Safety and efficacy of early aggressive versus cholesterol-driven lipid-lowering strategies in heart transplantation: A pilot, randomized, intravascular ultrasound study

Potena, Luciano; Grigioni, Francesco; Ortolani, Paolo; Magnani, Gaia; Fabbri, Francesca; Masetti, M.; Coccolo, Fabio; Fallani, Francesco; Russo, Antonio; Ionico, Teresa; Saia, Francesco; Rapezzi, Claudio; Branzi, Angelo

doi:10.1016/j.healun.2011.07.002

Cited by 20 publications

(21 citation statements)

References 29 publications

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“…Statins are the cornerstone of prevention of native atherosclerosis, as well as CAV, following the pivotal randomized studies with pravastatin and simvastatin . More recently, a small but randomized study found that high‐dose fluvastatin was associated with lower early CAV development and an observational study in adult heart recipients found that statin use was associated with lower mortality . When used in pediatric patients however, these drugs do not appear to be as effective .…”

Section: Discussionmentioning

confidence: 99%

Coronary artery disease in heart transplantation: new concepts for an old disease

et al. 2018

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Cardiac allograft vasculopathy (CAV) remains one of the main long-term complications after heart transplantation. We performed a systematic review focused on articles published in the previous 6 years to reappraise the novel evidences supporting risk factors, pathology, prevention, and treatment of CAV. We identified a search string for a literature search on PubMed. We excluded articles specifically focused on diagnosis/biomarkers/imaging only or complications of other diseases. We included 98 studies out of our search. Forty-eight articles describe risk factors for CAV, 13 pathology, 24 prevention, and 13 treatment for CAV. While confirming known concepts, we found supportive evidence that CAV pathophysiology may vary according to the time post-transplant and the prevalence of metabolic versus immune-mediated risk factors. Selective revascularization of focal lesions in patients with CAV may result in some clinical benefit, but CAV prevention, rather than treatment, by controlling risk factors and by using targeted immunosuppressive therapies is the most evidence-based approach to reduce disease progression.

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Section: Discussionmentioning

confidence: 99%

Coronary artery disease in heart transplantation: new concepts for an old disease

et al. 2018

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“…Both cases of muscular toxicity appeared early (<30 days) after the initiation of the drug, and the other was detected after ~10 months on treatment. With variable lengths of treatment duration among studies, the reported cumulative incidence of statin‐related toxicity in the HT population was around 8% with atorvastatin , 13% with fluvastatin and simvastatin , and significantly lower with pravastatin . In a previous study by our own group, we observed an overall cumulative incidence of statin toxicity of 12% in HT patients, being obesity the only risk factor independently associated with this complication.…”

Section: Discussionmentioning

confidence: 99%

Clinical evaluation of rosuvastatin in heart transplant patients with hypercholesterolemia and therapeutic failure of other statin regimens: short-term and long-term efficacy and safety results

Barge‐Caballero

Marzoa-Rivas

et al. 2015

Transpl Int

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Summary We conducted an observational study of 30 heart transplant recipients with serum low‐density lipoprotein cholesterol (LDL‐c) >100 mg/dl despite previous statin therapy, who were treated with rosuvastatin 10 mg daily (5 mg in case of renal dysfunction). Serum lipids, creatine phosphokinase (CPK), bilirubin, and hepatic enzymes were prospectively measured 2, 4, and 12 weeks after the initiation of the drug. Clinical outcomes of patients who continued on long‐term rosuvastatin therapy beyond this 12‐week period were reviewed in February 2015. Over the 12‐week period following rosuvastatin initiation, serum levels of total cholesterol (TC) and LDL‐c and the ratio TC/high‐density lipoprotein cholesterol (HDL‐c) decreased steadily (P < 0.001). Average absolute reductions of these three parameters were –48.7 mg/dl, –46.6 mg/dl, and –0.9, respectively. Seventeen (57%) achieved a serum LDL‐c < 100 mg/dl. No significant changes from baseline were observed in serum levels of triglycerides, HDL‐c, hepatic enzymes, bilirubin, or CPK. Twenty‐seven (90%) patients continued on long‐term therapy with rosuvastatin over a median period of 3.6 years, with no further significant variation in lipid profile. The drug was suspended due to liver toxicity in 1 (3.3%) patient and due to muscle toxicity in 2 (6.7%) patients. All adverse reactions resolved rapidly after rosuvastatin withdrawal. Our study supports rosuvastatin as a reasonable alternative for heart transplant recipients with hypercholesterolemia and therapeutic failure of other statin regimens.

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“…Following the first official consensus document dealing with the diagnosis of AMR in heart transplant recipients published in 2005 [10], only EMBs performed after 2005 were routinely screened for pathological AMR. Immunohistochemistry for C4d on paraffin embedded sections was performed only in biopsies with late cellular rejection, or histological picture suggestive of AMR, or in presence of hemodynamic compromise (i.e., capillary wedge pressure ≥18 mmHg, or drop in ejection fraction ≥15%, or symptoms of hear failure) [11]. Thus, we are able to report the incidence of pathological AMR (pAMR) only in the subgroup of patients who underwent complete immunohistochemistry stainings (Figure 1).…”

Section: Methodsmentioning

confidence: 99%

Occurrence of Fatal and Nonfatal Adverse Outcomes after Heart Transplantation in Patients with Pretransplant Noncytotoxic HLA Antibodies

Potena

Bontadini

Iannelli

et al. 2013

Journal of Transplantation

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HLA antibodies (HLA ab) in transplant candidates have been associated with poor outcome. However, clinical relevance of noncytotoxic antibodies after heart transplant (HT) is controversial. By using a Luminex-based HLA screening, we retested pretransplant sera from HT recipients testing negative for cytotoxic HLA ab and for prospective crossmatch. Out of the 173 consecutive patients assayed (52 ± 13y; 16% females; 47% ischemic etiology), 32 (18%) showed pretransplant HLA ab, and 12 (7%) tested positive against both class I and class II HLA. Recipients with any HLA ab had poorer survival than those without (65 ± 9 versus 82 ± 3%; P = 0.02), accounting for a doubled independent mortality risk (P = 0.04). In addition, HLA-ab detection was associated with increased prevalence of early graft failure (35 versus 15%; P = 0.05) and late cellular rejection (29 versus 11%; P = 0.03). Of the subgroup of 37 patients suspected for antibody mediated rejection (AMR), the 9 with pretransplant HLA ab were more likely to display pathological AMR grade 2 (P = 0.04). By an inexpensive, luminex-based, HLA-screening assay, we were able to detect non-cytotoxic HLA ab predicting fatal and nonfatal adverse outcomes after heart transplant. Allocation strategies and desensitization protocols need to be developed and prospectively tested in these patients.

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Safety and efficacy of early aggressive versus cholesterol-driven lipid-lowering strategies in heart transplantation: A pilot, randomized, intravascular ultrasound study

Cited by 20 publications

References 29 publications

Coronary artery disease in heart transplantation: new concepts for an old disease

Coronary artery disease in heart transplantation: new concepts for an old disease

Clinical evaluation of rosuvastatin in heart transplant patients with hypercholesterolemia and therapeutic failure of other statin regimens: short-term and long-term efficacy and safety results

Occurrence of Fatal and Nonfatal Adverse Outcomes after Heart Transplantation in Patients with Pretransplant Noncytotoxic HLA Antibodies

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