Screening for Asymptomatic CAD in Waitlisted Transplant Candidates

For the majority of patients with kidney failure, kidney transplantation offers superior survival and quality of life compared with maintenance dialysis therapy. For patients with cardiovascular disease, the risk for morbidity and mortality following transplantation is high. Because early detection of asymptomatic coronary artery disease (CAD) and treatment with revascularization may prevent perioperative myocardial infarction and cardiovascular deaths, screening for CAD prior to transplantation may provide additional prognostic data and facilitate early intervention and informed allocation of resources.

Guidelines from Kidney Disease Improving Global Outcomes call for annual CAD evaluation for diabetic patients on the transplant waitlist and re-evaluation for CAD every 24 to 36 months for all other patients. Previous trials in patients without kidney failure have not shown a survival benefit for screening for CAD in asymptomatic patients, and there are no data available on the cost-effectiveness of screening for asymptomatic CAD.

Researchers are currently conducting the Canadian-Australian randomized controlled trial of screening kidney transplant candidates for CAD (CARSK: ACTRN1261000736448 and NCT03674307) to test the hypothesis that after waitlist entry, no further screening for asymptomatic CAD is noninferior (with a margin of a 25% increase or 1.5% absolute difference) to regular screening for CAD in preventing major adverse cardiac events. One outcome of interest is the cost-effectiveness of regular CAD screening compared with no further screening and the subsequent economic impact of costs related to CAD from a health system perspective.

Results from the CARSK study are not expected until 2025. Researchers, led by Tracey Ying, PhD, conducted a cost-utility analysis to determine, prior to completion of CARSK, the cost-effectiveness of screening for asymptomatic CAD and to identify potential influential variables that may affect results of the economic evaluation in CARSK. Results of the current analysis were reported in the American Journal of Kidney Diseases [2020;75(5):693-704].

The researchers developed a Markov microsimulation model to replicate the natural history of a theoretical cohort of Australian kidney transplant candidates 18 to 69 years of age. The primary outcome of interest was incremental cost-effectiveness ratio (ICER), reported as cost per quality-adjusted life-year (QALY).

The analysis compared two strategies: in the no-further-screening arm, patients received no further noninvasive CAD screening following waitlist entry unless they developed CAD symptoms; in the regular screening arm, all patients commenced screening in the first year of the model. Screening tests were repeated every year in patients with diabetes mellitus and every 2 years in patients without diabetes mellitus. If a patient had a positive stress test in any given year, the test was repeated the following year. The model assumed 100% screening adherence in the regular screening group.

In the base-case model that used a single point estimate for each variable within the model, the total lifetime costs of a patient following waitlist entry were $506,092 for no further screening versus $502,288 for regular screening. No further screening accrued an average 9.38 life-years (LYs) and 7.67 QALYs compared with 8.89 LYs and 7.31 QALYs for regular screening. The ICER of no further screening compared with regular screening was $8171 per LY gained and $11,122 per additional QALY.

Among the patients in the no-further screening group, a higher proportion received a transplant after 5 years compared with patients in the regular-screening group (65% vs 63%, respectively). There was a slightly higher mortality rate at 5 years in the regular-screening arm than in the no-further-screening arm (26.0% vs 24.8%), likely due to invasive cardiac procedures and longer waitlist time.

Transportation costs in the first year and the prevalence of CAD in waitlisted candidates had the greatest effect on changes in the ICER. There was no substantial alteration in the ICER due to CAD-related expenditure items such as the cost of revascularization or the costs of screening tests. No further screening remained cost-effective until transplant costs exceeded $200,000 in the first year. CAD presence was influential in the model when tested between the ranges of 10% to 90%. The reduction in ICER was marked when the prevalence of CAD was reduced to <30%, an indication that no further screening would be very cost-effective in cohorts with low prevalence of CAD. There was no substantial increase in ICER associated with a CAD prevalence of 90%. However, when combined with changes in the cost of transportation in year 1, CAD prevalence was influential in the model.

The researchers performed two-way sensitivity analysis using the top two most influential variables to test the combined effects of a range of transportation costs in year 1 and the prevalence of CAD. When no further CAD screening was performed in a cohort with a high prevalence of CAD and health expenditure in year 1 exceeded $170,000 to $200,000, the ICER was >$50,000 per QALY gained, but remained <$100,000 per QALY gained.

Results of probabilistic sensitivity analyses showed that 94% of the simulations were cost-effective below a willingness-to-pay threshold of $50,000 per QALY gained.

In conclusion the researchers said, “By incorporating the best available evidence, our pretrial model has provided an estimate of the benefits and trade-offs of no further screening versus regular screening in asymptomatic CAD in patients on the kidney transplant waitlist. Our results challenge the belief that regular screening for asymptomatic CAD improves outcomes. The lack of randomized controlled trials among patients with kidney failure and the clinical uncertainties surrounding the efficacy of CAD screening reinforce the need for a large prospective multicenter trial.”

Takeaway Points

1. Researchers conducted a modeled cost-utility analysis to determine the cost-effectiveness of no further screening for asymptomatic coronary artery disease (CAD) in patients on the waitlist for kidney transplantation versus regular screening.
2. The incremental cost-effectiveness ratio of no further screening was $11,122 per quality-adjusted life year (QALY) gained compared with regular screening. No further screening increased survival by 0.49 LY or 0.35 QALY.
3. In probabilistic sensitivity analyses, 94% of the simulations were cost-effective below a willingness-to-pay threshold of $50,000 per QALY gained.