Drug-Eluting Stents – NOT SO BENEFICIAL (NOT SO CONFUSING) [an FDA Failure!] – Stardate: March 2nd, 2007; 04:50 am

Animation of Stents In Revascularization(unblocking) of Arterial Stenosis.

 

Drug-eluting stents have been extolled as the life saving means to permanently unblock stenosed arteries as compared to bare-metal stents.

for the layman:
Drug-eluting stents will help your heart problem and more likely prevent further problems for your heart in the future as compared to Bear-Metal(without drugs) stents.

CONCLUSION – FALSE

 

ELABORATION: Recent Studies(see below) have shown at least efficacious results of both stents and possibly a detrimental effect of the drug-eluting stents as compared to the bare-metal stents.

SIGNIFGANCE:
The cost of a Drug-eluting stent is at least double the cost of a bare-metal stent. When this does not offer any benefit to the patient, and possibly poses a risk, it is of tremendous questionable value to use it. This has substantial politico-economical meaning when one looks at the amount of tax dollars spent to give every citizen a drug-eluting stent instead of the the bare-metal stents; How much money have we flushed down the drain?

BASIS: The following articles have been presented in the New England Journal of Medicine detailing the results of various clinical trials. The following is an overview of the studies:

A Pooled Analysis of Data Comparing Sirolimus-Eluting Stents with Bare-Metal Stents

sample size: pooled analysis of 1748 patients in four randomized trials evaluating the safety of sirolimus-eluting stents as compared with bare-metal stents.

total sample size: 1748

Conclusions: In a pooled analysis of data from four trials comparing sirolimus-eluting stents and bare-metal stents, no significant differences were found between the two treatments in rates of death, myocardial infarction, or stent thrombosis.

ClinicalTrials.gov numbers: NCT00233805, NCT00381420, NCT00232765, and NCT00235144
pubmed: 10.1056/NEJMoa066633

Safety and Efficacy of Sirolimus- and Paclitaxel-Eluting Coronary Stents

sample size: a pooled analysis of data from four double-blind trials in which 1748 patients were randomly assigned to receive either sirolimus-eluting stents or bare-metal stents and five double-blind trials in which 3513 patients were randomly assigned to receive either paclitaxel-eluting stents or bare-metal stents.

total sample size: 5261

Conclusions: Stent thrombosis after 1 year was more common with both sirolimus-eluting stents and paclitaxel-eluting stents than with bare-metal stents. Both drug-eluting stents were associated with a marked reduction in target-lesion revascularization. There were no significant differences in the cumulative rates of death or myocardial infarction at 4 years.

pubmed: 10.1056/NEJMoa067193

Stent Thrombosis in Randomized Clinical Trials of Drug-Eluting Stents

sample size: a hierarchical classification of stent thrombosis set by the Academic Research Consortium (ARC) across randomized trials involving 878 patients treated with sirolimus-eluting stents, 1400 treated with paclitaxel-eluting stents, and 2267 treated with bare-metal stents.

total sample size: 3145

Conclusions: The incidence of stent thrombosis did not differ significantly between patients with drug-eluting stents and those with bare-metal stents in randomized clinical trials, although the power to detect small differences in rates was limited.

pubmed: 10.1056/NEJMoa067731

Long-Term Outcomes with Drug-Eluting Stents versus Bare-Metal Stents in Sweden

sample size: 6033 patients treated with drug-eluting stents and 13,738 patients treated with bare-metal stents

total sample size: 19771

Conclusions: Drug-eluting stents were associated with an increased rate of death, as compared with bare-metal stents. This trend appeared after 6 months, when the risk of death was 0.5 percentage point higher and a composite of death or myocardial infarction was 0.5 to 1.0 percentage point higher per year. The long-term safety of drug-eluting stents needs to be ascertained in large, randomized trials.

