Treatments to Prevent ESRD Are Less Effective in the “Real World”

In a real-world population of older adults at risk, interventions to prevent ESRD have a smaller effect size than reported in clinical trials, reports a study in JAMA Internal Medicine.

The simulation study used a retrospective cohort of more than 370,000 Department of Veterans Affairs (VA) patients with chronic kidney disease. Data from four major trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ACEIs/ARBs) for prevention of ESRD were applied to this real-world, high-risk population. In the trials, with follow-up times of 2.6 to 3.4 years, patients taking ACEIs/ARBS had relative risk reductions of 23 to 56 percent for ESRD.

The reported numbers needed to treat (NNT) ranged from nine to 25. The researchers analyzed the expected impact of a 30 percent relative risk reduction on the NNT to prevent one case of ESRD over 3 years.

In the real-world VA population, the estimated NNT values varied widely according to the patients’ baseline ESRD risk. For patients at highest risk (estimated GFR [eGFR] 15 to 29 mL/min per 1.73 m2 and dipstick proteinuria 2+ or greater), NNT was 16. In contrast, for those at lowest risk (eGFR 45 to 59 mL per min/1.73 m2 and negative or trace proteinuria, or eGFR 60 mL/min per 1.73 m2 or higher with 1+ proteinuria), the NNT to prevent one case of ESRD rose to 2500.

More than 90 percent of patients in the VA cohort fell into a group with an NNT of 100 or higher. The results were similar on sensitivity analysis and with up to 10 years of ACEI/ARB treatment. This was so in all sensitivity analyses and with exposure time of up to 10 years.

All four clinical trials of ACEI/ARBs excluded patients older than age 70, with varying eligibility requirements related to diabetes and proteinuria. The new simulation study suggests that the effect size of ACEI/ARB treatment for preventing ESRD is likely to be substantially smaller in a real-world population of older patients with renal insufficiency, compared with the trial results. The investigators conclude, “This study highlights the importance of interpreting treatment effects from randomized clinical trials in the context of risk information from real-world clinical settings” [O’Hare AM, et al. Interpreting treatment effects from clinical trials in the context of real-world risk information: end-stage renal disease prevention in older adults. JAMA Intern Med. Published online January 13, 2014. doi:10.1001/jamainternmed.2013.13328].

March 2014 (Vol. 6, Number 3)