This large study of 1400 consecutive patients with UA/NSTEMI treated uniformly very early and predominantly with PCI confirmed baseline renal function as a strong independent predictor of in-hospital and long term mortality and thereby extends this important finding to this latest revascularisation strategy. With its universal availability, calculated GFR may serve as an inexpensive new tool for risk stratification in UA/NSTEMI. The increased risk of death with chronic kidney disease was independent of and additive to the risk associated with diabetes, in full agreement with an observation in CABG patients reported by the BARI (bypass angioplasty revascularisation investigation) investigators.17
Moreover, when diabetes and renal function were taken into consideration together, chronic kidney disease was the dominant risk factor. The adjusted HR for long term mortality was 2.6 for those with a GFR of < 60 ml/min/1.73 m2
, whereas diabetes was no longer an independent predictor.
Among the explanations for why chronic kidney disease is such a potent risk factor for adverse outcomes in UA/NSTEMI, excess co-morbidity, less use of beneficial treatments for patients with chronic kidney disease, excess toxicity from conventional treatments used, and the unique pathobiology of the chronic kidney disease state seem to be the most decisive.8
Given the importance of the under use of cardioprotective treatments for patients with chronic kidney disease and the finding that low utilisation of reperfusion strategies contributed significantly to the poor prognosis of these patients in previous studies,10
this study appears particularly strong in that it is based on a prospective, consecutive, and unselected patient cohort and that a uniform revascularisation strategy was applied to all patients. These factors eliminate selection bias and ease the extrapolation of findings into clinical practice. Therefore, our data support the findings of the TACTICS-TIMI 18 (treat angina with Aggrastat and determine cost of therapy with an invasive or conservative strategy–thrombolysis in myocardial infarction 18) trial, where patients with a serum creatinine concentration of more than 2.5 mg/dl (221 μmol/l), a history of PCI or CABG within the preceding six months, factors associated with an increased risk of bleeding, cardiogenic shock, or severe systemic disorders were excluded.18
Moreover, the median time interval from admission to PCI was five hours in this study as compared with 25 hours in the invasive strategy of the TACTICS-TIMI 18 trial.18
Other particular features of the present study are the long term follow up and that the extent of coronary artery disease was quantified for all patients and entered into the multivariate analysis as a potential confounder.
Rationale for renal function as a predictor of outcome
Our results extend renal function as a powerful prognostic factor to an increasingly common disease treated with the latest revascularisation strategy. Very early revascularisation with predominantly PCI does not ameliorate the negative prognostic impact of renal function. The excess risk in patients with chronic kidney disease observed in previous studies can therefore not be sufficiently explained by lower efficacy and greater adverse events associated with thrombolytic treatment or extended periods of conservative antithrombotic and anti-ischaemic treatment. Our data support the importance of excess co-morbidities8
contributing to the inferior outcome for patients with impaired renal function. Firstly, patients with a GFR < 60 ml/min/1.73 m2
were older, they were more often diabetic, and coronary artery disease was more advanced with high rates of prior myocardial infarction and three vessel disease. Secondly, UA/NSTEMI was more severe in patients with a GFR < 60 ml/min/1.73 m2
, as cardiopulmonary resuscitation, defibrillation, ST segment depression, and increased troponin T were seen more often than among patients in the higher GFR ranges. However, even after adjustment for these differences, the presence of a GFR < 60 ml/min/1.73 m2
was still predictive of long term mortality. Therefore, the unique pathobiology of the chronic kidney disease state8
seemed to contribute additionally to mortality during follow up.
This study was not designed to clarify the causal mediators of renal risk. Candidate mechanisms may include the presence of left ventricular hypertrophy, diastolic left ventricular dysfunction,7,19
pharmacological interactions, endothelial dysfunction,7
more aggressive atherosclerosis related to increases in serum homocysteine,20
increased sympathetic nerve activity,21
activated inflammatory and procoagulant pathways,22
and angiography related complications such as contrast nephropathy.23,24
Renal function in patients undergoing elective PCI
Recent studies have extended the correlation between renal insufficiency and clinical outcome to patients undergoing elective PCI.25–27
Chronic kidney disease was independently associated with mortality and other adverse events during and after PCI, in a dose dependent manner. Risk increased even when renal insufficiency was mild, with a doubling of mortality at one year.25
Unique risks and benefits of revascularisation among patients with chronic kidney disease
Coronary angiography, PCI, and CABG are associated with increased morbidity and mortality among patients with chronic kidney disease.7,17,25–29
This excess in risk is at least partly explained by the patients’ baseline characteristics. However, patients with chronic kidney disease are a high risk subgroup of patients with UA/NSTEMI and that is exactly the subset of patients who derive the maximum benefit from early revascularisation.2–6
Randomised trials specifically including patients with chronic kidney disease are lacking but would be highly desirable. The cumulative three year survival rate was 76.8% among patients with GFR < 60 ml/min/1.73 m2
in this study. This compares favourably with cohorts treated primarily medically.9–11
Although any comparison with historical controls has important limitations, our data along with those of others suggest that patients with chronic kidney disease fair better with early revascularisation.2,3,5,6,18
This is further supported by recent registry data suggesting that coronary stenting, which was used in our study as the predominant revascularisation procedure, has significantly improved procedural success rates and long term outcome for patients with chronic kidney disease.29
Firstly, serum creatinine was used for the calculation of GFR. This measure has limitations, as it may not be in a stable state and may reflect hydration status. Secondly, any equation for the calculation of GFR inherently includes age, and age has been a consistent factor in predicting cardiac outcome.
Renal function is a strong independent predictor of in-hospital and long term mortality in UA/NSTEMI treated with very early revascularisation. With its universal availability, GFR may serve as an inexpensive new tool for risk stratification in UA/NSTEMI.