Association of Renal Insufficiency with Treatment and Outcomes after Myocardial Infarction in Elderly Patients

Context Renal insufficiency increases the risk for cardiovascular disease, but whether it affects survival after myocardial infarction is unknown. Contribution This large cohort study of Medicare beneficiaries hospitalized between April 1994 and July 1995 revealed the following: 1-year postmyocardial infarction mortality for no, mild, and moderate renal insufficiency was 24%, 46%, and 66%, respectively. Moderate renal insufficiency was more common in black and male patients and in patients with diabetes or previous stroke. Patients with moderate renal insufficiency received aspirin, -blockers, thrombolytic therapy, angiography, and angioplasty less often than patients with mild or no renal insufficiency. Implications Patients with moderate renal insufficiency have increased mortality after myocardial infarction. They also get fewer effective treatments for myocardial infarction, which may explain the higher death rate. The Editors Patients with end-stage renal disease who require dialysis have markedly increased mortality after myocardial infarction compared with other patients. One-year mortality in these patients is approximately 60% (1-3). After myocardial infarction, these patients are also unlikely to receive aggressive therapy, such as thrombolytic therapy and primary angioplasty, although these treatments have been associated with improved survival in these patients (4). Patients with renal insufficiency have a greater risk for cardiovascular disease events (5, 6), but the association between mild and moderate renal insufficiency and survival after myocardial infarction has not been evaluated in-depth (1, 7). Two earlier studies have included measures of renal function in prediction models for death after myocardial infarction. Normand and colleagues (8) incorporated both blood urea nitrogen and creatinine levels into a multivariate prediction model for 30-day mortality after myocardial infarction. Jacobs and colleagues included urea nitrogen levels as one of seven categories of predictors for death after hospital admission for acute coronary syndromes (9). However, studies have not compared survival after myocardial infarction among patients with and without renal insufficiency. In addition, the use of medical treatments and procedures after myocardial infarction among patients with and without renal insufficiency, and their association with survival, has not been studied. We hypothesized that patients with mild and moderate renal insufficiency would have substantially greater 1-year mortality than patients with no renal insufficiency. We also hypothesized that patients with renal insufficiency would be less likely to receive therapeutic interventions known to improve survival after myocardial infarction, such as -blockers, aspirin, angiotensin-converting enzyme (ACE) inhibitors, thrombolytic therapy, and primary angioplasty. Using data from the Cooperative Cardiovascular Project, we evaluated the treatment of patients with no renal insufficiency and patients with mild and moderate renal insufficiency. We also determined the independent association of renal insufficiency with survival after myocardial infarction. Methods Patients The Cooperative Cardiovascular Project collected data from all elderly (age 65 years) Medicare beneficiaries who were admitted between April 1994 and July 1995 to an acute-care hospital and discharged with the diagnosis of acute myocardial infarction (International Classification of Diseases, Ninth Revision, diagnosis code 410) (10). The diagnosis was confirmed by review of the medical records for each patient and required a serum creatine kinaseMB index greater than 5%; an elevated serum lactate dehydrogenase level with lactate dehydrogenase-1 greater than or equal to lactate dehydrogenase-2; or two of the following three criteria: chest pain, serum creatine kinase level more than twice the normal value, or electrocardiographic evidence of acute myocardial infarction (11). A total of 139 567 patients had confirmed myocardial infarction. Only the initial hospitalization for myocardial infarction during the period of evaluation was included. We excluded 6790 patients with severe renal insufficiency (serum creatinine level 4.0 mg/dL [354 mol/L]) or estimated creatinine clearance less than 0.17 mL/sec. We also excluded 10 570 patients (8.1%) for whom information on body weight was not available to estimate creatinine clearance. Measurements Within the Cooperative Cardiovascular Project, trained medical record abstracters collected the following data for each patient: date and location of hospitalization, demographic characteristics, comorbid conditions, severity of illness measures, electrocardiogram findings, laboratory values, results from invasive and noninvasive cardiac studies, contraindications to therapy, in-hospital treatments, and discharge medications (9). The reliability of the data