Drug-Eluting Stent Mortality Meta-Analysis

[Igor73]

Edward L. Hannan et al. Drug-Eluting Stents vs. Coronary-Artery Bypass Grafting in Multivessel Coronary Disease. NEJM 2008

[Ссылки доступны только зарегистрированным пользователям ]
Background Numerous studies have compared the outcomes of two competing interventions for multivessel coronary artery disease: coronary-artery bypass grafting (CABG) and coronary stenting. However, little information has become available since the introduction of drug-eluting stents.
Methods We identified patients with multivessel disease who received drug-eluting stents or underwent CABG in New York State between October 1, 2003, and December 31, 2004, and we compared adverse outcomes (death, death or myocardial infarction, or repeat revascularization) through December 31, 2005, after adjustment for differences in baseline risk factors among the patients.
Results In comparison with treatment with a drug-eluting stent, CABG was associated with lower 18-month rates of death and of death or myocardial infarction both for patients with three-vessel disease and for patients with two-vessel disease. Among patients with three-vessel disease who underwent CABG, as compared with those who received a stent, the adjusted hazard ratio for death was 0.80 (95% confidence interval [CI], 0.65 to 0.97) and the adjusted survival rate was 94.0% versus 92.7% (P=0.03); the adjusted hazard ratio for death or myocardial infarction was 0.75 (95% CI, 0.63 to 0.89) and the adjusted rate of survival free from myocardial infarction was 92.1% versus 89.7% (P<0.001). Among patients with two-vessel disease who underwent CABG, as compared with those who received a stent, the adjusted hazard ratio for death was 0.71 (95% CI, 0.57 to 0.89) and the adjusted survival rate was 96.0% versus 94.6% (P=0.003); the adjusted hazard ratio for death or myocardial infarction was 0.71 (95% CI, 0.59 to 0.87) and the adjusted rate of survival free from myocardial infarction was 94.5% versus 92.5% (P<0.001). Patients undergoing CABG also had lower rates of repeat revascularization.
Conclusions For patients with multivessel disease, CABG continues to be associated with lower mortality rates than does treatment with drug-eluting stents and is also associated with lower rates of death or myocardial infarction and repeat revascularization.

[Igor73]

Oscar C. Marroquin et al. NEJM 2008
A Comparison of Bare-Metal and Drug-Eluting Stents for Off-Label Indications.
[Ссылки доступны только зарегистрированным пользователям ]

Background Recent reports suggest that off-label use of drug-eluting stents is associated with an increased incidence of adverse events. Whether the use of bare-metal stents would yield different results is unknown.
Methods We analyzed data from 6551 patients in the National Heart, Lung, and Blood Institute Dynamic Registry according to whether they were treated with drug-eluting stents or bare-metal stents and whether use was standard or off-label. Patients were followed for 1 year for the occurrence of cardiovascular events and death. Off-label use was defined as use in restenotic lesions, lesions in a bypass graft, left main coronary artery disease, or ostial, bifurcated, or totally occluded lesions, as well as use in patients with a reference-vessel diameter of less than 2.5 mm or greater than 3.75 mm or a lesion length of more than 30 mm.
Results Off-label use occurred in 54.7% of all patients with bare-metal stents and 48.7% of patients with drug-eluting stents. As compared with patients with bare-metal stents, patients with drug-eluting stents had a higher prevalence of diabetes, hypertension, renal disease, previous percutaneous coronary intervention and coronary-artery bypass grafting, and multivessel coronary artery disease. One year after intervention, however, there were no significant differences in the adjusted risk of death or myocardial infarction in patients with drug-eluting stents as compared with those with bare-metal stents, whereas the risk of repeat revascularization was significantly lower among patients with drug-eluting stents.
Conclusions Among patients with off-label indications, the use of drug-eluting stents was not associated with an increased risk of death or myocardial infarction but was associated with a lower rate of repeat revascularization at 1 year, as compared with bare-metal stents. These findings support the use of drug-eluting stents for off-label indications.