pubmed: 10.1056/NEJMoa067722

Analysis of 14 Trials Comparing Sirolimus-Eluting Stents with Bare-Metal Stents

sample size: an analysis of individual data on 4958 patients enrolled in 14 randomized trials comparing sirolimus-eluting stents with bare-metal stents

total sample size: 4958

Conclusions: The use of sirolimus-eluting stents does not have a significant effect on overall long-term survival and survival free of myocardial infarction, as compared with bare-metal stents. There is a sustained reduction in the need for reintervention after the use of sirolimus-eluting stents. The risk of stent thrombosis is at least as great as that seen with bare-metal stents.

pubmed: 10.1056/NEJMoa067484


Excerpts taken from:

Stent Thrombosis Redux — The FDA Perspective

…”Both drug-eluting stents approved by the FDA (Cordis’s Cypher stent, approved in 2003, and Boston Scientific’s Taxus stent, approved in 2004) were shown to be effective in reducing repeated-revascularization rates, as compared with bare-metal stents. Moreover, there appeared to be no safety disadvantage: studies showed no increase in the rates of stent thrombosis, death, or myocardial infarction up to 1 year after implantation. Drugeluting stents were therefore enthusiastically adopted in the United States and were soon used in approximately 80% of percutaneous coronary interventions.

Given this widespread use, it should be noted that the FDA approved indications were limited to newly diagnosed coronary lesions, less than 28 to 30 mm long, in clinically stable patients without additional serious medical conditions. As a condition of approval, and in anticipation of U.S. usage patterns, the FDA required both manufacturers to follow patients in their original clinical trials for 5 years after implantation and to conduct registry studies of consecutively enrolled new patients to collect data on “real-world” use.”

…”Another study showed that stent thromboses occurred at a rate of 0.6% per year between 30 days and 3 years after implantation. These studies received wide attention, prompting the FDA to convene an advisory panel meeting to review the data.

The panel meeting focused on safety issues and the use of dual antiplatelet therapy. The discussions covered both on-label and off-label use of drug-eluting stents, since it is estimated that more than 60% of use is off-label — for example, the stents are implanted in types of lesions that were excluded from the pivotal trials or in patients such as those with diabetes who were not sufficiently represented in the trial populations for a specific labeled indication.

The panel agreed, and the FDA concurs, that when drug-eluting stents are used for their approved indications, the risk of thrombosis does not outweigh their advantages over bare-metal stents in reducing the rate of repeated revascularization. But the panel also concluded that, as compared with on-label use, off-label use is associated with increased risks of both early and late stent thrombosis, as well as death or myocardial infarction.”


Concluding Inferences and Implications

The above suggests, despite the laying down of guidelines, the guidelines were not appropriate; Perhaps they were not appropriately determined or they were not appropriately implemented. This is evidenced by the fact that approximately 60% of the 80% drug-eluting stents of all implanted stents since 2003 have been of off-label use. I wonder how the FDA has allowed this situation to occur and as a result, how many people have spent at least twice the cost to have an inadvertent time bomb inserted into them. The failure of the FDA to label patients with diabetes(who are more prone to heart disease and therefore more likely to have been stented) as an off-label demonstrates their inadequate inquiry into the safety disadvantages and reciprocally, the benefits, of using drug-eluting stents.

A tremendous financial loss of tax dollars has been incurred by wide-spread adoption of an intervention prematurely. The mistake of incorrectly recommended\used stents results in unnecessary morbidity and mortality.

This case expounds the need to evaluate the FDA’s approval process of new drugs and interventions. In the recent past, the FDA also failed patients in the inappropriate approval of pharmacological agents rofecoxib (Vioxx), celecoxib (Celebrex), valdecoxib (Bextra), and parecoxib (Dynastat), for the relief of pain, leading to a directly linked number of acute myocardial infarctions (heart attacks).

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2 Responses

  1. it’s true , many studies should be taken with a pinch of salt . many samples comparing 2 new products aren’t taken under similar conditions .for eg ,different stents or drugs like aspirin vs clopidogrel were compared in a previous era had patients never taking statins as compared to now where it is umbiquitous .

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