Sirolimus Adverse Event Profile in a Non-Clinical Trial Cohort of Heart Transplantation Patients.

BACKGROUND Sirolimus has been used increasingly in heart transplantation for its ability to reduce acute rejection, prevent the progression of cardiac allograft vasculopathy (CAV), and preserve renal function. We sought to assess the adverse reactions associated with the use of sirolimus compared to mycophenolate mofetil (MMF). MATERIAL AND METHODS We retrospectively reviewed the charts of 221 adult heart transplant patients who received either sirolimus or MMF as part of their immunosuppression from June 1, 2001 to April 1, 2005. Patients were assigned to 2 groups based upon immunosuppression use. The prevalence and types of complications were recorded in each group. RESULTS Sirolimus was received by 109 patients and 112 patients received MMF during the study period. Seventy-seven patients (71%) in the sirolimus group experienced adverse reactions compared to 45 patients (40%) in the MMF group (P<0.01). Compared to MMF, the use of sirolimus was associated with a higher prevalence of elevated triglyceride levels, lower-extremity edema, and oral ulcerations. Sirolimus was discontinued due to adverse reactions in 22% of patients, whereas no patients in the MMF group experienced adverse effects requiring drug discontinuation. CONCLUSIONS Compared to MMF, sirolimus use is associated with a higher prevalence of adverse reactions requiring drug discontinuation, but most patients were able to stay on therapy despite adverse effects.

Characterizing differences in mortality at the low end of the fitness spectrum.

PURPOSE: A graded nonlinear relationship exists between fitness and mortality with the most remarkable difference in mortality rates observed between the least-fit (first, Q1) and the next-least-fit (second, Q2) quintile of fitness. The purpose of this study was to compare clinical characteristics, exercise test responses, and physical activity patterns in Q1 versus Q2 in apparently healthy individuals. METHODS: A total of 4384 subjects referred for clinical treadmill testing from 1986 to 2006 were followed for a mean +/- SD period of 8.7 +/- 5.3 yr. All subjects had normal exercise ECG responses and no history of cardiovascular disease. Subjects were classified into quintiles of exercise capacity measured in METs. Clinical characteristics, physical activity patterns, and treadmill test results were compared between the first two quintiles (Q1: METs <5.9 (n = 693); Q2: METs 6.0-7.9 (n = 842)). RESULTS: Small differences in age (64 +/- 11 vs 60 +/- 10 yr, P < 0.001), use of antihypertensive medications, prevalence of diabetes (21% vs 16%, P = 0.02), and dyslipidemia (43% vs 49%, P = 0.04) were observed between Q1 and Q2. When the Cox proportional hazards model was adjusted for age and other clinical characteristics, the relative risk of mortality remained almost two times greater in Q1 versus Q2 (cardiovascular mortality: HR: 4.01 vs 2.01, P < 0.001; reference group: fittest subjects (Q5)). In a subset of 802 subjects, recent recreational physical activity was significantly lower in Q1 versus Q2. CONCLUSIONS: Reduced physical activity patterns rather than differences in clinical characteristics contribute to the striking difference in mortality rates between the least-fit and the next-least-fit quintile of fitness in healthy individuals.

Exercise capacity and body mass as predictors of mortality among male veterans with type 2 diabetes.

OBJECTIVE: To demonstrate the relation of exercise capacity and BMI to mortality in a population of male veterans with type 2 diabetes. RESEARCH DESIGN AND METHODS: After excluding two underweight patients (BMI <18.5 kg/m2), the study population comprised 831 consecutive patients with type 2 diabetes (mean age 61 +/- 9 years) referred for exercise testing for clinical reasons between 1995 and 2006. Exercise capacity was determined from a maximal exercise test and measured in metabolic equivalents (METs). Patients were classified both according to BMI category (18.5-24.9, 25.0-29.9, and > or =30 kg/m2) and by exercise capacity (<5.0 or > or =5.0 maximal METs). The association among exercise capacity, BMI, other clinical variables, and all-cause mortality was assessed by Cox proportional hazards. Study participants were followed for mortality up to 30 June 2006. RESULTS: During a mean follow-up of 4.8 +/- 3.0 years, 112 patients died, for an average annual mortality rate of 2.2%. Each 1-MET increase in exercise capacity conferred a 10% survival benefit (hazard ratio 0.90 [95% CI 0.82-0.98]; P = 0.01), but BMI was not significantly associated with mortality. After adjustment for age, ethnicity, examination year, BMI, presence of cardiovascular disease (CVD), and CVD risk factors, diabetic patients achieving <5 maximal METs were 70% more likely to die (1.70 [1.13-2.54]) than those achieving > or =5 maximal METs. CONCLUSIONS: There was a strong inverse association between exercise capacity and mortality in this cohort of men with documented diabetes, and this relationship was independent of BMI.