Sirolimus-Eluting Coronary Stents
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Although the randomized trial by Moses et al. (Oct. 2 issue)1 shows a benefit of sirolimus-eluting stents as compared with the same bare-metal stent without drug elution (Bx Velocity), the effect on clinical restenosis is overstated. With regard to the primary end point of the trial, failure of the target vessel at nine months, the 21 percent failure rate in the control group is much higher than that with other bare-metal stents and is not representative of clinical experience with such stents. A review of six clinical trials of bare-metal stents in a total of 6186 patients showed a target-vessel failure rate of only 13.6 percent,2 which is much closer to the 8.6 percent rate in the sirolimus-stent group in the SIRIUS study. Furthermore, in a review of "real world" rates of clinical restenosis by Kugelmass et al.,3 the rate of clinically driven target-lesion revascularization after bare-metal stenting of 3494 lesions was 6 percent — barely different from the nine-month target-lesion revascularization rate (4.1 percent in the group that received the sirolimus-eluting stent). Although drug-eluting stents may be an incremental improvement, the benefit is overstated and hardly justifies the $2 billion additional cost of a projected 80 percent conversion of clinical practice to drug-eluting stents.
Michael J. Mack, M.D.
Medical City Dallas Hospital
Dallas, TX 75230
References
Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315-1323.
Cutlip DE, Chauhan MS, Baim DS, et al. Clinical restenosis after coronary stenting: perspectives from multicenter clinical trials. J Am Coll Cardiol 2002;40:2082-2089.
Kugelmass AD, Cohen DJ, Houser F, et al. The influence of diabetes mellitus on the practice and outcomes of percutaneous coronary intervention in the community before drug-eluting stents: a report from the HCA database. J Invasive Cardiol 2003;15:568-574.
To the Editor: Moses et al. describe the use of stents in patients with complex lesions. However, the overall results were influenced by the inclusion of patients with low-to-moderate-risk lesions (type A or B1), according to the American College of Cardiology–American Heart Association (ACC-AHA) guidelines for stenting (44 percent of the total group).1 Also, the mean lesion length in the study by Moses et al. (14.4 mm) was shorter than the minimal length used as a criterion for inclusion in the study (15 mm). Thus, less complex lesions than claimed were included. A comment on this point would have been appropriate in the Discussion section.
In addition, why did the authors choose a lesion length of 13.5 mm as the cutoff point in the presentation of data on target-vessel revascularization, instead of using the ACC-AHA guidelines1 (<10 mm, 10 to 20 mm, or >20 mm)? An influential study such as this one should use standard classification, stratification, and presentation, providing comparable and applicable data.
The beneficial effect of sirolimus-coated stents is not questioned, but for type B2 or C lesions, for instance, in the proximal left anterior descending coronary artery, off-pump coronary surgery might be an excellent alternative. At three years of follow-up in a randomized trial, we found that the rate of target-vessel failure after off-pump arterial revascularization in this subgroup of patients was only 9.8 percent.2 Future trials of drug-eluting stents in patients with complex lesions should compare such stents with off-pump arterial revascularization.
Derk J. Drenth, M.D.
Felix Zijlstra, M.D., Ph.D.
Piet W. Boonstra, M.D., Ph.D.
University Hospital Groningen
9700 RB Groningen, the Netherlands
p.w.boonstra@thorax.azg.nl
References
Smith SC Jr, Dove JT, Jacobs AK, et al. ACC/AHA guidelines of percutaneous coronary interventions (revision of the 1993 PTCA guidelines) -- executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1993 Guidelines for Percutaneous Transluminal Coronary Angioplasty). J Am Coll Cardiol 2001;37:2215-2239.
Drenth DJ, Veeger NJ, Winter JB, et al. A prospective randomized trial comparing stenting with off-pump coronary surgery for high-grade stenosis in the proximal left anterior descending coronary artery: three-year follow-up. J Am Coll Cardiol 2002;40:1955-1960.
