Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group.

BACKGROUND AND METHODS: Although their clinical efficacy is unclear and they may cause serious adverse effects, systemic glucocorticoids are a standard treatment for patients hospitalized with exacerbations of chronic obstructive pulmonary disease (COPD). We conducted a double-blind, randomized trial of systemic glucocorticoids (given for two or eight weeks) or placebo in addition to other therapies, for exacerbations of COPD. Most other care was standardized over the six-month period of follow-up. The primary end point was treatment failure, defined as death from any cause or the need for intubation and mechanical ventilation, readmission to the hospital for COPD, or intensification of drug therapy. RESULTS: Of 1840 potential study participants at 25 Veterans Affairs medical centers, 271 were eligible for participation and were enrolled; 80 received an eight-week course of glucocorticoid therapy, 80 received a two-week course, and 111 received placebo. About half the potential participants were ineligible because they had received systemic glucocorticoids in the previous 30 days. Rates of treatment failure were significantly higher in the placebo group than in the two glucocorticoid groups combined at 30 days (33 percent vs. 23 percent, P=0.04) and at 90 days (48 percent vs. 37 percent, P=0.04). Systemic glucocorticoids (in both groups combined) were associated with a shorter initial hospital stay (8.5 days, vs. 9.7 days for placebo, P=0.03) and with a forced expiratory volume in one second that was about 0.10 liter higher than that in the placebo group by the first day after enrollment. Significant treatment benefits were no longer evident at six months. The eight-week regimen of therapy was not superior to the two-week regimen. The patients who received glucocorticoid therapy were more likely to have hyperglycemia requiring therapy than those who received placebo (15 percent vs. 4 percent, P=0.002). CONCLUSIONS: Treatment with systemic glucocorticoids results in moderate improvement in clinical outcomes among patients hospitalized for exacerbations of COPD. The maximal benefit is obtained during the first two weeks of therapy. Hyperglycemia of sufficient severity to warrant treatment is the most frequent complication.

Systemic Corticosteroids in Chronic Obstructive Pulmonary Disease Exacerbations (SCCOPE): rationale and design of an equivalence trial. Veterans Administration Cooperative Trials SCCOPE Study Group.

The Systemic Corticosteroids in Chronic Obstructive Pulmonary Disease Exacerbations Trial (SCCOPE) was a randomized, double-blind, placebo-controlled, multicenter trial sponsored by the U.S. Department of Veterans Affairs Cooperative Studies Program. Its principal purpose was to determine whether withholding systemic corticosteroids in patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD) who were treated with other usual therapy resulted in a clinically significant increase in the rate of treatment failure. Because placebo was compared to a standard therapy, the study was designed as an equivalence trial. If corticosteroids proved effective, the study would also determine whether a short course was as effective as a long one. SCCOPE was to enroll up to 1100 subjects from more than 20 Veterans Administration Medical Centers over 3 years. Patients were screened shortly after hospital admission for acute exacerbation of COPD. Principal criteria for eligibility were age of 50 years or older, smoking history of 30 pack-years or more, clinical diagnosis of COPD as opposed to asthma, nonuse of systemic corticosteroids in the previous 30 days, and forced expiratory volume in 1 sec (FEV1) of 1500 ml or less. Eligible subjects were randomized to one of three treatment arms: (1) short course (2 weeks) of systemic corticosteroids, (2) long course (8 weeks) of systemic corticosteroids, or (3) placebo. We standardized most other aspects of care. We followed patients for 6 months. The primary endpoint of the study was treatment failure, defined as death, intubation with mechanical ventilation, hospital readmission for COPD, or intensification of pharmacologic therapy. Secondary endpoints included length of hospital stay, changes in FEV1, and changes in dyspnea score. We also evaluated possible adverse effects from systemic corticosteroids.

VA Study of Unstable Angina. 10-year results show duration of surgical advantage for patients with impaired ejection fraction.

