Abstracts
BACKGROUND: Differences between geographic regions in patient characteristics and outcomes, particularly for acute coronary syndromes, have been demonstrated in clinical trials. Clinical outcomes after percutaneous coronary interventions with the Zotarolimus-eluting stent in a real-world population were assessed over time. OBJECTIVE: The influence of geographic location on clinical outcomes with the Zotarolimus-eluting stent was assessed in 3 regions: Asia Pacific, Europe, and Latin America. METHODS: A total of 8,314 patients (6,572 Europe, 1,522 Asia Pacific, and 220 Latin America) were followed for 1 year; 2,116 of these (1,613, 316, and 187, respectively) were followed for 2 years. Patient and lesion characteristics, dual antiplatelet therapy, and clinical outcomes were compared between Latin America and the other regions. RESULTS: Patients in Latin America had the highest proportions of risk factors and prior myocardial infarction. Dual antiplatelet therapy usage rapidly declined in Latin America, from 44.9% at 6 months to 22.5% at 1 year and 7.8% at 2 years (Europe: 87.4%, 61.5%, 19.7%; Asia Pacific: 82.4%, 67.0%, 45.7%). There were no significant differences between Latin America and Europe or Asia Pacific for any outcome at either time point. The incidence of Academic Research Consortium definite and probable stent thrombosis was low (<1.2%) among all patients at 1 year and 2 years. CONCLUSION: Clinical outcomes were comparable between patients in Latin America and Europe, and Latin America and Asia Pacific, despite less favorable clinical subsets in Latin America, a higher risk profile, and markedly lower use of dual antiplatelet therapy over time.
Eluting stents; multicenter studies; craft occlusion, vascular; coronary restenosis; angioplasty transluminal percutaneous coronary
FUNDAMENTO: Diferenças entre regiões geográficas em relação à características de pacientes e desfechos, particularmente em síndromes coronarianas agudas, tem sido demonstradas em testes clínicos. Os desfechos clínicos após intervenções coronarianas percutâneas com o stent eluidor de Zotarolimus em uma população real foram analisados com o tempo. OBJETIVO: A influência da localização geográfica sobre os desfechos clínicos com o stent eluidor de Zotarolimus foi avaliada em três regiões: Pacífico Asiático, Europa e América Latina. MÉTODOS: Um total de 8.314 pacientes (6.572 da Europa, 1.522 do Pacífico Asiático e 220 da América Latina) foram acompanhados por 1 ano; 2.116 desses (1.613, 316, e 187, respectivamente) foram acompanhados por 2 anos. Características dos pacientes e lesões, terapia antiplaquetária dupla e desfechos clínicos foram comparados entre a América Latina e as outras duas regiões. RESULTADOS: Os pacientes da América Latina apresentavam a maior proporção de fatores de risco e infarto do miocárdio prévio. O uso da terapia antiplaquetária dupla declinou rapidamente na América Latina, de 44,9% em 6 meses para 22,5% em 1 ano e 7,8% em 2 anos (Europa: 87,4%, 61,5%, 19,7%; Pacífico Asiático: 82,4%, 67,0%, 45,7%, respectivamente). Não houve diferenças significantes entre a América Latina e a Europa ou Pacífico Asiático para qualquer desfecho em qualquer ponto do tempo. A incidência de trombose de stent provável e definitiva pelo Academic Research Consortium foi baixa (<1,2%) entre todos os pacientes em 1 ano e 2 anos. CONCLUSÃO: Os desfechos clínicos foram comparáveis entre os pacientes da América Latina e Europa, e América Latina e Pacífico Asiático, a despeito dos subgrupos clínicos menos favoráveis na América Latina, perfil de risco mais elevado e menor uso acentuado de terapia antiplaquetária dupla com o tempo.
