Putting the record straight on aprotinin as safe and effective: results from a mixed treatment meta-analysis of trials of aprotinin.
OBJECTIVE
Meta-analysis of small, randomized, placebo-controlled trials demonstrated efficacy and safety of aprotinin. After highly publicized retrospective studies and the early stopping of the Blood Conservation Using Antifibrinolytics in a Randomized Trial (BART), aprotinin was withdrawn. We conducted a new meta-analysis (including BART) on safety and efficacy of aprotinin in cardiac surgery.


METHODS
We conducted a mixed treatment comparisons network meta-analysis estimating the effects of aprotinin and alternative agents in reducing blood loss during surgery. We implemented a combination of direct and indirect evidence in mixed treatment comparisons and estimated relative effects for different agents on all-cause mortality and return to the operating room for bleeding and conducted a supportive analysis of the effects of different agents with only directly randomized trials.


RESULTS
Mixed treatment analysis of 88 trials randomizing 15,528 patients to 1 of 3 antifibrinolytic agents demonstrated no difference in mortality between placebo and antifibrinolytic agents. Analysis of aprotinin versus tranexamic acid and ε-aminocaproic acid in 17 and 6 trials, respectively and tranexamic acid versus ε-aminocaproic acid in 5 trials demonstrated no difference in mortality between treatment allocations. All agents were superior to placebo in reducing reexploration for bleeding, with aprotinin numerically superior: aprotinin odds ratio, 2.6 (95% confidence interval, 1.9-3.7); tranexamic acid odds ratio, 1.79 (1.2-2.9), and ε-aminocaproic acid odds ratio, 2.4 (1.3-6.6).


CONCLUSIONS
This mixed treatment comparisons meta-analysis demonstrates no increased mortality risk with aprotinin versus other antifibrinolytic agents. All agents were superior to placebo in reducing reexploration for bleeding after adult cardiac surgery.
Department of Cardiac Surgery, University Hospital Birmingham, Birmingham, UK.
Neil
N
Howell
Eshan
E
Senanayake
Nick
N
Freemantle
Domenico
D
Pagano
D000933:Antifibrinolytic Agents / Q000009:adverse effects*; D007611:Aprotinin / Q000009:adverse effects*; D016063:Blood Loss, Surgical / Q000401:mortality / Q000517:prevention & control*; D019317:Evidence-Based Medicine; D017052:Hospital Mortality; D006801:Humans; D016017:Odds Ratio; D061214:Patient Safety; D019106:Postoperative Hemorrhage / Q000209:etiology / Q000401:mortality / Q000517:prevention & control* / Q000601:surgery; D016032:Randomized Controlled Trials as Topic; D012086:Reoperation; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
D000933:Antifibrinolytic Agents; D007611:Aprotinin