Treatment disparities in patients with acute coronary syndromes and kidney disease

Abstract

Management of acute coronary syndromes (ACS) has been considerably refined over the past several decades, with the advances in diagnostics including prompt electrocardiography, use of cardiac biomarkers including cardiac troponin, antiplatelet and antithrombotic agents, b-adrenergic blockers, statins, and targeted utilization of invasive management with coronary angiography and revascularization with percutaneous coronary intervention (PCI) in the majority, with amenable anatomy and coronary artery bypass surgery in a minority of patients with multivessel disease and critical stenoses in one or more vessels. In the optimal care of a patient with ACS, each of these advances has contributed to relative risk reductions in clinical outcomes including recurrent myocardial infarction (MI), rehospitalization for ACS, and cardiac death. Because the use of early invasive management depends on hospital facilities, the willingness of the physician, and consent from the patient, this component of treatment is particularly susceptible to treatment bias. Therefore, a previous meta-analysis of seven randomized trials (n ¼ 9212 ACS patients) is important as it demonstrated that death or MI was reduced from 14.4 to 12.2% in the routine invasive group (relative 18% risk reduction) with a non-significant trend toward fewer deaths (6.0% vs. 5.5%). 1 If a subgroup could be identified where this 8% relative mortality reduction was amplified 4-fold, most would agree this subset should be considered a priority for invasive management. In the analysis by Wong et al., patients with stage 4 and higher chronic kidney disease (CKD) denoted by an estimated glomerular filtration rate (eGFR) ,30 mL/min/1.73 m 2 who were selected for an early invasive management approach for ACS enjoyed a 33.7% relative risk reduction in mortality compared with those managed conservatively who ultimately had a 41.5% all-cause mortality. 2 The propensity analysis supported these findings with an adjusted 47% risk reduction, suggesting that much more than selection bias accounts for the disparities in outcomes. How can disparities in the use of invasive management account for such a large differential in mortality? The answer lies in a careful look at those patients who had the worst health in the three registries summarized. In the 639 (5.6%) with an eGFR ,30 mL/min/1.73 m 2 [serum creatinine (Cr) 2.7 mg/dL (238 mmol/L)] the median age was 76 years (interquartile range 68‐84), 50% had diabetes, 75% demonstrated positive biomarkers indicating acute MI, 55% had a history of previous MI, and 36% suffered from prior heart failure. Hence, the eGFR ,30 mL/min/1.73 m 2 or Cr 2.7 mg/dL (238 mmol/L) served as a proxy for a clinical ‘package’ containing elderly patients with the highest risk for mortality in ACS. So why was an invasive approach used in fewer than a third of patients in this group despite low rates of patient/family refusal? The answer appears to be in the response of ‘not high enough risk or not supported by evidence’ which is frankly disturbing. The evidence-based risk predictors in the eGFR ,30 mL/min/1.73 m 2 suggest clinicians are failing to recognize risk. 3 While this trend is slowly improving over the time course of these registries, these data point to much room for improvement in estimation of mortality risk in elderly ACS patients. The indicators from treating physicians highlight for the first time that concern over contrast-induced acute kidney injury,bleeding, and co-morbidities does not account for intentional ‘therapeutic nihilism’ in patients with CKD. In summary, there appears to be a perceived risk mismatch between the clinical impression and the real mortality risk of ACS in patients with eGFR ,30 mL/min/1.73 m 2 . Educational efforts should be directed towards understanding how traditional risk predictors including positive biomarkers, age, diabetes, and histories of MI and heart failure aggregate in patients with significant CKD. 4 If managed conservatively, the study of Wong et al. 2 and a study by Keeley et al. 5 suggest this ACS population has disastrous outcomes with a nearly 50% case fatality rate at 1 year. This rate can be cut in half with an invasive management approach in appropriate patients. Giving the ageing population structures of developed countries, we can and should expect considerable improvement in treatment outcomes for this important group of ACS patients. The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.