Long-Term Cardiovascular Safety of HIF-PHIs

Oral hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a common treatment for anemia of chronic kidney disease. To examine their long-term safety, Jeffrey T. Ha, PhD, and colleagues conducted a systematic review and meta-analysis of data from the MEDLINE, Embase, and Cochrane databases. Their results were published in NEJM Evidence.

The researchers searched the three databases for randomized trials comparing HIF-PHIs to an erythropoiesis-stimulating agent (ESA) or placebo with 48 weeks or more of follow-up. There were 25 trials and 26,478 participants included in the analysis. Thirteen trials enrolled 13,230 participants with dialysis-dependent CKD, while 12 trials enrolled 13,248 participants with nondialysis-dependent CKD. The primary outcome was a major adverse cardiovascular event (MACE; a composite of myocardial infarction, stroke, or all-cause death).

HIF-PHIs and ESA did not differ in terms of their effects on MACE in participants with dialysis-dependent CKD (risk ratio, 0.99; 95% CI, 0.92-1.08) or nondialysis-dependent CKD (risk ratio, 1.08; 95% CI, 0.95-1.22). HIF-PHIs and placebo also did not have different effects on MACE (risk ratio, 1.10; 95% CI, 0.96-1.27) in people with nondialysis-dependent CKD.

There was no observable difference between HIF-PHIs and ESA or placebo for individual aspects of MACE and cardiovascular death. The safety of HIF-PHIs compared to ESA was similar for other outcomes in participants with dialysis-dependent CKD. However, in those with nondialysis-dependent CKD, infections, dialysis access thrombosis, venous thromboembolism, and hyperkalemia were more prevalent with HIF-PHIs in placebo-controlled trials. However, that was not the case in ESA-controlled trials.

In summary, the researchers found no evidence that the long-term cardiovascular safety of HIF-PHIs differed from ESA in adults with dialysis-dependent CKD and adults with nondialysis-dependent CKD.

Source: NEJM Evidence