Patients with chronic kidney disease (CKD) have a disproportionate burden of coronary artery disease and commonly undergo revascularization. The role and safety of percutaneous coronary intervention (PCI) using drug-eluting stents (DESs) verses bare-metal stents in patients with CKD not on renal replacement therapy has not been fully evaluated. This study investigated the efficacy and safety of DES in patients with CKD not on renal replacement therapy. Patients were drawn from the National Heart, Lung, and Blood Institute Dynamic Registry and were stratified by renal function based on estimated glomerular filtration rate (GFR). Of the 4,157 participants, 1,108 had CKD (“low GFR” <60 ml/min/1.73 m 2 ), whereas 3,049 patients had normal renal function (“normal GFR” ≥60 ml/min/1.73 m 2 ). For each stratum of renal function we compared risk of death, myocardial infarction, or repeat revascularization between subjects who received DESs and bare-metal stents at the index procedure. Patients with low GFR had higher 1-year rates of death and myocardial infarction and a decreased rate of repeat revascularization compared to patients with normal GFR. Use of DESs was associated with a decreased need for repeat revascularization in the normal-GFR group (adjusted hazard ratio 0.63, 95% confidence interval 0.50 to 0.79, p <0.001) but not in the low-GFR group (hazard ratio 0.69, 95% confidence interval 0.45 to 1.06, p = 0.09). Risks of death and myocardial infarction were not different between the 2 stents in either patient population. In conclusion, presence of CKD predicted poor outcomes after PCI with high rates of mortality regardless of stent type. The effect of DES in decreasing repeat revascularization appeared to be attenuated in these patients.
Chronic kidney disease (CKD) affects >26 million Americans and is associated with significant cardiovascular morbidity and mortality. Clinical studies have shown that patients with CKD have poor outcomes after percutaneous coronary interventions (PCIs). Although this risk is highest in patients with end-stage renal disease on renal replacement therapy, patients with lesser degrees of renal dysfunction also appear to be at greater risk of cardiovascular morbidity and mortality after PCI. Previous small studies have demonstrated that risk of restenosis after PCI with balloon angioplasty and bare-metal stent (BMS) insertion is higher in patients with CKD compared to patients with normal renal function. The beneficial effects of drug-eluting stents (DESs) demonstrated in randomized clinical trials has led to their widespread use. However, there are limited data of their safety and efficacy in patients with renal dysfunction not on long-term renal replacement therapy. In addition to safety concerns, recent small observational studies and post hoc analyses of clinical trials have shown conflicting results regarding the efficacy of DESs compared to BMSs. Accordingly, we sought to explore the safety and efficacy of PCI with DESs compared to BMSs in patients with renal dysfunction not on long-term renal replacement therapy.
Methods
Patients were drawn from the National Heart, Lung, and Blood Institute Dynamic Registry. This study population is comprised of consecutive patients from multiple institutions undergoing elective and nonelective PCI. Study details and data collection methods have been documented previously. Briefly, patients were enrolled in 5 recruitment waves of approximately 2,000 patients. Our analysis included patients recruited from wave 3 (October 2001 to March 2002, n = 2,047), wave 4 (February to May 2004, n = 2,112), and wave 5 (February to August 2006, n = 2,178). Patients enrolled during waves 1 and 2 were excluded because baseline serum creatinine values were not collected.
Patients were stratified by their estimated glomerular filtration rate (eGFR) at time of angiography and stent type received during the intervention. The simplified 4-variable Modification of Diet in Renal Disease equation was used to estimate GFR using age, race, gender, and serum creatinine.
We stratified patients included in the present analysis into 2 groups based on baseline level of renal function. Patients with eGFR <60 but ≥10 ml/min/1.73 m 2 were included in the “low-GFR” group, and patients with eGFR ≥60 ml/min/1.73 m 2 were included in the “normal-GFR” group. Patients with missing data on age (n = 10), race (n = 2), and serum creatinine (n = 271) were excluded because of an inability to calculate GFR. Furthermore, patients with end-stage renal disease on renal replacement therapy or with GFR < 10 ml/min/1.73 m 2 were excluded (n = 94). Patients from wave 3 not receiving a stent were excluded (n = 273) as were patients from waves 4 and 5 who received a BMS because of a substantial bias in stent selection (BMS vs DES, n = 837). In addition, patients presenting with an ST-segment elevation myocardial infarction were excluded (n = 693).
Data from 4,157 patients were available for analysis. Baseline demographic, angiographic, and procedural information was collected. Incidence of death, myocardial infarction, repeat PCI, and coronary artery bypass grafting during hospitalization and during follow-up were recorded. Follow-up was obtained at 1 month and 6 and 12 months after the index procedure by telephone interview and chart review. All clinical centers received approval from their respective institutional review boards. Data were compiled and interpreted at the epidemiology data center of the University of Pittsburgh.
