Multiple overlapping systematic reviews facilitate the origin of disputes: the case of thrombolytic therapy for pulmonary embolism

Publication date: Available online 22 November 2017
Source:Journal of Clinical Epidemiology
Author(s): Nicoletta Riva, Livia Puljak, Lorenzo Moja, Walter Ageno, Holger Schünemann, Nicola Magrini, Alessandro Squizzato
ObjectiveTo explore disagreements in multiple systematic reviews (SRs) assessing the benefit-to-harm ratio of thrombolytic therapy in patients with intermediate-risk pulmonary embolism (PE).Study Design and SettingMEDLINE, EMBASE, CDSR and DARE were searched up to April 14, 2016. We included SRs and guidelines that evaluated thrombolytic therapy, compared to anticoagulation alone, in intermediate-risk PE. We calculated pooled risk ratio (RR) and absolute risk difference (RD), with interquartile range (IQR), for all-cause mortality, recurrent PE and major bleeding.ResultsWe marked PEITHO, the largest trial, as a research milestone. Since its release in 2014, twelve SRs (2-15 included trials) and two major guidelines were published. Studies were concordant in reporting that thrombolysis reduced all-cause mortality (median RD -1.55%, IQR -1.60 to -1.40%; median RR 0.55, IQR 0.48-0.61). Discordant results were found for major bleeding (median RD 4.70%, IQR 0.90-5.70%), with SRs reporting results in opposite directions. Relevant magnitude of effects and precision for benefits and harms were never pre-specified.ConclusionFourteen evidence syntheses were published within 25 months. Conclusions suggested mortality reduction associated with thrombolytics. Therapy harm was more dispersed and alternatively considered. Interpretation of the benefit-to-harm ratio was elusive, and modest incremental advantages might or not be important, facilitating the origin of disputes.



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