[Abugov]

Ножики пока не выкидываем:

CABG holds out over DES for multivessel disease
Coronary artery bypass grafting remains the best option for multivessel coronary artery disease, resulting in lower mortality and death or myocardial infarction, and fewer repeat revascularizations, than percutaneous coronary intervention with drug-eluting stents, latest research indicates.
N Engl J Med 2008; 358: 331-341

[Igor73]

ABBYY Lingvo 10.0 "sort out .. 2) улаживать ( проблемы ); выяснить ( вопрос, недоразумение и т. п. ) It's up to the director to sort out difficulties like this one. — Улаживание вопросов такого рода входит в компетенцию директора"
[Ссылки доступны только зарегистрированным пользователям ]
Title: Comparison of Paclitaxel- and Sirolimus-Eluting Stents in Everyday Clinical Practice (SORT OUT II)
Trial Sponsor: Unrestricted research grants from Boston Scientific and Cordis.
Year Presented: 2008
Year Published 2008
Summary Posted: 1/29/2008
Writer: [Ссылки доступны только зарегистрированным пользователям ]
Author Disclosure: Anthony Bavry, MD, has received honoraria from Boston Scientific and Access Closure.
Reviewer: [Ссылки доступны только зарегистрированным пользователям ]
Author Disclosure: Research Grants: Sanofi Aventis, Significant (>= $10,000); Research Grants: Heartscape, Significant (>= $10,000); Research Grants: Bristol Myers Squibb, Significant (>= $10,000); Research Grants: The Medicines Company, Significant (>= $10,000); Research Grants: Eisai, Significant (>= $10,000); Research Grants: Ethicon, Significant (>= $10,000)
Description
The goal of this trial was to evaluate symptom-driven clinical endpoints among unselected patients from the use of sirolimus-eluting stents, compared with paclitaxel-eluting stents.
Hypothesis
One type of drug-eluting stent may be more effective and safer than the other type in treating patients with obstructive coronary artery disease.
Drugs/Procedures Used
Among 11,766 patients undergoing percutaneous coronary intervention (PCI) who were eligible for study participation, 9,668 were excluded due to selection criteria. This resulted in 2,098 randomized patients (1,056 patients received sirolimus-eluting stents and 1,033 patients received paclitaxel-eluting stents).
Concomitant Medications
N/A
Principal Findings
The index diagnosis was stable angina in 45%, non-ST-elevation acute coronary syndrome in 33%, and ST-elevation myocardial infarction in 17%. There was one vessel treated in 78% of the patients, two vessels treated in 18%, and three vessels treated in 3%. Type C lesions were treated in 61%. The primary composite outcome occurred in 10% of the sirolimus group and 11.6% of the paclitaxel group (p = 0.21). There was no difference in cardiac death (1.7% vs. 1.5%, p = 0.80), acute myocardial infarction (4.2% vs. 5.1%, p = 0.32), target lesion revascularization (4.5% vs. 5.9%, p = 0.14), target vessel revascularization (6.6% vs. 7.8%, p = 0.25), or stent thrombosis (2.6% vs. 2.8%, p = 0.70) for sirolimus compared with paclitaxel stents, respectively.
Interpretation
Among unselected patients with obstructive coronary artery disease, including acute coronary syndromes and type C lesions, there is no appreciable difference in the efficacy or safety between sirolimus-eluting stents compared with paclitaxel-eluting stents. This finding is important since sirolimus-eluting stents have been associated with less late lumen loss and target lesion revascularization compared with paclitaxel-eluting stents. Moreover, comparison between these two stents has largely been conducted among select populations.

In addition to the broad patient population studied, one of the strengths of the study is that the outcomes were clinically driven and not a result of protocol-mandated angiography.

