Saturday, April 1, 2023
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Presenter: William W. O'Neill, MD, on behalf of the DELIVER Investigators
Following the success of the TAXUS trials in Europe, which evaluated paclitaxel-eluting stents (dose: 3 mcg/mm2) to prevent restenosis, DELIVER (the RX ACHIEVE Drug-Eluting Coronary Stent System (CSS) In the Treatment of Patients with De NoVo NativE CoronaRy Lesions) was a randomized, controlled trial involving 1041 patients that compared the safety and efficacy of the RX ACHIEVE paclitaxel-eluting stent (Guidant Corporation, Santa Clara, California) (n = 522) and the PENTA (Guidant; n = 519) bare metal stent for the treatment of de novo coronary artery lesions measuring 2.5-4.0 mm in diameter. All patients were treated with clopidogrel after the procedure for 90 days.
Inclusion criteria called for patients with target vessel reference diameter of 2.5-4.0 mm and target lesion length ≤ 25 mm, both of which were based on visual estimate. In addition, up to 2 native vessels could be treated, 1 target and 1 nontarget, with only 1 de novo lesion per vessel. Patients also had significant stenosis (≥ 50% and < 100%) with TIMI flow ≥ 1. Those patients with aorto-ostial lesions, an unprotected left main, angiographic evidence of thrombus, heavy calcification or extreme tortuosity, and ejection fractions < 30% were among those excluded from the study. The study's primary endpoint was target vessel failure (TVF) at 270 days, defined as the composite of death, myocardial infarction (MI), target lesion revascularization (TLR), and target vessel revascularization (TVR). In-stent angiographic binary restenosis was also evaluated at 240 days.
The baseline characteristics were similar for the 2 groups and also similar to the patient characteristics seen in the majority of other drug-eluting stent trials (Table 1).
Characteristic Paclitaxel Stent
(n = 522)Control
(n = 519)Age (yrs) 62 63 Male gender (%) 71 71 Diabetes (%) 31 29 Current smoker (%) 25 25 Prior MI (%) 26 27 Hyperlipidemia (%) 59 60 Reference vessel diameter (mm)* 2.85 2.77 Lesion length (mm)† 12 11 Stent length (mm) 20 20
*P = .02
† P = .04
Results of angiographic follow-up and quantitative coronary angiography in the in-stent segment at 240 days were available for 228 paclitaxel-eluting stent patients and 214 control patients. Compared with control, the use of paclitaxel-eluting stents was associated with significant favorable differences in minimal lumen diameter and in late loss (Table 2).
Measurement Paclitaxel Stent
(n = 228)Control
(n = 214)P Minimal lumen diameter (mm) 2.08 1.86 .001 Acute gain (mm) 1.91 1.91 NS Late loss (mm) 0.81 0.98 .003 Late loss ratio 0.45 0.54 .01
NS = not significant
When the analysis was performed for the whole segment, the results were similar, with a significantly lower rate of late loss in the paclitaxel-eluting stent. With regard to the primary endpoint, death, MI, TLR, and TVR rates were similar for the 2 groups, although there was a strong trend toward lower TLR rates in the paclitaxel group (Figure 1). Target vessel failure and major adverse cardiac event (MACE) rates were also similar, as shown in Figure 2. Regarding the binary restenosis rate (secondary endpoint) for the whole segment, there was a 16.7% restenosis rate for the paclitaxel stent compared with 22.4% for control (P = .14).
Figure 1. DELIVER: primary endpoint.
Figure 2. DELIVER: TVF and MACE rates.
Interestingly, when a multivariate analysis was performed for the independent predictors of restenosis, diabetes (OR = 2.2; confidence interval [CI] = 1.3-3.9; P = .005), vessel diameter (OR = 5.8; CI = 3.43-10.7; P < .0001), and the use of glycoprotein (GP) IIb/IIIa inhibitors (OR = 2.32; CI = 1.24-4.35, P = .009), each was associated with an increased risk of angiographic restenosis.
Investigators concluded that the use of the paclitaxel-coated ACHIEVE stent at a dose of 3 mcg/mm2 is safe. Although very effective in the prevention of neointimal hyperplasia, the magnitude of the effect was insufficient to meet prespecified endpoints. Likewise, a detrimental drug interaction with GP IIb/IIIa inhibitors was observed in this study; the true effect with this type of drug-eluting stent will have to be evaluated in the future.
The present study showed us that, although we have come a long way in the newly developed world of drug-eluting stents, there is still plenty of work to be done. As good as these results are, they are just not as good as we would have expected. We can speculate on the reasons, and probably attribute them to dose-related issues. Higher doses might be needed to inhibit neointimal growth. The interaction between these stents and GP IIb/IIIa inhibitors was interesting and will need serious evaluation in the future, as this interaction has not been noted in other drug-eluting studies.