Stents farmacológicos; estudos multicêntricos; oclusão de enxerto vascular; reestenose coronariana; angioplastia transluminal percutânea coronariana
FUNDAMENTO: Las diferencias entre las regiones geográficas en relación con las características de pacientes y desenlaces, sobre todo en los síndromes coronarios agudos se ha demostrado en ensayos clínicos. Los desenlaces clínicos después de las intervenciones coronarias percutáneas con stent liberador de zotarolimus en una población real se analizaron a través del tiempo. Objetivos: La influencia de la ubicación geográfica sobre los desenlaces clínicos con el stent liberador de zotarolimus se evaluó en tres regiones: Pacífico Asiático, Europa y América Latina. MÉTODOS: A total of 8,314 patients (6.572 Europe, 1.522 Asia Pacific, and 220 Latin America) were followed for 1 year; 2.116 of these (1.613, 316, and 187, respectively) were followed for 2 years. Patient and lesion characteristics, dual antiplatelet therapy, and clinical outcomes were compared between Latin America and the other regions. RESULTADOS: Los pacientes en América Latina tuvieron la mayor proporción de factores de riesgo e infarto de miocardio previo. Hubo un rápido descenso en el uso de la terapia antiplaquetaria en América Latina, el 44,9% en 6 meses para 22,5% en 1 año y 7,8% en 2 años (Europa: un 87,4%, un 61,5%, un 19,7%; Pacífico Asiático: un 82,4%, un 67,0%, un 45,7%, respectivamente). No hubo diferencias significativas entre América Latina y Europa o Pacífico Asiático para cualquier desenlace en cualquier momento. La incidencia de trombosis de stent probable y definitiva por el Academic Research Consortium fue baja (< 1,2%) entre todos los pacientes en 1 año y 2 años. CONCLUSIONES: Los desenlaces clínicos fueron comparables entre los pacientes de América Latina y Europa, y América Latina y Pacífico Asiático, pese a los subgrupos clínicos menos favorables en América Latina, perfil de riesgo más elevado y menor uso acentuado de terapia antiplaquetaria doble con el tiempo. (Arq Bras Cardiol 2011;96(5):353-362)
Stents farmacológicos; estudios multicéntricos; oclusión de injerto vascular; reestenosis coronaria; angioplastia transluminal percutánea coronaria
ORIGINAL ARTICLE
IHeart Institute, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel
IIMonash Heart Medical Centre, Monash University, Melbourne, Australia
IIIThe London Chest Hospital, Barts, and The London NHS Trust, Londres, Reino Unido
IVInstituto Dante Pazzanese de Cardiologia, São Paulo, Brasil
VInstituto Nacional de Cirugia Cardiaca, Montevideo, Uruguai
VIHospital de San Juan de Alicante, Alicante, Espanha
Mailing address
ABSTRACT
BACKGROUND: Differences between geographic regions in patient characteristics and outcomes, particularly for acute coronary syndromes, have been demonstrated in clinical trials. Clinical outcomes after percutaneous coronary interventions with the zotarolimus-eluting stent in a real-world population were assessed over time.
OBJECTIVES: The influence of geographic location on clinical outcomes with the zotarolimus-eluting stent was assessed in 3 regions: Asia Pacific, Europe, and Latin America.
METHODS: A total of 8,314 patients (6,572 Europe, 1,522 Asia Pacific, and 220 Latin America) were followed for 1 year; 2,116 of these (1,613, 316, and 187, respectively) were followed for 2 years. Patient and lesion characteristics, dual antiplatelet therapy, and clinical outcomes were compared between Latin America and the other regions.
RESULTS: Patients in Latin America had the highest proportions of risk factors and prior myocardial infarction. Dual antiplatelet therapy usage rapidly declined in Latin America, from 44.9% at 6 months to 22.5% at 1 year and 7.8% at 2 years (Europe: 87.4%, 61.5%, 19.7%; Asia Pacific: 82.4%, 67.0%, 45.7%). There were no significant differences between Latin America and Europe or Asia Pacific for any outcome at either time point. The incidence of Academic Research Consortium definite and probable stent thrombosis was low (< 1.2%) among all patients at 1 year and 2 years.
