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AUSTIN, Texas – Denosumab (Prolia, Xgeva) carried no increased risk of cardiovascular disease or stroke when compared with zoledronic acid (Reclast, Zometa) to combat osteoporosis, researchers found.

Compared with zoledronic acid, denosumab had no significant impact on myocardial infarction risk at 36 months in either the Optum medical database (adjusted RR 0.97, 95% CI 0.63-1.32) or the MarketScan database (aRR 1.22, 95% CI 0.77-1.66), reported Tzu-Chieh Lin, PhD, director of observational research at Amgen in Thousand Oaks, California.

In his oral presentation at the annual meeting of the American Society for Bone and Mineral Research, Lin said the analysis was similar for the incidence of stroke (aRR 0.87 in the Optum database, 95% CI 0.56-1.17, and aRR 1.00 in the MarketScan data, 95% CI 0.61-1.40).

Similar results were observed when the stroke outcome was restricted to only ischemic stroke and when death was treated as a competing risk in the Optum analyses, which had information on death available, Lin said.

"A slightly lower risk of myocardial infarction at 6 and 12 months observed in denosumab users translated to a very small reduction in absolute risk and therefore was not considered to be clinically meaningful," he said.

He explained that Amgen conducted the research because there had been inconsistent evidence published regarding the cardio- and cerebrovascular benefits and risks of anti-osteoporosis medications. "European Union regulators requested Amgen to evaluate the potential risk of these events in a real-world population of denosumab users treated for osteoporosis," which was the impetus for the study, Lin explained.

In commenting on the study, session co-moderator Tiffany Kim, MD, of the University of California at San Francisco, told 木瓜直播: "In my clinical experience, I haven't seen cardiovascular or stroke events, and it really isn't something that I have seen discussed in the medical literature. But this was helpful to review the data, because there were reports that hinted at some problems with denosumab."

"Those events were investigator-reported but were never adjudicated and there may have been some differences in the way data was collected," she said. "These findings confirm that there was not cardiovascular or stroke signal when comparing denosumab to zoledronic acid. It is reassuring," she added.

The retrospective study was conducted using the two major U.S. claims databases, identifying men and women who were at least 55 years old and who initiated treatment with two different classes of antiresorptive agents – either the RANKL inhibitor denosumab or zoledronic acid, a bisphosphonate. The study included people taking either of the agents from October 2010 through the end of June 2019, looking for instances of myocardial infarction or stroke.

The researchers scrutinized outcomes among 73,127 patients in Optum who were followed for a mean of 350 days, and 96,611 people in the MarketScan database who had a mean follow-up of 385 days. About 90% of the patients in the study were women. There were about 500 myocardial infarction events and 715 stroke events in the two databases.

Lin said that the size of the databases was one of the strengths of the study and results were "robust across multiple sensitivity analyses." He also suggested that the study was long enough to capture outcomes.

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