Controversial 'New Events' in RE-LY Trial Now Published

September 25, 2014

BOSTON, MA — Lead RE-LY investigators have published slightly revised outcomes numbers for the trial based on cases of stroke and major bleeding that came to light partly in conjunction with litigation against Boehringer Ingelheim (BI)[1]. The "additional events" are in fact not new information per se, as they have already been widely discussed in the media and even medical publications.

The tweaks to the outcomes database appear to only negligibly alter some relative risks, confidence intervals, and p values for stroke, embolism, and bleeding outcomes, based on a table accompanying the new paper, a letter published September 24, 2014 in the New England Journal of Medicine. And according to the correspondents, led by co–principal investigator Dr Stuart J Connolly (McMaster University, Hamilton, ON), they do not change the conclusions of the trial as previously published.

RE-LY, which pitted two dosages of Boehringer Ingelheim's oral direct thrombin inhibitor dabigatran (Pradaxa) against warfarin in patients with nonvalvular atrial fibrillation, showed steep and significant drops in the risks of stroke/peripheral embolic events and of hemorrhagic stroke with the new agent. But bleeding was an issue at its higher dosage, and the trial's legacy has been dogged by claims of originally unreported bleeding events and by cases of bleeding associated with dabigatran after it came to market.

The company conducted a review of the trial's 1387 deaths to determine whether those cases included any bleeding or embolic events that weren't included in the original report, according to the letter. "In addition, seven possible cases were identified by plaintiffs' attorneys in a lawsuit related to dabigatran."

Those cases were evaluated by leaders of the trial's adjudication committee, which "concluded that there were 20 cases in which another unreported event had occurred in addition to the reported death and two cases in which there was an additional major bleeding episode that was not related to the death."

Those 22 cases included two strokes and 20 major bleeding events. Of those 20 major bleeds, according to Connolly et al, 18 had been identified in patients whose deaths had already been included in the mortality data.

"Connolly reports grants and personal fees from Boehringer-Ingelheim, grants and personal fees from Bristol-Myers Squibb/Pfizer, grants from Merck, grants and personal fees from Sanofi, grants and personal fees from Bayer, personal fees from Portola, grants from St Jude Medical, grants from Boston Scientific outside the submitted work; and an institutional research grant from Boehringer-Ingelheim." Disclosures for the coauthors are listed here.

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