Safety and efficacy of drug-eluting stents for patients at high risk of bleedings: A network meta-analysis.

INTRODUCTION: Among different coronary stents implanted in High Bleeding Risk (HBR) patients with an indication for short antiplatelet therapy, no comparisons in terms of efficacy have been provided. METHODS: A Network Meta Analysis was performed including all randomized controlled trials comparing different coronary stents evaluated in HBR patients. Major Adverse Cardiovascular Events (MACEs) as defined by each included trial were the primary end point, whereas TLR (target lesion revascularization), TVR (target vessel revascularization), stent thrombosis and total and major (BARC3-5) bleedings were the secondary ones. RESULTS: A total of four studies (ONYX ONE, LEADERS FREE, SENIOR and HBR in BIO-RESORT) including 6637 patients were analyzed with different kind of stents and dual antiplatelet therapy (DAPT) length (1 or 6 months) on 12 months follow-up. About one-third of these patients were defined HBR due to indication for oral anticoagulation. All drug eluting stents (DESs) reduced risk of MACE compared to Bare Metal Stents (BMSs) when followed by a 1-month DAPT. At SUCRA analysis, Orsiro was the device with the highest probability of performing best. Rates of TLR and TVR were significantly lower when using Resolute Onyx, Synergy and BioFreedom stents in comparison to BMS when followed by 1-month DAPT, with Synergy ranking best. Synergy also showed a significantly lower number of stent thrombosis compared to BMS (RR 0.28, 95% CI 0.06-0.93), while Orsiro and Resolute Integrity showed the highest probability of performing best. CONCLUSION: In HBRs patients, all DESs were superior to BMSs in terms of efficacy and safety. Among DESs, Orsiro was the one with the highest ranking in terms of MACE, mainly driven by a reduced incidence of repeated revascularization and stent thrombosis.

Association of Periprocedural Inflammatory Activation With Increased Risk for Early Coronary Stent Thrombosis.

BACKGROUND: Stent thrombosis is a rare but deleterious event. Routine coronary angiography with percutaneous coronary intervention (PCI) is often deferred in the presence of laboratory markers of acute inflammation to prevent complications. The aim of this study was to investigate whether an acute inflammatory state is associated with an increased risk of early stent thrombosis. METHODS AND RESULTS: Within a prospective single-center registry, the association between preprocedural acute inflammatory activation, defined as C-reactive protein plasma levels >50 mg/L or a leukocyte count >12 g/L, and occurrence of early (≤30 days) stent thrombosis was evaluated. In total, 11 327 patients underwent PCI and of those, 6880 patients had laboratory results available. 49.6% of the study population received PCI for an acute coronary syndrome and 50.4% for stable ischemic heart disease. In patients with signs of acute inflammatory activation (24.9%), PCI was associated with a significantly increased risk for stent thrombosis (hazard ratio, 2.89; P<0.00001), independent of age, sex, kidney function, number and type of stents, presence of multivessel disease, choice of P2Y12 inhibitor, and clinical presentation. Elevated laboratory markers of acute inflammation were associated with the occurrence of stent thrombosis in both patients with acute coronary syndrome (hazard ratio, 2.63; P<0.001) and in patients with stable ischemic heart disease (hazard ratio, 3.57; P<0.001). CONCLUSIONS: An acute inflammatory state at the time of PCI was associated with a significantly increased risk of early stent thrombosis. Evidence of acute inflammation should result in deferred PCI in elective patients, while future studies are needed for patients with acute coronary syndrome.

An Aspirin-Free Strategy for Immediate Treatment Following Complex Percutaneous Coronary Intervention.

