Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:In the general population, an early invasive strategy of routine coronary angiography is superior to a conservative strategy of selective angiography in patients who are admitted with unstable angina or non-ST segment elevation myocardial infarction (MI), but the effectiveness of this strategy in individuals with chronic kidney disease (CKD) is uncertain. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:We conducted a collaborative meta-analysis with data provided by the main authors of identified trials to estimate the effectiveness of early angiography in patients with CKD. The Cochrane, Medline, and EMBASE databases were searched to identify randomized trials that compared invasive and conservative strategies in patients with unstable angina or non-ST MI. Pooled risks ratios were estimated using data from enrolled patients with estimated GFR <60 ml/min per 1.73 m(2). RESULTS:Five randomized trials that enrolled 1453 patients with CKD were included. An early invasive strategy was associated with nonsignificant reductions in all-cause mortality, nonfatal MI, and a composite of death or nonfatal MI. The invasive strategy significantly reduced rehospitalization. CONCLUSIONS:This collaborative study suggests that the benefits of an early invasive strategy are preserved in patients with CKD and that an early invasive approach reduces the risk for rehospitalization and is associated with trends of reduction in the risk for death and nonfatal re-infarction in patients with CKD. Coronary angiography should be considered for patients who have CKD and are admitted with non-ST elevation acute coronary syndromes.

Patients with chronic kidney disease have high rates of myocardial infarction and death following an initial attack. Proximal location of coronary atherosclerotic lesions has been linked to the risk of acute myocardial infarction and to infarction-associated mortality. To examine if the spatial distribution of lesions differs in patients with and without chronic kidney disease, we used quantitative coronary angiography to measure this in patients with acute coronary thromboses who were having angiography following acute myocardial infarction. Multivariable linear regression was used to adjust for differences in baseline characteristics. Among 82 patients with stage 3 or higher chronic kidney disease, 55.6% of lesions were located within 30 mm and 87.7% were within 50 mm of the coronary ostia. This compared to 34.7 and 71.8%, respectively, among 299 patients without significant kidney disease. Chronic kidney disease was independently and significantly associated with a 7.0 mm decrease in the distance from the coronary ostia to the problem lesion. Our study suggests that a causal link between a more proximal culprit lesion location in patients with chronic kidney disease and their high mortality rates after myocardial infarct is possible and may have important implications for interventions to prevent infarction.

BACKGROUND:Rates of restenosis following percutaneous coronary intervention with stent placement are high in patients with advanced renal failure. Whether mild to moderate chronic kidney disease (CKD) is associated with a similarly increased need for short or long-term target lesion revascularization (TLR) following coronary stenting is uncertain. METHODS:We analysed results from 1228 patients enrolled in four separate, randomized, controlled clinical trials who underwent elective coronary angioplasty with stenting and were prospectively followed for 5 years after the index procedure. Cox proportional hazards regression was used to correct for confounding and to estimate the short and long-terms risks of target lesion revascularization in patients with vs without mild to moderate CKD. RESULTS:During a median follow-up of 5 years, 205 patients (16.7%) required TLR with 59 (4.8%) requiring TLR after the first year. Mild (HR 1.07, 95% CI 0.74-1.53) and moderate (HR 0.95, 95% CI 0.552-1.64) CKD were not associated with an increase in the adjusted, overall-risk of TLR. However, mild to moderate CKD was associated with a non-significantly increased risk of late TLR (HR 1.40, 95% CI 0.73-2.69). CONCLUSIONS:Coronary stenting appears to be similarly effective in patients with mild to moderate CKD and patients with normal renal function. While target lesion revascularization is rarely needed beyond the first year after revascularization, long-term results of coronary stenting may be less-favourable in patients with CKD.

BACKGROUND:Dialysis patients have a high risk of cardiovascular death but may under-use coronary artery bypass grafting (CABG) because of the risk of peri-operative death. Whether operative mortality in dialysis patients has declined with contemporary techniques is uncertain. We undertook this study in order to compare peri-operative mortality in chronic dialysis (CD) and non-dialysis patients following CABG and to determine whether high levels of comorbidity in CD patients account for identified differences in operative risk. METHODS:This study is a retrospective analysis of the 2001 National Inpatient Sample, a stratified probability sample of over seven million admissions in 33 states. Administrative data and ICD-9CM codes were used to identify dialysis patients, comorbidities, procedures and operative outcomes. Multivariable logistic regression was used to adjust for confounding. RESULTS:In this study, 77 323 non-dialysis patients and 635 dialysis patients underwent CABG. In-hospital death occurred in 11.1% of dialysis patients compared to 3.4% of non-dialysis patients. Rates of stroke, sepsis and pneumonia were also increased in dialysis patients. After adjustment for other surgical risk factors, the odds of in-hospital death were 3.38 (2.54-4.50, P < 0.001) times higher in dialysis than non-dialysis patients. CONCLUSIONS:Operative mortality in dialysis patients remains high despite recent advances in CABG surgery and is not explained by the high rates of comorbidity in dialysis patients. Because there is a very high risk of cardiovascular death without intervention, CABG may nevertheless be a life-saving therapy in CD patients. Randomized trials are needed to better define the optimal role of CABG in dialysis patients.