Death was defined as all-cause mortality. Myocardial infarction was defined by evidence of ≥1 of the 2 following criteria: (1) evolutionary ST-segment elevation, development of new Q waves in ≥2 contiguous electrocardiographic leads, or new or presumably new left bundle branch block pattern on electrocardiogram and/or (2) biochemical evidence of myocardial necrosis manifested as (a) creatine kinase-MB ≥3 times the upper limit of normal, (b) total creatine kinase ≥3 times the upper limit of normal, or (c) troponin level above the upper limit of normal. Repeat PCI was defined as any repeat PCI in the follow-up period including target lesion and target vessel revascularizations. Repeat revascularization was defined as the combination of repeat PCI and/or coronary artery bypass grafting during the follow-up period.
Patients were stratified by GFR (low or normal) and stent type (BMS/wave 3 patients or DES wave 4 or 5 patients). Within each GFR stratum patient characteristics at index PCI were analyzed by stent type (BMS vs DES) including patient demographics, medical history, initial cardiac presentation, periprocedural medications, procedural characteristics, and in-hospital outcomes. Comparisons between groups were made using Student’s t test or Wilcoxon nonparametric test for continuous variables and chi-square test or Fisher’s exact test for categorical variables. Similar methods were used for lesion-level analyses. One-year cumulative incidence rates of individual clinical outcomes and composite outcomes were estimated by the Kaplan–Meier method and tested by log-rank statistic. Patients who did not develop the outcome of interest were censored at the last known date of contact or at 1 year if contact extended beyond 1 year.
Cox proportional hazards modeling was used to estimate 1-year hazard ratios for adverse clinical events in relation to stent type (DES vs BMS) on the study end points for each GFR category. A propensity-score approach was used to balance factors associated with the nonrandom assignment of treatment time (earlier recruitment wave vs later recruitment wave). Estimated propensity score for treatment with a DES once these devices were available was obtained from the fit of individual logistic regression models by GFR category for which demographic, angiographic, clinical, and procedural characteristics were considered. A c-statistic was calculated. Covariate balance between DES-treated patients and BMS-treated patients in each GFR stratum was assessed after adjustment for propensity score as a continuous covariate using logistic regression. Proportional hazards assumptions were evaluated and met. For all analyses a 2-sided p value <0.05 was considered statistically significant. All statistical analyses were performed using SAS 9.1 (SAS Institute, Cary, North Carolina).
Results
Of the 4,157 subjects, 1,108 (27%) had low GFR and 3,049 had normal renal function. Within the low-GFR group 345 (31%) patients received BMSs and 763 (69%) received DESs. Of patients with a normal GFR (eGFR ≥60 ml/min/1.73 m 2 ), 1,036 (34%) underwent stenting with BMSs and 2,013 (66%) received DESs.
Within the low-GFR stratum there was no difference in mean age, gender, race, previous myocardial infarction or coronary artery bypass grafting, prevalence of hypertension, severe noncardiac disease such as peripheral vascular disease, congestive heart failure, or smoking history by type of stent ( Table 1 ). Prevalence of hypercholesterolemia and a history of PCI were significantly higher in patients who received DESs compared to BMSs. In the normal-GFR stratum patients receiving DESs were younger and more often men and nonwhite. Prevalence of co-morbid conditions including diabetes, hypertension, hypercholesterolemia, and a history of kidney disease and previous PCI were significantly higher in DES-treated patients, whereas frequency of congestive heart failure was lower. In the 2 GFR groups the primary indication for revascularization differed with more acute myocardial infarction and less unstable angina in the DES-treated patients presenting with a normal GFR and more stable angina coupled with less unstable angina in DES-treated patients with low GFR.
