Introduction: The metabolic activators have been widely prescribed for patients with chronic cerebrovascular disorders in Japan. The scientific question has been recently raised with respect to their efficacy. Thus, large-scale RCTs are about to be launched in Japan. However, a thorough review of the previous studies may be necessary before initiating such costly studies.

Objective: We quantitatively assessed the relative efficacy of metabolic activators vs. placebo for the treatment of chronic cerebrovascular disorders.

Methods: A total of 10 articles containing the randomized, placebo-controlled trials were identified using the JAPIC-DOC database and complementary extensive access to their production companies. Metabolic activators included nilvadipine, ifenprodil, aniracetam, and others. The treatment duration ranged from 4 (in one trial) to 8 weeks. The primary end-point of efficacy was a clinical global impression (CGI) at 8 weeks, graded on a 5-point scale. A case graded the best two categories was defined to be effective. A meta-anlysis using the random-effects model was applied with the cumulation in chronological order.

Results: the odds ratio (OR) for efficacy was 1.71 (95% CI:1.36 to 2.15, 2P<0.00001) and the efficacy difference (ED) was 9.5% (95% CI: 5.6 to 13.3%). When limited to cerebral infarctions, the OR was 1.77 and the ED was 10,7% which was better than those for the cerebral haemorrhages (OR: 1.29; ED: 6.9%).

Discussion: Although there might be publication bias or new drug approval bias, the result of a cumulative meta-analysis suggests that metabolic activators may be effective on the CGI. However, the long-term effect of them is still unproven.