Drug-eluting stents: Do the outcomes justify their use?
MedWire - AHA (Orlando, Florida, USA), November 4, 2007: This session on the second day of the American Heart Association Congress focused on controversies in clinical cardiology, with speakers arguing for and against the motion. The highlight was a debate on the value of drug-eluting stents (DES), which is summarized below.
Yes
Gregg Stone, Columbia University Medical Center, New York, NY, USA
Dr. Stone spoke in favor of DES, which he described as a “transforming technology” in view of their proven ability to reduce restenosis compared with bare-metal stents (BMS). “It is a misconception that restenosis is benign,” he commented. “Restenosis negatively impacts quality of life and leads to symptoms as well as to repeat angioplasty and acute coronary syndromes (ACS) in a substantial number of patients.”
The “flipside” of the benefit of DES on restenosis is the risk of late stent thrombosis, which can be a devastating and even fatal complication in a “really small minority” of patients. However, he stressed that this risk needs to be put into perspective.
Dr. Stone then reviewed the data that triggered concerns about the safety of DES, much of which was presented at the annual European Society of Cardiology (ESC) congress in Barcelona, Spain, in 2006. In an episode dubbed the “ESC firestorm”, Salim Yusuf told ESC delegates that widespread use of DES is “an epidemic of madness”. DES use has since markedly declined in Europe and Canada.
At today’s session, Dr. Stone said that the studies presented at the ESC 2006 were methodologically flawed. Two of the meta-analyses used data from abstracts and the internet rather than primary sources and had never been subjected to peer review. Another study was retracted following publication, while another failed to adjust fully for potential confounders.
In December 2006, the US Food and Drug Administration reviewed the most robust available data, including registry studies and updated meta-analyses. The panel concluded that DES are not associated with an increased risk of death or myocardial infarction (MI) when used according to the labeled indication.
Dr. Stone then showed an assortment of new registry data, much of which was presented at the recent Transcatheter Cardiovascular Therapeutics 2007 meeting in Washington DC. These studies consistently found that DES are associated with a lower risk of mortality/MI when compared with BMS, as well as confirming their marked superiority in preventing restenosis.
“These findings still need to be confirmed in prospective randomized controlled trials,” Dr. Stone admitted. “Three such studies are currently underway.”
No
Salim Yusuf, McMaster University, Hamilton, ON, Canada
Dr. Yusuf was billed as the antagonist in the debate over whether or not outcomes justify the use of DES. However, he said the debate was “irrelevant” as it failed to address a “more important question”, namely, whether routine percutaneous intervention (and all its associated paraphernalia) justifies the widespread use of stents in stable and unstable coronary artery disease (CAD). “The real issue is what is good for patients and society, not what makes doctors feel good,” he said.
Instead of arguing against the use of DES, Dr. Yusuf discussed the broader question of how best to manage CAD. He said there were four main reasons for using any medical therapy: To improve survival; to reduce morbidity; to improve symptoms and quality of life; and/or to reduce costs.
In patients with CAD, angioplasty of the culprit lesion is of proven value in two settings: ST-elevation MI (in place of thrombolytics) to reduce mortality, stroke, and probably reinfarction; and in high-risk non-ST-elevation ACS to reduce new MI and avoid repeated rehospitalization for unstable angina. “In both these acute conditions, timely PCI in selected patients is an important advance,” Dr. Yusuf stated.
The problem, according to Dr. Yusuf, is that PCI is now routinely performed outside these two acute settings. In the United States, the use of PCI increased by 5,946% between 1987 and 2004, compared with a rise of 102% in coronary artery bypass surgery. “In 2005 over one million PCIs were performed,” he said. “Most of these were in patients with stable CAD.”
Dr. Yusuf said that neither epidemiology nor pathophysiology support the use of PCI in stable disease. Post-mortem studies show that most MIs originate from non-critical lesions that would not be considered suitable for stenting. Atherosclerosis is generalized, even when only one lesion is apparent on an angiogram. Furthermore, dilating a lesion - akin to “crushing” it - is not physiologic and can destabilize the lesion. Indeed, he said that stents actually worsen endothelial vascular dysfunction.
Since PCI is associated with both short- and long-term risks, these must be weighed against the small increased risk associated with stable angina. Studies comparing PCI with medical therapy in stable disease have found that the approaches are equivalent for reducing the risk of death and MI, but that PCI has much higher costs. In addition, stents have not been shown to reduce angina, improve quality of life, or prevent CABG. DES definitely reduces the rate of angiographic restenosis but this is merely a surrogate endpoint, and Dr. Yusuf warned against formulating clinical practice around surrogates.
“The overall cost of PCI plus DES plus prolonged dual antiplatelet therapy (possibly plus intravascular ultrasound to enhance stent deployment) is astronomical compared to initial medical therapy - but with little clinical gain,” Dr. Yusuf stated. “Prolonged antiplatelet therapy is also associated with an increased risk of bleeding, of a magnitude associated with warfarin therapy.”
Accordingly, he proposed that patients with stable CAD should be treated with medical therapy in the first instance, and that PCI and stenting should be reserved for those who remain symptomatic on maximal medical therapy. If stents are used, there is no evidence that DES offer clinical benefits over BMS, while they are undoubtedly associated with increased costs.
Dr. Yusuf ended by calling for patients with stable CAD to be managed with evidence-based pharmacologic therapy and lifestyle modification, and for a more selective use of PCI and stenting. “We are being seduced by technology,” he concluded. “We need to close down 50% of cath labs and retrain interventional cardiologists in the use of drugs and lifestyle modification.”