CONCLUSIONS: Clinical outcomes were comparable between patients in Latin America and Europe, and Latin America and Asia Pacific, despite less favorable clinical subsets in Latin America, a higher risk profile, and markedly lower use of dual antiplatelet therapy over time.
Keywords: Eluting stents; multicenter studies; graft occlusion, vascular; coronary restenosis; angioplasty transluminal percutaneous coronary.
Abstract
Results from the E-Five Registry indicate that geographic location does not affect clinical outcomes in patients treated with the zotarolimus-eluting stent. Patients in Latin America had the highest proportions of risk factors and prior myocardial infarction. Use of dual antiplatelet therapy declined rapidly in Latin America as compared with Europe and Asia Pacific. However, there were no significant differences between Latin America and Europe or Asia Pacific for any outcome at either time point. The incidence of Academic Research Consortium definite and probable stent thrombosis was low (<1.2%) among all patients at 1 year and 2 years
Introduction
International differences in patient characteristics and clinical outcomes have been demonstrated in cardiovascular clinical trials, specifically in the acute coronary syndrome (ACS) population1,2. In thrombolytic studies, patients in the United States (US) tended to have shorter time to treatment, lower Killip class and a higher proportion of inferior myocardial infarctions (MIs) than non-US patients. In studies comparing North American and Eastern European patients, North American patients were more likely to be male and to have fewer comorbidities, including hypertension, angina, heart failure and abnormal electrocardiogram findings, than patients enrolled in Eastern Europe. Several trials in the setting of ST-elevation MI have demonstrated higher mortality rates in non-US than in US sites, particularly in Latin America1.
Few data are available concerning international differences in the use of drug-eluting stents. Austin et al3 demonstrated a wide variation in the application of drug-eluting stents across 4 countries (US, Canada, United Kingdom, and Belgium), but they did not report on differences in patient characteristics or clinical outcomes. The E-Five Registry, a large prospective, nonrandomized, multicenter, international registry, assessed the safety and effectiveness of the Endeavor zotarolimus-eluting stent (ZES; Medtronic CardioVascular, Santa Rosa, California, US) in "real-world" patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention (PCI)4. The size of this global cohort provides a unique opportunity to explore the existence of geographic differences and whether such differences may influence clinical outcomes in patients undergoing PCI and stent implantation outside the confines of a clinical trial. Furthermore, this cohort allows a view of the different practices, geographically speaking, of dual antiplatelet therapy (DAPT) use and whether there is any clinical impact.
Methods
Study design and objectives
The E-Five Registry is a prospective, nonrandomized, multicenter registry conducted in 37 countries around the world. For this study, we selected 3 regions, Asia Pacific (AP), the European Union (EU), and Latin America (LA), based on physical location. No attempt was made to ensure equality between the numbers of patients enrolled in each region or between member countries.
A total of 8,314 adult patients enrolled at 188 centers were followed for 1 year. In addition, a subset of 2,116 patients from 26 centers was followed for 2 years. These centers were selected on the basis of enrollment and willingness to continue follow-up. Outcomes were evaluated at 1 year and 2 years for the respective cohorts.
Analyses were performed to determine differences in demographic and baseline characteristics among patients from each region and the potential influence of these differences on clinical outcomes, including major adverse cardiac events (MACE), cardiac death, MI, target lesion revascularization (TLR), target vessel revascularization (TVR), and definite and probable stent thrombosis as defined by the Academic Research Consortium (ARC)5.
Study population and protocol
The E-Five Registry contains data on adult patients who underwent single-vessel or multivessel PCI. Eligible patients had target lesions appropriate for stent intervention. Details of the study protocol were previously reported4.
All patients completed follow-up visits at discharge, 30 days, 6 months, and 1 year, and selected centers followed patients for up to 2 years (Figure 1). Outpatient clinic visits were the preferred means of follow-up, although phone calls were allowed.
