pravastatin group patients received 10 mg of pravastatin/day; the control group patients received no statins. The primary endpoint was the occurrence of stroke and transient ischemic attack (TIA), with the onset of each stroke subtype set to be one of the secondary endpoints.FindingAlthough 3000 patients were targeted, 1578 patients (491 female, age 66.2 years) were recruited and randomly assigned to pravastatin group or control group. During the follow-up of 4.9 ± 1.4 years, although total stroke and TIA similarly occurred in both groups (2.56 vs. 2.65%/year), onset of atherothrombotic infarction was less frequent in pravastatin group (0.21 vs. 0.64%/year, p = 0.0047, adjusted hazard ratio 0.33 [95%CI 0.15 to 0.74]). No significant intergroup difference was found for the onset of other stroke subtypes, and for the occurrence of adverse events.InterpretationAlthough whether low-dose pravastatin prevents recurrence of total stroke or TIA still needs to be examined in Asian, this study has generated a hypothesis that it may reduce occurrence of stroke due to larger artery atherosclerosis.FundingThis study was initially supported by a grant from the Ministry of Health, Labour and Welfare, Japan. After the governmental support expired, it was conducted in collaboration between Hiroshima University and the Foundation for Biomedical Research and Innovation.

Intensive Treat-to-Target Statin Therapy in High-Risk Japanese Patients With Hypercholesterolemia and Diabetic Retinopathy: Report of a Randomized Study

“…An inference of significant reduction cannot be supported given the lack of a statistically significant difference in the primary end point. However, we note that in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study (21), statin therapy effectively reduced cerebrovascular events when LDL-C was lowered to 70 mg/dL, whereas in the Japan Statin Treatment Against Recurrent Stroke (J-STARS) study (22), where LDL-C levels were reduced only to 100 mg/dL, no such efficacy was detected. Exploratory results from EMPATHY were similar to those from SPARCL in that LDL-C reached 70 mg/dL and may confirm that a decrease in LDL-C contributes to reducing the event risk for cerebral infarction.…”

Ezetimibe-Simvastatin Therapy Reduce Recurrent Ischemic Stroke Risks in Type 2 Diabetic Patients

“…However, the target achievement of LLT in stroke is not as good as in coronary artery disease (CAD) patients (9,10). Fewer trials have focused on the secondary preventive effects of LLT in stroke patients (11)(12)(13), and most supporting data comes from post hoc analyses or meta-analysis of studies that initially enrolled CAD patients (2, 14 -16). The protective effects of high-intensity statin therapy on recent stroke patients were significant in the SPARCL trial (11), but that of lower-intensity statins were uncertain in the J-STARS and HPS studies (12,13).…”

“…Fewer trials have focused on the secondary preventive effects of LLT in stroke patients (11)(12)(13), and most supporting data comes from post hoc analyses or meta-analysis of studies that initially enrolled CAD patients (2, 14 -16). The protective effects of high-intensity statin therapy on recent stroke patients were significant in the SPARCL trial (11), but that of lower-intensity statins were uncertain in the J-STARS and HPS studies (12,13). Nevertheless, the risks of adverse events may be higher in clinical practice and increased in high-intensity statin therapy.…”

“Get With the Guideline” Treatment With Statin

“…3 Recently, the Japan Stain Treatment Against Recurrent Stroke (J-STARS) study demonstrated that therapy with low-dose pravastatin (10 mg/day) reduced atherothrombotic infarction incidence by 67% compared with non-statins. 4 Percutaneous coronary intervention with statin therapy reduced in-hospital mortality 30 days after acute coronary disease. 5 In addition, statin use was associated with decreased mortality rates in patients with heart failure with preserved ejection fraction.…”

“…3 On the contrary, in J-STARS, low-dose pravastatin therapy did not increase hemorrhagic stroke incidence. 4 Chen et al report that only a limited number of patients (0.9%) received high-dose statin therapy while almost all other patients received low-dose (52.5%) or medium-dose statin therapy (46.7%). 13 Therefore, yperlipidemia is a well-known risk factor for ischemic stroke and cardiovascular disease, in addition to hypertension and diabetes mellitus.…”