Drug-Eluting Stent Mortality Meta-Analysis

[Igor73]

Presented by A.J. Nordmann, European Society of Cardiology Scientific Congress, September 2006.
DescriptionThe goal of the study was to evaluate treatment with drug-eluting stents (DES) compared with bare-metal stents (BMS) on mortality among randomized trials of DES in patients undergoing percutaneous coronary intervention (PCI) for de novo coronary lesions.
Drugs/Procedures UsedData were drawn from 17 randomized trials of DES compared with BMS. Endpoints evaluated were total mortality, cardiac mortality, and noncardiac mortality. Trials had to be randomized with follow-up of ≥1 year to be included in the meta-analysis.
Principal FindingsTotal mortality at 1 year did not differ between BMS compared with DES (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.66-1.34) or for the individual type of stents: sirolimus-eluting stents (SES) OR 0.86, 95% CI 0.49-1.51; paclitaxel-eluting stents (PES) OR 0.98, 95% CI 0.64-1.48. At 3 years, total mortality trended toward higher rates with DES compared with BMS (OR 1.25, 95% CI 0.91-1.73) as well as with SES versus BMS (OR 1.48, 95% CI 0.91-2.42).
Cardiac mortality at 3 years did not differ with DES versus BMS (OR 1.00, 95% CI 0.62-1.60). Noncardiac mortality at 3 years was directionally but not significantly higher with DES versus BMS (OR 1.45, 95% CI 0.93-2.25). However, for the individual stent type comparison, SES was associated with significantly higher rates of noncardiac death compared with BMS at both 2 years (OR 2.74, 95% CI 1.22-6.13, p < 0.05) and 3 years (OR 2.04, 95% CI 1.00-4.15, p < 0.05).
Interpretation. In a meta-analysis of 17 randomized trials of patients undergoing PCI for de novo coronary lesions, treatment with DES was not associated with a significant difference in total mortality at 3 years, but was associated with increased noncardiac mortality with SES compared with BMS.
Randomized trials of DES compared with BMS in de novo coronary lesions have consistently shown reductions in the need for repeat revascularization due to restenosis. However, none has been adequately powered to evaluate harder endpoints of death or myocardial infarction (MI). Restenosis, while a negative consequence of PCI, is a nonfatal event.
The present meta-analysis demonstrates a potential but nonsignificant hazard in late mortality with DES, possibly attributable to higher late stent thrombosis. Longer-term follow-up from these trials will provide further insight, as will a more detailed analysis of the specific causes of death. Another recent meta-analysis presented at European Society of Cardiology Scientific Congress 2006 demonstrated higher rates of long-term death or Q-wave MI with SES compared with BMS.

[indie]

а вот еще из обсуждения: для нашего здравоохранения в самое время.

ESC Event News


5 September 2006

The drug eluting stents debate - Hot Line Session Results
TWO SEPARATE, independent meta-analyses - presented in Hot Line session I at the World Congress of Cardiology 2006 - bring the long-term safety of DES firmly into the spotlight. Discussant Salim Yusuf (McMaster University, Canada) hailed the data as one of the most important presentations to come out of this year’s meeting.

“Six million people in the world have been implanted with DES, yet their long-term safety and efficacy is unknown,” said Yusuf. “I’ve a feeling the data we’re seeing today is only the tip of the iceberg. We need to encourage more public access to the data.”



Edoardo Camenzind

Presenter, Edoardo Camenzind (Geneva, Switzerland), said recent case reports had flagged up the problem of in-stent thrombosis resulting from DES. The BASKET-LATE data showed that the rate of cardiac death and nonfatal myocardial infarction (MI) was higher in patients with DES than in those with bare metal stents (BMS) (p=0.01). “The problem is likely to be significantly under-reported, since if people die on the street they don’t fulfil the angiographic criteria to be classified as in-stent thrombosis.”

