March 22nd, 2013
Macrolide Antibiotic Linked to Increased CV Risk in Patients with Lung Conditions
Nicholas Downing, MD
Use of the macrolide clarithromycin in patients admitted with exacerbations of chronic obstructive pulmonary disease or community-acquired pneumonia is associated with increased risk for cardiovascular events, a BMJ study finds.
Researchers examined outcomes among nearly 3000 patients admitted to U.K. hospitals with either condition. During 1 year of follow-up, there were roughly 450 new admissions for a CV event.
After multivariable adjustment, patients who had received at least one dose of clarithromycin during their initial hospitalization were over 50% more likely to be admitted for a CV event during follow-up than those who didn’t receive a macrolide. In addition, among COPD patients, clarithromycin use was associated with increased risk for CV mortality at 1 year.
The researchers say their study is the first to show that clarithromycin use among such patients might be associated with an increased CV risk that persists well after treatment has stopped. Several potential mechanisms for this effect are proposed in the paper.
2 Responses to “Macrolide Antibiotic Linked to Increased CV Risk in Patients with Lung Conditions”
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The same problem as Azithromycin.
These macrolides antibiotics are frequently prescribed by our colleagues pneumologists.
With Clarithromycin the risk seems to continue after stopping the drug!
Which mecanism?
I have not see in the literature the same long risk with Azithromycin which prolongs QT interval; only during the prescription?.
This kind of report looks like the very recent one concerning high dose of potent statin linked to high renal risk… however this needs to be confirmed by other studies, before carrying them away from the market!
First, the main limitation of this observational study is its observational nature and prone to bias. The authors were cautious in their conclusion:
“The use of Clarithromycin in the setting of acute exacerbations of chronic obstructive pulmonary disease or community acquired pneumonia may be associated with increased cardiovascular events. These findings require confirmation…”
The mechanism?
The authors explain the mechanism by a Clarithromycin mediated activation of the inflammatory cascade resulting in more vulnerable plaques leading to more ACS or death beyond the time of prescription. To support even more the biological causality, they mentioned a strong association between prolonged (more than seven days) courses of Clarithromycin and cardiovascular events. Nevertheless, bias could also explain the observation: prolonged therapy indicated to more sick patients and thus, high-risk patients after discharge leading to worse outcomes.
As a speculative exercise, both (acute exacerbations of chronic obstructive pulmonary disease and community acquired pneumonia cohorts) KM curves continue to diverge homogeneously throughout the one-year follow-up period; one would wonder whether a longer follow-up might result in a greater Hazard Ratio. If this were the case, it is biologically improbable that Clarithromycin would have been the responsible for such a strong biological effect (too toxic to be true) and thus, other explanations should be considered. One more simple and plausible explanation might be treatment bias: more severe patient condition were more likely to be prescribed Clarithromycin due to more severe infections and therefore, higher risk patients with worse outcomes during follow-up.