Response to Letter by Loh and Sharma
We appreciate the interest of Loh and Sharma in our multicenter observational study on low-dose intravenous (IV) recombinant tissue plasminogen activator (rtPA, 0.6 mg/kg alteplase) for Japanese patients with stroke (Stroke Acute Management with Urgent Risk-factor Assessment and Improvement [SAMURAI] rt-PA Registry).1 In addition to this SAMURAI study, several studies, including the Japan Alteplase Clinical Trial (J-ACT),2 a single-center observational study from our institute,3 and a prospective multicenter observational study (J-ACT II),4 reported that approximately ≥40% of patients with stroke had a modified Rankin Scale score ≤1 at 3 months. Thus, we are certain that low-dose IV rtPA (0.6 mg/kg) for Japanese patients is as effective as standard dose rtPA (0.9 mg/kg) for Western patients. The underlying rationale for the low-dose therapy was published on the Stroke web site for the J-ACT (Supplemental Appendix 2; available at http://stroke.ahajournals.org).2
We recently read a report by Sharma et al5 with great interest; standard dose IV rt-PA for 82 Singaporean patients brought much better 3-month outcome than low-dose IV rtPA (0.9 mg/kg, maximum dose 50 mg) for 48 patients (modified Rankin Scale score ≤1; 59% versus 35%), although a median 3-month National Institutes of Health Stroke Scale score estimated from their table was the same (6 for both) in the 2 groups. To the best of our knowledge, this is the best clinical outcome after standard dose rtPA. We should try a head-to-head comparison of the alteplase dose of 0.9 mg/kg versus 0.6 mg/kg for Japanese patients to ascertain if we could also obtain such a good clinical outcome.
In the Loh and Sharma letter, they discussed that low-dose rtPA results in lower rates of recanalization, causes delayed recanalization, and increases the risk of symptomatic intracerebral hemorrhage. We do not agree with their opinion. In the J-ACT II,4 recanalization of the middle cerebral artery was noted in 51.7% of patients receiving IV rtPA at 0.6 mg/kg on MR angiography 6 hours after stroke onset and in 69.0% on 24-hour MR angiography; these rates exceeded the predetermined value based on previous publications. After logistic regression analysis, recanalization on either 6-hour or 24-hour MR angiography as well as delayed recanalization (ie, arterial occlusion unchanged on 6-hour MR angiography but recanalized on 24-hour MR angiography) was an independent predictor for the 3-month modified Rankin Scale score ≤1. Previous studies reported comparatively low risk of symptomatic intracerebral hemorrhage after low-dose IV rtPA.1–4⇓⇓⇓
As Loh and Sharma proposed, hemorrhagic complication after thrombolysis or antithrombotic therapy is a critical problem for Asian populations.6 We think that there may be much differences in ethnic features and medical circumstances even in the same Asia.
Sources of Funding
SAMURAI rt-PA Registry is supported in part by Grants-in-Aid (H20-Junkanki-Ippan-019) from the Ministry of Health, Labour and Welfare, Japan.
- ↵Toyoda K, Koga M, Naganuma M, Shiokawa Y, Nakagawara J, Furui E, Kimura K, Yamagami H, Okada Y, Hasegawa Y, Kario K, Okuda S, Nishiyama K, Minematsu K; for the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) Study Investigators. Routine use of intravenous low-dose recombinant tissue plasminogen activator in Japanese patients: general outcomes and prognostic factors from the SAMURAI register. Stroke. 2009; 40: 3591–3595.
- ↵Yamaguchi T, Mori E, Minematsu K, Nakagawara J, Hashi K, Saito I, Shinohara Y; Japan Alteplase Clinical Trial (J-ACT) Group. Alteplase at 0.6 mg/kg for acute ischemic stroke within 3 hours of onset: Japan Alteprase Clinical Trial. Stroke. 2006; 37: 1810–1815.
- ↵Mori E, Minematsu K, Nakagawara J, Yamaguchi T, Sasaki M, Hirano T, for the J-ACT II Group. Effects of 0.6 mg/kg intravenous alteplase on vascular and clinical outcomes in middle cerebral artery occlusion: Japan Alteplase Clinical Trial II (J-ACT II). Stroke. 2010; 41: 461–465.