QUANTITATIVE RISK-BENEFIT ANALYSIS ON DOSAGE OF INTRAVENOUS TISSUE-TYPE PLASMINOGEN ACTIVATOR IN ASIAN PATIENTS WITH STROKE THROMBOLYSIS

Purpose: Intravenous tissue-type plasminogen activator (t-PA) is the only effective treatment for acute ischemic stroke in current practice. Recently, it has been used at lower dose in Asian countries due to the concerns of the safety and cost of the standard dose approved in the westerns countries. We aimed to evaluate the risk-benefit ratio of t-PA for the Asian stroke patients at diverse dosages of: (1) standard-dose (0.9 mg kg^-1) and (2) low-dose (0.7 mg kg^-1) to provide evidence for decision making of prescribing and reimbursement.

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.