Countries included in the LA region were Brazil, Chile, Mexico, and Uruguay. The AP region included Australia, China, Hong Kong, India, Korea, Malaysia, New Zealand, Singapore, and Thailand. The EU region included Austria, Belgium, Bulgaria, Czech Republic, Egypt, Estonia, Finland, Germany, Greece, Hungary, Israel, Italy, Latvia, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Spain, Switzerland, Turkey, and the United Kingdom. This study was conducted under the ethics guidelines of the Declaration of Helsinki. Before study initiation at any clinical site, the study was approved by a medical ethics committee to protect human subjects, depending on regional requirements. Written informed consent was obtained from all patients.
Device description
The Endeavor ZES (Medtronic) consists of a cobalt-alloy stent with an elution polymer-coated exterior that releases the antiproliferative drug zotarolimus (10 μg/mm stent length). The zotarolimus elution is designed to inhibit proliferation of smooth muscle cells; the phosphorylcholine-based polymer coating is designed to simulate red blood cells, thus mimicking the natural cell membrane6. These features are designed to reduce the typical biological response to an implanted device and enhance long-term safety. The ZES is available in diameters of 2.25 mm to 4.0 mm and in lengths of 8 mm to 30 mm.
Data collection and management
Electronic data capture by web-based case report forms was completed for all sites. To ensure quality control, random monitoring of clinical sites was conducted at prespecified intervals. Approximately 10% of the study data was reviewed to monitor compliance and to ensure accurate reporting of events, as well as accuracy of data.
The data designated for baseline collection included eligibility criteria, demographic characteristics, cardiac risk factors, current cardiac status, lesion characteristics and results from pre-procedure angiography. Investigators were required to conduct a visual examination of the lesion to estimate lesion characteristics.
Documented clinical outcomes compared between regions included MACE, death, cardiac death, MI, TLR, TVR, TVR (nontarget lesion) and target vessel failure (TVF). Antiplatelet medication use was documented at 30 days, 6 months, and 1 year for all patients and at 2 years for those in the 2-year cohort.
MACE and stent thrombosis events were reviewed by a central clinical events committee (Cardialysis, Rotterdam, The Netherlands). Stent thrombosis events were evaluated using ARC definitions. Data management for this study and study monitoring were completed by Medtronic CardioVascular staff or a contract research organization designated by Medtronic.
Study endpoints
The primary endpoint for the overall E-Five Registry was the rate of MACE, defined as death, MI (Q-wave and non-Q-wave), emergent cardiac bypass surgery, or TLR (repeat PCI or coronary artery bypass graft [CABG] surgery), at 1 year.
We report here clinical outcomes of MACE, all-cause death, cardiac death, MI, TLR, TVR, and TVF at 1 and 2 years of follow-up for each of the 3 regions. The rates of ARC-defined definite and probable stent thrombosis were analyzed for early (0 to 30 days), late (31 to 365 days), and very late events (366 to 730 days).
Statistical analyses
Patient, lesion, and procedural characteristics were recorded at each site and summarized by region for the overall population at 1 year and for the long-term follow-up cohort at 2 years. Percentages are reported for categorical variables, and means ± standard deviations are reported for continuous variables. Antiplatelet therapy was detailed at 30 days, 6 months, and 1 year for all patients and at 2 years for the smaller cohort. All clinical outcomes (including MACE, all-cause death, death due to cardiac complications, MI, TLR, TVR, TVF, and ARC definite and probable stent thrombosis) were compiled by region for all available patients at the 1- and 2-year time points. Although the LA region had the smallest number of patients, it represented a unique population of patients with higher rates of cardiac risk factors and prior MIs, but the shortest duration of DAPT use; therefore, we used this region as the reference comparator for the other 2 regions.