The second presenter, Alain Nordmann (Basel, Switzerland), had concerns that DES accounted for more than 90% of stents used in the USA and Switzerland now. Camenzind undertook a meta-analysis looking at death and Q-wave MI in all randomised DES trials where data were available. Results at the latest available followup (four years) showed the incidence of death or MI was 6.3% for the sirolimus stent and 3.9% for the control BMS stent (p=0.03). For the paclitaxel stent, rates were 2.6% compared to 2.3% for the BMS stent (p=0.68). He concluded that death and Q-wave MI were higher in firstgeneration DES than BMS. He stressed that the problem was in first-generation DES – sirolimus and paclitaxel – and might not arise in the second-generation.

In the second study, Nordmann undertook a meta-analysis of all randomised, controlled, first-generation DES trials comparing cardiac and non-cardiac deaths in DES versus BMS. At four years overall mortality was higher for both cardiac and non-cardiac deaths in DES patients. Of the 36 non-cardiac deaths identified, 15 were due to cancer, including lymphoma and cancers of the lung, prostate, pancreas, GI, kidney and rectum.

“At this time, we can’t prove a causal relationship, only a statistical association. What makes me concerned is how difficult it was to obtain this data from the manufacturer,” said Nordmann. He speculated that the increase in cancer might be due to a rapid impairment of the immune system.

Yusuf widened the debate to include percutaneous coronary intervention (PCI). “The overuse of PCI is an insidious change in the culture of cardiology that needs to be reversed,” he said. The use of PCI was established in MI, high-risk unstable angina and cardiogenic shock. However, its use in stable disease was a totally different question.

“There’s no beneficial influence on mortality – PCI does nothing to prevent heart attack. All we are doing is providing short-term relief of chest pain. It’s not re-stenosis that kills but the thousands of lesions you can’t see. Stable angina can be controlled with full medical management.” Yusuf said vested interests included pharmaceutical companies, who have invested billions of dollars in DES, and cardiologists in the US and Canada who are reimbursed according to PCI procedures undertaken. He called for Euro Heart Surveys to provide clear evidence on when PCI was needed, predicting the majority of indications would be uncertain.

Jean Marco, chairperson of the PCI Euro Heart Survey, said that the Euro Heart Survey had outlined evidence-based indications for PCI. “These meta-analyses shouldn’t be viewed as detracting from the value of PCI and DES, but promoting a precautionary attitude towards the indiscriminate use of first generation DES.”

Related Report and Slides Available


Reference:
Source:
ESC Congress News - 05/09/2006

[indie]

удалено

[alex_md]

Мне все равно DES, или не DES. Разница ничтожна - примерно 1% в год. Для меня проблема только в том, что пациента со стентом, особенно DES нужно держать на Плавиксе с аспирином. Поэтому уже год как направляя пациентов к кардиологам я пишу, что пациент НЕ КАНДИДАТ на длительный прием Плавикса, следовательно никто DES ему ставить не будет.

[Igor73]

Сообщение от alex_md

Мне все равно DES, или не DES. Разница ничтожна - примерно 1% в год. Для меня проблема только в том, что пациента со стентом, особенно DES нужно держать на Плавиксе с аспирином. Поэтому уже год как направляя пациентов к кардиологам я пишу, что пациент НЕ КАНДИДАТ на длительный прием Плавикса, следовательно никто DES ему ставить не будет.

Немного не согласен.
1. "However, until proved otherwise, PCI should be used only with reservation in diabetics with multy-vessel disease and in patients with unprotected LM stenosis. The use of drug-eluting stents might change this situation." В гайде по ТБКА надеятся, что покрытые стенты расширят показания для ТБКА и позволят стентировать не только диабетиков и пациентов с неприкрытым стенозом ПНА, но и другие стенозы. Они дипломатично надеятся. А на самом деле, в реальной жизни, уже как 4-5 лет покрытые стенты ставят направо и налево без чётких обоснований. 90% стентов - это DES. Около 10% - у диабетиков и при unprotected LM stenosis. Просто потому, что потом удобно и красиво показывать пациенту картинки "до" и "после" со словами "Вы были очень больны, а теперь Вы здоровы". Слоган для Cordis and Boston: "каждый последующий третий стент мы установим Вам бесплатно!"
2. Мне кажеться, что эта шумиха вокруг DES очень полезна и позволит более трезво отнестись к установке любых стентов.

