A double-blind placebo-controlled trial of low-dose ganciclovir to prevent cytomegalovirus disease after heart transplantation.

BACKGROUND: The aim of this double-blind, placebo-controlled study was to determine whether a prolonged course of low-dose ganciclovir prevented the development of clinical cytomegalovirus disease after heart transplantation. METHODS: Fifty-six consecutive patients were stratified into two groups: cytomegalovirus-positive recipients (n = 40) and cytomegalovirus-negative recipients of organs from cytomegalovirus-positive donors (n = 16). All patients received equine antithymocyte globulin induction for 7 days and maintenance doses of cyclosporine, azathioprine, and prednisolone. Ganciclovir (5 mg/kg intravenously) or matching placebo was given with the premedication, three times weekly for the first 6 weeks after transplantation and for another 2 weeks for each treated rejection episode between 6 and 12 weeks. RESULTS: Ganciclovir prophylaxis reduced the actuarial incidence of cytomegalovirus disease from 71% to 11% in cytomegalovirus-mismatched patients (p < 0.01). Ganciclovir prophylaxis did not reduce the incidence of cytomegalovirus disease in cytomegalovirus-positive recipients (25% in both placebo and ganciclovir groups) but did delay its onset and reduce its morbidity. There were no adverse reactions during ganciclovir administration. Gastritis was the most common clinical manifestation of cytomegalovirus disease. Pneumonitis and myocarditis were seen only in placebo-treated cytomegalovirus-mismatched patients. All patients with clinical cytomegalovirus disease responded to ganciclovir, 10 mg/kg/day for 2 weeks. CONCLUSIONS: Prolonged low-dose ganciclovir prophylaxis after heart transplantation reduces the incidence of cytomegalovirus disease in cytomegalovirus-mismatched patients and reduces the morbidity of cytomegalovirus disease in cytomegalovirus-positive recipients.

Five-year follow-up of a randomized double-drug versus triple-drug therapy immunosuppressive trial after heart transplantation.

To determine the role of maintenance steroids in a cyclosporine and azathioprine immunosuppressive regimen, 112 heart transplant recipients were prospectively randomized to group I (n = 59; cyclosporine, azathioprine, and prednisolone) or group II (n = 53; cyclosporine and azathioprine). All patients received 7 days of induction with antithymocyte globulin. Patients receiving double-drug therapy who required four treatments for rejection were converted to maintenance steroids. This was necessary in 47% of the patients. Actuarial survival at 5 years was 82% in group I and 85% in group II. Linearized rejection in the first 3 months was lower with triple-drug therapy than with double-drug therapy (1.5 +/- 0.18 versus 2.3 +/- 0.23 episodes/100 patient days, p less than 0.01) but did not differ beyond 3 months. No significant differences were noted in 3-year left ventricular ejection fraction (0.56 +/- 0.09 versus 0.58 +/- 0.12 units), serum creatinine level (0.14 +/- 0.04 versus 0.14 +/- 0.03 mmol/L), or number with coronary artery disease (10 versus 13), diabetes, or bone complications. Patients receiving triple-drug therapy, however, had higher serum cholesterol level at 3 years (6.2 +/- 0.9 versus 5.4 +/- 1.2 mmol/L; p = 0.022) and required more antihypertensive agents (1.3 +/- 0.8 versus 0.8 +/- 0.6; p = 0.016). Similar trends emerged when patients receiving true double-drug therapy were compared with those patients who were "converted." Therapy with double versus triple immunosuppressive therapy results in similar 5-year survival and systolic function, using this protocol of converting recurrent rejectors on double-drug therapy to maintenance steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Initial steroid-free versus steroid-based maintenance therapy and steroid withdrawal after heart transplantation: two views of the steroid question.

To determine any benefit of maintenance steroids in a cyclosporine and azathioprine immunosuppressive regimen, 112 heart transplant recipients were prospectively randomized to receive cyclosporine, azathioprine, and prednisolone (n = 59) or cyclosporine and azathioprine (n = 53). Of the 53 double-therapy patients, 47% were converted to maintenance steroids for resistant rejection or renal dysfunction. In a comparison of true double-therapy (n = 28) versus true triple-therapy (n = 59) groups, actuarial survival and systolic function did not differ. Linearized rejection during the first 3 months was lower with triple therapy than with double therapy (1.5 +/- 0.18 vs 2.3 +/- 0.23 episodes/100 patient-days; p less than 0.01) as were requirements for cytolytic therapy for rejection with hemodynamic compromise. Patients receiving triple therapy had significantly higher serum cholesterol levels and antihypertensive agent requirements at all annual time points up to 5 years. The rate of steroid-related morbidity (diabetes, bone complications, cataracts, and obesity) was low in both groups and did not differ significantly. Of the 204 patients receiving triple therapy at this unit, 45 underwent steroid withdrawal. The initial success rate was 69%, and an additional 14% of those who initially failed succeeded on the second attempt. Any rejection after steroid cessation tended to occur within 6 weeks. There were, however, no substantial short-term benefits in body weight or lipid or blood pressure control. In patients in whom infection or growth retardation was an indication for steroid withdrawal, these generally improved after cessation. Until predictive markers for the likely success of steroid withdrawal are identified, the case for steroid withdrawal, as opposed to steroid minimization, does not seem compelling.

Quality of life after heart transplantation in patients assigned to double- or triple-drug therapy.

The purpose of this study was to compare the quality of life after heart transplantation for patients treated with cyclosporine and azathioprine (double therapy) versus cyclosporine, azathioprine, and corticosteroids (triple therapy). This study was based on a randomized, prospective trial and was focused on patients from ages 17 to 57 years at 1-year after transplantation. Patients who received double therapy showed advantages on 10 of 11 measures of quality of life. Significant differences were found on measures of anxiety, sexual activity, physical well-being, and financial well-being. Patients who received double-drug therapy reported a lower frequency and less distress from the side effects of immunosuppression; a higher proportion of double-drug therapy patients had returned to full-time employment. In addition double-therapy patients were better able to control body mass. These features may explain why double-drug therapy patients reported a higher quality of life, and in the long term, could be important from a cost benefit analysis.

Rehabilitation after heart transplantation: the Australian experience.

This study was designed to assess aspects of the quality of life and rehabilitation of heart transplant recipients who had transplantations at St. Vincent's Hospital, New South Wales, Australia, between February 1984 and March 1987. Factors determining return to full-time employment were delineated. A questionnaire was sent to 51 recipients. The response rate was 92%. The questionnaire measured employment status and satisfaction with family, social, marital, and sexual life. Financial status, exercise ability, and participation in daily activities were also assessed. Analysis showed that 53% of recipients had returned to either full-time or part-time employment, home duties, or full-time study. A further 28% were receiving a pension, 9% had chosen voluntary retirement, 6% were receiving unemployment benefits, and 4% were getting paid leave. Ability to exercise was improved for 77% of recipients and remained the same for another 14%. Financial status was unchanged for 45% and improved for 17%. Thirty-eight percent believed that they were worse off financially. Ratings of social, family, and marital life showed nearly complete or complete satisfaction in most cases. Satisfaction with sex life was less favorable. Comparison of the group who had returned to full-time employment with the group receiving a pension identified two variables of work status--length of time since transplantation and employment status before transplantation. There were also some differences between the two groups on quality of life ratings.