Baseline variables were compared as follows: A 2-sided t test was used to calculate p values for continuous variables, and Fisher's exact test was used to determine p values for categorical variables. A p value of < 0.05 was considered statistically significant.
To adjust for differences in baseline characteristics in the 1-year and 2-year cohorts, the clinical outcomes at 1 year and 2 years were compared as follows: p values were based on logistic regression adjusted for propensity scores, which were calculated using the following baseline variables: age, sex, prior MI, prior percutaneous transluminal coronary angioplasty, prior CABG surgery, diabetes, acute MI (< 72 hours), hypertension, hypercholesterolemia, smoking, left anterior descending artery (vs non-left anterior descending artery), class B2/C (vs class A/B1), lesion length > 27 mm (if any lesion > 27 mm, vs < 27 mm), and reference vessel diameter > 3.5 mm (if any lesion is > 3.5 mm, vs < 3.5 mm).
The E-Five Registry is funded by the Medtronic Bakken Research Center, Medtronic CardioVascular, Maastricht, The Netherlands.
Results
Patient demographics and lesion characteristics
Overall population - the mean age of all patients enrolled in the E-Five Registry was 63.3 years. Patients in the EU region were older than patients in LA (64.2 vs 61.3 years, p < 0.001), and patients in LA were older than in AP, although this difference was not statistically significant (61.3 vs 59.9 years) (Table 1). The majority of patients in all regions were male: EU, 76.8%; AP, 77.1%; and LA, 70.0%. The most common comorbidities were hypercholesterolemia and hypertension. The prevalence of hypercholesterolemia was significantly higher in LA than in EU (75.0% vs 66.3%, p = 0.007) and AP (75.0% vs 47.6%, p < 0.001). The prevalence of hypertension was significantly greater in LA than in AP (76.4% vs 63.0%, p < 0.001) or EU (76.4% vs 69.6%, p = 0.036). The rate of prior MI also was higher in LA than in EU (47.3% vs 31.8%, p < 0.001) and AP (47.3% vs 31.5%, p < 0.001), as well as the rate of prior CABG (LA vs EU: 10.0% vs 8.3%, p = 0.384; LA vs AP, 10.0% vs 4.0%, p < 0.001). The prevalence of diabetes mellitus was more consistent between regions with approximately one third of patients being affected: LA, 34.5%; AP, 37.4%; and EU, 31.6% (p = NS for LA vs EU and LA vs AP).
Target vessel location varied among the regions and is detailed in Table 1. Reference vessel diameter was similar for patients in LA and AP but smaller for patients in EU. There was a significantly lower rate of class C lesions (American College of Cardiology/American Heart Association system) in LA as compared with both EU (10.7% vs 24.5%, p < 0.001) and AP (10.7% vs 30.2%, p < 0.001).
2-Year cohort - the baseline demographic data of the subset of patients followed for 2 years was similar to data of the overall population (Table 2). Patients in LA were significantly younger than EU patients (61.3 vs 63.2 years, p = 0.02), but significantly older than AP patients (61.3 vs 56.7 years, p < 0.001). In the 2-year cohort, there were significantly fewer males in LA than in AP (69.0% vs 83.5%, p < 0.001) and EU (69.0% vs 77.1%, p = 0.018). The LA region also had the highest rates of common cardiac risk factors, including hypertension, hypercholesterolemia, previous MI, previous CABG, unstable angina, and diabetes, as compared with the other 2 regions.
Target lesion characteristics of the 2-year cohort were similar to those of the overall 1-year patient population. Vessel location, lesion length, and the proportion of class B2 and C lesions were all significantly different between the LA and EU regions and between the LA and AP regions (Table 2). LA patients were significantly more likely to have class B2 lesions than AP patients (54.5% vs 27.6%, p < 0.001) and EU patients (54.5% vs 36.7%, p < 0.001) and significantly less likely to have class C lesions than AP patients (10.3% vs 37.2%, p < 0.001) and EU patients (10.3% vs 25.9%, p < 0.001). Reference vessel diameter was similar between the LA region and the EU and AP regions, whereas lesion length was again shorter in LA (16.94 ± 8.46 mm) as compared with both EU (18.85 ± 10.72 mm, p = 0.001) and AP (21.75 ± 11.01 mm, p < 0.001).
