Editorials
Cardiovascular diseases
Volume 195 - Issue 3

The fall and rise of drug-eluting stents

Authors:  Christopher J K Hammett, Peter J Stewart and John J Atherton

Med J Aust 2011; 195 (3): 110-111. || doi: 10.5694/j.1326-5377.2011.tb03234.x
Published online: 1 August 2011
Download PDF (142 KB)
Share: Share on Blue Sky Share on Facebook Share on LinkedIn Share by email

Earlier concerns put to rest as new evidence confirms their safety and efficacy

The three sentinel developments in percutaneous coronary intervention (PCI) have been the groundbreaking use of balloon angioplasty from 1977, the widespread uptake of bare metal stents (BMS) in the early 1990s, and the era of drug-eluting stents (DES) commencing in 2002. DES greatly reduce the incidence of vessel restenosis, and this has allowed the application of PCI to increasingly complex coronary anatomy that had previously been untreatable due to prohibitive restenosis rates. Uptake of this technology was immediate and widespread, with near ubiquitous use (95%) of DES for PCI in the Australian private sector by 2005 despite a fourfold higher cost and uncertain incremental cost-effectiveness over BMS.1 However, the initial unbridled optimism was tempered by case reports of “very late” stent thrombosis, and then shattered by the release of data at the 2006 World Congress of Cardiology in Barcelona suggesting DES were associated with higher mortality rates.2 This dramatically shook confidence in the use of this new technology with an immediate effect on DES use worldwide.3 In early 2007, the widely reported Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, in which outcomes were similar for medically and percutaneously treated patients with stable angina, further challenged the interventional paradigm.4

Criteria for drug-eluting stent use in Victorian state hospitals6

One or more of:

  • Diabetes mellitus

  • Chronic renal failure

  • Small diameter target vessel (< 2.5 mm diameter)

  • Long target lesion (> 20 mm in length)

  • Ostial lesion

  • Bifurcation lesion

  • Chronic total occlusion

  • Previous coronary artery bypass grafting

  • In-stent restenosis

So what was the effect on Australian DES use? In this issue of the Journal, the Melbourne Interventional Group (MIG) present their registry data for DES use in selected Melbourne public hospitals over a 4-year period spanning this crucial time.5 Even though there was already a selective policy in place restricting DES use to patients with lesions at high risk of restenosis (Box), DES implantation fell from a peak of 54% of all stents used between April 2004 and March 2005 to 32% in 2007–2008.5 Even more dramatic falls in DES use (91% to 34%) have been reported in the Melbourne private sector over this period.7 The change in DES use in public hospitals demonstrated by the MIG is revealing, as they have previously reported underuse of DES and calculated that greater than 65% of patients undergoing stent implantation met the criteria for selective use of DES.8 Of further interest is the decrease in the absolute number of patients undergoing PCI, and in particular elective PCI, that is perhaps related to the release of the COURAGE study. It is likely that the change in practice reflects uncertainty over safety of DES at that time. It is therefore reassuring that data reported from the MIG registry affirm the safety and efficacy of DES, with DES use being the only independent predictor of better clinical outcomes at 12 months (driven, as expected, by reduced target vessel revascularisation rates). Given this finding, we would have expected to have seen deterioration in clinical outcomes during the period of low DES use. Surprisingly, this did not happen — the MIG investigators report that the reduction in DES shown by their data was not associated with an adverse effect on overall clinical outcomes. One possible explanation for this is that there was concurrent change in several other variables including referral patterns, stent technologies, implantation techniques, and adjunctive pharmacological therapy (eg, increased use of dual antiplatelet therapy). These changes may have acted favourably on clinical outcomes, masking an adverse impact of reduced DES use. The inability to separate out these confounding influences is one of the limitations of registry data.

Following the Barcelona Congress, there was a rigorous reappraisal of the available studies using patient-level data, review by regulatory authorities (including the Australian Therapeutic Goods Administration) and further randomised trials. The safety and efficacy of DES were reaffirmed. Analyses showed they were not associated with an increased rate of myocardial infarction or death, but were associated with a reduction in need for revascularisation of up to 70% compared with BMS.9,10 Moreover, there has been an evolution to “second generation” stent platforms with very low stent thrombosis and restenosis rates,11 and greater understanding of the importance of dual antiplatelet therapy. Indeed, new registry data have provocatively shown a mortality benefit with liberal utilisation of DES.12

So who should receive a DES? If there was no cost difference, it would be appropriate to implant DES in the majority of patients. The main exceptions would be patients unlikely to tolerate 12 months of dual antiplatelet therapy because of increased bleeding risk, an anticipated need for elective surgery, or poor medication compliance. However, a significant cost differential remains and, therefore, rationing to those most likely to benefit (Box) is appropriate. This will, nonetheless, still result in much higher DES utilisation rates than those documented in the MIG registry in 2007. The reassurance that DES are safe has had an effect on practice at our institution, with implantation rates increasing from 43% to 70% over the past 3 years, bringing us back in line with the proportion of patients reported to meet selective utilisation criteria in Victoria.8

The information presented by the MIG gives a fascinating insight into physician behaviour by documenting the local change of practice that followed concerns regarding DES. Confidence has been restored by evidence affirming DES safety, the introduction of “second generation” platforms, and a better understanding of the importance of optimal medical therapy. It would be interesting to see how these more recent developments have affected DES use, and we look forward to ongoing insights from this important local registry.

Authors

  • Christopher J K Hammett MBChB, FRACP, FCSANZ1,2
  • Peter J Stewart MB BS, FRACP, FCSANZ1
  • John J Atherton PhD, FRACP, FCSANZ1,2
  • 1. Department of Cardiology, Royal Brisbane and Women's Hospital, Brisbane, QLD.
  • 2. School of Medicine, University of Queensland, Brisbane, QLD.

Correspondence: Christopher_Hammett@health.qld.gov.au

References

Provenance: Commissioned; externally peer reviewed.

View this article on Wiley Online Library