A Prospective, Randomized Trial of Single-Drug Versus Dual-Drug Immunosuppression in Heart Transplantation

Baran, David A.; Zucker, Mark; Arroyo, Luis H.; Camacho, M.; Goldschmidt, Marc E.; Nicholls, Stephen J.; Prevost-Fernandez, J.; Carr, C.; Adams, Laura L.; Pardi, S.; Hou, V.; Binetti, M.; McCahill, J.; Chichetti, Joanne; Viloria, Valerie; SanAgustin, Mary Gladys; Ebuenga-Smith, Jennifer; Mele, L; Martin, A; BLICHARZ, DONNA; Wolski, Kathy; Olesnicky, Ludmilla; Qian, Fang; Gass, Alan; Cohen, Marc

doi:10.1161/circheartfailure.110.958520

Cited by 61 publications

(32 citation statements)

References 27 publications

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“…Importantly, modification of immunosuppressive therapy in Group I was not associated with increased incidence of rejections (P = 0.0534). These findings are consistent with the results of the TICTAC trial 24 which showed that addition of MMF to single-agent immunosuppression does not provide any advantage over single-agent immunosuppression in terms of rejections. Similar results were also found by Teuteberg 25 who reported a regimen consisting of a dose reduced MMF in patient after HTx.…”

Section: Discussionsupporting

confidence: 90%

Bone marrow suppression and associated consequences in patients after heart transplantation: A 6-year retrospective review

Pazderník¹,

Málek²,

Koudelková³

et al. 2015

BIOMED PAP

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Aims.To evaluate the incidence of bone marrow suppression and consequences of MMF dose adjustment in patients within the first year after heart transplantation. Methods. Group I (n=47) was treated with a regimen currently used in patients after heart transplantation (mycophenolatemofetil -MMF, valganciclovir -VGC and trimethoprim/sulfamethoxazole -TMP-SMX). Group II (n=47) received only MMF of potentially myelotoxic medications. The myelotoxic effect and need for dose modification were assessed. The incidence of rejections and infectious episodes associated with MMF adjustment were analyzed during the first 12 months in Group I.Results. There was a significantly greater proportion of patients with leukopenia (leukocyte count < 4 x 10^9/L) at 3 months after orthotopic heart transplantation in Group I compared with Group II (19.1% vs 2.1%; P = 0.02). The difference in lymphopenia (lymphocyte count < 0.8 x 10^9/L) at 3 months follow-up was highly significant (38.3 % vs 6.4 %; P = 0.0002). MMF was modified due to bone marrow suppression or severe infection in 63.8% patients in Group I and in only 8.5% of patients in Group II (P < 0.001). Reducing or stopping MMF was not associated with increased rejections. In Group I, at least 1 episode of higher degree cellular or humoral rejection occurred in 35% of patients with the standard MMF dosage compared with only 26% in patients with modified MMF (P = 0.0534). Conclusions. Addition of VGC+TMP-SMX to current immunosuppressive medication regimen in patients after heart transplantation is associated with significant lymphocytopenia and leukopenia. Importantly, modification of immunosuppressive prophylaxis (reducing or stopping MMF) leads to normalization of blood count without increased incidence of rejections.

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Section: Discussionsupporting

confidence: 90%

Bone marrow suppression and associated consequences in patients after heart transplantation: A 6-year retrospective review

Pazderník¹,

Málek²,

Koudelková³

et al. 2015

BIOMED PAP

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“…2,3 The well-known adverse effects of tacrolimus include nephrotoxicity, 4 hypertension, 5 neurotoxicity, [6][7][8][9][10] and glucose intolerance. 11,12 Posterior reversible encephalopathy syndrome was f irst reported in 1996 by Hinchey and colleagues, 13 who described a reversible syndrome associated with headache, altered mental function, seizures, and visual disturbances.…”

Section: Discussionmentioning

confidence: 99%

Posterior Reversible Encephalopathy Syndrome after Heart Transplantation: Diagnosis and Immunosuppressive Therapy