Antiplatelet therapy
Postprocedure antiplatelet therapy, which was based on clinical standard practice, was common in all regions. Although most patients continued to take aspirin throughout the 2-year follow-up period, DAPT usage rates decreased considerably over time (Table 3). In particular, the most rapid and steep decline in DAPT usage was seen among LA patients: at 6 months, 44.9% of LA patients were receiving DAPT, whereas 87.4% of patients in EU and 82.4% of patients in AP continued DAPT. By the 1-year time point, only 22.5% of LA patients were still using DAPT, compared with 61.5% of EU patients and 67.0% of AP patients. Among patients followed up through 2 years, DAPT usage dropped to 7.8% in LA, 19.7% in EU, and 45.7% in AP by 2 years (Figure 2).
Clinical outcomes
Overall outcomes at 1 year - there were no statistically significant differences in most of the clinical outcomes at 1 year between the LA region and the EU or AP region (Table 3). The 1-year rate of MACE was 4.3% for LA, 6.2% for AP, and 7.9% for EU patients (p = NS for both LA vs. EU and LA vs AP). There were no MI events in the LA region and rates of only 1.6% in EU and 1.9% in AP (p = NS for LA vs EU and LA vs AP). Cardiac death and MI was statistically different for LA compared with AP (0.5% vs 3.5%, p = 0.039), but not for LA compared with EU. Rates of early (0 to 30 days) and late (31 to 365 days) ARC probable and definite stent thrombosis were low across all regions, and again, there were no significant differences between the LA region and the EU or AP region. There were no late ARC definite and probable stent thrombosis events in LA, compared with a rate of 0.5% in EU (p = 0.977) and 0.2% in AP at the same time point (p = 0.968).
2-year cohort outcomes - similar to the results of the entire E-Five cohort followed at 1 year, there were no statistically significant differences in clinical outcomes between the LA region compared with the EU or AP region throughout 2 years of follow-up (Table 4). Rates of MACE at 2 years were 6.3% in LA, 4.5% in AP, and 9.5% in EU patients. In all major cardiac endpoints, the outcomes and prevalence rates at 2 years were similar to the rates observed at 1 year. The rates of TVR were similar in the LA and EU regions (6.8% vs 6.6%, p = 0.795); however, the rate of TVR was lower in the AP region than in the LA region, although the difference did not reach statistical significance (6.8% vs 1.9%, p = 0.052). There were no very late (366 to 730 days) ARC definite and probable stent thrombosis events in the LA or AP regions among the 2-year cohort and only 2 (0.1%) in the EU region.
Discussion
The primary endpoint of MACE at 12 months and the secondary endpoint of MACE in the 2-year cohort, in addition to cardiac death, MI, TLR, TVF, and ARC definite and probable stent thrombosis at the same time points, were similar between the LA and EU regions and the LA and AP regions, despite considerable variations in cardiac risk factors, lesion characteristics, and DAPT use. At 1 year, the lowest rate of MACE was observed in the LA region, even though this region had the lowest DAPT use at that time point. In the smaller 2-year cohort of patients, the lowest MACE rate was found in the AP region. Patients in the LA region had a greater incidence of prior MI, unstable angina, and previous revascularization (PCI and CABG) and higher rates of hypertension, hypercholesterolemia and diabetes. It is possible that patients with a higher incidence of cardiac risk factors received more rigorous secondary preventive treatments, although these data are not available for analysis.