[Igor73]

Occluded Artery Trial (OAT – Presented at AHA 2006 )

Year Presented
2006
Year Published
2006
Description
The goal of the trial was to evaluate percutaneous coronary intervention (PCI) compared with medical therapy among stable, high-risk patients with persistent total occlusion of the infarct-related artery post-myocardial infarction (MI).
Hypothesis
A strategy of routine PCI for total occlusion of the infarct-related artery 3-28 days after acute MI would reduce the occurrence of the composite of death, reinfarction, or New York Heart Association (NYHA) class IV heart failure.
Drugs/Procedures Used
Patients with persistent total occlusion of the infarct-related artery 3-28 days post-MI were randomized to PCI with stenting (n = 1,082) or medical therapy (n = 1,084). A core laboratory evaluated the qualifying angiogram.
Concomitant Medications
Aspirin, anticoagulation if indicated, angiotensin-converting enzyme inhibitors, beta-blockers, and lipid-lowering therapy, unless contraindicated
Principal Findings
Intial treatment with thrombolytic therapy was used in 19% of patients within the first 24 hours of the index MI. Median time from MI to randomization was 8 days. PCI was successful in 87% of the PCI cohort. Stents were used in 87% of patients, 8% of which were drug-eluting stents, and glycoprotein IIb/IIIa inhibitors in 72%. PCI was performed in 3% of the medical therapy cohort. Medication use at discharge was similar between the groups, with the exception of thienopyridine use, which was higher in the PCI group.

The primary endpoint of death, reinfarction, or NYHA class IV heart failure occurred in 17.2% of the PCI group and 15.6% of the medical therapy group (hazard ratio [HR] 1.16, p = 0.20). Total reinfarction trended higher in the PCI group (7.0% vs. 5.3%, HR 1.36, p = 0.13), as did nonfatal reinfarction (6.9% vs. 5.0%, HR 1.44, p = 0.08). Repeated elevation of cardiac biomarkers within 48 hours of randomization occurred significantly more frequently in the PCI group (10.0% vs. 3.3%, p < 0.001). There was no difference in the individual endpoints of death (9.1% for PCI vs. 9.4% for medical therapy, p = 0.83) or NYHA class IV heart failure (4.4% vs. 4.5%, p = 0.92) between the treatment groups.
Interpretation
Among stable, high-risk patients with persistent total occlusion of the infarct-related artery post-MI, performance of PCI 3-28 days post-MI was not associated with a difference in the composite of death, reinfarction, or NYHA class IV heart failure through a mean follow-up of 3 years compared with medical therapy.

Despite no reduction in the composite endpoint, PCI was associated with a trend toward higher rates of reinfarction compared with medication therapy. The reinfarctions were not only procedural-related infarcts (i.e., early procedural enzymatic leaks), but true ST elevation reinfarctions that accumulated throughout follow-up. One explanation for the trend toward an increase in reinfarctions with PCI may be embolization resulting in myocardial damage and impaired collateral flow. Presence of persistent total occlusion remains a problem for a sizeable cohort of patients for whom suitable treatment is lacking.

Early reperfusion therapy, the goal of ST elevation MI treatment, with either primary PCI or thrombolysis, is not indicated for patients who present late, often with persistent total occlusion. The present study, the largest randomized trial to date in this population, does not support the hypothesis of late PCI for stable but persistent total occlusion.

