Late acute thrombotic occlusion after endovascular brachytherapy and stenting of femoropopliteal arteries

the importance of appropriate placebo controls in evaluating novel therapies in improving angina pectoris. DM

teal arteries and the optimal duration of anti-platelet therapy is probably a year or even longer. DM

Late Acute Thrombotic Occlusion after Endovascular Brachytherapy and Stenting of Femoropopliteal Arteries

Early and Late Effects of Clopidogrel in Patients With Acute Coronary Syndromes

Bonvini R, Baumgartner I, Do DD, et al. J Am Coll Cardiol 2003; 41:409 –12.

Yusuf S, Mehta SR, Zhao F, et al., on Behalf of the CURE (Clopidogrel in Unstable angina to prevent Recurrent Events) Trial Investigators. Circulation 2003;107:966 –72.

Study Question: The authors sought to evaluate the incidence of late acute thrombotic occlusion after endovascular brachytherapy (EVBT) and intravascular stenting of the femoropopliteal arteries. Methods: The study design was a preliminary subgroup analysis of a randomized clinical trial in which patients were randomized to undergo EVBT (iridium 192; 14 Gy at a depth of the radius of the vessel ⫹2 mm) after percutaneous recanalization of femoropopliteal obstructions. Of the 204 patients who completed the 6 months follow-up, 94 were randomized to EVBT. The primary end point of the trial was to quantify the incidence of binary (⬎50%) restenosis at 6 months follow-up. Late acute thrombotic occlusion (LATO) was defined as an acute occlusion of the dilated vascular segment occurring beyond the 3 months follow-up in a patient without any evidence of progression or restenosis at the preceding duplex scanning. Results: Late acute thrombotic occlusion occurred exclusively in six of 22 patients (27%) receiving EVBT after intravascular stenting and always in conjunction with reduction of antithrombotic drug therapy (clopidogrel). Conversely, none of the 13 patients with stents and without EVBT (0%; p⬍0.05) and none of the 72 patients (0%; p⬍0.01) undergoing EVBT after simple balloon angioplasty presented with LATO. Conclusions: The investigators concluded that late thrombotic occlusion occurs not only in patients undergoing EVBT after percutaneous coronary intervention but also after stenting of the femoropopliteal arteries and may compromise the benefits of endovascular radiation. The fact that all cases with LATO occurred concomitantly with stopping clopidogrel may indicate a possible rebound mechanism. The authors’ suggest that intensive and prolonged antithrombotic prevention may be indicated in patients undergoing EVBT and concomitant stenting of peripheral arteries. Perspective: This preliminary analysis of a randomized multicenter trial shows that clinical benefit of brachytherapy may be attenuated by the occurrence of LATO in patients treated by stenting in the peripheral circulation. In this study, late thrombosis occurred only in patients after stopping clopidogrel and suggests that optimal duration of dual antiplatelet therapy after brachytherapy should be longer than the currently recommended 6 months. This study has significant clinical implications in that concomitant stenting should be avoided with brachytherapy in femoropopli-

Study Question: The investigators examined the benefits and risks associated with the use of adding clopidogrel to aspirin within the first 30 days and later (31 days to 12 months) in patients with acute coronary syndromes (ACS). Methods: The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) Trial was a randomized, doubleblind placebo-controlled trial that compared clopidogrel with placebo in patients with ACS, who presented to a hospital within 24 hours. A total of 12,562 ACS patients were randomized to receive clopidogrel (300 mg initially followed by 75 mg/d) or placebo for 3–12 months. The present study explores the rapidity with which treatment was effective and its sustainability over 1 year. Results: The proportion of patients experiencing cardiovascular death, myocardial infarction or strokes (primary outcome) at 30 days was 5.4% in the placebo group and 4.3% in the active group (relative risk 0.79, 95% CI 0.67– 0.92). Beyond 30 days, the corresponding rates were 6.3% vs. 5.2% (relative risk 0.82, 95% CI 0.70 – 0.95). There was no significant excess in life-threatening bleeds in each period (0.97% vs. 1.28%, relative risk 1.32, 95% CI 0.95–1.84 for 0 to 30 days; 0.83% vs. 0.91%, relative risk 1.09, 95% CI 0.75–1.59 for 31 days to 12 months). Further subdivision of the early data indicates benefits within 24 hours with consistently lower rates of the primary outcome in combination with refractory or severe ischemia. Conclusions: The authors concluded that clopidogrel reduces the risk of ischemic vascular events, with the benefits emerging within 24 hours of initiation of treatment and continuing throughout the 12 months (mean 9 months) of the study. Perspective: This large clinical trial demonstrated that dual antiplatelet therapy with aspirin and clopidogrel significantly reduces the risk of ischemic vascular events within 24 hours of therapy with sustained benefit throughout the 12 months of therapy. Aspirin has been shown to be significantly beneficial in patients with ACS. Apart from aspirin, clopidogrel is the only antithrombotic agent that has been demonstrated to be of benefit both in the early phase and during long-term treatment after ACS. Based on currently available data and concordant with ACC/AHA guidelines, both aspirin and clopidogrel should be initiated early in the management of ACS and continued for 1–9 months. These high-risk patients should also receive statins, beta-blockers and ACE inhibitors for optimal secondary prevention. DM

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