Maurizio Menichelli

Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis

BACKGROUND Whether the two drug-eluting stents approved by the US Food and Drug Administration-a sirolimus-eluting stent and a paclitaxel-eluting stent-are associated with increased risks of death, myocardial infarction, or stent thrombosis compared with bare-metal stents is uncertain. Our aim was to compare the safety and effectiveness of these stents. METHODS We searched relevant sources from inception to March, 2007, and contacted investigators and manufacturers to identify randomised controlled trials in patients with coronary artery disease that compared drug-eluting with bare-metal stents, or that compared sirolimus-eluting stents head-to-head with paclitaxel-eluting stents. Safety outcomes included mortality, myocardial infarction, and definite stent thrombosis; the effectiveness outcome was target lesion revascularisation. We included 38 trials (18,023 patients) with a follow-up of up to 4 years. Trialists and manufacturers provided additional data on clinical outcomes for 29 trials. We did a network meta-analysis with a mixed-treatment comparison method to combine direct within-trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. FINDINGS Mortality was similar in the three groups: hazard ratios (HR) were 1.00 (95% credibility interval 0.82-1.25) for sirolimus-eluting versus bare-metal stents, 1.03 (0.84-1.22) for paclitaxel-eluting versus bare-metal stents, and 0.96 (0.83-1.24) for sirolimus-eluting versus paclitaxel-eluting stents. Sirolimus-eluting stents were associated with the lowest risk of myocardial infarction (HR 0.81, 95% credibility interval 0.66-0.97, p=0.030 vs bare-metal stents; 0.83, 0.71-1.00, p=0.045 vs paclitaxel-eluting stents). There were no significant differences in the risk of definite stent thrombosis (0 days to 4 years). However, the risk of late definite stent thrombosis (>30 days) was increased with paclitaxel-eluting stents (HR 2.11, 95% credibility interval 1.19-4.23, p=0.017 vs bare-metal stents; 1.85, 1.02-3.85, p=0.041 vs sirolimus-eluting stents). The reduction in target lesion revascularisation seen with drug-eluting stents compared with bare-metal stents was more pronounced with sirolimus-eluting stents than with paclitaxel-eluting stents (0.70, 0.56-0.84; p=0.0021). INTERPRETATION The risks of mortality associated with drug-eluting and bare-metal stents are similar. Sirolimus-eluting stents seem to be clinically better than bare-metal and paclitaxel-eluting stents.

Percutaneous Implantation of the CoreValve Self-Expanding Valve Prosthesis in High-Risk Patients With Aortic Valve Disease The Siegburg First-in-Man Study

Background— The morbidity and mortality of surgical aortic valve replacement are increased in elderly patients with multiple high-risk comorbid conditions. Therefore, a prospective, single-center, nonrandomized study was performed in high-risk patients with aortic valve disease to evaluate the feasibility and safety of percutaneous implantation of a novel self-expanding aortic valve bioprosthesis (CoreValve). Methods and Results— Symptomatic high-risk patients with an aortic valve area <1 cm2 were considered for enrollment. CoreValve implantation was performed under general anesthesia with extracorporeal support using the retrograde approach. Clinical follow-up and transthoracic echocardiography were performed after the procedure and at days 15 and 30 after device implantation to evaluate short-term patient and device outcomes. A total of 25 patients with symptomatic aortic valve stenosis (mean gradient before implantation, 44.2±10.8 mm Hg) and multiple comorbidities (median logistic EuroScore, 11.0%) were enrolled. Device success and procedural success were achieved in 22 (88%) and 21 (84%) patients, respectively. Successful device implantation resulted in a marked reduction in the aortic valve gradients (mean gradient after implantation, 12.4±3.0 mm Hg; P<0.0001). The mean aortic regurgitation grade was unchanged. Major in-hospital cardiovascular and cerebral events occurred in 8 patients (32%), including mortality in 5 patients (20%). Among 18 patients with device success surviving to discharge, no adverse events occurred within 30 days after leaving the hospital. Conclusions— Percutaneous implantation of the self-expanding CoreValve aortic valve prosthesis in high-risk patients with aortic stenosis with or without aortic regurgitation is feasible and, when successful, results in marked hemodynamic and clinical improvement.

Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis

Objective To compare the effectiveness and safety of three types of stents (sirolimus eluting, paclitaxel eluting, and bare metal) in people with and without diabetes mellitus. Design Collaborative network meta-analysis. Data sources Electronic databases (Medline, Embase, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, book chapters, and proceedings of advisory panels for the US Food and Drug Administration. Manufacturers and trialists provided additional data. Review methods Network meta-analysis with a mixed treatment comparison method to combine direct within trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. Overall mortality was the primary safety end point, target lesion revascularisation the effectiveness end point. Results 35 trials in 3852 people with diabetes and 10 947 people without diabetes contributed to the analyses. Inconsistency of the network was substantial for overall mortality in people with diabetes and seemed to be related to the duration of dual antiplatelet therapy (P value for interaction 0.02). Restricting the analysis to trials with a duration of dual antiplatelet therapy of six months or more, inconsistency was reduced considerably and hazard ratios for overall mortality were near one for all comparisons in people with diabetes: sirolimus eluting stents compared with bare metal stents 0.88 (95% credibility interval 0.55 to 1.30), paclitaxel eluting stents compared with bare metal stents 0.91 (0.60 to 1.38), and sirolimus eluting stents compared with paclitaxel eluting stents 0.95 (0.63 to 1.43). In people without diabetes, hazard ratios were unaffected by the restriction. Both drug eluting stents were associated with a decrease in revascularisation rates compared with bare metal stents in people both with and without diabetes. Conclusion In trials that specified a duration of dual antiplatelet therapy of six months or more after stent implantation, drug eluting stents seemed safe and effective in people both with and without diabetes.