The cumulative incidence of definite and probable stent thrombosis was somewhat generous (2.7%), although there was no bare-metal stent group for comparison. Another limitation of this trial was lack of power to detect a clinically meaningful difference because the event rates were lower than anticipated. There were also relatively few diabetics.
Conditions
• Arteriosclerosis
• Coronary heart disease / Acute MI
• Coronary heart disease / Angina pectoris / Stable
• Coronary heart disease / Angina pectoris / Unstable

Therapies
• Stent/drug-eluting

Study Design
Randomized. Blinded.
Patients Screened: 11,766
Patients Enrolled: 2,098
Mean Follow-Up: Approximately 18 months
Mean Patient Age: 64 years
% Female: 25%

Primary Endpoints
Change in the composite endpoint of cardiac death, acute myocardial infarction, target lesion revascularization, and target vessel revascularization at 18 months
Secondary Endpoints
Change in individual components of the composite endpoint of cardiac death, acute myocardial infarction, target lesion revascularization, and target vessel revascularization. Additional secondary endpoints were all-cause mortality and stent thrombosis.
Patient Population
Unselected patients undergoing PCI with the planned use of a drug-eluting stent
Exclusions:
Planned use of a bare-metal stent or balloon angioplasty only during PCI

References: First presented by Dr. Anders M. Galloe at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2006), Washington, DC, October 2006.
Galloe AM, Thuesen L, Kelbaek H, et al. Comparison of paclitaxel- and sirolimus-eluting stents in everyday clinical practice: the SORT OUT II randomized trial. JAMA 2008;299:409-16.

[rsp]

а качельки-то теперь в другую сторону качнулись...

"Off-Label" Stent Therapy

2-Year Comparison of Drug-Eluting Versus Bare-Metal Stents

Objective: The aim was to compare 2-year outcomes with the routine use of drug-eluting stents (DES) (>75% "off-label") with a comparable group treated with bare-metal stents (BMS).

Background: Safety concerns >1 year from implantation have been raised about DES used "off-label." There are limited data comparing DES and BMS in "off-label" patients.
Methods: Clinical outcomes (nonfatal myocardial infarction [MI], all-cause mortality) were assessed in 1,164 consecutive patients who received BMS in the year before introduction of DES at Wake Forest University Baptist Medical Center and 1,285 consecutive patients who received DES after it became our routine choice. "On-label" stent use was defined as treatment for a single de novo lesion <30 mm, without recent MI or other major illnesses.
Results: At 2 years, the hazard ratio for DES compared with BMS for nonfatal MI or death was 0.77 (95% confidence interval [CI] 0.62 to 0.95), for all-cause mortality 0.71 (0.54 to 0.92), and stent thrombosis (ST) 0.97 (0.49 to 1.91). "On-label" stent procedures were associated with lower risk of MI, death, and ST than "off-label" stent procedures. For "off-label" stent procedures, the hazard ratio for DES compared with BMS for nonfatal MI or death was 0.78 (95% CI 0.62 to 0.98), all-cause mortality 0.72 (0.54 to 0.94), and ST 0.91 (0.46 to 1.80). The hazard of nonfatal MI or death was similar or lower for DES than BMS in high-risk subgroups, including renal failure and recent MI. Conclusions: The routine clinical use of drug-eluting stents for "off-label" indications was associated with lower nonfatal MI and death at 2 years than in a comparable group of patients treated with BMS.
[Ссылки доступны только зарегистрированным пользователям ]

[Abugov]

Смазываем железки, смазываем:

DES 'do more good than harm'
The weight of evidence suggests that drug-eluting stents "do more good than harm," conclude US researchers after reviewing the benefits and risks associated with these stents in current clinical data.
Ann Intern Med 2008; 148: 234-238

[dmblok]

Сообщение от Abugov

Смазываем железки, смазываем:

DES 'do more good than harm'
The weight of evidence suggests that drug-eluting stents "do more good than harm," conclude US researchers after reviewing the benefits and risks associated with these stents in current clinical data.
Ann Intern Med 2008; 148: 234-238

За ключевую фразу статьи может быть также принято принято предложение: "However, there are few overall safety data from adequately controlled trials on the use of drug-eluting stents for “off-label” indications." ИМХО, конечно.

[Ссылки доступны только зарегистрированным пользователям ]

[dmblok]

Сообщение от rsp

а качельки-то теперь в другую сторону качнулись...

[Ссылки доступны только зарегистрированным пользователям ]

Срок 2 года, не такой уж большой.

"In spite of the benefits of DES observed in this study, recent studies raise important questions about long-term DES safety in a broader population of patients than was studied in the initial RCT. Longer-term follow-up safety and effectiveness studies of DES use will need to be obtained to
determine if late DES-related events will affect the balance of safety and effectiveness more than 2 years after DES implantation."