BACKGROUND: In a randomized study of unstable angina, medically treated patients with impaired left ventricular (LV) ejection fractions (EF = 0.3 to 0.58) were at significantly higher risk of mortality than patients treated by coronary artery bypass graft surgery (CABG). Because the duration of this surgical advantage is unknown, 10-year cumulative mortality rates of patients with impaired LVEF were determined and compared with the previously observed rates at 2, 5, and 8 years. METHODS AND RESULTS: Of 468 patients with unstable angina, 237 were randomized to receive medical treatment alone and 231 patients to have CABG. Baseline characteristics, which were equally distributed between the two treatment groups, included age, LVEF, number of diseased coronary arteries, diabetes, clinical presentation (type I or type II), prior myocardial infarction, and smoking. Mortality was determined by life-table analysis and risk factors by logistic regression analysis. Patients were divided into terciles according to LVEF, and the mortality rates of medical and surgical patients in the lowest tercile were compared. The 10-year mortality rate for all medical patients was 38% and for all surgical patients, 39%. When LVEF was treated as a continuous variable, there was a significant relation between mortality and LVEF for medically treated patients but not for surgical patients. The cumulative mortality rate for the lowest-tercile (EF 0.3 to 0.58) medical patients was 49%; for the lowest-tercile surgical patients, 41% (P = .15). CONCLUSIONS: The surgical advantage for patients with impaired LVEF that was significant at 5 years (P = .03) and 8 years (P = .05) appears to have diminished at 10 years (P = .15).

Identification of unstable angina patients who have favorable outcome with medical or surgical therapy (eight-year follow-up of the Veterans Administration Cooperative Study).

To identify patients with unstable angina (UA) who have favorable outcomes with medical therapy or surgery, 468 patients who had been randomized in the Veterans Administration Cooperative Study of UA were risk-stratified based on angiographic criteria of the number of coronary arteries diseased and left ventricular ejection fraction (LVEF). Patients at high risk for UA were defined as those with 3-vessel disease or LVEF of < or = 58%, and patients at low risk were those with 1- or 2-vessel disease and LVEF of > 58%. Of the 468 UA patients randomized, 287 patients belonged to the high-risk and 181 to the low-risk category. In the low-risk group, cumulative mortality after 8 years of follow-up was significantly lower in the medically treated patients (16.8%) than in the surgically treated patients (32.2%) (p = 0.022); in the high-risk group, cumulative mortality was significantly lower in the surgically treated patients (24.1%) than in the medically treated patients (35.3%) (p = 0.03). The relative risk of surgery (the ratio of surgical to medical risk) in the low-risk patients was 1.67, indicating a significant survival advantage with medical treatment (p = 0.05), whereas the relative risk of surgery for the high-risk group was 0.71, indicating a significant survival benefit with surgical treatment (p < 0.05). Thus, medical therapy appears to be the preferred therapy for UA patients with only 1- or 2-vessel disease and normal LVEF, and surgery is preferred for UA patients with 3-vessel disease or LVEF in the lowest tercile.

A randomized clinical trial of two basic removable partial denture designs. Part I: Comparisons of five-year success rates and periodontal health.

A randomized clinical trial was undertaken to compare the effectiveness of two partial denture designs, one with I-bar (bar) and the other with circumferential retainers (circumferential), in 134 patients with Kennedy class I and class II edentulous conditions. A total of 30 partial dentures were considered failures, five because of abutment failures and 25 because of the lack of removable partial denture use for eating. The 5-year success rate of 71.3% for the circumferential design did not differ significantly from the 76.6% for the bar design (p > 0.05). There were no discernible changes in the nine periodontal health components of abutment teeth with either of the two designs after 60 months. The results indicate that the two designs do not differ significantly in terms of success rates, maintenance care, and effects on abutment teeth. A well-constructed removable partial denture of either design, supported by favorable abutments and accompanied by a regular recall program offers a satisfactory treatment modality.

Surgery or balloon angioplasty for peripheral vascular disease: a randomized clinical trial. Principal investigators and their Associates of Veterans Administration Cooperative Study Number 199.

