From the Departments of Medicine (B.R.H., B.F.C., L.B.M., M.L.K., W.A.G.) & Community Health Sciences (B.R.H., W.A.G.) và the Centre for Health & Policy Studies (D.S., W.A.G.), University of Calgary, Calgary, Alberta, Canada.
Danielle Southern

From the Departments of Medicine (B.R.H., B.F.C., L.B.M., M.L.K., W.A.G.) & Community Health Sciences (B.R.H., W.A.G.) and the Centre for Health & Policy Studies (D.S., W.A.G.), University of Calgary, Calgary, Alberta, Canada.
Bruce F. Culleton

From the Departments of Medicine (B.R.H., B.F.C., L.B.M., M.L.K., W.A.G.) & Community Health Sciences (B.R.H., W.A.G.) và the Centre for Health and Policy Studies (D.S., W.A.G.), University of Calgary, Calgary, Alberta, Canada.
L. Brent Mitchell

From the Departments of Medicine (B.R.H., B.F.C., L.B.M., M.L.K., W.A.G.) & Community Health Sciences (B.R.H., W.A.G.) and the Centre for Health & Policy Studies (D.S., W.A.G.), University of Calgary, Calgary, Alberta, Canadomain authority.
Merril L. Knudtson

From the Departments of Medicine (B.R.H., B.F.C., L.B.M., M.L.K., W.A.G.) & Community Health Sciences (B.R.H., W.A.G.) và the Centre for Health & Policy Studies (D.S., W.A.G.), University of Calgary, Calgary, Alberta, Canadomain authority.
William A. Ghali

From the Departments of Medicine (B.R.H., B.F.C., L.B.M., M.L.K., W.A.G.) & Community Health Sciences (B.R.H., W.A.G.) và the Centre for Health và Policy Studies (D.S., W.A.G.), University of Calgary, Calgary, Alberta, Canadomain authority.

From the Departments of Medicine (B.R.H., B.F.C., L.B.M., M.L.K., W.A.G.) and Community Health Sciences (B.R.H., W.A.G.) & the Centre for Health and Policy Studies (D.S., W.A.G.), University of Calgary, Calgary, Alberta, Canada.
& for the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) Investigators
Originally published27 Sep 2004https://doi.org/10.1161/01.CIR.0000143629.55725.D9Circulation. 2004;110:1890–1895

Background— The optimal approach to lớn revascularization in patients with kidney disease has not been determined. We studied survival by treatment group (CABG, percutaneous coronary intervention , or no revascularization) for patients with 3 categories of kidney function: dialysis-dependent kidney disease, non–dialysis-dependent kidney disease, & a reference group (serum creatinine Methods & Results— Data were derived from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH), which captures information on all patients undergoing cardiac catheterization in Alberta, Canada. Characteristics và patient survival in 662 dialysis patients (1.6%) and 750 non–dialysis-dependent kidney disease patients (1.8%) were compared with the remainder of the 40 374 patients (96.6%). For the reference group, the adjusted 8-year survival rates for CABG, PCI, and no revascularization (NR) were 85.5%, 80.4%, và 72.3%, respectively (PPPP=0.48 for PCI versus NR) & 44.8% for CABG, 41.2% for PCI, and 30.4% for NR in the dialysis group (P=0.003 for CABG versus NR; P=0.03 for PCI versus NR).

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Conclusions— Compared with no revascularization, CABG was associated with better survival in all categories of kidney function. PCI was also associated with a lower risk of death than no revascularization in reference patients và dialysis-dependent kidney disease patients but not in patients with non–dialysis-dependent kidney disease. The presence of kidney disease or dependence on dialysis should not be a deterrent to revascularization, particularly with CABG.


Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with end-stage renal disease1 and begins well before the onset of dialysis.2,3 Once CVD is established, patients with kidney disease are at high risk for subsequent CVD events.4 Although guidelines exist for many aspects of medical care for CVD,5,6 the optimal approach to revascularization in patients with kidney disease has not been determined.

