Section D
Stent Selection
Clinical Rationale for Drug-eluting Stents in Percutaneous Revascularisation of Coronary Occlusions
The appeal of drug-eluting stents (DES) for improving long-term vessel patency following CTO recanalisation is related not only to the success of DES in other complex lesion morphologies, but also to the clinical inadequacies of bare metal stents in sustaining restenosisfree patency in this particular lesion subset.71 As an example, in the Total occlusion study of Canada 1 (TOSCA-1) trial, rates of restenosis and re-occlusion six months after bare metal stent revascularisation exceeded 50 % and 10 %, respectively.72
The failure to achieve or sustain patency after CTO recanalisation has been associated with an impairment in the regional and global left ventricular systolic function, recurrent angina and target vessel revascularisation, and a greater need for late bypass surgery.73 Therefore, improving long-term, restenosis-free patency in coronary occlusions may have a potentially significant clinical impact.
Contemporary DES Trials in CTO Revascularisation
In the randomised Primary stenting of totally occluded native coronary arteries (PRISON) II trial (N=200), treatment with sirolimus-eluting stents (SES) was associated with statistically significant reductions in angiographic restenosis at six months (in-stent, 36 % versus 7 %, p<0.0001), reocclusion at six months (13 % versus 4 %, p<0.04) and repeat revascularisation at one year (21 % versus 5 %, p<0.0001).74 At five years, the benefit of SES was sustained, demonstrating significant reductions in target lesion revascularisation (TLR, 30 % versus 12 %, p=0.001) and major adverse cardiac events, despite a greater number of cases of definite or probable stent thrombosis (ST).75 Similar clinical and angiographic benefit using first-generation DES has been supported in non-randomised studies.76–84 Among the 200 CTO patients treated with SES in the prospective Approaches to chronic occlusions with sirolimus-eluting stents/total occlusion study of coronary arteries-4 (ACROSS/TOSCA-4) trial, the three-year rate of TLR and ST remained favourable at 10.9 % and 1.0 %, respectively, with no occurrences of ST beyond one year.83 However, stent fracture was associated with higher restenosis rates.
The growing clinical trial experience with DES in CTO revascularisation has also enabled meta-analyses of angiographic and clinical outcomes.85,86 Among 17 studies evaluating SES and/or paclitaxeleluting stents (PES) against bare metal stents in CTO revascularisation, treatment with DES was associated with a significant reduction in angiographic restenosis (odds ratio (OR) 0.15; 95 % CI, 0.08–0.26) and repeat revascularisation (OR 0.13; 95 % CI, 0.06–0.26), with a similar long-term incidence of death, myocardial infarction and ST.85
While these findings further support the safety and efficacy of DES following CTO recanalisation, they also have implications regarding procedural technique. For example, restenosis in the entire treated segment after recanalisation occurs nearly twice as often beyond the stent margins than in-stent. Therefore, DES treatment of the entire segment exposed to pre-dilatation angioplasty may yield greater reductions in restenosis and subsequent TLR than with balloon angioplasty alone or in combination with bare metal stents.83,87 Nevertheless, percutaneous revascularisation of CTOs is routinely associated with more extensive stent placement. As a consequence, it is unclear whether the improvement in restenosis is offset by a potentially higher risk of thrombotic occlusion, by complications associated with stent fracture or by acquired late malapposition.83,88
The question as to whether disparities in angiography and clinical outcome arise in more complex lesion morphologies is an issue of ongoing study and is especially relevant to coronary total occlusions. At present, at least five comparative trials of SES and PES in CTOs have been performed.89 In general, these studies have been limited by their small study populations, which limit statistical comparisons – variability in trial design and limited clinical and angiographic follow-up. The demonstration of differences in clinical outcomes across the individual trials has been less consistent. More recently, the PRISON III trial randomised 300 CTO patients to receive either SES or two different zotarolimus-eluting stents, Endeavor and Resolute, Medtronic CardioVascular (Santa Rosa, CA).90 Compared with SES, the primary endpoint of in-segment late lumen loss at the eight-month angiographic follow-up was significantly higher with Endeavor but similar with Resolute. Given the overall small sample size, the clinical outcomes did not vary statistically according to the DES assignment.
Additional studies have evaluated everolimus-eluting stents (EES) compared with PES,91,92 reporting lower angiographic and clinical restenosis with EES. In the Non-acute coronary occlusIon treated by everolimus eluting stent (CIBELES) randomised trial that compared SES with EES (N=207), the nine-month in-stent late loss (primary endpoint, 0.13 ± 0.69 mm EES versus 0.29 ± 0.60 mm SES, p=0.12) and angiographic restenosis were similar between the stent types.93,94 At 12 months, TLR and ST were numerically, but not significantly, higher among SES-treated patients. In a recent meta-analysis, compared with first-generation DESs, second-generation DESs were associated with lower incidence of death (odds ratio [OR], 0.37; 95 % confidence intervals [CI], 0.15-0.91), target vessel revascularisation (OR, 0.59; 95 % CI, 0.40-0.87), binary angiographic restenosis (OR, 0.68; 95 % CI, 0.46-1.01) and reocclusion (OR, 0.35; 95 % CI, 0.17–0.71), but similar incidence of myocardial infarction (OR, 0.45; 95 % CI, 0.10–1.95) and stent thrombosis (OR, 0.34; 95 % CI, 0.07–1.59).95
Additional studies evaluating EES in CTO revascularisation are forthcoming and include the Angiographic evaluation of the everolimus-eluting stent in chronic total occlusions (ACE CTO, clinicaltrials.gov identifier NCT01012869) and the evaluation of the XIENCE PRIME™ LL and XIENCE Nano™ everolimus eluting coronary stent coronary stents, performance, and technique in chronic total occlusions (EXPERT CTO, NCT01435031).
The authors would like to thank Ms Sheila Agyeman for her invaluable effort in coordinating the manuscript creation process.