PURPOSE: Surgical revascularization and angioplasty (PTA) are effective therapies for patients with peripheral arterial disease, but there are no data on long-term survival, limb salvage, and hemodynamic status from a randomized study of such patients. A multicenter, prospective trial compared PTA with bypass surgery (BP) in 263 men who had iliac, femoral, or popliteal artery obstruction. PATIENTS AND METHODS: Lesions in the iliac versus the femoropopliteal artery and rest pain versus claudication were separately randomized to the two treatment interventions. One hundred twenty-six patients underwent BP, 129 patients underwent PTA, and eight patients were not treated for lower extremity ischemia. RESULTS: Three operative deaths occurred in the BP group and none in the PTA group. For the entire study, average annual mortality was higher in the BP group, but survival was not significantly different on life-table analysis (P = .08). Primary success favored BP, while limb salvage favored PTA, but differences were not statistically significant (P = .08 and .35, respectively). Patients with iliac disease or claudication fared better, but there was no statistical difference in response to PTA or BP. CONCLUSION: Patients in both treatment groups had prompt and sustained increases in hemodynamics and quality of life. This study of patients randomly assigned to BP or PTA shows no significant difference in outcomes during a median follow-up of 4 years.

Unexpected, late cardiovascular effects of surgery for peripheral artery disease. Veterans Affairs Cooperative Study 199.

In reviewing late morbidity of a multicenter clinical trial comparing balloon angioplasty (percutaneous transluminal angioplasty) with bypass surgery for lower-extremity ischemia, an unexpectedly high incidence of adverse systemic events in surgical patients was uncovered. The study was prospective and randomized, and included a total of 263 patients, with follow-up from 2 to 6 years. When end points of related deaths, amputations, and intervention failures were summed, surgery was favored over percutaneous transluminal angioplasty at 4 years. Progression of cardiac and renal dysfunction and mortality differed between groups. A total of 42 deaths were in the group who underwent surgery and 27 in those who underwent percutaneous transluminal angioplasty. The percentage difference in death rate between the two groups increased each year to reach 10% at 5 years. A significant difference in renal function was noted in nine patients who underwent surgery and zero who underwent percutaneous transluminal angioplasty. Myocardial infarctions were greater on follow-up of surgical patients. After 6 years, congestive heart failure had occurred in 19 patients who underwent surgery and eight who underwent percutaneous transluminal angioplasty. The trends in this study of patients with only moderately severe peripheral arterial disease suggest an increased rate of deterioration of cardiac and renal function in patients who have arterial operations. In surgical patients, mortality was 13.1% per year, whereas it was 8.4% for patients treated with percutaneous transluminal angioplasty. Future intervention studies should include long-term follow-up of such cardiovascular events.

Coronary bypass surgery improves survival in high-risk unstable angina. Results of a Veterans Administration Cooperative study with an 8-year follow-up. Veterans Administration Unstable Angina Cooperative Study Group.

To identify high-risk subgroups, 468 patients with unstable angina were prospectively stratified according to the clinical presentation of unstable angina (type I or type II) and left ventricular function (normal or abnormal) and were randomized to conventional medical therapy or surgical treatment with coronary bypass surgery. Type I patients (n = 374) were those who had progressive effort angina or recent angina at rest. Type II patients (n = 94) were those who had severe rest angina associated with ST-T changes on the electrocardiogram. Follow-up for 8 years showed that the cumulative mortality rates for type II patients with abnormal left ventricular function were significantly lower in the surgical patients compared with the medical cohorts (13% versus 46%, p less than 0.04). In the other subgroups, cumulative medical and surgical mortality rates were not different. Thus, type II patients with abnormal left ventricular function appear to be the subgroup of patients who are at the highest risk with medical therapy. Coronary bypass surgery significantly reduces the mortality in this high-risk subgroup of patients with unstable angina.

Outcome predictors in selection of balloon angioplasty or surgery for peripheral arterial occlusive disease. Veterans Administration Cooperative Study No. 199.

