Randomized comparison of cost‐saving and effectiveness of oral rapamycin plus bare‐metal stents with drug‐eluting stents: Three‐year outcome from the randomized oral rapamycin in Argentina (ORAR) III trial

Rodríguez, Alfredo E.; Rodriguez‐Granillo, Alfredo M.; Antoniucci, David; Mieres, Juan; Fernández‐Pereira, Carlos; Rodríguez-Granillo, Gastón A.; Santaera, Omar; Rubilar, Bibiana; Palacios, Igor F.; Serruys, Patrick W.

doi:10.1002/ccd.23352

Cited by 14 publications

(4 citation statements)

References 26 publications

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“…At the present time, in no TCAD patients, short‐term oral administration of either sirolimus or prednisone after PCI with BMS implantation demonstrated in all randomized clinical studies (seven), a significant reduction in restenosis and TVR compared to BMS alone . Furthermore, when compared with similar DES designs as authors used in the study , OI therapy showed similar clinical results to DES which were sustained at long‐term outcome .…”

supporting

confidence: 53%

Lack of clinical benefit of drug‐eluting compared to bare‐metal stents for treatment of transplant coronary artery disease: Why we do not need drug‐eluting stents?

Fernández‐Pereira

Mieres

Rodríguez

2012

Cathet Cardio Intervent

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In the online version of the Journal, Lee et al. [1] reported a 5-year follow-up data from 105 patients with transplant coronary artery disease (TCAD) who underwent first vessel percutaneous coronary interventions (PCIs) either with drug-eluting stents (DESs) or bare metal stents (BMSs). Patients who were eligible for DES underwent PCI with either sirolimus-(Cypher, Cordis, Johnson & Johnson Corporation, Miami, FL) or paclitaxel-eluting stents (Taxus, Boston Scientific Corporation, Natick, MA). At our knowledge, this report was the largest follow-up available comparing these two stent strategies in TCAD patients. In this retrospective data, no difference in major adverse events was found, and furthermore, target vessel revascularization (TVR) was similar in both groups 25.5% with DES and 26.5% with BMS log rank P 5 0.76. Authors have been previously reported at short-term follow-up of a significant clinical TVR benefit with DES which was lost at 5 years. As usual in this study, all patients with TCAD were also under oral immusuppressive (OI) or antiproliferative therapy with oral sirolimus, everolimus, or prednisone.Despite the benefit of DES over BMS described in TCAD (2), the majority of these advantages were controversial: short-term outcome in most of them, nonrandomized data, and mixed results [1][2][3].Therefore, clinical value is uncertain.The nonrandomized nature of all of these studies could be one of the most attractive explanations from these findings; however, all authors [1-3] failed to mention and quoted the value of the role of OI therapy that led to similar TVR rate in many of these studies.At the present time, in no TCAD patients, shortterm oral administration of either sirolimus or prednisone after PCI with BMS implantation demonstrated in all randomized clinical studies (seven), a significant reduction in restenosis and TVR compared to BMS alone [4]. Furthermore, when compared with similar DES designs as authors used in the study [1], OI therapy showed similar clinical results to DES [5,6] which were sustained at long-term outcome [6].Finally, there is no doubt of the clinical benefit of DES over BMS alone in non-TCAD; however, that is not the case of TCAD patients undergoing PCI with stent implantation where most of them are receiving oral sirolimus, prednisone, or both. Thus, the lack of benefit of DES over BMS in TCAD should not be a surprise, although as authors stated [1], randomized studies are warranted.

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supporting

confidence: 53%

Lack of clinical benefit of drug‐eluting compared to bare‐metal stents for treatment of transplant coronary artery disease: Why we do not need drug‐eluting stents?

