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AHA: Prevention Down, Endocarditis Up in U.K.

— Are guidelines to blame?

Last Updated November 21, 2014
MedpageToday

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CHICAGO -- The British policy against any antibiotic prophylaxis to prevent infective endocarditis might have led to an increase in cases, a study suggested, although the observational data drew some criticism.

After guidelines changed in 2008, above the population-adjusted projection from historical trends, , of England's University of Sheffield School of Clinical Dentistry, and colleagues found.

That translated to 35 more cases per month (0.11 per 10 million per month) across the U.K. by March 2013 than expected (P<0.0001) in their analysis of U.K. national health service databases.

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • Prescriptions of antibiotic prophylaxis fell substantially and the incidence of infective endocarditis increased significantly in England after introduction of new guidelines.
  • Note that this study cannot prove causality.

"This increase in the incidence of infective endocarditis was significant for both individuals at high risk of infective endocarditis and those at lower risk," with statistically significant increases in trend lines for both (P=0.025 and P=0.0002, respectively), the group reported here at the American Heart Association meeting and online in The Lancet.

The shift point in infectious endocarditis cases found in the study came just 3 months after the guideline introduction.

Before that, national policy from the U.K. National Institute for Health and Clinical Excellence (NICE) was antibiotics for high- and moderate-risk patients during dental procedures, colonoscopy, and a range of other procedures.

From the roughly 4-year period before the change to the last 6 months of the study (up to March 2013), single-dose amoxicillin or clindamycin prescriptions (almost all issued by dentists) dropped nearly 88% across the country.

The mean went from 10,900 prescriptions per month from January 2004 through March 2008 down to 2,236 prescriptions per month from April 2008 through March 2013 (P<0.0001).

Around the world, infectious endocarditis prevention guidelines have shifted to shorter durations and a higher threshold for prescription. Since 2007, U.S. guidelines have recommended antibiotic prophylaxis only for high-risk patients.

The data could suggest that the British policy went too far and that other countries should not follow suite.

"Although there is a temporal association, we cannot conclude there is a cause-effect relationship," Thornhill cautioned.

The study also showed a nonsignificant upward shift in infectious carditis mortality rate over that period, for a potential 1.5 extra deaths per month or 18 per year.

"I would argue there are reasons to be skeptical," said study discussant Dhruv S. Kazi, MD, of the University of California San Francisco.

Historical controls give an imperfect adjustment for background infectious endocarditis rates, in particular because the method used to control for population growth didn't take into account that the subgroup of people at highest risk is growing faster than the general population, he cautioned.

"We were unable to obtain data for other groups of individuals potentially at risk of developing infective endocarditis such as people with diabetes, elderly people, and those living in residential care," Thornhill and colleagues acknowledged in the Lancet paper.

If indexed instead by overall hospitalization rates, there appeared to be a slight inflection point in 2008 for unknown reasons, Kazi noted.

"Obviously, endocarditis hospitalizations are a tiny fraction of all-cause hospitalizations, so we need an alternative explanation for this," he told reporters at a press conference.

Also, there was no bacteriology data, there have been no rises in endocarditis in other countries as guidelines have changed, and the infectious endocarditis mortality rate was unexpectedly low, Kazi added, urging a "very cautious interpretation."

"At the present time, these [data] should not prompt changes in prescription practices," he said, adding in an interview with MedPage Today, "they tell us how little we know about the connection between antibiotics and endocarditis."

All U.S. studies done around the American Heart Association guideline changes on antibiotic prophylaxis for infectious endocarditis have been smaller, shorter, or both compared with the British national databases, Thornhill's group countered.

NICE issued a statement declaring an immediate review of their infectious endocarditis prophylaxis guideline but also urged clinicians not to change their practice yet.

Both Thornhill and Kazi agreed that a prospective, randomized controlled trial is now warranted.

"I think we've established sufficient equipoise in this connection between antibiotics and endocarditis that at this point we have to go forward with a large randomized trial," Kazi told MedPage Today.

"Previously, the challenge to this trial has been that infectious endocarditis is rare, so we would need a very large sample size," he explained. "But pragmatic trials have now made it possible to recruit a large number of patients at relatively low cost. I think we need to bring those to bear on this very important question."

A cost analysis is also planned from the database, Thornhill noted, although no mention was made of the number of antibiotic prophylaxis-related adverse drug reactions that might have been prevented through the guideline update in 2008.

Disclosures

The study was funded by Heart Research U.K., Simplyhealth, and the U.S. National Institutes of Health.

Thornhill disclosed no relevant relationships with industry.

Kazi disclosed no relevant relationships with industry.

Primary Source

The Lancet

Dayer MJ, et al "Incidence of infective endocarditis in England, 2000–13: a secular trend, interrupted time-series analysis" Lancet 2014; DOI: 10.1016/S0140-6736(14)62007-9.