Within the E-Five Registry, stent thrombosis events were adjudicated to confirm per-protocol and ARC-defined outcomes. As previously reported4, ARC definite and probable stent thrombosis events occurred more commonly early (0 to 30 days) than late (31 to 365 days). This held true for the subset of patients followed for 2 years in all regions, with extremely low rates of ARC probable and definite stent thrombosis reported. Premature cessation of DAPT may be related to increased risk of stent thrombosis7 and the optimal duration of DAPT that is both safe and effective in reducing late stent thrombosis events remains an important unanswered question8,9. Despite the low rates of prolonged DAPT use in the LA region, stent thrombosis rates were not significantly different from those reported in the other 2 regions. LA patients generally had shorter and less complex lesions, which may have decreased the risk of stent thrombosis7. It is unclear how these multiple factors (early cessation of DAPT, less complex lesions and more comorbidity) may have interacted and influenced the risk of stent thrombosis. This finding warrants further investigation.
Of note, ongoing prospective clinical trials are evaluating optimal DAPT duration. One such trial is the OPTIMIZE study for ZES, which randomized 3,120 patients to 3 months versus 12 months of DAPT and will report 1-year outcomes for death, MI, stroke, major bleeding, and ARC-defined stent thrombosis events9.
In contrast to these findings, other analyses of international variations have shown differences in clinical outcomes by geographic region. In the Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, enrollment in LA was an independent predictor of mortality at 30 days (odds ratio 2.42, 95%; 95% confidence interval 1.60-3.67) and 6 months (odds ratio 2.5; 95% confidence interval 1.8-3.4)10. This finding was observed even after adjustment for differences in baseline risk, suggesting that the outcome difference may have been due to more conservative practice patterns (i.e., lower use of evidence-based therapies for acute MI, lower and later use of revascularization procedures and less use of invasive management such as angiography). Other ACS studies have also reported significantly higher mortality rates among patients enrolled in LA centers. In these studies, mortality ranged from 10.4% to 12.4% in LA, compared with 5.7% to 7.8% in the US and Europe, respectively1. It has been hypothesized that low rates of coronary angiography and revascularization may explain these observed differences in clinical outcome1.
Of note, however, Cardoso et al11 evaluated the use of drug-eluting stents in Brazil from 2000 to 2005 and observed a progressive increase in use (from 0.14% to 14%) and after 2001, an increase in success rates (from 96.58% to 99.56%) and a decrease in hospital mortality rates (1.59% to 0.21%).
Our findings from E-Five, showing that DAPT use was lowest in the LA region, are consistent with other reports. In PURSUIT, patients in LA were significantly less likely to receive in-hospital ticlopidine, heparin, angiotensin-converting enzyme inhibitors, oral beta-blockers, lipid-lowering agents and oral nitrates. They were also prescribed fewer evidence-based discharge medicines, including antiplatelet agents, beta-blockers, lipid-lowering agents, and oral nitrates10.
It is unclear why no differences in clinical outcomes were observed in the LA group in E-Five. It is possible that there is less opportunity for practice variation in PCI and stent implantation, as compared with ACS management, where differences have been observed. It is also plausible that the LA centers participating in the E-Five Registry may have been more clinically experienced than sites participating in ACS trials, so that practice variations that may have influenced outcome were minimal. Finally, patients enrolled in E-Five may have been at lower risk of events than patients enrolled in ACS trials, decreasing the likelihood that a difference in clinical events would have been observed.
Limitations
It should be noted that this study was not originally designed or powered to evaluate regional subgroups. The LA and AP regions together include fewer patients than the EU region and may not be representative of all patients presenting for implantation of a drug-eluting stent in those regions. In our analysis, even though we adjusted for baseline differences in the comparison tests of outcomes between regions, other patient-level factors that were unaccounted for could have affected outcomes independently of geographic region. The 2-year patient cohort is a subset of the overall E-Five population; thus, formal comparisons of baseline patient and lesion characteristics for the two groups are inappropriate, although it is nonetheless important to show the overall similarity of the patient groups at 1 and 2 years. Finally, because follow-up could be conducted by phone, extensive information on medical therapies and interventions specific to each region was not available.
