MO016MYOCARDIAL INFARCTION IN THE PIVOTAL STUDY OF IV IRON IN HAEMODIALYSIS: A PRE-SPECIFIED SECONDARY ANALYSIS

Abstract

Abstract Background and Aims Coronary artery disease is prevalent in patients with CKD but how often a myocardial infarction (MI) occurs in patients on maintenance haemodialysis, and the prognostic importance of these MIs, is uncertain. The PIVOTAL trial investigated the effects of proactive high-dose versus reactive low-dose intravenous (IV) iron in incident haemodialysis patients. We now report the rates of MI, sub-types of MI, and the prognostic importance of these MIs, as well as the effect of high versus low dose iron on this event. Method This was a pre-specified secondary analysis of 2141 patients enrolled in the PIVOTAL trial. All potential endpoints in the trial, including MIs were adjudicated by a blinded Endpoint Adjudication Committee. The outcomes of time-to-first MI (type 1 or type 2 MI, STEMI or NSTEMI) and the composite outcome of MI and death due to MI were reported. In addition to time-to-first MI, we also analysed recurrent events, to account for the cumulative burden of events over time, as well as case-fatality related to MI. The time-to-event analyses of the primary, secondary and post hoc outcomes were performed in the intention-to-treat population using Cox proportional hazards regression, with treatment group as the only explanatory variable. The Kaplan–Meier method was used to estimate event rates. Recurrent events were analysed using the proportional-means model of Lin et al. and described in the form of mean frequency functions. Results 8.4% of patients experienced a MI over a median of 2.1 years follow-up. Rates of type 1 MIs (3.2/100 patient years) were 2.5 times higher than type 2 MIs (1.3/100 patient years). NSTEMIs (3.3/100 patient years) were 6.6 times more common than STEMIs (0.5/100 patient years). Mortality was high after non-fatal MI (30-day and 1-year mortality were 11.3% and 39.8%, respectively). In time-to-first event analyses, proactive high-dose IV iron reduced the rate of non-fatal MI (HR 0.69, 95% CI 0.51-0.93; p=0.01) and the composite endpoint of non-fatal and fatal MI (HR 0.69, 95% CI 0.52-0.93, p=0.015) (Figure) when compared to low dose reactive IV iron. The benefits of a proactive high-dose IV iron strategy were seen in type 1 MIs but not type 2 MIs. Conclusion Most MIs in patients on HD were type 1 and NTEMIs. Patients randomised to the high-dose group of PIVOTAL had a substantial reduction in fatal and non-fatal MI compared to those in the low-dose group.