BASKET-LATE: Late Clinical Events Related to Late Stent Thrombosis After Stopping Clopidogrel: Drug-Eluting vs Bare-Metal Stenting

Luis Gruberg, MD, FACC

Disclosures

July 20, 2006

Editorial Collaboration

Medscape &

"The results of this small study and the conclusions reached by the authors are certainly a cause for concern."

Presenter: Matthias E. Pfisterer, MD (University Hospital Basel, Switzerland), for the BASKET-LATE Investigators

Subacute and late stent thrombosis are rare but feared complications following percutaneous coronary intervention. Whereas acute stent thrombosis usually occurs while the patient is still in the hospital and is quite dramatic, subacute and late stent thrombosis usually occur after the patient has been discharged home. Therefore, rapid restoration of normal coronary blood flow is often not possible, and the patient may sustain an acute myocardial infarction, which confers a high risk of mortality.

Because of the growing concern that delayed endothelialization after implantation of a drug-eluting stent (DES) may cause late stent thrombosis, prolonged dual antiplatelet therapy is currently recommended for at least 3 months after sirolimus-eluting stent placement and 6 months after paclitaxel-eluting stent placement.

The BAsel Stent Kosten Effektivitäts Trial - LAte Thrombotic Events (BASKET-LATE)[1] trial was conducted to determine the incidence of late clinical events (> 6 months following intervention) related to stent thrombosis in patients treated with DES vs bare-metal stent (BMS) after patients discontinued clopidogrel therapy. The study was also designed to identify the predictors, timing, and outcome of such thrombotic events in relation to type of implanted stent.

Study Design

Between May 2003 and May 2004, patients treated with percutaneous coronary intervention and stenting were enrolled in the BASKET[2] trial and randomized in a 2:1 fashion to receive DES or BMS. Patients who remained event-free at 6-month follow-up were subsequently enrolled in the BASKET-LATE trial. Patients were followed for an additional 12 months to determine the incidence of cardiac death or nonfatal myocardial infarction (MI) (primary endpoint) and clinically driven restenosis-related target vessel revascularization. Dual antiplatelet therapy was administered for 6 months in all patients regardless of stent type, and clopidogrel was discontinued in all patients after 6 months.

Results

In the BASKET trial, a total of 826 patients were randomized in a 2:1 fashion to receive either DES (n = 545) or BMS (n = 281). From this cohort, BASKET-LATE included 502 patients treated with DES (data are available for 499 patients) and 244 patients treated with BMS. Baseline clinical and lesion characteristics are shown in Table 1.

Table 1. BASKET-LATE: Baseline Characteristics
DES
(n = 499)
BMS
(n = 244)
Age (yrs) 63 64
Male gender (%) 79 79
Diabetes (%) 18 17
Hypercholesterolemia (%) 77 77
Hypertension (%) 67 66
Current smoker (%) 28 27
S/P MI (%) 27 28
S/P PCI (%) 16 17
S/P CABG (%) 12 13
Unstable angina (%) 37 37
ST-elevation MI (%) 21 21
Stable angina (%) 42 42
Culprit vessel (%)
LAD 51 52
LCx 31 31
RCA 35 35
Bypass graft (%) 5 6
GP IIb/IIIa inhibitors (%) 26 26
Stents/patient (%) 1.5 ± 0.7 1.5 ± 0.7
BMS = bare-metal stent; CABG = coronary artery bypass graft; DES = drug-eluting stent; GP = glycoprotein; LAD = left anterior descending; LCx = left circumflex; MI = myocardial infarction; RCA = right coronary artery; S/P = status-post

The rates of nonfatal MI and cardiac death/nonfatal MI during 7-18 months of follow-up were significantly higher in the DES group than in the BMS group; however, the overall rate of major adverse cardiac events did not differ between the 2 groups (Figure 1).

Figure 1. BASKET-LATE: major cardiac events during 7- to 18-month follow-up.

Angiographically documented thrombosis rates were also similar between the 2 groups (Figure 2). Cardiac death, nonfatal MI, and the combined endpoint of cardiac death and MI were more frequently related to late stent thrombosis (Figure 3). These events occurred at a median of 116 (range, 15-362) days after stopping clopidogrel. By multivariate analysis, prior MI (odds ratio [OR] 3.0, P < .007), need for glycoprotein IIb/IIIa inhibitor use (OR 3.4, P < .003), and DES (OR 3.9, P < .03) were independent predictors of late cardiac death/nonfatal MI.

Figure 2. BASKET-LATE: rate of late-stent thrombosis.
Figure 3. BASKET-LATE: outcomes related to late-stent thrombosis.
Conclusions
  1. After clopidogrel discontinuation, late-stent thrombosis-related events:

    • were 2-3 times more frequent among those who had received DES than among those who had received BMS;

    • carried 4 times higher risk of cardiac death/MI vs non-thrombosis-related events;

    • occurred up to 1 year after clopidogrel discontinuation; and

    • were more frequent in patients with prior MI, those who needed glycoprotein IIb/IIIa inhibitors initially, or those who had received DES.

  2. From these results, the authors calculated that real-world DES use in 100 patients avoids 5 target vessel revascularization events at 6 months but leads to 3.3 late deaths or MI.

Viewpoint

The results of this small study and the conclusions reached by the authors are certainly a cause for concern. As has been demonstrated by previous studies, the rate of late stent thrombosis after DES implantation was not significantly higher than the rate associated with BMS, but, nevertheless, the consequences are dire.

What I find especially troublesome is the fact that we cannot predict with certainty which patients are prone to develop late stent thrombosis and when stent thrombosis is likely to occur -- the latter of which is extremely variable in relation to clopidogrel discontinuation. I am not completely convinced that we should advise all patients treated with a DES to continue dual antiplatelet therapy indefinitely, especially when considering high costs and the potential for bleeding complications. This issue generated plenty of debate at the ACC meeting and is far from being resolved.

References
  1. Pfisterer ME, Kaiser CA, Bader F, Brunner-La Rocca HP, Bonetti PO, Buser PT. Late clinical events related to late stent thrombosis after stopping clopidogrel: prospective randomized comparison between drug-eluting versus bare-metal stenting. Program and abstracts from the American College of Cardiology 55th Annual Scientific Session; March 11-14, 2006; Atlanta, Georgia. Abstract 422-11.

  2. Kaiser C, Brunner-La Rocca HP, Buser PT, et al; BASKET Investigators. Incremental cost-effectiveness of drug-eluting stents compared with a third-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitats Trial (BASKET). Lancet. 2005;366:921-929.

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