Trials on newer generation drug-eluting stents in small coronary vessels needed

George Siontis and Stephan Windecker
George Siontis and Stephan Windecker

A network meta-analysis (published in JACC: Cardiovascular Interventions) of early generation, drug-eluting stents, bare metal stents, drug-coated balloons, and balloon angioplasty indicate that sirolimus-eluting stents are associated with the most favourable angiographic and clinical outcomes for lesions in small coronary arteries. Study authors George Siontis and Stephan Windecker (both at the Department of Cardiology, University Hospital Bern, Bern) discuss the implications of these results for newer generation drug-eluting stents.

What percentage of patients present with small coronary vessels?

Coronary artery disease located in vessels of small diameter (≤2.5mm), as assessed by quantitative coronary angiography, is a common finding and has been reported in up to 40% of the patients recruited in contemporary randomised trials.

Why are small coronary vessels associated with a significantly increased risk of restenosis?

Percutaneous coronary intervention (PCI) in small vessels is associated with a higher risk of restenosis and a higher risk of repeat revascularisation—irrespective of the type of stent implanted—compared with PCI in larger vessels.

In a large real-world cohort of patients treated with a stent, small-vessel diameter was identified as the most powerful predictor of restenosis. Additionally, small vessel coronary artery disease is often encountered in complex populations, such as patients with diabetes mellitus, multivessel disease or female gender. As neointimal hyperplasia is independent of vessel size, restenosis is more common in vessels of smaller diameter due to their limited ability to accommodate neointimal hyperplasia. Therefore, the relative reduction in lumen diameter is greater in small than in large vessels for a fixed amount of neointimal tissue.

What were the key findings of your study?

The key findings of our network meta-analysis can be summarised as follows:

  • Early generation drug-eluting stents were the most effective treatment in terms of angiographic performance assessed by percent diameter stenosis at angiographic follow-up, which also translated into a significant decrease in risk of target-lesion revascularisation compared with other treatments
  • Bare metal stents and simple balloon angioplasty should not be considered as treatment options for stenoses located in small coronary arteries
  • No dedicated randomised controlled trial was identified evaluating newer generation drug-eluting stents in this setting. Therefore, such devices were not included in our network meta-analysis.

What do we know about the use of newer drug-eluting stents in small coronary vessels?

Based on pre-specified subgroup analyses of large trials, PCI with newer generation drug-eluting stents in vessels of small diameter has been shown to decrease the risk of target lesion failure and target lesion revascularisation compared PCI with early-generation drug-eluting stents (ie. SPIRIT III and IV, CENTURY II trials).

Why, potentially, could newer drug-eluting stents provide an even greater benefit than the one observed with sirolimus-eluting stents?

Newer generation drug-eluting stents with thinner stent struts, biocompatible polymers, and different limus-eluting drug analogues are expected to further improve outcomes beyond early generation drug-eluting stents, as the relationship between stent strut thickness and restenosis is particularly evident in small vessels. Moreover, newer generation drug-eluting stents have been associated with an improved safety and efficacy profile compared to early-generation drug-eluting stents in different settings (ie. in-stent restenosis).

Do you think there is a need for a randomised controlled trial specifically looking at the use of newer drug-eluting stents in small coronary vessels?

Although our findings pertain to early-generation sirolimus-eluting stents, the observed relative reduction of approximately 30% in risk of target-lesion revascularisation in this meta-analysis may have relevant implications for decision-making, as the potential clinical benefit may be even greater with newer generation drug-eluting stents. However, in the absence of dedicated randomised comparisons, definitive conclusions on the effect of benefit of newer generation drug-eluting stents in small coronary vessels disease are not possible. Therefore, dedicated future trials are warranted to validate the findings of subgroup analyses of previous trials and to corroborate the results of this meta-analysis.