BACKGROUND: There was no study evaluating the effects of an aspirin-free strategy in patients undergoing complex percutaneous coronary intervention (PCI). OBJECTIVES: The authors aimed to evaluate the efficacy and safety of an aspirin-free strategy in patients undergoing complex PCI. METHODS: We conducted the prespecified subgroup analysis based on complex PCI in the STOPDAPT-3 (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3), which randomly compared low-dose prasugrel (3.75 mg/d) monotherapy to dual antiplatelet therapy (DAPT) with low-dose prasugrel and aspirin in patients with acute coronary syndrome or high bleeding risk. Complex PCI was defined as any of the following 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or a target of chronic total occlusion. The coprimary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. RESULTS: Of the 5,966 study patients, there were 1,230 patients (20.6%) with complex PCI. Regardless of complex PCI, the effects of no aspirin relative to DAPT were not significant for the coprimary bleeding (complex PCI: 5.30% vs 3.70%; HR: 1.44; 95% CI: 0.84-2.47; P = 0.18 and noncomplex PCI: 4.26% vs 4.97%; HR: 0.85; 95% CI: 0.65-1.11; P = 0.24; P for interaction = 0.08) and cardiovascular (complex PCI: 5.78% vs 5.93%; HR: 0.98; 95% CI: 0.62-1.55; P = 0.92 and noncomplex PCI: 3.70% vs 3.10%; HR: 1.20; 95% CI: 0.88-1.63; P = 0.25; P for interaction = 0.48) endpoints without significant interactions. CONCLUSIONS: The effects of the aspirin-free strategy relative to standard DAPT for the cardiovascular and major bleeding events were not different regardless of complex PCI. (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111).

Infliximab Limits Injury in Myocardial Infarction.

BACKGROUND: The purpose of this study was to investigate a therapeutic approach targeting the inflammatory response and consequent remodeling from ischemic myocardial injury. METHODS AND RESULTS: Coronary thrombus aspirates were collected from patients at the time of ST-segment-elevation myocardial infarction and subjected to array-based proteome analysis. Clinically indistinguishable at myocardial infarction (MI), patients were stratified into vulnerable and resilient on the basis of 1-year left ventricular ejection fraction and death. Network analysis from coronary aspirates revealed prioritization of tumor necrosis factor-α signaling in patients with worse clinical outcomes. Infliximab, a tumor necrosis factor-α inhibitor, was infused intravenously at reperfusion in a porcine MI model to assess whether infliximab-mediated immune modulation impacts post-MI injury. At 3 days after MI (n=7), infliximab infusion increased proregenerative M2 macrophages in the myocardial border zone as quantified by immunofluorescence (24.1%±23.3% in infliximab versus 9.29%±8.7% in sham; P<0.01). Concomitantly, immunoassays of coronary sinus samples quantified lower troponin I levels (41.72±7.34 pg/mL versus 58.11±10.75 pg/mL; P<0.05) and secreted protein analysis revealed upregulation of injury-modifying interleukin-2, -4, -10, -12, and -18 cytokines in the infliximab-treated cohort. At 4 weeks (n=12), infliximab treatment resulted in significant protective influence, improving left ventricular ejection fraction (53.9%±5.4% versus 36.2%±5.3%; P<0.001) and reducing scar size (8.31%±10.9% versus 17.41%±12.5%; P<0.05). CONCLUSIONS: Profiling of coronary thrombus aspirates in patients with ST-segment-elevation MI revealed highest association for tumor necrosis factor-α in injury risk. Infliximab-mediated immune modulation offers an actionable pathway to alter MI-induced inflammatory response, preserving contractility and limiting adverse structural remodeling.

Bilateral subconjunctival hemorrhage secondary to abciximab use: case report

ABSTRACT CONTEXT: There are no reports on cases of subconjunctival hemorrhage due to use of glycoprotein IIb/IIIa inhibitors. In this report, we present the case of a patient with bilateral subconjunctival hemorrhage after receiving abciximab. CASE REPORT: A 40-year-old male patient underwent coronary angiography after acute anterior myocardial infarction and a coronary stent was placed. Abciximab was added to the therapy because of stent thrombosis. Bilateral subconjunctival hemorrhage was observed after the administration of the abciximab treatment. We treated our patient by stopping abciximab and administering artificial tears. CONCLUSİON: For the first time in the literature, we presented the case of a patient with bilateral subconjunctival hemorrhage after receiving abciximab, which was managed conservatively.