Revascularization approaches available include CABG and percutaneous coronary artery intervention (PCI). Amuốn patients with normal kidney function, randomized trials suggest that compared with PCI, CABG is associated with a lower rate of repeat interventions7–9 và an improved quality of life,10 but other than in a subgroup of diabetic patients,11 it offers no survival advantage.9,12 In contrast, observational data propose that for dialysis patients, CABG may provide a survival benefit.13–16 These reports, however, vì not include a reference patient population whose CVD is managed by medical therapy alone, which limits the scope of the findings. Aước ao patients with non–dialysis-dependent kidney disease, a survival benefit for CABG over PCI was reported in some17 but not all14 of the previous studies.

The value, therefore, of coronary revascularization in patients with kidney disease & CVD is uncertain. The purpose of this study was lớn compare survival by treatment group (CABG, PCI, or no revascularization) for patients with 3 categories of kidney function: dialysis-dependent kidney disease, non–dialysis-dependent kidney disease, & a reference group (serum creatinine 18 All patients enrolled at the time of catheterization are followed up prospectively, thus permitting the outcomes of patients who were not revascularized khổng lồ also be determined.

The study cohort consisted of all Alberta resident patients undergoing cardiac catheterization from January 1, 1995, lớn December 31, 2001. At the time of cardiac catheterization, data were collected by laboratory personnel through direct inquiry to patients và the procedure physician & review of medical documentation on clinical risk factors including age, gender, and presence of diabetes, peripheral vascular disease, chronic lung disease, cerebrovascular disease, congestive heart failure, hypertension, hyperlipidemia, liver or gastrointestinal disease, và neoplastic disease. Race was not recorded, although census data indicate that fewer than 1% of the population are reported lớn be blaông chồng.19 The results of the cardiac catheterization, specifically left ventricular ejection fraction & coronary anatomy, were also recorded & were used to lớn define severity of coronary artery disease. Patients with normal coronary anatomy or missing data on coronary anatomy were excluded because we wanted khổng lồ confine this prognostic study to lớn patients with documented coronary artery disease.

The exposure variable of interest, kidney function, was defined within APPROACH as dialysis-dependent kidney disease (on hemodialysis or peritoneal dialysis), nondialysis kidney disease (serum creatinine >2.3 mg/dL <>200 μmol/L> but not on dialysis), and reference patients (the remainder of the cohort). Lack of absolute serum creatinine measurements in APPROACH for all years studied precluded us from estimating glomerular filtration rate.

Patients were followed up through December 31, 2002, for ascertainment of the primary outcome, death due to all causes. Revascularization status (CABG or PCI) was also determined & was defined as the first procedure that occurred within 1 year of the cardiac catheterization. All-cause mortality was determined through semiannual linkage to the Alberta Bureau of Vital Statistics. The ethics Reviews boards of the Universities of Calgary & Alberta approved the APPROACH study protocol.

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Statistical Analysis

Patient characteristics for the reference patient population, nondialysis kidney disease patients, and dialysis kidney disease patients were compared with χ2 tests. A Cox proportional hazards analysis was used to lớn compare survival within each category of kidney function according khổng lồ treatment received (CABG, PCI, or no revascularization). The primary outcome variable was all-cause mortality. Survival time was calculated from the date of cardiac catheterization khổng lồ the date on which the patient was censored (ie, at end of follow-up) or the outcome event occurred. Risk-adjusted survival curves were plotted from the proportional hazards model by the corrected group prognosis method.trăng tròn The proportional hazard assumption was evaluated and satisfied for these multivariable survival analyses by examining plots of the log-negative-log within-group survivorship functions versus log-time, examining Schoenfeld residuals, và comparing Kaplan-Meier (observed) with Cox (expected) survival curves.

