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Original Contribution
Clinical Outcomes after Percutaneous Coronary Intervention with Drug-Eluting Stents in Dialysis Patients
June 2006
The major cause of mortality in dialysis patients is attributable to cardiovascular diseases.1,2 The higher prevalence of coronary artery disease in this population is thought to be related to a higher risk factor distribution, platelet thrombogenicity and premature coronary calcification, when compared with nondialysis subjects. Treatment of ischemic heart disease with percutaneous revascularization techniques has remained controversial because of consistent exclusion of dialysis patients from major clinical trials. To our knowledge, the literature has been composed of retrospective, single-institution experiences with only small numbers of patients, and has led to the conclusion that percutaneous coronary intervention (PCI) in dialysis patients is less successful and associated with more adverse outcomes when compared to nondialysis patients.3,4 Drug-eluting stents (DES) have recently proven an impressive tool in the reduction of repeat revascularization in the overall population and clinical indications. The aim of the present study was to evaluate the outcomes of dialysis versus nondialysis patients treated with PCI and DES.
Materials and Methods
Patient population. We analyzed the medical records of 3,442 consecutive patients who underwent PCI with DES at our institution since March 2003. All patients treated with DES only during this period were included. Patients were classified into dialysis and nondialysis groups. Dialysis patients were defined as having been treated with dialysis for greater than or equal to 90 days prior to the intervention. We identified a total of 72 dialysis patients, of whom 57 (79%) had hemodialysis and 15 (21%) had peritoneal dialysis. The diagnosis of acute myocardial infarction (MI) included all patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). STEMI was determined by the presence of > 30 minutes of continuous chest pain, a new or presumed new ST-segment elevation greater than or equal to 2 mm on at least 2 contiguous ECG leads, and creatine kinase > 2 times normal. NSTEMI was diagnosed by the presence of chest pain and a positive cardiac biochemical marker of necrosis (troponin and/or creatine kinase-MB) without new ST-segment elevation. Risk factors and previous cardiovascular disease were reviewed. Diabetes mellitus was defined as hyperglycemia requiring insulin and/or oral hypoglycemic drug treatment. Hyperlipidemia was defined as receiving lipid-lowering therapy and/or the presence of a total serum cholesterol > 5 mmol/l or serum triglycerides > 2 mmol/l. Hypertension was defined as receiving medication to lower blood pressure or measured blood pressure values of greater than or equal to 140 mmHg systolic or greater than or equal to 90 mmHg diastolic on two or more occasions. Cardiogenic shock was defined as maximal systolic pressure 2 and pulmonary capillary wedge pressure > 18 mmHg. Persistence of hypotension or pump failure after correction of contributing extramyocardial factors (e.g., hypovolemia, hypoxemia or acidosis) and/or peripheral signs of hypoperfusion (e.g., peripheral vasoconstriction, urine output Procedures. Contemporary percutaneous coronary angioplasty was performed after obtaining written, informed consent. Patients received single or multiple DES for various lesions with or without predilatation or the use of ablative devices for plaque modification. Intravascular ultrasound guided the procedure in almost 80% of the cases. After stent implantation, angiographic optimization was performed by high-pressure dilatation to achieve an acceptable angiographic result with 250 seconds in all patients.
Endpoint definitions. Endpoints were death and all clinical events in-hospital at 1- and 6-month follow up. Death was defined as all causes of mortality. Q-wave and non-Q-wave MI were defined as a total creatinine kinase elevation greater than or equal to 2 times normal and/or creatinine kinase-MB greater than or equal to 20 ng/ml ± new pathological Q-waves in greater than or equal to 2 contiguous leads. Neurologic events included stroke or transient ischemic attack. Acute renal failure was defined as an increase of greater than or equal to 25% over baseline creatinine levels with or without dialysis. Target lesion revascularization (TLR) and target vessel revascularization (TVR) were characterized by repeated percutaneous or surgical intervention of the treated lesion or vessel, respectively, and were clinically driven. Major adverse cardiac events (MACE) were defined as a composite of death, Q-wave MI, or repeat revascularization. Subacute stent thrombosis was defined as evidence of angiographic thrombus of the target lesion greater than or equal to 30 days from the implantation of the DES.
Clinical follow up. A dedicated data coordinating center (Data Center, MedStar Research Institute, Washington, D.C.) performed the data management and analyses. Prespecified clinical and laboratory data during hospitalization periods were obtained from hospital charts that were reviewed by
independent research personnel blinded to the objectives of the study. The data were entered prospectively into the database. Clinical follow ups at 1 and 6 months were conducted by telephone contact or office visits. The occurrence of major late clinical events was recorded, including death (all-cause), MI, TLR and TVR. All clinical events were adjudicated by source documentation by independent physicians who were not involved in the procedures.
