Do HIF-PHIs lower cholesterol but not heart death risk in kidney disease?
HIF-PHIs (hypoxia-inducible factor prolyl hydroxylase inhibitors) are oral drugs used to treat anemia in chronic kidney disease (CKD). A large meta-analysis confirms they lower LDL cholesterol and total cholesterol, but this does not translate into fewer heart-related deaths or heart attacks. The cholesterol-lowering effect appears separate from cardiovascular protection.
What the research says
A systematic review and meta-analysis of 20 randomized controlled trials involving 12,155 patients found that the HIF-PHI roxadustat significantly reduced LDL cholesterol by about 16 mg/dL, total cholesterol by about 25 mg/dL, and triglycerides by about 20 mg/dL 29. However, it also lowered HDL cholesterol (the 'good' cholesterol) by about 5 mg/dL 29. When looking at cardiovascular outcomes, the same analysis found no significant difference in cardiovascular death, myocardial infarction, stroke, or all-cause mortality between HIF-PHIs and erythropoiesis-stimulating agents (ESAs) or placebo 29. A 2022 review of HIF-PHIs noted that overall, non-inferiority was shown for major cardiovascular events, except for one molecule in the non-dialysis population 10. So while HIF-PHIs improve anemia and lower certain lipids, they do not appear to reduce heart death risk in CKD patients.
What to ask your doctor
- Given that HIF-PHIs lower my cholesterol but not my heart risk, should I still take a statin or other cholesterol medication?
- Are there other treatments for anemia in CKD that might have better heart outcomes?
- How do my current cholesterol levels and heart risk factors affect the choice between HIF-PHIs and ESAs?
- Should I have my HDL cholesterol monitored if I start a HIF-PHI?
- What is my individual risk of cardiovascular events, and how does that factor into anemia treatment decisions?
This question is drawn from common patient questions about this topic and answered using cited medical research. We do not provide individualized advice.