Superior Prevention of Acute Rejection by Tacrolimus vs. Cyclosporine in Heart Transplant Recipients—A Large European Trial

Grimm, Michael; Rinaldi, Mauro; Yonan, Nizar; Arpesella, Giorgio; Prado, José María Arizón del; Pulpón, L. Alonso; Villemot, Jean‐Pierre; Frigerio, Maria; Lambert, José Luis; Crespo-Leiro, María G.; Almenar, Luís; Duveau, D.; Ordoñez, Antonio; Gandjbakhch, J; Maccherini, Massimo; Laufer, Günther

doi:10.1111/j.1600-6143.2006.01300.x

Cited by 175 publications

(97 citation statements)

References 31 publications

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“…Tacrolimus not only offers better protection against acute rejection compared to cyclosporine [131][132][133] , but it is also superior against CAV [134] . Moreover, Petrakopoulou et al [135] showed that tacrolimus is better than cyclosporine in the prevention of microvascular endothelial dysfunction.…”

Section: Calcineurin Inhibitorsmentioning

confidence: 99%

Diagnosis and management of coronary allograft vasculopathy in children and adolescents

Dedieu

Greil

Wong

et al. 2014

WJT

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Coronary allograft vasculopathy remains one of the leading causes of death beyond the first year post transplant. As a result of denervation following transplantation, patients lack ischaemic symptoms and presentation is often late when the graft is already compromised. Current diagnostic tools are rather invasive, or in case of angiography, significantly lack sensitivity. Therefore a non-invasive tool that could allow early diagnosis would be invaluable.This paper review the disease form its different diagnosis techniques,including new and less invasive diagnostic tools to its pharmacological management and possible treatments. DEFINITION AND PHYSIOPATHOLOGYIn children, coronary allograft vasculopathy (CAV) remains the main limiting survival factor after heart transplantation and the major cause of mortality after the first year post transplant leading ultimately to graft loss [1,2] . One elegant etiological description of CAV is that of "immunologic mechanisms operating in a milieu of nonimmunologic risk factors" [3] . The process is believed to start off as a response to endothelial injury in the graft, originated by a complex interaction of multiple donor and recipient factors. The resulting endothelial dysfunction, leads to altered endothelial permeability and subsequent intimal hyperplasia as a consequence of the vascular remodeling originated by the inflammatory response. The immunologic events constitute the original trigger and noninflammatory events such as cytomegalovirus infection, ischemic time (reperfusion injury), increased donor age and classical cardiovascular risk factors (i.e., diabetes, dyslipidemias, smoking and hypertension), perpetuate the inflammatory response and increase the endothelial injury [4] . Typical lesions (Figures 1 and 2) consist of diffuse intimal proliferation leading to the development of luminal stenosis and small vessels occlusion which then limits blood supply to the graft causing chronic vascular injury and ultimately myocardial ischemia [5] . The lesions develop earlier and quicker than atherosclerotic lesions. REVIEW 276December 24, 2014|Volume 4|Issue 4|

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Section: Calcineurin Inhibitorsmentioning

confidence: 99%

Diagnosis and management of coronary allograft vasculopathy in children and adolescents

Dedieu

Greil

Wong

et al. 2014

WJT

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“…Introduction of CNIs shifted the paradigm of solid organ transplant. Although there is improved survival and reduced burden of rejection with CNI use, increased incidence of post-transplant hypertension is observed since the introduction of CNI therapy [112]. CNIs are known to cause hypertension in post-transplant patients by inducing endothelial dysfunction and imbalance between vasodilator and vasoconstrictive substances.…”

Section: Hypertensionmentioning

confidence: 99%

Cardiac Allograft Vasculopathy: A Review of Risk Factors and Pathogenesis

Munagala¹,

Phancao²

2018

obm.transplant

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Heart transplant remains the gold standard therapy for patients with end stage heart disease and offers improved survival and quality of life. Significant progress has been achieved in improving one-year mortality after heart transplantation. Nonetheless, longterm graft survival has not changed significantly over the past few decades. Long term survival of heart transplant recipients is limited by chronic rejection, cardiac allograft vasculopathy (CAV), and malignancy. CAV is a major contributor for graft failure and mortality after the first year of in heart transplant recipients. CAV is a proliferative vasculopathy characterized by diffuse myointimal hyperplasia and progressive narrowing of the graft vessels. Both immune dependent and independent factors have been shown to contribute to the pathogenesis of CAV. Understanding these risk factors is essential in developing preventative and therapeutic strategies. Angiography with Intravascular ultrasound has become the key diagnostic tool in the early detection of CAV as well as prognostication. Echocardiographic assessment of allograft function in conjunction with coronary angiographic findings are used in assessing the severity of CAV. Adjustment of immunosuppression and statins remain the initial steps in the management of CAV. Retransplantation is the definitive treatment for severe CAV, however, the paucity of organs along with increased mortality associated with retransplantation makes it a less desirable option. Remarkable progress has been achieved in the understanding of pathogenesis, risk factors for CAV and plaque morphology. Nevertheless, significant knowledge gaps persist in scientific understanding of risk factors, pathogenesis, prevention and treatment of CAV. Further research is warranted to fill these gaps, develop diagnostic modalities to facilitate early detection of CAV, and management strategies to Improve graft tolerance and immune modulation. This review focuses on summarizing the pathogenesis and risk factors for CAV.