Efficacy and safety of drug-eluting stents in ST-segment elevation myocardial infarction: a meta-analysis of randomized trials

BACKGROUND Recent concerns have emerged on the potential higher risk of stent thrombosis after DES implantation, that might be even more pronounced among STEMI patients. Thus, the aim of the current study was to perform a meta-analysis to evaluate the benefits and safety of DES as compared to BMS in patients undergoing primary angioplasty for STEMI. METHODS The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of DES for STEMI. The following key words were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, stenting, DES, sirolimus-eluting stent (SES), Cypher, paclitaxel-eluting stent (PES), Taxus. Information on study design, type of stent, inclusion and exclusion criteria, primary endpoint, number of patients, angiographic and clinical outcome, were extracted by two investigators. Disagreements were resolved by consensus. RESULTS A total of 11 trials were included in the meta-analysis, involving 3605 patients (1888 or 52.3% randomized to DES and 1719 or 47.7% randomized to BMS). At 12 months follow-up, no significant difference was observed in mortality (4.1% vs 4.4%, OR [95% CI]=0.91 [0.66-1.27], p=0.59, reinfarction (3.1% vs 3.4%, OR [95% CI]=0.85 [0.58, 1.23], p=0.38 or stent thrombosis (1.6% vs 2.2%, OR [95% CI]=0.76 [0.47, 1.23], p=0.22), whereas DES were associated with a significant reduction in TVR (5.0% vs 12.6%, OR [95% CI]=0.36 [0.28, 0.47], p<0.0001). Safety and efficacy of DES were confirmed at 18 to 24 months follow-up (data available from 4 trials including 1178 patients). CONCLUSIONS This meta-analysis shows that among selected STEMI patients undergoing primary angioplasty, SES and PES, as compared to BMS, are safe and associated with a significant reduction in TVR at 1 and 2 years follow-up.

Stents liberadores de fármacos frente a stents convencionales en pacientes diabéticos con infarto agudo de miocardio con elevación del segmento ST: un análisis combinado de los datos de pacientes individuales de 7 ensayos aleatorizados

Introduccion y objetivos. Los resultados obtenidos con los stents liberadores de farmacos (SLF) en el grupo de pacientes de alto riesgo formado por los pacientes diabeticos con infarto agudo de miocardio con elevacion del segmento ST (IAMCEST) tratados con angioplastia primaria no se han estudiado con anterioridad. Nuestro objetivo fue evaluar la eficacia y la seguridad de los SLF en pacientes diabeticos con IAMCEST. Metodos. Llevamos a cabo un analisis combinado de los datos de pacientes individuales de siete ensayos aleatorizados en los que se comparo el empleo de stents liberadores de sirolimus o de paclitaxel (SLF) con el de stents convencionales (SC) en el contexto de un IAMCEST. Se incluyo en este analisis a 389 pacientes con diabetes mellitus de un grupo total de 2.476. Los objetivos del estudio fueron la revascularizacion de la lesion diana, la trombosis del stent, la muerte y la variable combinada de muerte o infarto de miocardio recurrente durante un periodo de seguimiento de 12-24 meses. Resultados. Hubo 206 pacientes diabeticos tratados con SLF y 183 tratados con SC. El riesgo de que se practicara una revascularizacion de la lesion diana fue significativamente inferior en los pacientes tratados con SLF en comparacion con los pacientes tratados con SC (razon de riesgos [HR] = 0,44; intervalo de confianza [IC] del 95%, 0,23-0,88; p = 0,02). El riesgo de trombosis del stent no presento diferencias significativas entre los pacientes tratados con SLF y los tratados con SC (HR = 0,33; IC del 95%, 0,09-1,13; p = 0,08). De forma analoga, el riesgo de la variable de valoracion combinada formada por la muerte y el infarto de miocardio no presento diferencias significativas entre los pacientes tratados con SLF y los tratados con SC (HR = 0,64; IC del 95%, 0,36-1,13; p = 0,12). Conclusiones. En comparacion con los SC, los SLF mejoran los resultados clinicos en los pacientes diabeticos a los que se practica una angioplastia primaria por un IAMCEST, al reducir la necesidad de reintervencion sin incrementar la tasa de mortalidad o infarto de miocardio.

