A Randomized Comparison of a Sirolimus-Eluting Stent With a Standard Stent for Coronary Revascularization - RAVEL

Description:

The purpose of this study was to compare the performance of sirolimus-releasing stents with that of standard uncoated stents in patients undergoing percutaneous coronary intervention.

Hypothesis:

Sirolimus-releasing stents will be associated with a lower rate of restenosis.

Study Design

Study Design:

Patients Enrolled: 138
Mean Follow Up: 5 years
Mean Patient Age: Mean age 61 years
Female: 75

Patient Populations:

Age 18-85 years; diagnosis of stable or unstable angina or silent ischemia; presence of a single primary target lesion in a native coronary artery that was 2.5-3.5 mm in diameter and that could be covered by an 18 mm stent; stenosis of 51-99% of the luminal diameter, as estimated visually; and a TIMI flow grade of 1 or higher

Exclusions:

Evolving MI, stenosis of the left main coronary artery, unprotected by a graft, ostial lesion, a calcified lesion that could not be completely dilated before stenting, an angiographically visible thrombus within the target lesion, a left ventricular ejection fraction of <30%, or an intolerance of aspirin, clopidogrel, ticlopidine, heparin, stainless steel, or contrast material

Drug/Procedures Used:

Patients with a single de-novo coronary artery stenosis were randomized to implantation of a sirolimus-coated, 18 mm Bx Velocity stent (120 patients) or of a standard stainless steel uncoated Bx Velocity stent (118 patients). The sirolimus-coated stent was designed to release 80% of the drug within 30 days from implantation. Quantitative coronary angiography (QCA) was performed at baseline, immediately after stent implantation, and at 180 ± 30 days of follow-up. The primary angiographic endpoint was in-stent late luminal loss, as determined by QCA.

Secondary endpoints included percent diameter stenosis at follow-up, minimal lumen diameter of the stented segment, and of the edges (5 mm distal and proximal to the stented segment), and restenosis defined as >50% diameter stenosis. The primary clinical endpoint was a composite of major adverse cardiac events (MACE) including death, Q-wave and non-Q-wave myocardial infarction (MI), coronary artery bypass grafting, and revascularization of the target lesion or of the target vessel at 30 days, 6 months, and 12 months.

Principal Findings:

Baseline clinical, angiographic, and procedural characteristics were similar between the two groups. At 180 days of follow-up, in-stent late luminal loss was -0.01 ± 0.33 mm in the sirolimus stent group and 0.8 ± 0.53 mm in the standard stent group (p < 0.001). Distal edge late luminal loss (–0.09 ± 0.30 mm vs. 0.12 ± 0.44 mm; p < 0.001), and proximal edge late luminal loss (0.05 ± 0.39 mm vs. 0.29 ± 0.48 mm; p < 0.001) were also significantly lower in the sirolimus stent group when compared with the standard stent group. These changes in late lumen morphology were associated with restenosis rates of 0% and 26.6%, respectively (p < 0.001).

At 1-year follow-up, the rate of MACE was 5.8% in the sirolimus stent group, and 28.8% in the standard stent group (p < 0.001). The difference between the two groups was due exclusively to a higher repeat target vessel revascularization rate in the standard stent group. There was no subacute or late stent thrombosis.

The recently reported 4-year follow-up data showed a MACE-free rate of 78% in the sirolimus group compared with 65% in the control group (p = 0.04). The MACE benefit continued to be driven by a reduction in freedom from target lesion revascularization (91.8% for sirolimus group vs. 73.4% for bare-metal stent group; p < 0.001). There were 13 deaths in the sirolimus group and seven in the bare-metal stent group.

At 5-year follow-up, death or MI trended higher in the sirolimus group compared with the bare-metal group (18.9% vs. 10.5%, p = 0.09). Death had occurred in 12.1% of the sirolimus group and 7.1% of the bare-metal group (p = 0.20). Target lesion revascularization remained lower in the sirolimus group (11.3% vs. 26%, p = 0.0004), but based on visual estimation of the Kaplan-Meier curves, the reduction appeared to occur only at the time of the trial-driven 6-month angiographic follow-up, with no visual increase in late revascularization in the bare-metal group.

Interpretation:

Among patients with single de-novo coronary artery stenoses, implantation of sirolimus-eluting stent is associated with lower rates of angiographic restenosis at 1 year. Larger trials such as SIRIUS have shown similar results of the efficacy in reducing the need for repeat revascularization with sirolimus-eluting stents compared with bare-metal stents.

While target vessel revascularization was lower in the sirolimus-eluting stent group compared with bare metal stents, the rate of death or MI at 5 years trended higher in the sirolimus-eluting stent group, with a 7.4% higher absolute death or MI rate compared to bare-metal stents. These findings, along with those of recent meta-analyses of randomized drug-eluting stent trials, continues to highlight the concern of late death or MI associated with drug-eluting stents.

The recently reported 5-year follow-up data show that the reduction in target vessel revascularization was maintained in the long-term, although the reduction appeared to be due to the trial-driven 6-month angiographic follow-up, as the large majority of the revascularizations were performed at the time of the 6-month protocol-driven angiogram in the bare-metal stent group, with only a few additional revascularizations between 6 months and 5 years in the bare-metal group.

References:

Five-year follow-up data presented by P.W. Serruys at the European Society of Cardiology Scientific Congress, September 2006.

Four-year follow-up data presented at the EuroPCR meeting, Paris, France, May 2005.

Morice MC, Serruys PW, Sousa JE, et al., on behalf of the RAVEL Study Group. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002;346:1773-80.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Aortic Surgery, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Myocardial Infarction, Follow-Up Studies, Drug-Eluting Stents, Sirolimus, Constriction, Pathologic, Percutaneous Coronary Intervention, Stents, Stainless Steel, Coronary Angiography, Coronary Stenosis, Thrombosis, Coronary Vessels, Coronary Artery Bypass


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