A multivariable analysis was also performed khổng lồ control for the propensity21 of being selected for either CABG or PCI compared with no revascularization. This was undertaken by conducting 2 logistic regression analyses to lớn model predictors of undergoing either CABG or PCI. The resulting models (with a c statistic of 0.86 for CABG và 0.80 for PCI) were used khổng lồ calculate a probability (ie, propensity) of being selected for either CABG or PCI. These 2 propensity scores (1 each for CABG và PCI) were then included in the final multivariable analyses to assess the association between CABG & PCI with no revascularization. Statistical analyses were performed with SAS version 8.1 (SAS Institute).


Results

After excluding 6156 patients (12.7%) with normal coronary anatomy và 520 (1.1%) with missing data, the final study population was 41 786. Of these, 662 (1.6%) were on dialysis (dialysis kidney disease), 750 (1.8%) had serum creatinine >2.3 mg/dL but were not on dialysis (nondialysis kidney disease), và 40 374 (96.6%) had serum creatinine Table 1. Other than known hyperlipidemia, the prevalence of clinical risk factors was significantly higher in patients with kidney disease, both nondialysis & dialysis dependent, than in the reference patient group. Overall, the most common indication for cardiac catheterization was myocardial infarction in the reference and nondialysis kidney disease patients; in the dialysis kidney disease patients, other indications were cited. Other indications most frequently cited were congestive sầu heart failure, suspected silent ischemia, and atypical symptoms. The majority of dialysis and nondialysis kidney disease patients did not undergo revascularization after their cardiac catheterization despite results of the catheterization showing that these patients had more severe coronary anatomy (Table 2).


The median follow-up time after cardiac catheterization was 3.7 years for the reference patient group, 1.9 years for patients with nondialysis kidney disease, và 2.1 years for dialysis patients. The risk-adjusted survival curves for the reference patient group, nondialysis kidney disease patient group, & dialysis patient group are shown in the Figure. Treatment with CABG was associated with the best adjusted survival rates và no revascularization with the worst for each of the 3 categories of kidney function. The adjusted 8-year survival rates in the reference patient group associated with CABG, PCI, và no revascularization were 85.5%, 80.4%, and 72.3%, respectively (Figure, A). For patients with nondialysis kidney disease, the adjusted 8-year survival rates were 45.9% with CABG, 32.7% with PCI, & 29.7% with no revascularization (Figure, B). For patients on dialysis, the adjusted 8-year survival rates were 44.8% with CABG, 41.2% with PCI, & 30.4% with no revascularization (Figure, C).

*


Survival curves for reference patient group (A), nondialysis kidney disease patient group (B), and dialysis patient group (C), adjusted for age, gender, clinical risk factors, & severity of coronary artery disease. revasc indicates revascularization.

A summary of 8-year unadjusted and adjusted survival rates for CABG và PCI, with their associated adjusted survival differences and hazard ratquả táo relative sầu lớn no revascularization, are provided in Table 3. CABG was associated with a survival advantage compared with no revascularization for all 3 categories of kidney function, with nondialysis kidney disease patients experiencing the greakiểm tra survival advantage for CABG compared with no revascularization, at 16.2%.


Discussion

The value of aggressive coronary artery revascularization compared with no revascularization in improving outcomes for patients with kidney disease is unknown. In the present study, we have sầu shown that revascularization with CABG was associated with a lower risk of death than no revascularization for all categories of kidney function. Revascularization with PCI was also associated with a lower risk of death than no revascularization in reference patients and dialysis kidney disease patients but not in patients with nondialysis kidney disease. However, regardless of the treatment received, patients with kidney disease had poorer survival than the reference group.

These results must be interpreted in view of the observational nature of the data. Although an association between revascularization & outcome has been demonstrated, the observed associations may or may not be causal. Although randomized controlled trials are the best means of confirming causation, large observational studies such as this can also be informative sầu.