Statistical analysis. Statistical analysis was performed using the Statistical Analysis System, version 8.2 (SAS Institute, Inc., Cary, North Carolina). Data are expressed as mean ± SD for continuous variables and as percentages for categorical variables. The Student’s t-test was used to compare continuous variables and the Chi-square test or Fischer’s exact test was used to compare categorical variables. A p-value p-value Clinical findings. Patients’ baseline clinical characteristics are summarized in Table 1. There was a higher prevalence of female gender (p = 0.03), African Americans (p p p p = 0.02) and have a smoking history (p p = 0.04) at the time of presentation, cardiogenic shock (p = 0.01), and heart failure (p p p p p p Angiographic characteristics. The angiographic and procedural characteristics are shown in Table 2. Dialysis patients were more likely to have multivessel disease (p = 0.04) and more stents implanted (p = 0.02). Culprit lesion localizations were similar between the two groups. Implantation of Cypher™ (Cordis Corporation, Miami, Florida) and Taxus®(Boston Scientific Corporation, Natick, Massachusetts) stents was similar in both groups. Angiographic success, however, was achieved more often in the nondialysis group (p = 0.05).
In-hospital complications. In-hospital complications are presented in Table 3. There was a trend toward a higher mortality rate (p = 0.08) in the dialysis group. Other in-hospital complications were similar except for less transfusions (p Clinical follow up at 1 and 6 months. These clinical outcomes are presented in Table 4. Mortality rate (p p p p Independent predictors of mortality at six-month follow up in dialysis patients. Independent predictors of mortality at 6 months in univariate analysis included cardiogenic shock (p p = 0.007), body mass index (p = 0.07), and African American race (p = 0.07). The only variable associated with higher odds of mortality in a subsequent multivariate analysis (Table 5) was cardiogenic shock during hospitalization (p = 0.04).
Discussion
The main findings of the present study were that DES implantation in chronic dialysis patients is clinically safe and feasible, with very low rates of repeat target revascularization at 6 months. The poor survival rate observed at follow up was strongly influenced by the high risk factor distribution, comorbidities, and severe clinical presentation in this patient subgroup.
Clinical findings. Chronic dialysis patients were more likely to be female and African American. The higher incidence of end-stage renal disease and the lower access to medical care for effective risk factor control among African Americans could account for the racial differences in the incidence of dialysis patients. Moreover, the gender and racial disparities for receiving renal transplants may also contribute to these findings.5–7 Dialysis patients had more extensive cardiac disease with an increased prevalence of negative prognostic factors, including diabetes, hypertension, anemia, heart failure, low ejection fraction and multivessel disease. Our findings are consistent with those of several studies8,9 which reported a higher prevalence of risk factors and comorbidities in dialysis patients. Accelerated atherosclerosis with lipid abnormalities, hypercoagulation, and coronary calcification related to secondary hyperparathyroidism may explain the higher cardiovascular risk within this population. This is further emphasized by previous results reported by Rubenstein et al.,10 and our findings showing that dialysis patients were more likely to present with acute coronary syndromes and cardiogenic shock. The observed lower low-density lipoprotein levels related to chronic inflammation and malnutrition may explain the less common prescription of statins at discharge in dialysis patients. Although Mason et al. showed that statins are associated with reduced mortality in hemodialysis patients, this does not, apparently, translate into current clinical practice. Therefore, future prospective studies are warranted to evaluate the cardiovascular benefits of statin use in this population.11,12Procedural characteristics and in-hospital complications. Despite the high prevalence of multivessel disease, left ventricular dysfunction and complex lesions, our study showed that PCI with DES for elective and urgent procedures in dialysis patients is highly feasible, with a procedural success rate of 96%. There was a trend toward higher in-hospital mortality (1.3% vs 0.1%; p = 0.08) in dialysis patients, while procedural complication rates were comparably low. The trend toward more in-hospital deaths may be the result of comorbidities and clinical presentation (more acute coronary syndromes) in these patients. This is further emphasized by the results from a multivariate analysis identifying cardiogenic shock (p = 0.04) to be an independent predictor of mortality at 6 months in dialysis patients. Similar results have been previously reported by Rubenstein et al. in a study of 3,334 dialysis patients.10 In the bare metal stent era, some studies have reported significantly higher in-hospital events in association with chronic dialysis3,13,14 (Figure 1). New technologies, including better balloon and stent profiles, distal protection, rotational atherectomy, IVUS use (77% of dialysis patients), and closure devices may explain the overall lower in-hospital events observed in this analysis. Furthermore, the use of new anticoagulant agents, including clopidogrel, glycoprotein IIb/IIIa inhibitors and bivalirudin, and the growing experience of interventional cardiologists may also have contributed to the observed improved outcomes.
Clinical follow up. With DES implantation, chronic dialysis patients had a favorable repeat revascularization rate (5.4%) which is similar to that from the nondialysis group, although the incidence of subacute thrombosis was higher. These results, however, need to be taken with caution, as 2 patients had prematurely stopped clopidogrel, with consequent development of thrombosis. We did not observe any late thrombosis in this group.
Study limitations. This is a single-center, nonrandomized registry, which needs to be validated on prospective randomized studies. It represents, however, a relatively large “real life” experience of PCI in dialysis patients.
Conclusions
PCI with DES implantation for end-stage renal disease patients treated with dialysis is associated with a low risk for repeat target revascularization at 6 months. Despite the use of new technologies and higher procedural success rates, dialysis patients still have significantly higher short- and long-term mortality when compared to patients with normal renal function. Optimal risk factor control and regular cardiovascular screening in this patient population is warranted to further improve clinical outcomes.
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