The authors reply: Dr. Mack's comments highlight some of the difficulties in comparing event rates among different clinical trials. Variations in case mix and definitions can make for misleading conclusions. In the case of the SIRIUS trial, lower-risk lesions were intentionally excluded in order to ensure a relatively event-rich and challenging population. Thus, Dr. Mack's citation of a lower rate of target-vessel failure in the report by Cutlip et al.1 is misleading on two accounts. First, the data in that analysis were predominantly from patients with simpler lesions who were included in the many trials designed for the approval of bare-metal stents. Second, the definition of target-vessel failure in these trials (unlike the definition in the SIRIUS trial) did not include in-hospital events. The "real world" event rate of 6 percent cited by Dr. Mack is curious, given that a more recent report from the same data base cites a 12-month rate of repeated intervention that exceeds 25 percent (38 percent in patients with diabetes), which we believe can be improved dramatically with drug-eluting stents.2
Dr. Drenth and colleagues point out some of the discrepancies frequently seen between on-site visual estimates of angiograms and blinded angiographic analyses performed at core laboratories. Thus, we are not surprised by the finding of a shorter lesion on the basis of core laboratory analysis than on the basis of on-site visual estimation. In addition, the risk stratification in the ACC-AHA guidelines pertains to the anticipated rates of complications and short-term procedural success, without reference to late clinical outcomes such as restenosis. Thus, the choice of a simple median cutoff point of 13.5 mm for lesion length seems reasonable for a subgroup analysis. The ultimate vindication of the strategy of case selection was the high restenosis rate in the control group, which provided confirmation that the SIRIUS cohort was in fact a group of patients at high risk for restenosis.
Finally, the question of the merits of sirolimus-eluting stents as compared with off-pump surgery in patients with lesions in the left anterior descending artery is intriguing. Given the fact that the subgroup of patients with such lesions in the SIRIUS study had a 12-month rate of major adverse cardiac events of 10 percent, which is similar to the rates in published reports of single-vessel bypass for lesions in the left anterior descending artery,3 the time is indeed ripe for a randomized trial.
Jeffrey W. Moses, M.D.
Martin B. Leon, M.D.
Lenox Hill Heart and Vascular Institute of New York
New York, NY 10021
jmoses@lenoxhill.net
References
Cutlip DE, Chauhan MS, Baim DS, et al. Clinical restenosis after coronary stenting: perspectives from multicenter clinical trials. J Am Coll Cardiol 2002;40:2082-2089.
Kugelmass AD, Cohen DJ, Houser F, et al. The influence of diabetes mellitus on the practice and outcomes of percutaneous coronary intervention in the community before drug-eluting stents: a report from the HCA database. J Invasive Cardiol 2003;15:568-574.
Drenth DJ, Veeger NJ, Winter JB, et al. A prospective randomized trial comparing stenting with off-pump coronary surgery for high-grade stenosis in the proximal left anterior descending coronary artery: three-year follow-up. J Am Coll Cardiol 2002;40:1955-1960.
Michael J. Mack, M.D.
Medical City Dallas Hospital
Dallas, TX 75230
References
Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315-1323.
Cutlip DE, Chauhan MS, Baim DS, et al. Clinical restenosis after coronary stenting: perspectives from multicenter clinical trials. J Am Coll Cardiol 2002;40:2082-2089.
Kugelmass AD, Cohen DJ, Houser F, et al. The influence of diabetes mellitus on the practice and outcomes of percutaneous coronary intervention in the community before drug-eluting stents: a report from the HCA database. J Invasive Cardiol 2003;15:568-574.
To the Editor: Moses et al. describe the use of stents in patients with complex lesions. However, the overall results were influenced by the inclusion of patients with low-to-moderate-risk lesions (type A or B1), according to the American College of Cardiology–American Heart Association (ACC-AHA) guidelines for stenting (44 percent of the total group).1 Also, the mean lesion length in the study by Moses et al. (14.4 mm) was shorter than the minimal length used as a criterion for inclusion in the study (15 mm). Thus, less complex lesions than claimed were included. A comment on this point would have been appropriate in the Discussion section.
In addition, why did the authors choose a lesion length of 13.5 mm as the cutoff point in the presentation of data on target-vessel revascularization, instead of using the ACC-AHA guidelines1 (<10 mm, 10 to 20 mm, or >20 mm)? An influential study such as this one should use standard classification, stratification, and presentation, providing comparable and applicable data.