Clinical outcome of patients with chronic total occlusion treated with drug-eluting stents

BACKGROUND There is limited evidence on the medium-term prognosis of patients with chronic total occlusion successfully treated with drug-eluting stent (DES) implantation. METHODS We compared the medium-term outcome of 111 patients with chronic total occlusion (CTO) successfully treated with implantation of sirolimus-or paclitaxel-eluting stents versus 112 patients treated with bare metal stents. RESULTS During an overall follow-up period of 18 months, the composite endpoint of death, myocardial infarction or target lesion revascularization was significantly lower in the drug-eluting stent than in the bare metal stent group: 8.1% vs. 21.6%, respectively (p=0.005). The difference was due to the reduction of target lesion revascularization with DES compared to bare metal stents: 3.6% vs. 18.9%, respectively (p<0.001). The Cox proportional hazards model identified DES as an independent predictor of adverse cardiac events (adjusted hazard ratio, 0.16; 95% confidence interval 0.05 to 0.52, p=0.002). CONCLUSIONS During medium-term follow-up use of DES is associated with improved outcome compared to use of bare metal stents in patients with CTO.

Drug-eluting stents versus bare-metal stents in diabetic patients with ST-segment elevation acute myocardial infarction: a pooled analysis of individual patient data from seven randomized trials.

INTRODUCTION AND OBJECTIVES The performance of drug-eluting stents (DESs) in high-risk patients with diabetes and acute ST-elevation myocardial infarction (STEMI) who have undergone primary angioplasty has not been previously studied. The objective was to evaluate the efficacy and safety of DESs in diabetic patients with STEMI. METHODS We performed a pooled analysis of individual patient data from seven randomized trials that compared DESs (i.e., sirolimus- or paclitaxel-eluting stents) with bare-metal stents (BMSs) in patients with STEMI. The analysis involved 389 patients with diabetes mellitus from a total of 2476 patients. The outcomes of interest were target-lesion revascularization, stent thrombosis, death and the composite endpoint of death or recurrent myocardial infarction during a follow-up of 12-24 months. RESULTS Overall, 206 diabetic patients received a DES and 183, a BMS. The risk of target-lesion revascularization was significantly lower in patients treated with a DES compared to those treated with a BMS (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.23-0.88; P=.02). There was no significant difference in the risk of stent thrombosis between those treated with a DES or a BMS (HR 0.33, 95% CI 0.09-1.13; P=.08). Similarly, the risk of the combined endpoint of death or myocardial infarction was not significantly different between patients treated with a DES or a BMS (HR 0.64, 95% CI 0.36-1.13; P=.12). CONCLUSIONS Compared with BMSs, DES use improved clinical outcomes in diabetic patients undergoing primary angioplasty for STEMI: the need for reintervention was reduced, with no increase in mortality or myocardial infarction.

TCT-12 Clinical, Angiographic and Procedural Correlates of Very Late Absorb Scaffold Thrombosis – Multi-Study Registry Results

Recent analyses suggest an increased risk of very late scaffold thrombosis (VLST) beyond 1 year after implantation of Absorb BVS compared to metallic DES, but insights as to correlates of risk emanate from a limited number of patients. We sought to identify and verify independent correlates of

Response to Letter Regarding Article, “Percutaneous Implantation of the CoreValve Self-Expanding Valve Prosthesis in High-Risk Patients With Aortic Valve Disease: The Siegburg First-in-Man Study”

BACKGROUND The morbidity and mortality of surgical aortic valve replacement are increased in elderly patients with multiple high-risk comorbid conditions. Therefore, a prospective, single-center, nonrandomized study was performed in high-risk patients with aortic valve disease to evaluate the feasibility and safety of percutaneous implantation of a novel self-expanding aortic valve bioprosthesis (CoreValve). METHODS AND RESULTS Symptomatic high-risk patients with an aortic valve area <1 cm2 were considered for enrollment. CoreValve implantation was performed under general anesthesia with extracorporeal support using the retrograde approach. Clinical follow-up and transthoracic echocardiography were performed after the procedure and at days 15 and 30 after device implantation to evaluate short-term patient and device outcomes. A total of 25 patients with symptomatic aortic valve stenosis (mean gradient before implantation, 44.2+/-10.8 mm Hg) and multiple comorbidities (median logistic EuroScore, 11.0%) were enrolled. Device success and procedural success were achieved in 22 (88%) and 21 (84%) patients, respectively. Successful device implantation resulted in a marked reduction in the aortic valve gradients (mean gradient after implantation, 12.4+/-3.0 mm Hg; P<0.0001). The mean aortic regurgitation grade was unchanged. Major in-hospital cardiovascular and cerebral events occurred in 8 patients (32%), including mortality in 5 patients (20%). Among 18 patients with device success surviving to discharge, no adverse events occurred within 30 days after leaving the hospital. CONCLUSIONS Percutaneous implantation of the self-expanding CoreValve aortic valve prosthesis in high-risk patients with aortic stenosis with or without aortic regurgitation is feasible and, when successful, results in marked hemodynamic and clinical improvement.