[Ссылки доступны только зарегистрированным пользователям ]

[rsp]

to Dmblok: Спасибо за полный текст этой статьи.
Конечно 2 года небольшое наблюдение, и не исключено, что к 4-5и годам кривые выживаемости могут сравняться. Даже, если это и произойдет, всё равно есть серьезный повод задуматься какому виду кривой выживаемости отдать предпочтение...той, которая в течение первых 2-х лет достоверно выше или той, которая теоретически на сроках от 2-х лет будет якобы иметь меньшую отрицательную динамику

[Igor73]

Local Delivery of Paclitaxel to Inhibit Restenosis during Angioplasty of the Leg

Gunnar Tepe et al. NEJM 2008
[Ссылки доступны только зарегистрированным пользователям ]
Background Drug-eluting stents reduce restenosis in coronary arteries, but clinical trials have failed to prove their efficacy in peripheral arteries. We investigated the use of paclitaxel-coated angioplasty balloons and paclitaxel dissolved in the angiographic contrast medium during angioplasty of the leg.
Methods In a small, multicenter trial, we randomly assigned 154 patients with stenosis or occlusion of a femoropopliteal artery to treatment with standard balloon catheters coated with paclitaxel, uncoated balloons with paclitaxel dissolved in the contrast medium, or uncoated balloons without paclitaxel (control). The primary end point was late lumen loss at 6 months.
Results The mean (±SD) age of the patients was 68±8 years, 24% were smokers, and 49% had diabetes. Twenty-seven percent of the lesions were total occlusions, and 36% were restenotic lesions. The mean lesion length was 7.4±6.5 cm. There were no significant differences in baseline characteristics between the groups. There were no adverse events attributable to the paclitaxel-coated balloons. At 6 months, the mean late lumen loss was 1.7±1.8 mm in the control group, as compared with 0.4±1.2 mm (P<0.001) in the group treated with paclitaxel-coated balloons and 2.2±1.6 mm (P=0.11) in the group treated with paclitaxel in the contrast medium. The rate of revascularization of target lesions at 6 months was 20 of 54 (37%) in the control group, 2 of 48 (4%) in the group treated with paclitaxel-coated balloons (P<0.001 vs. control), and 15 of 52 (29%) in the group treated with paclitaxel in the contrast medium (P=0.41 vs. control); at 24 months, the rates increased to 28 of 54 (52%), 7 of 48 (15%), and 21 of 52 (40%), respectively.
Conclusions Use of paclitaxel-coated angioplasty balloons during percutaneous treatment of femoropopliteal disease is associated with significant reductions in late lumen loss and target-lesion revascularization. No significant benefit is seen with the use of a paclitaxel-containing contrast medium. (ClinicalTrials.gov number, NCT00156624 [Ссылки доступны только зарегистрированным пользователям ] .)

[Maltsev]

Сообщение от dmblok

Применение двойной антиагрегантной терапии, безусловно повышает риск кровотечений во время операции, поэтому возможны различные способы уменьшения осложнений и сокращения сроков от PCI до основного вмешательства. Например: а)использование BMS;

Именно по этому и был использован BMS, не требующий длительной двухкомпонентной антитромбоцитарной терапии. Отмена клопи была запланированной, период применения - превышающий таковой в ACC/AHA Guidelines.

Сообщение от dmblok

2) Операция является значительной нагрузкой для организма, поэтому консервативная тактика, которая может быть оправданной у большинства больных со стабильной стенокардией/ишемией, не может быть оптимальной для той же группы больных, которым планируется серезное вмешательство.
Больной с декомпенсированным коронарным кровобращением, может запросто перенести ИМ во время операции и без окклюзируещего тромбоза артерии (субтотального стеноза ПКА, для этого вполне достаточно), тем более, что риск тромбоза у таких больных значительно выше. Не говоря уже о том, что контролировать и лечить ишемию во время операции анестезиологу весьма проблематично.
С уважением.

Вот в том то и вопрос: снизит ли PCI риск периоперационного ИМ или ИМ в раннем послеоперационном периоде... Данные уж больно противоречивые...