In a selected group of men, surgical bypass and percutaneous balloon angioplasty (PTA) are equally effective therapy for ileo-femoropopliteal occlusive disease, provided immediate PTA failures are disregarded. Can we predict those patients likely to experience immediate PTA failure? Do any preintervention factors exist that favor PTA or surgical bypass for the remaining patients? Logistic regression analysis determined variables predictive of failure for the 19 immediate PTA failures and for the 17 patients with PTA and the 24 patients with surgical bypass who failed after initial intervention but before the end of 2 years. Two hundred sixty-three patients were enrolled. The analysis evaluated patient characteristics (age, weight, smoking status, diabetic status, and sickness impact profile score) as well as lesion site, percent lesion stenosis, runoff status, hemodynamic parameters, and indications. Two independent predictors of immediate PTA failure were diastolic hypertension (p = 0.032) and percent stenosis of study site (p = 0.035). The probability equation defined by the logistic regression analysis delineates patients at high risk for immediate PTA failure. Interestingly, no factor uniquely predicted delayed PTA or surgical failure. These data suggest that selected patients with diastolic hypertension and a severely stenotic or occluded artery are poor candidates for PTA. Either PTA or surgical bypass is effective therapy for the remaining patients.

Quality of life after bypass surgery for unstable angina. 5-year follow-up results of a Veterans Affairs Cooperative Study.

To assess the effect of bypass surgery on outcome from unstable angina, 468 patients were randomized to medical treatment (237 patients) or surgery plus medical treatment (231 patients) and have been followed for comparison of survival, cardiac end points, and quality of life; the latter end point is discussed in the present report. Data were available at 3 and 5 years for 80% and 82% of patients in the medical group, respectively, and 77% and 80% of patients in the surgery group, respectively. At 3 months after randomization to therapy, 79.8% of patients in the surgery group reported subjective improvement, compared with 58% of the medical group, 12.6% of the surgery group reported no change compared with 24.5% of the medical group, and 5.5% of the surgery group reported worsening compared with 24.5% of the medical group (p less than 0.01 by chi 2). Similar data were found for chest pain status, and the benefit to the surgery group remained statistically significant through 5 years of follow-up. Crossover rate to surgery was 43% by 5 years. Treadmill duration was increased in the surgery group compared with the medical group (6.5 +/- 0.25 versus 5.3 +/- 0.25 minutes at 6 months, p less than 0.01), and a significant difference was again demonstrated at 3 and 5 years. A trend toward decreased recurrence of unstable angina was present in the surgery group at 1 year (six of 168 [3.6%] versus 13 of 187 [6.9%] in the medical group, p = 0.158), but the two groups were similar at 3 and 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Medical compared with surgical management of unstable angina. 5-year mortality and morbidity in the Veterans Administration Study.

We evaluated medical in comparison to surgical plus medical (surgical) treatment of unstable angina using a prospective randomized protocol that stratified patients by clinical presentation and by invasive evaluation of left ventricular (LV) function. Clinical presentations were as follows--type 1: progressive or new onset angina relieved by medication; type 2: prolonged bouts of angina poorly or incompletely relieved by medication. Abnormal LV function was arbitrarily defined as ejection fraction less than 0.50 or LV end-diastolic pressure 16 mm Hg or more. Of 468 patients, 237 were assigned to medical and 231 to surgical therapy. There were 374 type 1 and 94 type 2 patients. LV function was normal in 334 and abnormal in 134 patients. Compared with results at 24 months, this 60-month follow-up study showed important differences in survival for patients with three-vessel disease: 75% for medical and 89% for surgical patients (p less than 0.02). The cumulative 5-year rate of repeat hospitalizations for cardiac reasons was less with surgical patients for either clinical presentation. For type 1, medical patients had a 56% rate, and surgical patients had a 42% rate (p = 0.004). For type 2, medical patients had a 62% rate, and surgical patients had a 43% rate (p = 0.05). Overall mortality did not differ between the two treatments, and this remained true in type 1 versus type 2 patients and in those with normal versus abnormal LV function. However, regression analysis of medical and surgical groups with ejection fraction as a continuous variable showed that mortality of medical patients depended on ejection fraction (p = 0.004), whereas the mortality of surgical patients did not (p = 0.76), and survival in the surgical group was higher in the lowest ejection fraction tercile-73% for medical and 86% for surgical patients, p = 0.03. We conclude that surgery improves survival in patients with three-vessel disease and leads to fewer subsequent hospitalizations for cardiac reasons. An impaired ejection fraction had an adverse impact on survival of medical patients but not on surgical patients, and mortality in surgical patients was improved compared with medical patients in the lowest ejection fraction tercile.