Previous studies have sầu also suggested a survival benefit for CABG in dialysis patients.13–16 The present study had the added advantage over other studies13,15,16 of being able to lớn adjust for severity of cardiac disease and left ventricular function. The reduced survival for dialysis patients treated with PCI compared with CABG may be related lớn an increased risk of restenosis.22–24 Despite the reduced survival for dialysis patients treated with PCI compared with CABG, the results of the present study nonetheless suggest a survival advantage for PCI over no revascularization

We also found a lower risk of death for CABG over both PCI and no revascularization for patients with nondialysis kidney disease (serum creatinine >2.3 mg/dL). These results are in contrast khổng lồ those reported by Szczech et al,14 in which CABG was not associated with better survival aước ao patients with a creatinine >2.5 mg/dL (hazard ratio 0.86, 95% CI 0.56 khổng lồ 1.33). This discrepancy may be explained by their shorter duration of follow-up (3 years).14 To the best of our knowledge, only 1 other study of patients with nondialysis kidney disease has included a nonrevascularized group.17 Similar to lớn the present results, CABG was associated with a survival benefit across all levels of kidney function, whereas PCI failed to offer a significant benefit among patients with severe (creatinine clearance 17

The laông chồng of an improvement in survival for PCI amuốn nondialysis kidney disease patients is less likely to be explained by atherosclerotic risk factors và accelerated atherogenesis, because dialysis patients would also be so exposed, and yet a benefit of PCI over no revascularization was apparent in the dialysis group. A possible mechanism for the poor survival after PCI among mỏi nondialysis kidney disease patients is their increased risk of acute renal failure, an event associated with a greater risk of adverse outcomes after coronary intervention.25,26 The potential for increased complications after PCI, but not after CABG, in patients with kidney disease has been described.27 Another explanation may be higher rates of incomplete revascularization.28 Completeness of revascularization, as defined by the Duke jeopardy score,29 has been shown khổng lồ vary by level of kidney function in a previous study from the APPROACH database,30 with complete revascularization obtained in 67.6% of reference patients, 64.3% of dialysis kidney disease patients, and only 42.4% of nondialysis kidney disease patients. Although speculative sầu, incomplete revascularization in patients with nondialysis kidney disease may be related khổng lồ conservative sầu use of dye during angiography.

Survival after revascularization for dialysis kidney disease patients was better in the present study than previously reported in the United States.13–15 A possible explanation for this finding is that unlike previous studies that included only patients hospitalized after revascularization, the APPROACH database includes both inpatients và outpatients after catheterization, thus including patients with less urgent indications for catheterization. A second explanation may be that there are differences in outcomes between healthcare systems, a possibility supported by recent retìm kiếm showing better survival in dialysis patients in Canadomain authority than in the United States.31

Given the observational nature of the present study, it has important limitations. First, selection bias is likely in that healthier patients may have sầu been chosen for surgical interventions. Nevertheless, multivariate analysis và propensity adjustment were used to lớn mitigate the impact of selection bias. A selection process & possible bias are also likely in the decision to pursue a cardiac catheterization. Second, the dichotomy of creatinine into values greater or less than 2.3 mg/dL (200 μmol/L) in the definition of nondialysis kidney disease limits an assessment of risk for various levels of kidney function. Third, the inception point for the cohort was cardiac catheterization. These patients are a submix of all patients with CVD and bởi not reflect the outcomes of all patients with CVD. Fourth, information on medication use during follow-up was not available, which prevented us from characterizing the medical treatment provided to lớn the nonrevascularized group. Finally, we were unable khổng lồ traông chồng patients who may have left the province. This, however, is unlikely to have a major influence given the stability of the population, with a general trend in Alberta for increased inward rather than outward migration. In addition, we limited our study lớn residents of Alberta, and it would be rather atypical for a patient to lớn move out of the province during a cardiac evaluation.


To summarize, we found a survival advantage for CABG compared with no revascularization for patients with all categories of kidney function. PCI was also associated with a survival advantage over no revascularization except in patients with non–dialysis-dependent kidney disease. These results indicate that the presence of kidney disease or dependence on dialysis treatment should not be a deterrent to lớn revascularization, particularly with CABG. A better understanding of the factors associated with poor outcomes after PCI in patients with non–dialysis-dependent kidney disease may lead khổng lồ improved management strategies for such patients.