SAT-801 - Cardiovascular Risk Associated with Romosozumab Treatment in Osteoporosis

Background

Patients were characterized by the original studies using the Raloxifene Use for the Heart (“RUTH”) cardiovascular risk scoring system. Comparing the ARCH vs FRAME trials, the subjects in ARCH were older (74 ± 8 vs 71 ± 7 years), had greater percentage >75 years of age (53% vs 31%), and had a higher prevalence of RUTH scores >6 (28% vs 20%),(all p < 0.001). In the current analysis, the cardiovascular event rates (CVE) in the comparator groups were used to estimate the baseline CVE rates and to calculate the rate differences (RD) in CVE between romosozumab vs. comparators. An increased CVE RD was observed in the romosozumab group which was best fit by an exponential regression (r = 0.97, p < 0.001), such that at a baseline CVE rate >0.02 per year (20% 10-year risk rate) there was an increased RD for CVE of 0.01/year (number needed to harm =100). There were no increases in the RD for cerebrovascular events or deaths. The FRAME and ARCH trials included 2-year follow-ups. As expected with increases in baseline age from 70.9 to 72.9 years in FRAME and from 74.4 to 76.4 years in ARCH, there was an age associated increase in CVE rates (r = 0.735, p = 0.049). When CVE events during year one of ARCH (romosozumab vs alendronate) was compared with CVE during the 2-year follow up (romosozumab followed by alendronate vs alendronate followed by alendronate ) there was a significant RD in ischemic CVE only during the romosozumab treatment year , which was not sustained during follow-up years (RD year 1 vs year 3 = 0.006 ± 0.002, p = 0.014).

Discussion

Although the FDA regulatory recommendations were to avoid romosozumab in patients who sustained recent cardiovascular events, these events were not prespecified. From the current analysis, cardiovascular risk may be assessed using alternative risk engines. Patients exceeding a 20% 10-year cardiovascular risk demonstrated an exponential increase in CVE during romosozumab treatment. This excess risk does not appear to be sustained after discontinuation. These findings support the use of baseline cardiovascular risk assessment when considering romosozumab therapy. Further analyses would be necessary to evaluate these short-term cardiovascular risks against the potential survival benefits associated with romosozumab fracture-prevention.

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