Distinguishing the antihypertensive and electrolyte effects of eplerenone.

In two clinical trials on the antihypertensive effects of the mineralocorticoid receptor antagonist eplerenone 397 essential hypertensives were dose titrated (50, 100, and 200 mg/d) over successive 4-wk periods until they reached target blood pressure levels. Of the total, 44% reached target on 50 mg/d, 17% on 100 mg/d, and 19% on 200 mg/d, with 20% failing to do so despite stepwise dose increases. At each dose level, those who reached target (responders) were compared with those who did not (nonresponders), with three major findings. First, at each dose level, the blood pressure fall in responders (systolic, 16-20 mm Hg; diastolic, approximately 15 mm Hg) was markedly more than mean values in nonresponders (systolic, 2-5 mm Hg; diastolic, 1-3 mm Hg). Second, sensitivity to eplerenone varied widely across the population studied in terms of blood pressure reduction. Third, there was no difference in plasma [K+] levels between responders and nonresponders at any dose level. We interpret these data as evidence for the major antihypertensive effect of eplerenone being via mechanisms other than those involving epithelial electrolyte and fluid transport. The modest (< or =0.2 mEq/liter at 200 mg/d) mean elevation in plasma [K+] suggests that titration to effect rather than forced titration may minimize the risk of hyperkalemia, even where relatively high (100-200 mg/d) doses of the specific mineralocorticoid receptor antagonist eplerenone may ultimately be required.

Antibiotics and Clostridium difficile diarrhea in the ambulatory care setting.

OBJECTIVE: The goal of this study was to determine the prevalence of Clostridium difficile diarrhea (CDD) and the risk for CDD associated with different oral antibiotics commonly used in the ambulatory care setting. METHODS: The prevalence of CDD was determined for enrollees in 4 UnitedHealth Group-affiliated health plans between January 1, 1992, and December 31, 1994. Cases were identified based on the presence of an inpatient or outpatient claim with a primary diagnosis of diarrhea, a pharmacy claim for a prescription drug used to treat CDD, or a physician or facility claim for the C. difficile toxin test, and were confirmed using full-text medical records. Within a retrospective cohort design, periods of risk for CDD were defined on the basis of duration of antibiotic therapy. To control for potential selection bias created by heterogeneous rates of C. difficile testing and to limit confounding due to multiple antibiotic exposures, we used a nested case-control design, restricting eligibility to subjects who underwent screening for C. difficile and who had been exposed to only 1 antibiotic risk period with a single antibiotic. RESULTS: The global prevalence of CDD in 358,389 ambulatory care enrollees was 12 per 100,000 person-years. In the nested case-control study, after controlling for other risk factors, 2 antibiotics demonstrated an increased association with CDD: cephalexin (odds ratio [OR] = 7.5, 95% CI = 1.8 to 34.7) and cefixime (OR = 6.4, 95% CI = 1.2 to 39.0). CONCLUSIONS: Although CDD is thought to occur primarily in hospitalized patients, it was found to be present in an ambulatory care population, but at a low frequency. In this population, it appeared to be associated with 2 cephalosporins but not with other types of antibiotics usually linked with nosocomial CDD. Because the frequency of C. difficile testing was shown to be more common with high-risk antibiotics, CDD may be underdiagnosed in the ambulatory care setting.

Changes in patients undergoing coronary artery bypass grafting: 1987-1990. Northern New England Cardiovascular Disease Study Group.

A prospective study of 7,590 consecutive patients undergoing isolated coronary artery bypass grafting at five medical centers in Maine, New Hampshire, and Vermont between July 1987 and December 1990 assessed changes in patient characteristics over time. Variables included age, sex, surgical priority, ejection fraction, left ventricular end-diastolic pressure, and left main coronary artery stenosis of 90% or greater. Trends were assessed for each variable and for predicted mortality using linear regression. The mean age increased significantly, whereas ejection fraction decreased. The percentage of urgent cases increased, whereas the elective cases became less frequent. No changes were observed in the percentages of emergent cases, female patients, or patients with severe left main coronary artery disease. The predicted in-hospital mortality rose significantly from 4.2% to 5.2% (p < 0.001). The increase in urgent surgical intervention was the most substantial contributor. Subgroup analyses did not support a systematic misclassification of elective patients into the urgent group. This study demonstrates that the characteristics of the cohort of patients undergoing coronary artery bypass grafting changed substantially from 1987 to 1990. These changes should be considered when interpreting surgical outcomes.

Differences between men and women in hospital mortality associated with coronary artery bypass graft surgery. The Northern New England Cardiovascular Disease Study Group.