Kapoor¹,

Birks²,

Lenneman³

et al. 2017

Texas Heart Institute Journal

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Posterior reversible encephalopathy syndrome (PRES) is an infrequent neurologic sequela occurring in response to tacrolimus therapy. One of our recent cases is a prime example of the difficulties faced by physicians when they attempt to balance immunosuppression and drug toxicities. We highlight the most relevant features of our case, in an attempt to bring greater understanding of the pathophysiology of PRES. Further, we discuss the methods typically used to diagnose PRES, and we attempt to consolidate previous knowledge within the scope of PRES in a patient who was receiving immunosuppression after orthotopic heart transplantation. Case ReportA 37-year-old woman with a medical history of type 2 diabetes mellitus and hypothyroidism presented with generalized tonic-clonic seizures 16 days after orthotopic heart transplantation. Her home medications included 6 mg of tacrolimus, 1,500 mg of mycophenolate mofetil, and 20 mg of prednisone, each taken orally twice daily; trimethoprim/sulfamethoxazole; and valganciclovir. She had had 3 seizures that involved tongue-biting and stool incontinence. Initially, she was treated with diazepam, intravenous phenytoin, and intravenous ceftriaxone for suspected meningitis, a frequent sequela in an immunocompromised patient. On admission, the patient was somnolent but rousable and reported a throbbing temporal headache. Her blood pressure was 130/77 mmHg, and her pulse was 110 beats/min. No focal deficits were present upon neurologic examination. Laboratory data included a white blood cell count of 16.4 ×10 9 cells/L, a potassium level of 5.4 mmol/L, a magnesium level of 1.77 mmol/L, a blood urea nitrogen level of 47 mg/dL, and a creatinine level of 1.25 mg/dL with an anion gap of 23 mmol/L. Her tacrolimus levels at the time of admission were 8.4 ng/mL. Her previous tacrolimus levels had been 9.7 to 13.9 µg/mL, which, in a normotensive patient without a tremor, made toxicity less likely. Her examination included a lumbar puncture that was negative for any infectious process, an electroencephalogram that showed no evidence of seizure activity, and a computed tomogram of the head that showed no intracranial bleeding. A brain magnetic resonance image (MRI) was ordered, and the findings suggested PRES (Fig. 1A).On the basis of these findings, we discontinued tacrolimus and replaced it with 2 mg/d of oral sirolimus. A repeat MRI showed resolution of the patient's high signal intensities (Fig. 1B). The mycophenolate mofetil was continued at 1,500 mg and the prednisone was slightly reduced to 15 mg, twice a day. The patient was discharged

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“…These conclusions are tempered by the limited statistical power associated with a sample size of only 150 patients. 4 Chronic Kidney Disease and the Risk of Heart Failure in Men Summary: Individuals with chronic kidney disease (CKD) have higher prevalence of left ventricular hypertrophy and cardiovascular disease; however, it remains unclear if development of CKD is associated with higher incidence of heart failure, independent from diabetes and hypertension. We analyzed the relations of CKD to incident heart failure and to cardiovascular disease (CVD) death or heart failure (combined end point) in 10 181 Physicians' Health Study male participants (mean age, 67 years).…”

Section: Discussionmentioning

confidence: 99%

Circulation: Heart Failure Editors' Picks

2012

Circulation

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The following articles are being highlighted as part of Circulation's Topic Review series. This series summarizes the most important manuscripts, as selected by the editors, published in Circulation and the Circulation subspecialty journals. The studies included in this article represent the Editors' Picks for each Circulation: Heart Failure issue published in 2011.

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A Prospective, Randomized Trial of Single-Drug Versus Dual-Drug Immunosuppression in Heart Transplantation

Cited by 61 publications

References 27 publications

Bone marrow suppression and associated consequences in patients after heart transplantation: A 6-year retrospective review

Bone marrow suppression and associated consequences in patients after heart transplantation: A 6-year retrospective review

Posterior Reversible Encephalopathy Syndrome after Heart Transplantation: Diagnosis and Immunosuppressive Therapy

Circulation: Heart Failure Editors' Picks

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