Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medication in several countries, including Thailand. NSAIDs have been associated with hepatic side effects; however, the frequency of these side effects is uncertain. Aim of the Review To systematically review published literature on randomized, controlled trials that assessed the risk of clinically significant hepatotoxicity associated with NSAIDs. Methods Searches of bibliographic databases EMBASE, PubMed, and the Cochrane Library were conducted up to July 30, 2016, to identify randomized controlled trials of ibuprofen, naproxen, diclofenac, piroxicam, meloxicam, mefenamic acid, indomethacin, celecoxib, and etoricoxib in adults with any disease that provide information on hepatotoxicity outcomes. Results Among the 698 studies, 18 studies met the selection criteria. However, only 8 studies regarding three NSAIDs (celecoxib, etoricoxib, and diclofenac) demonstrated clinically significant hepatotoxic evidence based on hepatotoxicity justification criteria. Of all the hepatotoxicity events found from the above-mentioned three NSAIDs, diclofenac had the highest proportion, which ranged from 0.015 to 4.3 (×10−2), followed by celecoxib, which ranged from 0.13 to 0.38 (×10−2), and etoricoxib, which ranged from 0.005 to 0.930 (×10−2). Conclusion Diclofenac had higher rates of hepatotoxic evidence compared to other NSAIDs. Hepatotoxic evidence is mostly demonstrated as aminotransferase elevation, while liver-related hospitalization or discontinuation was very low.

To cite this article: Saokaew S, Permsuwan U, Chaiyakunapruk N, Nathisuwan S, Sukonthasarn A. Effectiveness of pharmacist-participated warfarin therapy management: a systematic review and meta-analysis. J Thromb Haemost 2010; 8: 2418-27.Summary. Objective: Although pharmacist-participated warfarin therapy management (PWTM) has been accepted and implemented in various parts of the world, the evidence demonstrating the effects of PWTM compared with usual care on clinical outcomes is lacking. We performed a systematic review and meta-analysis to compare the effects of PWTM with usual care on bleeding and thromboembolic outcomes. Methods: We searched MEDLINE, SCOPUS, EMBASE, IPA, CINAHL, Cochrane CENTRAL, Thai Index Medicus and Thai Medical Index, and reference lists of studies, without language restriction. Databases were searched from their inception to July 2009. The studies using warfarin as an anticoagulant with sufficient data for compilation of 2 · 2 tables were included. Both randomized controlled trials (RCTs) and non-RCTs were considered. Two authors independently reviewed each study, assigned quality scores and extracted data for all outcomes using a standardized form. Pooled effect estimates (risk ratio; RR) were obtained using a random effects model. Result: Of 661 articles identified, 24 studies with 728,377 patients were included. In the random-effects meta-analysis of RCTs, the PWTM group had statistically significant effects on the prevention of total bleeding [RR, 0.51; 95% confidence interval (CI), 0.28-0.94]. However, the effects on major bleeding (RR, 0.64; 95% CI, 0.18-2.36), thromboembolic events (RR, 0.79; 95% CI, 0.33-1.93), all-cause mortality (RR, 0.93; 95% CI, 0.41-2.13) and warfarin-related mortality (RR, 0.65; 95% CI, 0.18-2.42) were not significant. Conclusion: PharmacistÕs participation in the management of warfarin therapy significantly reduces total bleeding, with a non-significant trend towards decreases in other warfarin-related complications.

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Pharmacist-managed warfarin therapy resulted in a significantly better anticoagulation control. This study showed that a collaborative approach in anticoagulation management can be successfully implemented in a developing country. Implementation of such care model in other developing countries should be considered.

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