SUN-119 COMPARING SURVIVAL IN PATIENTS WITH CHRONIC KIDNEY DISEASE ACROSS THREE COUNTRIES - RESULTS FROM THE STUDY OF HEART AND RENAL PROTECTION-EXTENDED REVIEW (SHARP-ER)

Abstract

Chronic kidney disease (CKD) is a key determinant of health outcomes and an important driver of mortality. International comparison is important to better understand how inter-regional differences affect clinical outcomes. We examined whether survival differed between participants from Australia (AUS), Malaysia (MYL) and New Zealand (NZ) in the SHARP-ER study. SHARP-ER did not involve allocation to further study treatment, but was a 5-year post-trial extended follow-up of participants from AUS, MYL and NZ in the SHARP trial, a randomized double-blind trial of simvastatin and ezetimibe vs. placebo in CKD participants in 18 countries with median follow up of 4.9 years. Baseline demographic and laboratory variables were recorded at SHARP commencement. Initiation of renal replacement therapy and death were identified through adverse event records (SHARP) and linkage to national registries (SHARP-ER). All study participants from AUS, MYL and NZ who entered SHARP were included in this analyses. For those not eligible for inclusion in SHARP-ER, study completion date was recorded as the date of last SHARP follow up. For participants eligible for SHARP-ER, study completion date was 5 years after the last SHARP follow up visit. Multi-variable Cox regression models were constructed with and without censoring for transplantation. Of 2029 participants randomized in the SHARP trial from AUS, MYL and NZ, 1533 were alive at the end of SHARP, of whom 1136 participants (74.1% of those alive) entered the SHARP-ER follow up study. 803 participants (70.7 % of those entering SHARP-ER) were alive at completion of SHARP-ER. Baseline characteristics varied between countries; Malaysian participants were younger than those from AUS and NZ and diabetes was more prevalent in participants from MYL. The requirement for maintenance dialysis at study commencement was also more prevalent in MYL. Median duration of follow up from randomization was 5.6 (IQR 4.2-9.7) years in AUS, 9.4 (IQR 5.8-10.6) years in MYL and 5.5 (IQR 4.3-9.5) years in NZ. There was a significantly greater risk of mortality for participants from MYL (HR 4.24, 95% CI 1.66-10.82, p<0.01) and NZ (HR 4.82, 95% CI 1.31-17.70, p=0.02) compared with participants from AUS. Other predictors of mortality included worsening CKD stage, with highest risk associated with maintenance dialysis requirement at study commencement (HR 3.91, 95%CI 3.06-5.00, p<0.01) compared with participants with stage III CKD. Diabetes (HR 1.83, 95% CI 1.58-2.13, p<0.01) and cerebrovascular disease (1.39, 95% CI 0.99-1.95, p=0.05)) at study commencement were also associated with a greater risk of mortality. Rates of kidney transplantation were higher in AUS (20.5%) and NZ (17.9%) than MYL (1.9%). When analyses were censored at transplantation the effect of country on risk of mortality was reduced for participants in MYL (HR 1.20, 95% CI 1.01-1.43, p=0.04) and NZ (HR 1.26, 95 CI 1.02-1.56, p=0.04). Analysis of international post-trial cohorts are useful in exploring differing clinical outcomes between countries in comparable patients. When doing such analyses it is important to consider differences in practice patterns, such as transplantation rates, which may materially influence the findings.