Prevención de eventos tromboembólicos con aspirina exclusiva post reemplazo valvular aórtico con bioprótesis / Prevention of thrombo-embolic events with aspirin alone after aortic valve replacement with a biologic prosthesis

Introducción: La principal ventaja de las bioprótesis es no requerir tratamiento anticoagulante. Sin embargo, algunas guías de manejo clínico recomiendan este tratamiento los primeros meses post cirugía. En los últimos años varios autores han demostrado la seguridad del uso exclusivo de aspirina en los primeros 3 meses después del reemplazo valvular aórtico con bioprótesis. Objetivo: Evaluar la morbimortalidad y complicaciones trombo embólicas y hemorrágicas en pacientes sometidos a reemplazo valvular aórtico (RVA) con bioprótesis tratados exclusivamente con aspirina (100 mg) los primeros tres meses post cirugía. Métodos: Estudio retrospectivo de 229 pacientes (137 hombres. edad 65,3 +/- 11,76 años) operados de RVA con bioprótesis entre junio 2006 y diciembre 2011. Hubo 178 cirugías aisladas y 51 combinadas y 20 pacientes tenían endocarditis. Se estudió la morbimortalidad, complicaciones trombo embólicas y sangrado a 30 y 90 días y en el seguimento alejado hasta el 30 de junio de 2012. Resultados: A 30 días hubo 4 accidentes cerebrovasculares, 3 accidentes isquémicos transitorios y una isquemia mesentérica. Fallecieron 8 pacientes (3,5 por ciento). A los 90 días hubo 2 hemorragias (1 hemorragia digestiva, 1 hemotórax), no hubo nuevos eventos trombo embólicos ni otros fallecidos. El seguimiento promedio fue 27.8+/-17,7 meses (rango 6 - 72 meses). Durante el seguimiento fallecieron 17 pacientes y no se registraron eventos trombo embólicos ni hemorrágicos. Conclusión: En pacientes operados de reemplazo valvular aórtico con bioprótesis el uso exclusivo de aspirina fue seguro para prevenir complicaciones trombo embólicas.

Background: The abscense of a need for anticoagulant therapy is a significant advantage of biologic valve prosthesis. However, according to some clinical guidelines conventional anti-coagulant therapy is recommended for the initial 3 months following aortic valve replacement. Aim: The aim of this study was to evaluate morbi-mortality and thrombo-embolic events in patients undergoing aortic valve replacement with a bioprosthesis receiving aspirin during the first 3 months after surgery. Methods: Data on 229 patients (137 males), aged 65.3+/-11.8 years who received biologic aortic valve prosthesis between June 2006 and December 2011 was retrospectively analyzed. 51 patients underwent combined (coronary and/or mitral valve surgery) and 20 patients had infectious endocarditis. Morbidity, mortality, thrombo-embolic and hemorrhagic events were tabulated up to June 30, 2012. Results: During the first 30 days after surgery there were 4 cerebro-vascular events and 1 episode of mesenteric ischemia. Operative (30 day) mortality was 3.5 percent (8 patients). At 90 days, 2 patients had a hemorrhagic event (GI bleeding and hemotho-rax, respectively), but no further embolic events or deaths occurred. Patients were followed for a mean of 27.8 +/-17,7 months (range 6 to 72 months). 17 patients died but no cases of embolism or bleeding were observed. Conclusion: Aspirin was safe and effective for prevention of thrombo-embolic complications following aortic valve replacement with a biologic prosthesis.

Os stents farmacológicos são seguros e eficazes em longo prazo? / Are drug-eluting stents safe and effective in the long term? / ¿Los stents farmacológicos son seguros y eficaces a largo plazo?

A introdução de stents farmacológicos em 2002 revolucionou a cardiologia invasiva através da redução de reestenoses. No final de 2006 surgiram relatos de aumento da incidência de trombose tardia de stent com esses stents em comparação com os de metal sem revestimento, provavelmente em decorrência do atraso de endotelização. No entanto, esses estudos continham sérias falhas metodológicas. Meta-análises posteriores mostraram de forma clara um risco apenas discretamente aumentado de trombose tardia de stent entre todos os grupos de pacientes. Um achado importante foi o de que os stents farmacológicos proporcionaram benefício significativo e mantido devido à redução de reestenose e, portanto, de revascularização de repetição. Vários registros obtidos na prática clínica confirmaram esses resultados e sugeriram que o uso de stents farmacológicos em situações mais complexas não está associado a resultados desfavoráveis. A trombose de stent é um problema multifatorial no qual o stent é apenas um dos elementos. Novos estudos serão necessários para determinar a técnica para o procedimento e o esquema antiplaquetário ideais. Os stents farmacológicos são seguros e eficazes em longo prazo, embora estudos intensivos continuem sendo realizados com o propósito de reduzir o risco de trombose de stent na próxima geração.

