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Three Part Question

In [patients with significant coronary artery stenoses] are [drug eluting stents compared to conventional CABG] the optimal method to achieve [long term graft patency]?

Clinical Scenario

You are seeing a 70 year old American man with three discrete 70% stenoses in the mid LAD, mid Circumflex and Proximal RCA. He has grade III angina and apart from Hypertension and a high cholesterol he has no other significant past history. You advise him that his best option is certainly to have Coronary Arterial Bypass grafts in terms of relief of symptoms. However he tells you that he had a friend in the States with the same problems as him who had 3 stents that were impregnated with drugs that will keep his arteries open forever. You wonder whether drug-eluting stents would be just as good for him if he could get them.

Search Strategy

Medline 1966-06/03 using the OVID interface.
[exp sirolimus/ OR sirolimus.mp OR exp paclitaxel/ OR paclitaxel.mp OR Drug-eluting.mp OR heparin-coated.mp OR rapamycin.mp] AND [exp Stents/ OR stent.mp]

Search Outcome

197 papers were found of which 8 were deemed to be relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Moer et al, 2001	145 patients with stable or unstable angina were randomly assigned to elective stenting treatment with the heparin (Hepamed)-coated beStent or PTCA	Double blind RCT	Event-free survival at follow up	Stent group: 90.5% PCTA 76.1%, p=0.016	Non-significant primary outcome
			Minimal luminal diameter	Stent group: 1.69 +/-0.52mm Control group 1.57 +/-0.44mm, p=0.096
Morice et al, 2002	120 patients with a single coronary lesion up to 18mm long were randomly assigned to receive the sirolimus-eluting stent, and 118 were assigned to receive the standard stent. Angiographic follow up at 6 months, clinical follow up for 12 months	Double blind RCT	In stent stenosis >50%	Eluting Stent group: 0% Control group: 26.6%, p<0.001	High control stenosis rate
			Major cardiac events	Eluting Stent group: 5.8% Control group 28.8%, p<0.001
Liistro et al, 2002, Italy	Fifteen consecutive patients with elective indication for PTCA for in-stent restenosis were treated with the QuaDS-QP2 stent implantation (taxol)		Angiography at 6 months	Restenosis of 2 vessels at 6 months Mean lumen loss 0.47% +/-1.01mm
			Angiography at 12 months	8 of 13 patients (61.5%) had angiographic restenosis (late loss 1.36 +/-0.94mm)
			Complications	1 post procedural MI (NQWMI) 1 MI 2 months post stent insertion
Park et al, 2003, South Korea	177 patients with discrete coronary lesions, randomised to paclitaxel-eluting stents (low dose n=59, or high dose n=60,) or control stents n=58 (15mm long) Pts all had 1-2 vessel disease Angiography at 6 months	'triple blind ' RCT	Percentage luminal loss	High dose: 14 +/-21% Low dose: 23 +/-25% Control group 39 +/-27%, p<0.001
			Percentage restenosis	High Dose 4% Low dose 12% Control 27%
Sousa et al, 2003 Brazil	30 patients treated with sirolimus-eluting Bx Velocity stenting (slow release, n=15, and fast release, n=15) (not randomised) Angiographic and intravascular USS findings at 2 years	2 arm cohort study	In-stent lumen loss at 2 years	Slow release group 0.28+/-0.4 mm Fast release group 0.09 +/-0.23mm, P=0.007	Small study Data on patient that had an MI not included
			Stenosis requiring re-intervention	1 patient in the fast release group had a 52% in-stent stenosis requiring revascularisation
			Complications	1 patient had an MI with occlusion of a stented vessel, precluding 2 year angiographic follow up
Hong et al, 2003, South Korea	81 patients with single lesions, randomised to high dose paclitaxel-coated stents n=28, low dose paclitaxel stents n=28, and bare metal stents n=25 6 month intravascular ultrasound performed	'triple blind' RCT	Volume of In-stent lumen loss at 6 months	Control group: 31 +/-22mm3 Low dose group 18 +/-15mm3 High dose group 13 +/-14mm3, p=0.001
			Complications	1 case of late malopposition occurred in the high dose group
Ferreira et al, 2003	196 consecutive coronary angiograms and medical records of patients referred for coronary bypass surgery were reviewed	Cohort study	Change in management if 100% stenosis free stents were available	79% of patients would have still required CABG, 21% would have had stents instead	Single Cardiologist determined change of management Single USA centre
Haude et al, 2002, Germany	588 patients with vessels from 2-2.6mm in size (small coronary arteries), randomised to angioplasty (n=195), bare stenting (n=196), or heparin-coated stenting (n=197). 6 month angiography	Double blind RCT	Restenosis after 6 months	Restenosis rate was 32.2% after PCTA, 24.8% after bare stenting, 29.6% after heparin-coated stenting, (P=0.34)	20% of patients refused follow up angiography
			Complications	2 stent embolisations during procedure

Comment(s)

The two major studies in this area are currently the RAVEL and the ASPECT trials. They report a virtual elimination of in-stent stenosis at 6 months in patients receiving a single sirolimus or paclitaxel eluting stent. Good patency has been demonstrated for upto 2 years. However other studies using taxol or heparin coated stents have not demonstrated significant benefits. More worryingly two further large trials have recently been stopped and no results published. The ACTION trial of actinomycin-D eluting stents was stopped early and Guidant refused to release the early data in 2001. Then in 2003 Guidant also stopped the DELIVER trial (a paclitaxel-coated stent trial). Thus publication bias is becoming a significant concern in this area with the market for these stents in the USA being worth an estimated $6.5 billion. However assuming that a failure free stent is found Ferreira et al showed that this would reduce the number of CABG referrals in the USA by around 20-25%.

Clinical Bottom Line

Sirolimus and paclitaxel eluting stents seem to have very good patency in patients treated with mainly single lesions. No studies of CABG vs Drug eluting stents have yet been performed.

References

1. Moer R, Myreng Y, Molstad P, et al. Stenting in small coronary arteries (SISCA) trial. A randomized comparison between balloon angioplasty and the heparin-coated beStent. Journal of the American College of Cardiology 2001;38:1598-603.
2. Morice MC, Serruys PW, Sousa JE et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. NEJM 2002;346:1773-80.
3. Liistro F, Stankovic G, Di Mario C, et al. First clinical experience with a paclitaxel derivate-eluting polymer stent system implantation for in-stent restenosis: immediate and long-term clinical and angiographic outcome. Circulation 2002;105:1883-6.
4. Park SJ, Shim WH, Ho DS, et al. A paclitaxel-eluting stent for the prevention of coronary restenosis. NEJM 2003;348:1537-45.
5. Sousa JE, Costa MA, Sousa AG, et al. Two-year angiographic and intravascular ultrasound follow-up after implantation of sirolimus-eluting stents in human coronary arteries. Circulation 2003;107:381-3.
6. Hong MK, Mintz GS, Lee CW, et al. Paclitaxel coating reduces in-stent intimal hyperplasia in human coronary arteries: a serial volumetric intravascular ultrasound analysis from the Asian Paclitaxel-Eluting Stent Clinical Trial ASPECT Circulation 2003;107:517-20.
7. Ferreira AC, Peter AA, Salerno TA, et al. Clinical impact of drug-eluting stents in changing referral practices for coronary surgical revascularization in a tertiary care center. Annals of Thoracic Surgery 2003;75:485-9.
8. Haude M, Konorza TF, Kalnins U, et al. Heparin-coated stent placement for the treatment of stenoses in small coronary arteries of symptomatic patients. Circulation 2003;107:1265-70.