abstraction process has been demonstrated (10, 12). We classified renal function using both the admission serum creatinine level and the estimated creatinine clearance. We defined no renal insufficiency as a serum creatinine level less than 1.5 mg/dL (<132 mol/L), mild renal insufficiency as a serum creatinine level between 1.5 and 2.4 mg/dL (132 to 212 mol/L), and moderate renal insufficiency as a serum creatinine level between 2.5 and 3.9 mg/dL (221 to 345 mol/L). We estimated creatinine clearance by using the CockroftGault equation (13) and divided patients into tertiles. Data on serum creatinine levels were available for all patients. Data on mortality during the first year after hospital admission were obtained from Social Security Administration records. Statistical Analysis We compared the characteristics and treatments of patients with no renal insufficiency, mild renal insufficiency, and moderate renal insufficiency using analysis of variance and chi-square tests. We compared the proportions of patients treated with -blockers among all patients in each category of renal function and in just the patients without relative contraindications to -blockers (previous heart failure, diabetes, chronic obstructive pulmonary disease, and pulmonary edema at presentation). We compared use of ACE inhibitors among all patients and then restricted the comparison to patients with hypertension or diabetes. For thrombolytic therapy, we compared treatment as a proportion of all patients treated and as a proportion of ideal patients treated. Ideal candidates were defined by ST-segment elevation or left bundle-branch block on the electrocardiogram; onset of chest pain within 6 hours of presentation; age of 80 years or younger; and the absence of peptic ulcer disease, chronic liver disease, metastatic cancer, and terminal illness (14). To determine the association of renal function with survival after myocardial infarction, we constructed KaplanMeier curves for the three groups of serum creatinine levels (and the tertiles of creatinine clearance); statistical significance was assessed by using the log-rank test. We repeated these analyses within subgroups of patients who presented without pulmonary edema or cardiogenic shock (Killip class I and class II) to determine whether the association of renal function with 1-year survival persisted among patients with less severe myocardial infarctions. We used Cox proportional-hazards models to determine whether mild and moderate renal insufficiency were independent predictors of 1-year mortality (15). These models were adjusted for patient demographic characteristics (age, sex, race, rural or urban setting, and region of the United States); comorbid conditions (history of diabetes mellitus, hypertension, hypercholesterolemia, tobacco use, congestive heart failure, stroke, peripheral vascular disease, angina, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery, chronic obstructive pulmonary disease, dementia, inability to ambulate, depression, and incontinence); severity of clinical presentation (Killip class, electrocardiogram findings, heart rate, mean arterial blood pressure, alertness and orientation according to the Glasgow coma scale, duration of chest pain, and blood urea nitrogen level [< 30 mg/dL; <10.7 mmol/L as urea or 30 mg/dL; 10.7 mmol/L as urea]); hospital characteristics (capability to do coronary angiography and revascularization; volume of myocardial infarction admissions); in-hospital treatments (aspirin, -blockers, ACE inhibitors, thrombolytic therapy, intravenous nitroglycerin, coronary angiography, percutaneous transluminal coronary angioplasty, and coronary artery bypass graft surgery); and discharge medications (aspirin, -blockers, calcium-channel blockers, and ACE inhibitors). We evaluated the inclusion of a categorical variable for each hospital (n = 4200) in a 10% sample of our data set, but it had little effect on the association of renal function with survival after myocardial infarction. We also checked for violations of linearity by examining augmented models, which included quadratic terms for continuous predictors. We tested the validity of the proportional hazards assumption by determining whether the risk estimates for the renal function categories varied significantly over time. Because we found a significant interaction of the risk for renal function over time, we elected to explore stratified models over time. We separately evaluated the association of our renal function categories with survival after myocardial infarction for the following time intervals: months 1, 2 to 3, 4 to 6, 7 to 9, and 10 to 12. Because the association of renal insufficiency with mortality was the same for months 7 to 9 and 10 to 12, we combined these follow-up intervals. We confirmed that there were no residual violations of the proportional hazards assumption within each time strata by again testing for the presence of an interaction of each renal function predictor with time in predicting mor