Conclusion
Regional results from the E-Five Registry suggest that despite differences in patient and lesion characteristics and DAPT use between different geographic regions, outcomes, including rates of MACE, cardiac death, MI, and ARC-defined probable and definite stent thrombosis, are similar. Although DAPT use in LA was less than half that in the other regions, this did not result in increased rates of MACE or late stent thrombosis. The other cardiac and lesion outcomes at 1 year and 2 years were comparable between the LA and both the EU and AP regions.
These data suggest that considerable differences in lesion complexity and comorbidities across geographic regions do not translate into differences in outcomes after PCI. It may be that the risks of premature cessation of DAPT are partially mitigated by simpler lesion anatomy. These results provide evidence of the safety and effectiveness of the Endeavor ZES in real-world patients despite potential patient, lesion, and practice differences between the major geographic regions.
Sources of Funding
This study was funded by Medtronic Bakken Research Center, Medtronic CardioVascular, Maastricht and The Netherlands.
Study Association
This study is not associated with any post-graduation program.
References
- 1. O'Shea JC, Califf RM. International differences in cardiovascular clinical trials. Am Heart J. 2001;141(5):866-74.
- 2. Chang WC, Midodzi WK, Westerhout CM, Boersma E, Cooper J, Barnathan ES, et al. Are international differences in the outcomes of acute coronary syndromes apparent or real? A multilevel analysis. J Epidemiol Community Health. 2005;59(5):427-33.
- 3. Austin D, Oldroyd KG, Holmes DR Jr, Rihal CS, Galbraith PD, Ghali WA, et al. Drug-eluting stents: a study of international practice. Am Heart J. 2009;158(4):576-84.
- 4. Lotan C, Meredith IT, Mauri L, Liu M, Rothman MT, for the E-Five Investigators. Safety and effectiveness of the Endeavor zotarolimus-eluting stent in real-world clinical practice: 12-month data from the E-Five registry. JACC Cardiovasc Interv. 2009;2(12):1227-35.
- 5. Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, et al. for the Academic Research Consortium. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007;115(17):2344-51.
- 6. Burke SE, Kuntz RE, Schwartz LB. Zotarolimus (ABT-578) eluting stents. Adv Drug Deliv Rev. 2006;58(3):437-46.
- 7. Iakavou I, Schimdt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA. 2005;293(17):2126-30.
- 8. Waksman R, Buch AN, Torguson R, Xue Z, Smith K, Javaid A, et al; for the REWARDS Registry. Long-term clinical outcomes and thrombosis rates of sirolimus-eluting versus paclitaxel-eluting stents in an unselected population with coronary artery disease (REWARDS registry). Am J Cardiol. 2007;100(1):45-51.
- 9. Kandzari DE, Angiolillo DJ, Price MJ, Teirstein PS. Identifying the "optimal" duration of dual antiplatelet therapy after drug-eluting stent revascularization. JACC Cardiovasc Interv. 2009;2(12):1279-85.
- 10. Cohen MG, Pacchiana CM, Corbalán R, Perez JE, Ponte CI, Oropeza ES, et al. Variation in patient management and outcomes for acute coronary syndromes in Latin America and North America: results from the Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial. Am Heart J. 2001;141(3):391-401.
- 11. Cardoso CO, Quadros AS, Mattos LA, Gottschall CA, Sarmento-Leite RE, Marin-Neto JA. Use of drug-eluting stents in Brazil: the CENIC (National Registry of Cardiovascular Interventions) Registry. Arq Bras Cardiol. 2007;89(6):323-7.
Clinical outcomes by geographic region for patients implanted with the zotarolimus-eluting stent
Publication Dates
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Publication in this collection
01 Apr 2011 -
Date of issue
May 2011
History
-
Received
26 Aug 2010 -
Accepted
04 Oct 2010 -
Reviewed
26 Aug 2010
