Credit: Original article published here.
Patients being evaluated for kidney transplant routinely undergo screening for coronary heart disease (CHD). Testing, both noninvasive and invasive, in asymptomatic patients is prevalent in clinical practice, and 40% of Medicare beneficiaries who underwent kidney transplantation were screened for CHD in the year prior to transplantation.
Numerous studies published in the 2000s argued against CHD screening in asymptomatic patients. However, proponents of screening contend that the trials did not include patients with advanced kidney disease and/or did not examine perioperative risk specifically. In addition, regulatory agencies have used posttransplant survival as the primary metric to evaluate and accredit transplant programs, creating an incentive to avoid perioperative events that may be associated with early death.
According to Xingxing S. Cheng, MD, MS, and colleagues, there are few data demonstrating the positive association of CHD screening with kidney transplant outcomes. The researchers conducted a retrospective cohort study designed to estimate the association of pretransplant CHD testing with rates of death and myocardial infarction (MI). Results were reported online in JAMA Internal Medicine [doi:10.1001/jamainternmed.2022.6069].
The study included all adult, first-time kidney transplant recipients from January 2000 through December 2014 in the US Renal Data System. Eligible patients had at least 1 year of Medicare enrollment prior to and following the transplant. The study utilized an instrumental variable (IV) analysis; the IV was the program-level CHD testing rate in the year of the transplant. Because the rate of CHD testing varied over time, analyses were stratified by study period. Exposure, IV, covariates, and outcomes were determined using a combination of US Renal Data System variables and Medicare claims.
The study exposure was receipt of nonurgent invasive or noninvasive CHD testing during the 12 months preceding kidney transplant. The primary outcome of interest was a composite of death or acute MI within 30 days after kidney transplant, adjusted for age, sex, race, education, dialysis vintage, history of CHD, diabetes, and transplant type (living vs deceased donor).
The IV cohort included 121,101 waitlist candidates. To examine outcomes, the researchers created a study cohort of 79,334 adult, first-time kidney transplant recipients with 1 year of Medicare Parts A and B coverage before and after kidney transplantation from 2000 to 2014. Of the 79,334 patients, 38% (n=30,147) were women, 21% (n=25,387) were Black, and 61% (n=48,394) were White. Mean age was 56 years during 2012 to 2014.
The proportion of low-risk, waitlisted patients who underwent elective CHD (IV cohort: eligible patients on the waitlist on January 1 of each year) was 0.13 (range, 0 to 0.44 across programs).
Patients were stratified into quintiles of the IV by era. Era 2000-2003: quintile [range] of program-predicted CHD testing rate: 0-6.6; 6.6-8.4; 8.4-10.0; 10.0-13.7; and 13.7-44.4. Era 2004-2007: 0-7.8; 7.8-10.8; 10.8-13.1; 13.1-15.2; and 15.3-31.5. Era 2008-2011: 0-9.2; 9.2-12.2; 12.2-15.3; 15.3-17.8; and 17.8-33.3. Era 2012-2014: 0-10.7; 10.7-13.9; 13.9-16.9; 16.9-21.6; and 21.6-46.7. The proportion of study patients who underwent CHD testing during the 12 months before kidney transplant increased monotonically across increasing IV quintiles.
Of the 34,688 kidney transplant recipients who underwent CHD testing in the year prior to transplant, the median time between CHD testing and transplant was 188 days. A total of 8125 patients (23%) underwent testing on or prior to joining the waitlist; 77% (n=26,563) underwent testing after joining the waitlist.
The primary outcome of death or acute MI occurred in 5.3% (n=4604) of the study cohort within 30 days of kidney transplant. During the study period, there was a decrease in the 3-day event rate from 6.6% in the 2000 to 2003 era to 4.4% in the 2012 to 2014 era.
During the 2012 to 2014 era, the CHD testing rate was 56% in patients in the fifth IV quintile (the most test-intensive quintile) and 24% in patients in the first IV quintile (the least test-intensive quintile), P<.001. The pattern was similar across study periods.
Results of the main IV analysis demonstrated that, compared with a reference of no testing, there was no association between CHD testing and change in the rate of the primary outcome at 30 days posttransplant (rate difference, 1.9%; 95% CI, 0%-3.5%). The effect sizes were constant across the eras, with the exception of 2000 to 2003 when a slight increase in event rate (greater than the basal rate of 6.6%) associated with CHD testing was observed (6.8%; 95% CI, 1.8%-12.3%). In sensitivity analysis that excluded covariates from the model and used the alternative definition of IV (program-level CHD testing rate in high-risk candidates), results were generally similar.
Citing limitations to the study findings, the researchers included residual confounding that may not be fully resolved by the quasiexperimental IV study design; different kidney transplant programs may have different thresholds for risk acceptance overall; the study determined CHD testing based on Medicare A claims and did not include testing submitted to private insurers or financed via the Organ Acquisition Cost Center; and the inability to identify the actual indication for CHD testing.
In conclusion, the authors said, “This quasiexperimental cohort study using program-level CHD testing as an IV was unable to demonstrate that pretransplant CHD testing was associated with reduced early death and MI within 30 days of kidney transplant. There is even a potential signal that CHD testing was associated with harm during the earlier study eras. Ideally, a US-based, randomized controlled trial can verify or disprove these results. However, in places where such a study is not possible, pragmatic studies in countries with less perceived regulatory pressure and a more integrated health delivery system (eg, CARSK [Canadian-Australian Randomised trial of Screening Kidney Transplant Candidates for Coronary Artery Disease]) offer the best hope. Studies such as ours, in an US population using quasiexperimental methods, potentially help to complement these interventional studies in other countries and may pave the way to deescalating CHD testing before kidney transplantation.”
Takeaway Points
- Researchers reported results of a retrospective cohort study designed to examine the association between pretransplant coronary heart disease (CHD) testing and rates of death and myocardial infarction following transplant.
- The primary outcome (death or myocardial infarction within 30 days after kidney transplantation) occurred in 5.3% of the 79,334 patients in the study cohort.
- The study results suggested that testing for CHD may not be associated with reduced adverse outcomes early after kidney transplant.