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“…Multiple agents are frequently needed [14]. It is known that the frequency of HTN is higher with Cyclosporine (CSA) compared to Tacrolimus (TAC) [15]. However, TAC cannot be recommended solely on this basis as it could double the risk of new onset diabetes itself a risk factor for CKD.…”

Section: Treatment Of Htnmentioning

confidence: 99%

“…However, TAC cannot be recommended solely on this basis as it could double the risk of new onset diabetes itself a risk factor for CKD. Many agents have been studied in animal models but few have been assessed in patients [15].…”

Section: Treatment Of Htnmentioning

confidence: 99%

Cardiac Troponin I Level in STEMI and Clinical Correlation with Left Ventricular Dysfunction in Indian Population

Sharma¹,

Sharma²

2013

J Cardiovasc Dis Diagn

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Calcium Channel Blockers (CCBs): CNIs cause vasoconstriction as noted above. CCBs, specifically vasodilating dihydropyridines, have been shown to improve renal plasma flow and GFR [9,16]. A small prospective study comparing amlodipine to placebo showed a slower decline in GFR at one year [13]. There was no effect on LV mass and only a modest decrease in proteinuria. Diltiazem did not appear to offer the same protection [14]. RAAS Inhibitors:The use of RAAS inhibitors is beneficial in most patients with CKD; however, this has not been shown in OHT patients. A systematic review of randomized studies in CSA-treated kidney AbstractBackground: The use of calcineurin inhibitors revolutionized transplantation by prolonging patients' survival. However, their utility is limited by the development of significant chronic kidney disease. Methods:We reviewed the English literature looking for recent publications regarding the management of chronic kidney disease in cardiac transplant patients. We chose relevant papers based on design, number of patients and clinical utility.Results: Most publications on the subject involve small populations with few prospective, randomized studies. Early use of tacrolimus appears to be associated with better kidney function after one year compared to cyclosporine. Once chronic kidney disease is established, successful strategies include reduction or elimination of calcineurin inhibitors while relying on mycophenolate mofetil, proliferation signal inhibitors or anti-CD 25 antibodies to prevent rejection. There is no follow up longer than two years with these approaches. Kidney transplantation might offer improved long-term survival compared to dialysis in end-stage disease. Conclusions:Prospective studies with long-term follow-up are needed to decide about the timing and to confirm the utility of replacing calcineurin inhibitors with other agents in cardiac transplant patients with chronic kidney disease. transplant patients show, after a median of 27 months, a reduction in GFR (around 5.8 cc/min) with a reduction of proteinuria (decrease of 470 mg/day) [17]. It is uncertain if the reduction in proteinuria would translate into better outcomes in the long run. In fact, Opelz et al. showed, in a retrospective study of 1,744 OHT patients, that the use of RAAS inhibitors did not improve patient survival after 6 years [18]. The same study looked at 17,209 kidney transplant patients and showed no difference in graft or patient survival [18]. The use of spironolactone in rat models prevented the decline in GFR and the histologic changes seen with CSA [19]. There are no data in patients. Management of Calcineurin Modification of immunosuppressive drugsTransplant centers have tried multiple immunosuppressive strategies in OHT patient with CKD to prevent progression of renal dysfunction. Most of the data come from small studies, limiting the strength of recommendations that can be made. Larger studies come usually from kidney transplantation literature. Tacrolimus:In small studies, Tacrolimus (TAC) do...

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Superior Prevention of Acute Rejection by Tacrolimus vs. Cyclosporine in Heart Transplant Recipients—A Large European Trial

Abstract: We compared efficacy and safety of tacrolimus (Tac)-based vs. cyclosporine (CyA) microemulsion-based immunosuppression in combination with azathioprine (Aza) and corticosteroids in heart transplant recipients. During antibody induction, patients were randomized

Cited by 175 publications

References 31 publications

Diagnosis and management of coronary allograft vasculopathy in children and adolescents

Diagnosis and management of coronary allograft vasculopathy in children and adolescents

Cardiac Allograft Vasculopathy: A Review of Risk Factors and Pathogenesis

Cardiac Troponin I Level in STEMI and Clinical Correlation with Left Ventricular Dysfunction in Indian Population

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