MedWire - AHA (Orlando, Florida, USA), November 4, 2007: This session on the second day of the American Heart Association Congress focused on controversies in clinical cardiology, with speakers arguing for and against the motion. The highlight was a debate on the value of drug-eluting stents (DES), which is summarized below.
Yes
Gregg Stone, Columbia University Medical Center, New York, NY, USA
Dr. Stone spoke in favor of DES, which he described as a “transforming technology” in view of their proven ability to reduce restenosis compared with bare-metal stents (BMS). “It is a misconception that restenosis is benign,” he commented. “Restenosis negatively impacts quality of life and leads to symptoms as well as to repeat angioplasty and acute coronary syndromes (ACS) in a substantial number of patients.”
The “flipside” of the benefit of DES on restenosis is the risk of late stent thrombosis, which can be a devastating and even fatal complication in a “really small minority” of patients. However, he stressed that this risk needs to be put into perspective.
Dr. Stone then reviewed the data that triggered concerns about the safety of DES, much of which was presented at the annual European Society of Cardiology (ESC) congress in Barcelona, Spain, in 2006. In an episode dubbed the “ESC firestorm”, Salim Yusuf told ESC delegates that widespread use of DES is “an epidemic of madness”. DES use has since markedly declined in Europe and Canada.
At today’s session, Dr. Stone said that the studies presented at the ESC 2006 were methodologically flawed. Two of the meta-analyses used data from abstracts and the internet rather than primary sources and had never been subjected to peer review. Another study was retracted following publication, while another failed to adjust fully for potential confounders.
In December 2006, the US Food and Drug Administration reviewed the most robust available data, including registry studies and updated meta-analyses. The panel concluded that DES are not associated with an increased risk of death or myocardial infarction (MI) when used according to the labeled indication.
Dr. Stone then showed an assortment of new registry data, much of which was presented at the recent Transcatheter Cardiovascular Therapeutics 2007 meeting in Washington DC. These studies consistently found that DES are associated with a lower risk of mortality/MI when compared with BMS, as well as confirming their marked superiority in preventing restenosis.
“These findings still need to be confirmed in prospective randomized controlled trials,” Dr. Stone admitted. “Three such studies are currently underway.”
No
Salim Yusuf, McMaster University, Hamilton, ON, Canada
Dr. Yusuf was billed as the antagonist in the debate over whether or not outcomes justify the use of DES. However, he said the debate was “irrelevant” as it failed to address a “more important question”, namely, whether routine percutaneous intervention (and all its associated paraphernalia) justifies the widespread use of stents in stable and unstable coronary artery disease (CAD). “The real issue is what is good for patients and society, not what makes doctors feel good,” he said.
Instead of arguing against the use of DES, Dr. Yusuf discussed the broader question of how best to manage CAD. He said there were four main reasons for using any medical therapy: To improve survival; to reduce morbidity; to improve symptoms and quality of life; and/or to reduce costs.
In patients with CAD, angioplasty of the culprit lesion is of proven value in two settings: ST-elevation MI (in place of thrombolytics) to reduce mortality, stroke, and probably reinfarction; and in high-risk non-ST-elevation ACS to reduce new MI and avoid repeated rehospitalization for unstable angina. “In both these acute conditions, timely PCI in selected patients is an important advance,” Dr. Yusuf stated.
The problem, according to Dr. Yusuf, is that PCI is now routinely performed outside these two acute settings. In the United States, the use of PCI increased by 5,946% between 1987 and 2004, compared with a rise of 102% in coronary artery bypass surgery. “In 2005 over one million PCIs were performed,” he said. “Most of these were in patients with stable CAD.”
Dr. Yusuf said that neither epidemiology nor pathophysiology support the use of PCI in stable disease. Post-mortem studies show that most MIs originate from non-critical lesions that would not be considered suitable for stenting. Atherosclerosis is generalized, even when only one lesion is apparent on an angiogram. Furthermore, dilating a lesion - akin to “crushing” it - is not physiologic and can destabilize the lesion. Indeed, he said that stents actually worsen endothelial vascular dysfunction.
Since PCI is associated with both short- and long-term risks, these must be weighed against the small increased risk associated with stable angina. Studies comparing PCI with medical therapy in stable disease have found that the approaches are equivalent for reducing the risk of death and MI, but that PCI has much higher costs. In addition, stents have not been shown to reduce angina, improve quality of life, or prevent CABG. DES definitely reduces the rate of angiographic restenosis but this is merely a surrogate endpoint, and Dr. Yusuf warned against formulating clinical practice around surrogates.
“The overall cost of PCI plus DES plus prolonged dual antiplatelet therapy (possibly plus intravascular ultrasound to enhance stent deployment) is astronomical compared to initial medical therapy - but with little clinical gain,” Dr. Yusuf stated. “Prolonged antiplatelet therapy is also associated with an increased risk of bleeding, of a magnitude associated with warfarin therapy.”
Accordingly, he proposed that patients with stable CAD should be treated with medical therapy in the first instance, and that PCI and stenting should be reserved for those who remain symptomatic on maximal medical therapy. If stents are used, there is no evidence that DES offer clinical benefits over BMS, while they are undoubtedly associated with increased costs.
Dr. Yusuf ended by calling for patients with stable CAD to be managed with evidence-based pharmacologic therapy and lifestyle modification, and for a more selective use of PCI and stenting. “We are being seduced by technology,” he concluded. “We need to close down 50% of cath labs and retrain interventional cardiologists in the use of drugs and lifestyle modification.”
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