Fernández‐Pereira

Mieres

Rodríguez

2012

Cathet Cardio Intervent

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“…However, the drug-eluting benefit of EES may be attenuated by the use of chronic oral immunosuppression. As demonstrated in studies in native coronary disease, the use of oral immunosuppression with BMS resulted in improved stent patency, rates that were similar as with the use of DES [11][12][13]. A randomized control trial of BMS versus EES in the chronically immunosuppressed post-transplant population has not been done.…”

Section: Discussionmentioning

confidence: 99%

“…This may be because oral immunosuppression may offset the drug-eluting benefit of DES. For instance, in the treatment of native coronary disease, the use of oral immunosuppression with BMS resulted in improved stent patency, rates that were similar as with the use of DES [11][12][13]. Furthermore, in spite of stenting with first-generation DES, redo transplantation occurred frequently, placing into question the utility of stenting as an option to delay retransplantation [14,15].…”

Section: Introductionmentioning

confidence: 99%

Long‐term clinical and angiographic outcomes of percutanenous coronary intervention with everolimus‐eluting stents for the treatment of cardiac allograft vasculopathy

Cheng¹,

Vanichsarn²,

Patel³

et al. 2016

Cathet Cardio Intervent

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“…Moreover, after 3 years of follow‐up in humans, oral administration of rapamycin during the first 14 days following implantation of a BMS proved to be superior to BMS alone and had only minimal side effects, such as gum sores or diarrhoea . Importantly, it was also shown that this combination was as effective as the use of DES . As for indirect mTORC1 inhibitors, metformin is known to reduce neointimal formation through inhibition of SMC proliferation and migration as well as via potent induction of autophagy, making it the only anti‐diabetic drug with proven reduction of micro‐ and macrovascular complications in diabetic patients .…”

Section: Mtorc1 Inhibition In Atherosclerosismentioning

confidence: 99%

Potential therapeutic effects of mTOR inhibition in atherosclerosis

Kurdi

Meyer

Martinet

2015

Brit J Clinical Pharma

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Despite significant improvement in the management of atherosclerosis, this slowly progressing disease continues to affect countless patients around the world. Recently, the mechanistic target of rapamycin (mTOR) has been identified as a pre-eminent factor in the development of atherosclerosis. mTOR is a constitutively active kinase found in two different multiprotein complexes, mTORC1 and mTORC2. Pharmacological interventions with a class of macrolide immunosuppressive drugs, called rapalogs, have shown undeniable evidence of the value of mTORC1 inhibition to prevent the development of atherosclerotic plaques in several animal models. Rapalog-eluting stents have also shown extraordinary results in humans, even though the exact mechanism for this anti-atherosclerotic effect remains elusive. Unfortunately, rapalogs are known to trigger diverse undesirable effects owing to mTORC1 resistance or mTORC2 inhibition. These adverse effects include dyslipidaemia and insulin resistance, both known triggers of atherosclerosis. Several strategies, such as combination therapy with statins and metformin, have been suggested to oppose rapalog-mediated adverse effects. Statins and metformin are known to inhibit mTORC1 indirectly via 5' adenosine monophosphate-activated protein kinase (AMPK) activation and may hold the key to exploit the full potential of mTORC1 inhibition in the treatment of atherosclerosis. Intermittent regimens and dose reduction have also been proposed to improve rapalog's mTORC1 selectivity, thereby reducing mTORC2-related side effects.

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Randomized comparison of cost‐saving and effectiveness of oral rapamycin plus bare‐metal stents with drug‐eluting stents: Three‐year outcome from the randomized oral rapamycin in Argentina (ORAR) III trial

Abstract: At 3 years follow-up, there were no differences in effectiveness between the two strategies, and DES strategy was not more cost-effective as compared to OR plus BMS.

Cited by 14 publications

References 26 publications

Lack of clinical benefit of drug‐eluting compared to bare‐metal stents for treatment of transplant coronary artery disease: Why we do not need drug‐eluting stents?

Lack of clinical benefit of drug‐eluting compared to bare‐metal stents for treatment of transplant coronary artery disease: Why we do not need drug‐eluting stents?

Long‐term clinical and angiographic outcomes of percutanenous coronary intervention with everolimus‐eluting stents for the treatment of cardiac allograft vasculopathy

Potential therapeutic effects of mTOR inhibition in atherosclerosis

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