| Variable | Normal GFR | Low GFR | ||||
|---|---|---|---|---|---|---|
| BMS | DES | p Value | BMS | DES | p Value | |
| (n = 1,036) | (n = 2,013) | (n = 345) | (n = 763) | |||
| Mean age (years) | 63.1% | 62.1% | 0.03 | 71% | 70.5% | 0.65 |
| Women | 31.5% | 26.8% | 0.007 | 48.1% | 46.9% | 0.71 |
| White | 80.5% | 74.7% | 79.4% | 79.7% | ||
| Black | 12.1% | 16.3% | 12.5% | 12.1% | ||
| Hispanic | 4% | 5.6% | 3.5% | 4.7% | ||
| Asian | 3.5% | 3% | 4.7% | 3.3% | ||
| Diabetes mellitus | 27.1% | 31.2% | 0.04 | 41.4% | 47.6% | 0.06 |
| Hypertension | 74.1% | 78% | 0.01 | 87.1% | 87.8% | 0.75 |
| Hypercholesterolemia | 73.9% | 80.1% | <0.001 | 70.7% | 84.4% | <0.001 |
| Renal disease | 0.7% | 1.7% | 0.03 | 25.3% | 25.6% | 0.92 |
| Peripheral vascular disease | 7.4% | 7.6% | 0.92 | 17.4% | 13% | 0.92 |
| Previous myocardial infarction | 27.5% | 24.9% | 0.13 | 31.3% | 28.3% | 0.32 |
| Previous percutaneous coronary intervention | 29.3% | 35.8% | <0.001 | 29.6% | 39.1% | 0.002 |
| Previous coronary artery bypass grafting | 16.3% | 17.6% | 0.36 | 31.6% | 29.5% | 0.48 |
| Congestive heart failure | 9.5% | 6.9% | 0.01 | 24.6% | 20.1% | 0.10 |
| Mean left ventricular ejection fraction (%) | 53.8% | 53.4% | 0.58 | 50% | 51.3% | 0.16 |
| Number of coronary arteries narrowed | 0.42 | 0.94 | ||||
| 1 | 39.7% | 36.8% | 29% | 27.5% | ||
| 2 | 33.5% | 34.2% | 27.5% | 29.1% | ||
| 3 | 26.5% | 28.8% | 42.9% | 42.9% | ||
| Acute myocardial infarction | 14.5% | 16.5% | <0.001 | 15.7% | 16% | 0.005 |
| Unstable angina | 49.3% | 39.6% | 48.4% | 39.4% | ||
| Stable angina | 26.3% | 24.6% | 16.2% | 24.6% | ||
| Asymptomatic | 8.4% | 14.7% | 15.1% | 13.6% | ||
Angiographic and procedural data for all groups are presented in Table 2 . Within the low-GFR group patients receiving BMSs were more often treated urgently or emergently compared to DES-treated subjects. Emergency and elective interventions were more common in DES-treated patients compared to the BMS group in those with normal renal function. Intervened lesions were similar in their coronary distribution and their American College of Cardiology/American Heart Association classification in the 2 stent types within the low-GFR stratum, whereas more class C lesions were treated in DES-treated patients with normal GFR. Mean lesion length of DES-treated lesions, however, was significantly longer compared to those treated with BMSs regardless of renal function. Total angiographic success was similar across all groups.
| Variable | Normal GFR | Low GFR | ||||
|---|---|---|---|---|---|---|
| BMS | DES | p Value | BMS | DES | p Value | |
| (n = 1,036) | (n = 2,013) | (n = 345) | (n = 763) | |||
| Timing of procedure | <0.001 | 0.004 | ||||
| Elective | 54.7% | 63.1% | 56.8% | 66.5% | ||
| Urgent | 42.9% | 33.4% | 38.3% | 31.1% | ||
| Emergency | 2.4% | 3.5% | 4.3% | 2.4% | ||
| Cardiogenic shock | 0.5% | 0.1% | 0.09 | 0.3% | 0.1% | 0.56 |
| Mean number of lesions attempted | 1.4% | 1.4% | 0.11 | 1.5% | 1.4% | 0.39 |
| Number | 1,492 | 2,803 | 510 | 1,070 | ||
| Left anterior descending coronary artery lesions | 34.9% | 38.3% | 0.07 | 31.6% | 34% | 0.67 |
| Mean reference vessel size (mm) | 3% | 3% | 3.1% | 3% | 0.79 | |
| Mean lesion length (mm) | 13.1% | 16.6% | <0.001 | 13.5% | 16.7% | <0.001 |
| American College of Cardiology/American Heart Association classification | <0.001 | 0.90 | ||||
| A | 19.4% | 11.8% | 12.5% | 11.6% | ||
| B1 | 37.3% | 35.2% | 30.8% | 30% | ||
| B2 | 29.4% | 28.7% | 32% | 32.5% | ||
| C | 13.8% | 24.2% | 24.7% | 25.9% | ||
| Drug-eluting stent type | ||||||
| Sirolimus | 0% | 65.7% | N/A | 0% | 36.7% | N/A |
| Paclitaxel | 0% | 37.3% | N/A | 0% | 66.2% | N/A |
| Angiographic success | 97.9% | 98.3% | 0.30 | 95.9% | 97.1% | 0.37 |
Within the low-GFR group incidence of in-hospital mortality was significantly higher in those treated with BMSs compared to DES-treated subjects (2.9% vs 1.1%, p = 0.02). There was no difference in in-hospital mortality by stent type in patients with normal GFR (0.1% for the 2 groups, p = 0.98). Incidence of in-hospital myocardial infarction was similar by stent type regardless of renal function (normal GFR 2.1% for the 2 groups, p = 0.98; low GFR 2.0% for BMS and 2.4% for DES, p = 0.73).
There were no differences in incidence of death at 1 year or myocardial infarction between DES- and BMS-treated patients ( Table 3 ). However, absolute rates of these outcomes were significantly greater in the low-GFR group compared to those with normal GFR (death 6.5% vs 2.0%, p <0.001; myocardial infarction 5.7% vs 4.2%, p = 0.05). Within the normal-GFR group incidence of repeat revascularization was significantly lower in DES-treated subjects compared to BMS-treated subjects (10.7% vs 16.4%, p <0.001). In contrast, there was no decrease in need for repeat revascularization in DES-treated patients compared to BMS-treated patients in those with impaired renal function (9.9% vs 12.2%, p = 0.23).