BACKGROUND: A prospective study of patients undergoing coronary artery bypass graft surgery (CABG) was conducted to examine differences in hospital mortality by sex. Outcome data on 3055 CABG patients undergoing operation between 1987 and 1989 were examined for differences in patient, disease, and treatment factors. METHODS AND RESULTS: Odds ratios (OR), risk differences, and 95% confidence intervals (CI95%) were calculated. Mortality rates for women (7.1%) and men (3.3%) differed, the OR (women versus men) being 2.23 (CI95%, 1.58 to 3.15). Women were older, more often diabetic, and had more urgent or emergent surgery; adjustment yielded an OR (women versus men) of 1.75 (CI95%, 1.17 to 2.63). Body surface area (BSA) was associated with risk of death in both sexes (P = .007) and positively associated with coronary artery luminal diameters. After adjustment for BSA, sex was no longer significantly associated with mortality (OR [women versus men] of 1.18; CI95%, 0.72 to 1.95). Internal mammary artery (IMA) grafting was performed less frequently among women than men (64.8% versus 78.4%, P < .001). Smaller BSA and absence of IMA grafting were each associated with increased risk of death (RD) from heart failure. Risk of death from heart failure (RD [women minus men] = 2.05; CI95%, 0.89 to 3.22) and hemorrhage (RD [women minus men] = 0.63; CI95%, 0.13 to 1.13) was greater among women; these accounted for 71.1% of the sex-specific difference in mortality rates. CONCLUSIONS: Excess risk of hospital mortality among women having CABG was largely the consequence of death from heart failure and, to a lesser extent, from hemorrhage. Smaller BSA (probably because of its association with coronary artery luminal diameter) and the absence of IMA grafting were each associated with increased risk of death from heart failure.

Prophylactic nitroglycerin infusion during noncardiac surgery does not reduce perioperative ischemia.

We evaluated the impact of prophylactic nitroglycerin on the incidence of perioperative myocardial ischemia in patients with known or suspected coronary artery disease who undergo noncardiac surgery. Our goals were to better define the role of nitroglycerin in the management of high-risk patients and to explore the mechanisms of perioperative myocardial ischemia. Patients were assigned randomly to either a control group (n = 23) or to receive 0.9 micrograms.kg-1.min-1 of intravenous nitroglycerin (n = 22). The diagnosis of myocardial ischemia was based on a review of Holter electrocardiogram (ECG) recordings. There was no difference in the incidence of ischemia between groups. Seven control patients (30%) and seven nitroglycerin patients (32%) exhibited ECG evidence of ischemia. The preponderance of myocardial ischemia occurred during emergence from anesthesia (of the 14 patients exhibiting ischemia, 12 did so at emergence). There was an acute increase in heart rate at the onset of ischemia in all patients exhibiting ischemia with 14 of 18 episodes associated with an increase of 20% or greater. The heart rate associated with the onset of ischemia was greater in the nitroglycerin-treated patients than in the control group. We also found that the occurrence of myocardial ischemia on a preoperative Holter recording was strongly predictive of the subsequent occurrence of perioperative ischemia. In conclusion, the addition of nitroglycerin to standard anesthetic management of these high-risk patients does not measurably reduce perioperative ischemia.

Multivariate prediction of in-hospital mortality associated with coronary artery bypass graft surgery. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: A prospective regional study was conducted to identify factors associated with in-hospital mortality among patients undergoing isolated coronary artery bypass graft surgery (CABG). A prediction rule was developed and validated based on the data collected. METHODS AND RESULTS: Data from 3,055 patients were collected from five clinical centers between July 1, 1987, and April 15, 1989. Logistic regression analysis was used to predict the risk of in-hospital mortality. A prediction rule was developed on a training set of data and validated on an independent test set. The metric used to assess the performance of the prediction rule was the area under the relative operating characteristic (ROC) curve. Variables used to construct the regression model of in-hospital mortality included age, sex, body surface area, presence of comorbid disease, history of CABG, left ventricular end-diastolic pressure, ejection fraction score, and priority of surgery. The model significantly predicted the occurrence of in-hospital mortality. The area under the ROC curve obtained from the training set of data was 0.74 (perfect, 1.0). The prediction rule performed well when used on a test set of data (area, 0.76). The correlation between observed and expected numbers of deaths was 0.99. CONCLUSIONS: The prediction rule described in this report was developed using regional data, uses only eight variables, has good performance characteristics, and is easily available to clinicians with access to a microcomputer or programmable calculator. This validated multivariate prediction rule would be useful both to calculate the risk of mortality for an individual patient and to contrast observed and expected mortality rates for an institution or a particular clinician.