Clinical research study
Late Thrombosis of Drug-Eluting Stents: A Meta-Analysis of Randomized Clinical Trials

This manuscript was presented at the 78th Annual American Heart Association Scientific Sessions, Dallas, Tex, November 16, 2005.
https://doi.org/10.1016/j.amjmed.2006.01.023Get rights and content

Abstract

Purpose

Drug-eluting stents are commonly used for percutaneous coronary intervention. Despite excellent clinical efficacy, the association between drug-eluting stents and the risk for late thrombosis remains imprecisely defined.

Methods

We performed a meta-analysis on 14 contemporary clinical trials that randomized 6675 patients to drug-eluting stents (paclitaxel or sirolimus) compared with bare metal stents. Eight of these trials have reported more than a year of clinical follow-up.

Results

The incidence of very late thrombosis (>1 year after the index procedure) was 5.0 events per 1000 drug-eluting stent patients, with no events in bare metal stent patients (risk ratio [RR] = 5.02, 95% confidence interval [CI], 1.29 to 19.52, P = .02). Among sirolimus trials, the incidence of very late thrombosis was 3.6 events per 1000 sirolimus stent patients, with no events in bare metal stent patients (RR = 3.99, 95% CI, .45 to 35.62, P = .22). The median time of late sirolimus stent thrombosis was 15.5 months, whereas with bare metal stents it was 4 months. Among paclitaxel trials, the incidence of very late thrombosis was 5.9 events per 1000 paclitaxel stent patients, with no events in bare metal stent patients (RR = 5.72, 95% CI, 1.08 to 32.45, P = .049). The median time of late paclitaxel stent thrombosis was 18 months, whereas it was 3.5 months in bare metal stent patients.

Conclusions

Although the incidence of very late stent thrombosis more than 1 year after coronary revascularization is low, drug-eluting stents appear to increase the risk for late thrombosis. Although more of this risk was seen with paclitaxel stents, it remains possible that sirolimus stents similarly increase the risk for late thrombosis compared with bare metal stents.

Section snippets

Literature Review

We searched the MEDLINE and Cochrane databases for randomized clinical trials in English language from 2000 to 2005 using the Medical Subject Heading terms “Angioplasty, Transluminal, Percutaneous Coronary”, “Stents”, “Paclitaxel”, “Sirolimus” and “Thrombosis.” We also hand-searched relevant journals, obtained recently presented data at cardiology conferences (scientificsessions.americanheart.org, www.acc.org, and www.tctmd.com), corresponded with authors and experts in the field, and used the

Duration of Dual AntiPlatelet Therapy and Duration of Clinical Follow-Up

In all, there were 14 studies with 6675 total patients included for analysis. There were 9 sirolimus trials, largely represented by the SIRIUS and RAVEL Trials (Table 1),9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 and 5 paclitaxel trials represented by the TAXUS Trials (Table 2).23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 Most of the sirolimus trials mandated aspirin and clopidogrel for 2 to 3 months, except for the Pache et al Trial21 and the DIABETES Trial,20 which required 6 and 12

Discussion

In this analysis of 14 studies in over 6000 patients, the incidence of early thrombosis was similar between drug-eluting stents and bare metal stents. Increased risk with drug-eluting stents was suggested as early as 1 month after revascularization; however, more than 6 to 12 months after the procedure there was a 4- to 5-fold excess of drug-eluting stent thrombosis compared with bare metal stents. The time until late thrombosis was equally protracted for both sirolimus and paclitaxel stents,

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