[Gilarov]

Наверное успеха не было, т.к. "Stents were used in 87% of patients, 8% of which were drug-eluting stents..." Полный текст в [Ссылки доступны только зарегистрированным пользователям ]


ЗЫ: Что-то наши инвазивные коллеги не спешат высказаться...

[alex_md]

А чего тут высказываться. Вроде и так все понятно. Нестабилку лечить стентами нужно. С этим сейчас спорить никто не будет. Острый инфаркт тоже нужно. Вся шумиха из-за стабильной стенокардии. В США очень силен стенозно-баллонный рефлекс. Многие считают, что НИКАКУЮ ишемию терпеть не нужно. Все также знают, что стенты за редким исключением не лечут заболевание как таковое, а значит не снижают смертность. За то как хорошо они порой лечат СИМПТОМЫ. Пришел ко мне пациент и говорит мол, что не может он 18 лунок в гольф играть, я ему сестамиби, а там небольшая нижняя ишемия. Ему кардиологи стент в RCA, после этого через 3 недели он эти 18 лунок играет как родной. Умрет он и так в 95 лет от Альцгеймера с ишемией со стентами или без, или без, но со стентами он живет счастливее .
Вот только сегодня получил нового пациента: одна неделя после переднего инфаркта слева два Сайфера, справа два Таксуса. One patien randomized trial . Еще для полного счастья нужно было ему BMS в циркумфлекс влепить. Ничего, получил аспирин, плавикс, 80 мг Липитора, зетию. Нужно заметить, что до инфаркта симптомов не было.

[papadoctor]

Не совсем понял траекторию полёта мысли, особенно по поводу гольфера. Поясните плиз!

[alex_md]

Сообщение от papadoctor

Не совсем понял траекторию полёта мысли, особенно по поводу гольфера. Поясните плиз!

Stents treat symptoms, not the disease. They do not decrease morbidity or mortality but for some patients in used wisely improve quality of life (18 holes instead of 9 in this case).

[Igor73]

Видимо, надо просто объяснять пациенту ситуацию, пусть он сам и выбирает. Недавно мой пациент принёс Newsweek с дебатами о DES. Интересно, не приведёт ли научная дисскуссия о стентах к "газетному" резонансу и другой крайности - пациенты начнут отказываться от стентов, когда это действительно нужно? Ведь теперь любой новый стент будет рассматриваться через электронный микроскоп.

[dmblok]

Сообщение от alex_md

Stents treat symptoms, not the disease. They do not decrease morbidity or mortality but for some patients in used wisely improve quality of life (18 holes instead of 9 in this case).

Если, речь не идет о каком-то конкретном случае - это не совсем так. По крайней мере эта фраза:"Stents treat symptoms, not the disease" не вполне соотносится с официальными американскими рекомендациями:

American College of Cardiology Foundation, American Heart Association. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina

Revascularization With PCI (or Other Catheter-Based Techniques) (....)in Patients With Stable Angina

Class I
(....)

Percutaneous coronary intervention (PCI) for patients with two- or three-vessel disease with significant proximal LAD CAD, who have anatomy suitable for catheter-based therapy and normal LV function, and who do not have treated diabetes. (Level of Evidence: B)

Percutaneous coronary intervention or CABG for patients with one- or two-vessel CAD without significant proximal LAD CAD but with a large area of viable myocardium and high-risk criteria on noninvasive testing. (Level of Evidence: B)

Percutaneous coronary intervention or CABG for patients who have not been successfully treated by medical therapy (see guideline text) and can undergo revascularization with acceptable risk. (Level of Evidence: B)
(...)

Class IIa
(...)
Use of PCI or CABG for patients with one- or two-vessel CAD without significant proximal LAD disease but with a moderate area of viable myocardium and demonstrable ischemia on noninvasive testing. (Level of Evidence: B)

Use of PCI or CABG for patients with one-vessel disease with significant proximal LAD disease. (Level of Evidence: B)

Понятно, что доказательность не максимальная. Однако это только 2002 г Существуют несколько больших исследований в которых речь идет именно о влиянии не только на симптомы, но и на прогноз.