Patients with chronic kidney disease (CKD) have high mortality following myocardial infarction (MI), but are less likely to undergo coronary angiography than those without CKD. Whether this phenomenon is explained by differences in the presentation of MI or by bias against performing coronary angiography in patients with CKD is unclear. We examined the clinical presentation of 1876 elderly patients who presented with MI and categorized them by estimated glomerular filtration rate: >60 ml/min (no/mild CKD), 30-60 ml/min (CKD Stage 3) or <30 ml/min (CKD Stage 4/5). Compared with patients with no/mild CKD, patients with CKD Stage 3 or Stage 4/5 had more comorbidity, greater prior nursing home use, and higher frequency of conduction abnormalities or anterior infarction. By contrast, peak creatinine kinase-MB fraction (CK-MB) concentrations were lower and ST-elevation MI was less common in patients with CKD Stage 3 or Stage 4/5. In univariate analyses, patients with CKD Stage 4/5 (odds ratio (OR)=0.34, 95% confidence interval (CI): 0.23-0.50) or Stage 3 (OR=0.57, 95% CI: 0.45-0.73) were markedly less likely to undergo angiography than subjects with no/mild CKD. After multivariable adjustment, the association of CKD Stage 3 with the use of coronary angiography was attenuated (OR=0.78, 95% CI: 0.60-1.03), but CKD Stage 4/5 remained strongly associated with lower use (OR=0.52, 95% CI: 0.34-0.80). Clinical features of MI are different in patients with and without CKD and may partly explain the low use of angiography in patients with CKD Stage 3. However, the clinical features of MI do not account for its underuse in MI patients with CKD Stages 4/5. Whether reduced use of angiography in patients with advanced CKD is justified must be evaluated in formal risk-benefit analyses.

BACKGROUND:Long-term dialysis patients have a high incidence of myocardial infarction and cardiovascular death, but the incidence of coronary artery disease (CAD) in asymptomatic patients, distribution of coronary obstruction, and relationship between lesion location and mortality are unknown. METHODS:We studied 67 asymptomatic hemodialysis patients who volunteered for coronary angiography. Coronary stenoses of 50% or greater were documented, and the location of each within the proximal, midportion, or distal segment of the coronary vessel was recorded. Patients were followed up until death or renal transplantation. Cox proportional hazards regression was performed to analyze the relationship of lesion location with mortality. RESULTS:Obstructive CAD was common. Twenty-eight subjects (41.7%) had 50% or greater stenosis in at least 1 epicardial vessel, and 19 subjects (28.5%) had evidence of CAD within the proximal third of an epicardial vessel. After a median follow-up of 2.7 years, the presence of proximal CAD was associated with a marked increase in risk of death (adjusted hazard ratio, 3.14; 95% confidence interval, 1.34 to 7.33; P = 0.008) and was associated more strongly with mortality than multivessel disease or left anterior descending disease. CONCLUSION/CONCLUSIONS:CAD is common in asymptomatic dialysis patients, and stenoses frequently are located within the proximal coronary arteries, where they are associated with markedly increased risks of death. Additional studies are needed to determine whether proximal disease is a modifiable risk factor for cardiovascular mortality in dialysis patients.

Chronic kidney disease (CKD) is associated with a high risk of death from coronary artery disease and may modify the response to standard cardiovascular therapies. Treatment of subjects with CKD should ideally be based on evidence from randomized, clinical trials, but how often subjects with CKD have been excluded from these trials is uncertain. We undertook this study in order to quantify how often subjects with moderate to advanced CKD were excluded from large cardiovascular trials. MEDLINE and the reference list of selected articles were searched in order to identify large, randomized, controlled trials of five different coronary artery disease therapies published between 1998 and 2005. Exclusion criteria and reported clinical characteristics of subjects were abstracted. Rates of exclusion and reporting of baseline characteristics of study participants were compared for CKD, diabetes, history of smoking, and hypertension. Eighty-six trials randomizing 411 653 patients were identified. More than 80% of trials excluded subjects with end-stage renal disease and 75.0% excluded patients with CKD. Subjects with diabetes, hypertension, or a history of smoking were excluded less than 4% of the time. Baseline renal function of study participant was reported in only 7% of trials. Patients with CKD are frequently excluded from coronary artery disease trials and renal function of randomized subjects is rarely reported. These findings reinforce the notion that available data on the treatment of coronary artery disease in subjects with CKD have significant limitations and should be generalized to the treatment of subjects with CKD cautiously.