The beneficial effect of sirolimus-coated stents is not questioned, but for type B2 or C lesions, for instance, in the proximal left anterior descending coronary artery, off-pump coronary surgery might be an excellent alternative. At three years of follow-up in a randomized trial, we found that the rate of target-vessel failure after off-pump arterial revascularization in this subgroup of patients was only 9.8 percent.2 Future trials of drug-eluting stents in patients with complex lesions should compare such stents with off-pump arterial revascularization.
Derk J. Drenth, M.D.
Felix Zijlstra, M.D., Ph.D.
Piet W. Boonstra, M.D., Ph.D.
University Hospital Groningen
9700 RB Groningen, the Netherlands
p.w.boonstra@thorax.azg.nl
References
Smith SC Jr, Dove JT, Jacobs AK, et al. ACC/AHA guidelines of percutaneous coronary interventions (revision of the 1993 PTCA guidelines) -- executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1993 Guidelines for Percutaneous Transluminal Coronary Angioplasty). J Am Coll Cardiol 2001;37:2215-2239.
Drenth DJ, Veeger NJ, Winter JB, et al. A prospective randomized trial comparing stenting with off-pump coronary surgery for high-grade stenosis in the proximal left anterior descending coronary artery: three-year follow-up. J Am Coll Cardiol 2002;40:1955-1960.
The authors reply: Dr. Mack's comments highlight some of the difficulties in comparing event rates among different clinical trials. Variations in case mix and definitions can make for misleading conclusions. In the case of the SIRIUS trial, lower-risk lesions were intentionally excluded in order to ensure a relatively event-rich and challenging population. Thus, Dr. Mack's citation of a lower rate of target-vessel failure in the report by Cutlip et al.1 is misleading on two accounts. First, the data in that analysis were predominantly from patients with simpler lesions who were included in the many trials designed for the approval of bare-metal stents. Second, the definition of target-vessel failure in these trials (unlike the definition in the SIRIUS trial) did not include in-hospital events. The "real world" event rate of 6 percent cited by Dr. Mack is curious, given that a more recent report from the same data base cites a 12-month rate of repeated intervention that exceeds 25 percent (38 percent in patients with diabetes), which we believe can be improved dramatically with drug-eluting stents.2
Dr. Drenth and colleagues point out some of the discrepancies frequently seen between on-site visual estimates of angiograms and blinded angiographic analyses performed at core laboratories. Thus, we are not surprised by the finding of a shorter lesion on the basis of core laboratory analysis than on the basis of on-site visual estimation. In addition, the risk stratification in the ACC-AHA guidelines pertains to the anticipated rates of complications and short-term procedural success, without reference to late clinical outcomes such as restenosis. Thus, the choice of a simple median cutoff point of 13.5 mm for lesion length seems reasonable for a subgroup analysis. The ultimate vindication of the strategy of case selection was the high restenosis rate in the control group, which provided confirmation that the SIRIUS cohort was in fact a group of patients at high risk for restenosis.
Finally, the question of the merits of sirolimus-eluting stents as compared with off-pump surgery in patients with lesions in the left anterior descending artery is intriguing. Given the fact that the subgroup of patients with such lesions in the SIRIUS study had a 12-month rate of major adverse cardiac events of 10 percent, which is similar to the rates in published reports of single-vessel bypass for lesions in the left anterior descending artery,3 the time is indeed ripe for a randomized trial.
Jeffrey W. Moses, M.D.
Martin B. Leon, M.D.
Lenox Hill Heart and Vascular Institute of New York
New York, NY 10021
jmoses@lenoxhill.net
References
Cutlip DE, Chauhan MS, Baim DS, et al. Clinical restenosis after coronary stenting: perspectives from multicenter clinical trials. J Am Coll Cardiol 2002;40:2082-2089.
Kugelmass AD, Cohen DJ, Houser F, et al. The influence of diabetes mellitus on the practice and outcomes of percutaneous coronary intervention in the community before drug-eluting stents: a report from the HCA database. J Invasive Cardiol 2003;15:568-574.
Drenth DJ, Veeger NJ, Winter JB, et al. A prospective randomized trial comparing stenting with off-pump coronary surgery for high-grade stenosis in the proximal left anterior descending coronary artery: three-year follow-up. J Am Coll Cardiol 2002;40:1955-1960.