Method: A decision model was created to compare the risk-benefit of the standard- and low- doses of t-PA. The risk measures were the occurrence of symptomatic intracerebral hemorrhage (SICH) and mortality respectively and in combination; the efficacy measures was the proportion of patients with a modified Rankin Scale (mRS) score ≤ 1 at 3 months. The estimates were obtained from the published meta-analysis literature about Asian population. The risk and benefit of both dosages were compared in the form of incremental risk-benefit ratios (IRBRs). Probabilistic sensitivity analysis and one-way sensitivity analysis were conducted to incorporate uncertainty in model parameters and to estimate the impact of changing each key parameter individually.
Result: When SICH was used as the risk measure, low-dose t-PA (IRBR = 0.3729) showed increased risk and benefit as compared to standard-dose t-PA. However, standard-dose t-PA was dominated over by low-dose t-PA (IRBR = -2.3333), when mortality was used as the risk measure. Furthermore, the result of combined SICH and mortality revealed that the standard-dose t-PA was favorable as compared with low-dose t-PA with the IRBR of -0.3529. In sensitivity analyses, the IRBR ratios were robust to variations in utility of effectiveness and mortality of low-dose t-PA.
Conclusion: Our results indicated that the standard-dose t-PA might be preferred over low-dose t-PA considering both risks and benefits. Selecting appropriate dosage of t-PA according to both risk and benefit simultaneously is suggested in order to achieve better treatment goals for acute ischemic stroke in Asian population.