Veterans Administration Cooperative Study for treatment of patients with unstable angina. Results in patients with abnormal left ventricular function.

In a prospective randomized trial, 468 patients with unstable angina pectoris who were stratified according to clinical presentation (Type I or Type II angina) and left ventricular function (normal or abnormal) were assigned to medical or surgical treatment groups. Left ventricular function was defined as abnormal if the ejection fraction was less than 0.50, or if the end-diastolic pressure was 16 mm Hg or greater. Left ventricular function was abnormal in 134 patients, 66 of whom were assigned to surgical and 68 to medical treatment groups. The cumulative 3-year mortality for surgical patients was 6.1% and for medical patients, 17.6% (p = 0.039). This 3-year figure represents a 65% reduction in mortality with surgery. Survival was significantly better for surgical patients whose ejection fractions ranged from 0.30 to 0.49 (p = 0.05). Survival of patients whose ejection fractions were greater than 0.69 was better with medical treatment (p = 0.049). Thus, surgery appears to be the treatment of choice for patients with unstable angina pectoris and abnormal left ventricular function.

Comparison of medical and surgical treatment for unstable angina pectoris. Results of a Veterans Administration Cooperative Study.

We conducted a multicenter, randomized, prospective study comparing medical therapy alone with coronary-artery bypass surgery plus medical therapy in 468 men with unstable angina pectoris. Patients were entered in the study from June 1, 1976, to June 30, 1982. Among those assigned to surgery who received bypass grafts, operative mortality was 4.1 percent. Arteriography performed after one year of follow-up revealed that 74.8 percent of the grafts studied were patent. The cumulative rate of crossover from medical to surgical therapy after two years was 34 percent; the operative mortality among patients crossed over was 10.3 percent. Nonfatal myocardial infarction occurred in 11.7 percent of the patients treated surgically and 12.2 percent of those treated medically (no significant difference). Most of the nonfatal myocardial infarctions in the surgical group occurred in the perioperative period. Overall, the two-year survival rate computed by life-table analysis did not differ between the two groups. However, the curves reflecting mortality as a function of left ventricular ejection fraction were significantly different (P = 0.03); surgery was associated with a significantly reduced mortality among patients with lower ejection fractions. We conclude that patients with unstable angina pectoris have a similar outcome after two years whether they receive medical therapy alone or coronary bypass surgery plus medical therapy. However, patients with reduced left ventricular ejection fractions may have a better two-year survival rate after coronary bypass surgery.

Recurrent urinary tract infections in men. Characteristics and response to therapy.

All men with recurrent urinary tract infections entered into a study had a positive antibody-coated bacteria test, and 52% had evidence for prostate infection. Escherichia coli infection was present in 74% and urinary tract symptoms in 57% of those randomized. Thirty-eight patients were randomized in a double-blind clinical trial to receive either 10d of treatment with trimethoprim/sulfamethoxazole or a 12-week course of the drug. The cure rate in patients receiving 12 weeks of therapy (nine of 15) was higher than that in patients receiving a single 10-d course (three of 15); difference was marginally significant (P = 0.06). Recurrences were usually with the same organism, and most (78%) occurred within 4 weeks of discontinuing therapy. This study indicates that a standard 10-d course of therapy usually fails to cure men with recurrent urinary tract infections with a positive antibody-coated bacteria test.