С Уважением,
Мальцев Андрей Александрович

[Maltsev]

Сообщение от alex_md

Stents treat symptoms, not the disease.

А что вылечивает атеросклероз??? Шунты ? IMHO атеросклероз - заболевание, пока неизлечимое... Даже статинами ...

[dmblok]

Сообщение от Maltsev

Именно по этому и был использован BMS, не требующий длительной двухкомпонентной антитромбоцитарной терапии. Отмена клопи была запланированной, период применения - превышающий таковой в ACC/AHA Guidelines.

Освежил в памяти, случай полуторамесячной давности. Обращу Ваше внимание, что я старался высказать лишь общие соображения, т.к. для адекватных рекомендаций в конкретном случае нехватает исходных данных. Как я понял для больного все закончилось успешно - значит вы молодцы.

Сообщение от Maltsev

Вот в том то и вопрос: снизит ли PCI риск периоперационного ИМ или ИМ в раннем послеоперационном периоде... Данные уж больно противоречивые...

Как уже говорилось выше, в подобных случаях требуется исключительно индивидуальный, взвешанный подход. Условный пример: наверняка Вам известны случаи развития ОИМ у больных без окклюзирующего тромбоза КА, при исходно декомпенсированном коронарном кровобращении, например на фоне значительной кровопотери. Очевидно, что кровотечение во время больших операций вполне возможно, следовательно возможен инфаркт.

[Maltsev]

Абсолютно согласен, особенно про ОРКК на фоне кровопотери. Но интересует именно т.н. "идеальный" случай, без дополнительных факторов риска, таких, как кровопотеря. Прекрасно понимаю, что этот вопрос не ясен, т.к. не хватает входных данных, поэтому не претендую на четкие рекомендации. Форум полезен тем, что можно узнать субъективные мнения конкретных людей по тому или иному вопросу.

[Igor73]

[Ссылки доступны только зарегистрированным пользователям ] et al.
A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial.
The Lancet 2008; 371:899-907
[Ссылки доступны только зарегистрированным пользователям ]
BackgroundA fully bioabsorbable drug-eluting coronary stent that scaffolds the vessel wall when needed and then disappears once the acute recoil and constrictive remodelling processes have subsided has theoretical advantages. The bioasorbable everolimus-eluting stent (BVS) has a backbone of poly-L-lactic acid that provides the support and a coating of poly-D,L-lactic acid that contains and controls the release of the antiproliferative agent everolimus. We assessed the feasibility and safety of this BVS stent.

MethodsIn this prospective, open-label study we enrolled 30 patients who had either stable, unstable, or silent ischaemia and a single de-novo lesion that was suitable for treatment with a single 3·0×12 mm or 3·0×18 mm stent. Patients were enrolled from four academic hospitals in Auckland, Rotterdam, Krakow, and Skejby. The composite endpoint was cardiac death, myocardial infarction, and ischaemia-driven target lesion revascularisation. Angiographic endpoints were available for 26 patients and intravascular-ultrasound endpoints for 24 patients. Clinical endpoints were assessed in all 30 patients at 6 and 12 months. In a subset of 13 patients, optical coherence tomography was undertaken at baseline and follow-up. Analysis was by intention to treat. This study is registered with [Ссылки доступны только зарегистрированным пользователям ], number NCT00300131.

FindingsProcedural success was 100% (30/30 patients), and device success 94% (29/31 attempts at implantation of the stent). At 1 year, the rate of major adverse cardiac events was 3·3%, with only one patient having a non-Q wave myocardial infarction and no target lesion revascularisations. No late stent thromboses were recorded. At 6-month follow-up, the angiographic in-stent late loss was 0·44 (0·35) mm and was mainly due to a mild reduction of the stent area (−11·8%) as measured by intravascular ultrasound. The neointimal area was small (0·30 [SD 0·44] mm2), with a minimal area obstruction of 5·5%.

InterpretationThis study shows the feasibility of implantation of the bioabsorbable everolimus-eluting stent, with an acceptable in-stent late loss, minimal intrastent neointimal hyperplasia, and a low stent area obstruction.

FundingAbbott Vascular.