PS Европейские рекомендации более консервативные. Однако и в них в случае доказаной обширной ишемии отмечается влияние PCI и на прогноз в том числе.

[Dr.Vad]

А Александр-то прав: нет никаких преимуществ при стабильной ИБС:

Circulation. 2005 Jun 7;111(22):2906-12.
Percutaneous coronary intervention versus conservative therapy in nonacute coronary artery disease: a meta-analysis.Katritsis DG, Ioannidis JP.
Department of Cardiology, Athens Euroclinic, Athens, Greece.

BACKGROUND: Percutaneous coronary intervention (PCI) has been shown to improve symptoms compared with conservative medical treatment in patients with stable coronary artery disease (CAD); however, there is limited evidence on the effect of PCI on the risk of death, myocardial infarction, and subsequent revascularization. Therefore, we performed a meta-analysis of 11 randomized trials comparing PCI to conservative treatment in patients with stable CAD. METHODS AND RESULTS: A total of 2950 patients were included in the meta-analysis (1476 received PCI, and 1474 received conservative treatment). There was no significant difference between the 2 treatment strategies with regard to
mortality 0.94 (0.72 to 1.24) ,
cardiac death or myocardial infarction 1.17 (0.88 to 1.57),
nonfatal myocardial infarction 1.28 (0.94 to 1.75),
CABG 1.03 (0.80 to 1.33),
PCI 1.23 (0.80 to 1.90) during follow-up (the risk ratios (95% CIs) for the PCI versus conservative treatment arms). A possible survival benefit was seen for PCI only in trials of patients who had a relatively recent myocardial infarction (risk ratio 0.40, 95% CI 0.17 to 0.95). Except for PCI during follow-up, there was no significant between-study heterogeneity for any outcome. CONCLUSIONS: In patients with chronic stable CAD, in the absence of a recent myocardial infarction, PCI does not offer any benefit in terms of death, myocardial infarction, or the need for subsequent revascularization compared with conservative medical treatment.

И вот их выводы:

...we conclude that for patients with chronic CAD and good left ventricular function, PCI does not confer any clear benefit in terms of long-term hard clinical outcomes compared with conservative medical treatment... By comparing the benefits, if any, against cost considerations, we believe that many percutaneous interventions that currently are performed in patients with nonacute CAD probably are not justified.

[Dr.Vad]

Японские 3-летние наблюдения тоже указывают на лучшие отдаленные результаты при невмешательствах:

During the 3.4-year follow-up, additional PCI or coronary artery bypass grafting was required in 9.4% of the M group and in 33.2% of the P group. The rates of cardiac death were similar (1.6% in M and 2.6% in P). The overall rate of cardiac death and acute coronary syndrome was 2.1% in M and 4.7% in P, but the difference was not significant. The grade of anginal symptoms 12 months later was well improved in both M (1.6+/-1.4 to 0.6+/-0.9) and P (1.7+/-1.4 to 0.3+/-0.7) and there was no significant difference.

Circ J. 2006 Apr;70(4):365-9.
Outcomes of patients with stable low-risk coronary artery disease receiving medical- and PCI-preceding therapies in Japan: J-SAP study 1-1.

С другой стороны, совсем немного осталось подождать до окончания Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE): A total of 2287 patients have been enrolled, and follow-up will conclude in June 2006 тогда и расставятся все точки над Ё...

[Gilarov]

Сообщение от dmblok

... в них в случае доказаной обширной ишемии ...

А обширная, это сколько? Надо делать КАГ при стабильной стенокардии II ФК? А III ФК?
Вот тема. Гражданина со стабильной стенокардией стентировали. Результат не самый хороший. В исследовании CAST симптомы (экстрасистолия) тоже замечательно убирались, только помирали те, кто без симптомов чаще. А если учесть, сколько это все стоит...