The introduction of drug-eluting stents in 2002 revolutionized interventional cardiology by minimizing restenosis. Reports of increased late stent thrombosis with these stents compared with bare metal stents, probably due to delayed endothelialization, emerged late in 2006. These studies contained serious methodological flaws, however. Subsequent meta-analyses clearly showed only a small incremental risk of late stent thrombosis across all patient groups. Importantly, a significant and sustained benefit of drug-eluting stents due to reduced restenosis and thus repeat revascularization was also shown. Several 'real-world' registries have confirmed these results and suggested that the use of these stents in more complex situations is not associated with adverse outcomes. Stent thrombosis is a multifactorial problem, in which the stent is only one element. Further research is required to determine optimal procedural technique and antiplatelet regimens. Drug-eluting stents are safe and effective in the long-term, though intensive research continues into ways to reduce the risk of stent thrombosis in the next generation.

La introducción de stents farmacológicos en 2002 revolucionó la cardiología invasiva a través de la reducción de reestenosis. En el final de 2006 surgieron relatos de aumento de la incidencia de trombosis tardía de stent con esos stents en comparación con los de metal sin revestimientos, probablemente en consecuencia del atraso de endotelización. Mientras tanto, esos estudios contenían serias fallas metodológicas. Metanálisis posteriores mostraron de forma clara un riesgo apenas discretamente aumentado de trombosis tardía de stent entre todos los grupos de pacientes. Un hallazgo importante fue el de que los stents farmacológicos proporcionaron beneficio significativo y mantenido debido a la reducción de reestenosis y, por lo tanto, de revascularización de repetición. Varios registros obtenidos en la práctica clínica confirmaron esos resultados y sugirieron que el uso de stents farmacológicos en situaciones más complejas no está asociado a resultados desfavorables. La trombosis de stent es un problema multifactorial en el cual el stent es apenas uno de los elementos. Nuevos estudios serán necesarios para determinar la técnica para el procedimiento y el esquema antiplaquetario ideales. Los stents farmacológicos son seguros y eficaces a largo plazo, aunque estudios intensivos continúen siendo realizados con el propósito de reducir el riesgo de trombosis de stent en la próxima generación.

Aspirina, ticlopidina ou clopidogrel? / Aspirin, ticlopidine or clopidogrel?

Os quadros isquêmicos miocárdicos agudos iniciam-se a partir da formação do trombo sobre a placa aterosclerótica. Em circunstâncias em que ocorre lesão endotelial - ruptura da placa - , a adesão, a ativação e a agregação das plaquetas desencadeiam o processo de formação do trombo. O objetivo da terapêutica antiplaquetária nas síndromes isquêmicas agudas é modificar as funções da plaqueta no sentido de inibir a formação e o desenvolvimento do trombo arterial sem prejuízo da hemostasia. Entre as substâncias antiplaquetárias destaca-se a aspirina, que atua impedindo a formação da tromboxane A2, que é importante no processo de formação do trombo. A aspirina, comprovadamente, trouxe grande impacto na modificação da evolução clínica dos pacientes com angina instável ou infarto agudo do miocárdio. Os derivados tienopiridínicos, ticlopidina e clopidogrel, agem inibindo a ação do difosfato de adenosina e, portanto, impedindo a ativação plaquetária. Importantes estudos clínicos demonstraram que esses fármacos apresentam benefícios comparáveis aos da aspirina. São, portanto, recomendados na impossibilidade de se utilizar esta última. Os dados dos estudos que avaliam os efeitos da associação dos tienopiridínicos com a aspirina demonstram as vantagens de se atuar concomitantemente em mecanismos diferentes da ativação das plaquetas para a prevenção de eventos isquêmicos miocárdicos, tanto no contexto dos procedimentos invasivos como no tratamento clínico da angina instável.