Wheel of Reason Activity: Analyze the Logic of Drug-Eluting versus Bare Metal Stents for the Treatment of Coronary Artery Stenosis

Drug-Eluting versus Bare Metal Stents for the Treatment of Coronary Artery Stenosis

Background Information: Two drug-eluting stents were approved by the FDA in 2003 for use in patients with coronary artery disease. Before drug-eluting stents were available, bare metal stents were used to correct for coronary artery stenosis. By the end of 2004, drug-eluting stents were used in nearly 80% of patients. Initial approval of the two drug-eluting stents was based on the results of randomized, controlled trials that showed superiority of drug-eluting stents over bare metal stents up to 1 year after implantation. Shortly after drug-eluting stents were approved, reports of late stent thrombosis began to appear. This complication can lead to restenosis, which may result in myocardial infarction or even death.

In 2006, the results of a large study suggested that between 7 and 18 months after implantation, the rates of nonfatal myocardial infarction, death from cardiac causes, and angiographically documented stent thrombosis were higher with drug-eluting stents than with bare metal stents. Over the next 6 months, the two manufacturers of the drug-eluting stents issued 19 press releases touting the effectiveness of their devices and never mentioned the potential risk of late thrombosis. Other studies presented conflicting results, some showing an increased risk of death or myocardial infarction with drug- eluting stents and others showing no difference in mortality between patients with drug-eluting stents and bare metal stents.

Upon further investigation into these studies, two important factors emerged as possible explanations for the conflicting results including differences in the characteristics of patients and coronary lesions. Drug-eluting stents were approved for use in patients with newly diagnosed coronary lesions and without additional serious medical conditions, like those studied in the clinical trials that led to FDA approval. However, since FDA approval was granted, more than 60% of drug-eluting stents have been implanted in patients with complex conditions (such as multi-vessel disease or acute myocardial infarction) or with complex lesions. These should be considered as off-label use.

On-label use of drug-eluting stents is associated with a persistent, long-term (>3year) reduction in the need for repeated revascularization (another stent, angioplasty, or clot dissolving therapy), without increasing the rates of mortality or myocardial infarction. Therefore, the risk of thrombosis associated with drug-eluting stents does not outweigh their advantages over bear metal stents in reducing the rate of repeated revascularization procedures.

On the other hand, off-label use of drug-eluting stents is associated with increased risk of both early and late stent thrombosis, as well as death and myocardial infarction. For this reason, patients who receive drug-eluting stents should be placed on extended (at least 12 months) antiplatelet therapy as an added measure of protection against stent thrombosis. More studies are needed to determine if extended antiplatelet therapy will improve the overall outcome of drug-eluting stents in patients with multi-vessel disease or concomitant serious medical conditions.

(* Adapted from two articles that appeared in the New England Journal of Medicine, March 2007, pages 981-987)

Use this template for working through the text now:

Specimen answers will become visible once your answers are submitted.

Specimen Answer:

The main purpose of this article is:

To address the safety and efficacy of drug eluting stents (in comparison with bare metal stents) in the treatment of coronary artery disease; to illuminate why drug eluting stents (though superior to BMS) may lead to thrombosis in patients with coronary artery disease; to suggest a practical intervention strategy which will reduce risk in complex cases.

The key question the author is addressing is:

What are the actual risks in using DES and how can they be minimized?

The most important information in this article is:

1. “Initial approval of the two drug-eluting stents was based on the results of randomized, controlled trials that showed superiority of drug-eluting stents over bare metal stents up to 1 year after implantation.”

2. “By the end of 2004, drug-eluting stents were used in 80% of patients.”

3. After FDA approval, a large study indicated that the rates of MI, death from cardiac causes, and stent thrombosis were higher with drug-eluting stents.

4. Other studies suggested that long-term mortality did not differ between
drug-eluting and bare metal stents.

5. Late thrombosis in patients with DES occurs primarily in patients with complicated lesions.

6. “On-label use of drug-eluting stents is associated with persistent, long-term reduction in the need for repeated revascularization...without increasing the rates of mortality or myocardial infarction.”

The main inferences or conclusions the author has come to, as represented in this article, are:

1. Drug eluting stents are superior to bare metal stents in stable patients with non-complex coronary lesions.

2. Differences in types of patients in the randomized trials and post-FDA approval studies may explain the conflicting results. The latter group tended to have more advanced and more complex disease.

3. The use of stents off label (e.g., in patients with complex conditions such as multi-vessel disease) affects the performance of drug-eluting stents.

4. The risk of thrombosis associated with drug-eluting stents does not outweigh their advantages over bare metal stents in reducing the rates of repeated revascularization procedures.

The key concept(s) we need to understand in this article is (are):

1. Drug-eluting stents

2. Bare metal stents

3. Coronary artery disease (CAD)

4. Thrombosis

5. Anti-platelet therapy

The main assumption(s) underlying the author's thinking is:

1. Clinical professionals need to take into account the overall health of a patient before deciding on treatment options.

2. When we identify problems in treatment options, we should use search out the underlying causes..

3. The only real options for effectively treating coronary artery stenosis is through using drug-eluting or bare metal stents.

4. Antiplatelet therapy is generally useful in reducing risk of stent thrombosis.

5. Medical treatments should be used in accordance with their FDA approval.

If we accept this line of reasoning (completely or partially), some important implications are:
If we fail to accept this line of reasoning, some important implications are:

1. If I accept the logic of the author, I will most likely use drug-eluted stents in patients with coronary artery disease, but will combine it with antiplatelet therapy as a precautionary measure (especially in complex cases). I will also realize that more studies are needed to determine whether the combined DES/antiplatelet therapy adequately protects against stent thrombosis.

2. If I choose not to accept the argument or if I believe that the question has not been adequately addressed, I may seek additional information about this issue, or I might use drug-eluted stents without the antiplatelet therapy (which may cause serious problems in complex coronary cases), or I might decide to use bare metal stents instead, which have their own set of implications.

The main point(s) of view presented in this article is (are):

1. The author is looking at the research on drug-eluted stents as pointing to the need for an intervening (antiplatelet) therapy for maximizing efficacy and minimizing risk (especially in complex cases). The author is also seeing the need for further research on the question of whether antiplatelet intervention can in fact significantly reduce negative effects of drug-eluted stents.