LONDON, UK ( updated ) — Authors of a scathing analysis in the BMJ today are calling on the European Society of Cardiology (ESC) to revise its recent guidance pertaining to the use of beta-blockers in patients undergoing noncardiac surgery, to overhaul its guideline process to be more transparent, and to act much more swiftly to revise recommendations when patient lives are at risk.
"We need to reinvigorate guideline systems so that experts can act swiftly and openly to prioritize patient safety," Drs Darrel P Francis and Graham D Cole (National Heart and Lung Institute, Imperial College London, UK) write.
Lead author on the guidelines, however, Dr Steen Dalby Kristensen (Aarhus University Hospital, Skølby, Denmark), who spoke with heartwire after the BMJ paper was published, insisted that beta-blockers still have a role to play in this setting and defends both the time it took to put the guidelines together and the confidentiality required of guideline writing groups.
As reported by heartwire , both the ESC and AHA/ACC released new guidelines earlier this month. Both downgraded recommendations for initiating beta-blockers in high-risk patients undergoing noncardiac surgery, and both endeavored to exclude the DECREASE papers from their revised guidelines.
The DECREASE series of trials formed the basis for 2009 guidance supporting the use of beta-blockers in patients at high CV risk who are undergoing high-risk, non-CV surgery. Those trials have since been deemed to be "unreliable" and include "fictitious data," Francis and Cole write.
As such, the new guidelines include a "softened" recommendation—from a class I recommendation to class IIb ("usefulness/efficacy is less well established"), something the BMJ authors argue "is not enough."
"We believe that the ESC should reduce their recommendation to class III ('not recommended') to reflect the significant increase in mortality in the credible randomized trials."
Francis and Cole were both authors on a 2013 analysis that suggested initiation of beta-blockers in patients undergoing noncardiac surgery increased the risk of mortality by 27%, potentially resulting in the deaths of as many as 10 000 patients per year in the UK alone.
Disgraced DECREASE Still Taint Guidelines
In their analysis today in the BMJ, they point out that despite the stated efforts to exclude the discredited DECREASE studies, they do actually make their way into both the American and European guidance via inclusion in meta-analyses that were considered by the 2014 guideline writers.
"We are now all agreed that certain trials are so untrustworthy that their results must not be used in guidelines," Francis pointed out to heartwire . "Can it be right to use, instead, meta-analyses that depend mostly—or entirely—on those results?"
Of note, the American guidelines are accompanied by an evidence review, published shortly after the AHA/ACC and ESC released their guideline documents. In this evidence review, authors conclude that when the DECREASE trials are excluded from analyses, the remaining randomized controlled trials show a significantly increased mortality rate. This pooled estimate is dominated by the POISE trial, they note, which has been criticized for the dose it used. But according to the evidence reviewers, even when POISE is excluded, the "pooled effect in the remaining studies was qualitatively similar."
Speaking with heartwire , Francis said, "I applaud the evidence review committee [ERC] for their meticulous work. . . . Their report is excellent and rightly focuses on the reliable randomized trials. I'm just not sure to what extent the full American guideline fits the ERC conclusion. Doesn't the ERC clearly say the trials show a significant increase in mortality?"
Kristensen, in an interview, stands by the ESC's decision, noting that any analyses that exclude the DECREASE studies are so overwhelming driven by the results of POISE that these, too, are problematic. POISE, he explained, not only used high doses of metoprolol but did not uptitrate the drug and started it right before surgery, rather than having the drug infused over a longer period. "I'm not claiming that POISE is invalid, but the way that the beta-blocker was used in POISE is really not how we've been practicing today," he said. As a result, the guidelines need to take that into account.
Moreover, Kristensen said, the guidelines do give a class III recommendation in specific instances—namely, giving beta-blockers without titration and giving beta-blockers in the setting of lower-risk noncardiac surgeries.
More Transparency Needed
Also troubling to Francis and Cole is the fact that concerns about the integrity of the DECREASE trials—which ultimately led to lead author Dr Don Poldermans's dismissal —were raised in July 2011. In November 2011, the ESC released a press release acknowledging Poldermans's dismissal, saying it was "saddened" by the situation but promising to "carefully" review the guidelines. New guidance was not ultimately released until another year and a half went by.
"For a matter of life and death, it has taken almost three years from research being discredited to the recommendation level being reduced," Francis commented to heartwire . "Can we build ways to move faster in future?"
Kristensen, in response, observed that while some critics have charged the guideline committee with being too slow, others have complained they rushed the document out. "The fact is that we have been putting this document together over one and a half years"—no mean feat, given the 20 to 25 experts involved in the writing process, plus approximately 100 outside reviewers. Moreover, the guidelines deal with a much broader range of topics than just beta-blockers. "To get all of this together and come up with a document that both the authors and the reviewers actually agree upon is a process that takes time," he insisted.
Cole and Francis argue that the entire guideline process needs to change, pointing out that ESC guideline committee members currently sign confidentiality statements that require all discussions during guideline development to remain "secret and confidential."
"There seems to be no clause permitting ESC experts to raise the alarm when needed, even to prevent loss of life," Cole and Francis lament.
On this point, Kristensen countered that confidentiality agreements are an unavoidable necessity that guarantee the independent views of the participating experts.
"I don't like to use the word 'secrecy,' because it implies you are trying to hide something, but we need confidentiality because, while we need something that in the end is a recommendation for physicians to follow, there are a lot of intermediate steps that might cause confusion. There are also commercial issues, because clearly there would be an interest from industry that have either drugs or devices [that would be used to greater or lesser degrees] in the new guidance."
He added that if a "huge issue" arose during the guideline process that more than one person was concerned about, "then of course we would consider how to deal with that. But I think, while the committee is working, it has to be in a room where we have confidentiality: anything else would make for a lot of confusion."
Francis and Cole have no conflicts of interest.
Heartwire from Medscape © 2014
Cite this: Analysis Decries Beta-Blocker Stance in Noncardiac-Surgery Guidelines - Medscape - Aug 29, 2014.