Rheumatology update: New CV safety information

Abstract

In November 2017, FDA released a drug safety communication that described data suggesting that febuxostat (Uloric—Takeda) may be associated with an increased risk of heart-related deaths compared with allopurinol.1www.fda.gov/downloads/Drugs/DrugSafety/UCM584803.pdfGoogle Scholar In February 2018, Arthritis Care and Research published an article exploring whether rheumatoid arthritis (RA) could be considered a diabetes risk equivalent for cardiovascular (CV) events.2Arthritis Care Res (Hoboken). 2018; ([Epub ahead of print])https://doi.org/10.1002/acr.23535Crossref Scopus (8) Google Scholar A safety trial conducted in more than 6,000 patients with gout who were treated with febuxostat or allopurinol showed that use of febuxostat increased the risk of heart-related deaths and death from all causes compared with allopurinol. The trial, which was a Phase IV commitment to FDA, showed that febuxostat did not significantly increase the risk of the composite primary endpoint (e.g., heart-related death, nondeadly myocardial infarction [MI], nondeadly stroke, urgent CV surgery), but it did increase two of these components (heart-related deaths and death from all causes) when analyzed separately. On the basis of these data, FDA released a drug safety communication to alert the public about this finding and also stated it will continue to evaluate this potential safety issue. The “Warnings and Precautions” section of the current label for febuxostat states that a higher rate of CV thromboembolic events have been observed in patients treated with the drug compared with allopurinol in clinical trials. The label states that a causal relationship with febuxostat and CV events has not been established. The manufacturer recommends that clinicians monitor patients for signs and symptoms of both MI and stroke. FDA advises that clinicians consider the risks and benefits of treatment when deciding whether to prescribe or continue patients on febuxostat. The agency recommends that patients discuss any concerns they have with their provider and not to stop the medication on their own. As more information on this topic emerges in the future, clinicians will have a better understanding of the CV risks associated with the use of febuxostat compared with other gout agents. Data suggest that patients with RA are at an increased risk of CV events, but some researchers have wondered if the risk is as high as it is for patients with diabetes. Curtis and colleagues conducted a retrospective cohort study to assess the potential effect of RA on CV risk.2Arthritis Care Res (Hoboken). 2018; ([Epub ahead of print])https://doi.org/10.1002/acr.23535Crossref Scopus (8) Google Scholar The researchers used 2006 to 2010 data from commercial and public health plans to identify patients with RA and diabetes, RA alone, diabetes alone, or neither of these two conditions. The occurrence of three outcomes—acute MI, stroke, and coronary revascularization—was assessed in these patients. A total of 920,772 patients were included in the analysis, with 9,921 in the RA and diabetes group, 46,229 in the RA-alone group, 251,822 in the diabetes-alone group, and 636,520 in the “neither” group. The incidence rates (IRs) of the outcomes, standardized to the 2010 U.S. census age and sex distribution, were calculated for the four cohorts. The researchers reported that the calculated age–sex standardized IRs (per 1,000 person-years) for MI were highest for patients with RA and diabetes (IR = 12.6 [95% CI 10.7–14.7]), followed by patients with diabetes only (IR = 10.7 [10.3–11.0]), RA only (IR = 5.7 [5.2–6.3]), and finally, neither condition (IR = 4.2 [4.1–4.3]). The same pattern was observed for stroke, with the risk higher in those with diabetes alone than RA alone. The researchers concluded that RA increases CV risk but not to the extent that diabetes does, so the data do not support the hypothesis that RA is a diabetes risk equivalent for CV events. They wrote, “Given these findings, lipid management in RA patients may not need to be as aggressive as compared to recommendations for patients with DM [diabetes].” Clinicians should be aware of the elevated CV risks in patients with RA and educate them on lifestyle modifications and preventive therapies as appropriate.