Early Systemic Inflammatory Response to Drug-Eluting Stents Implantation: The Heart of the Difference?

Abstract

Percutaneous coronary intervention (PCI) is the main treatment for the revascularization of coronary arteries in patients with coronary artery disease. Intracoronary stent deployment causes arterial wall trauma which elicits a local inflammatory wound-healing response to mechanical injury leading to an increase of inflammatory mediators in the target coronary artery segment [1]. Consequently, an early systemic inflammatory response is triggered, as observed by an almost immediate rise (within minutes after PCI) in systemic inflammatory markers, such as interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). The production of acute phase reactants in the liver is stimulated, like C-reactive protein (CRP) and serum amyloid A protein (SAA), which rapidly increase in the circulation and which may directly amplify the local response to the inflammatory stimulus [2, 3]. Furthermore, coronary stenting in patients with stable angina causes an elevated systemic inflammatory response compared with patients treated with angioplasty only [4]. The relationship of the systemic inflammatory response and restenosis outcome is still unclear. The majority of the studies show a correlation between (early) post-PCI systemic inflammatory markers and restenosis outcome [4]. Nonetheless, some studies report no association [5, 6]. Several factors may contribute to this discrepancy. First, differences in baseline demographic, clinical and lesion characteristics may affect the inflammatory response and, therefore, the clinical prognosis. More complex lesions and/or lesions presenting high inflammatory infiltrates may show hypersensitivity to stent implantation leading to a higher inflammatory reaction. Second, inflammatory mediators have different half-lives (e.g., IL-6≈4 h; CRP and SAA≈19 h) and measurement in a certain time course may not correspond to their highest peak value and not detect differences in concentrations between groups. Third, the widespread use of statins, glycoprotein IIb/IIIa antagonists, and clopidogrel may attenuate the systemic inflammatory response to PCI and mask the predictive association between systemic inflammatory values and clinical outcome. On the whole, nowadays it is considered that inflammation plays an important role after PCI with regard to restenosis [7], and this is strengthened by the fact that polymorphisms in genes coding for inflammatory proteins, e.g. TNF-α, IL-10, caspase-1 and colony-stimulating factor 2 (CSF2) have been shown to be associated and causally involved in (clinical) restenosis [2, 8–10]. The introduction of drug-eluting stents (DES) in clinical practice was a milestone in the history of interventional cardiology. The two initially main worldwide available DES, i.e. Sirolimus(SES, CypherTM) and Paclitaxeleluting (PES, TAXUSTM) stents, reduce restenosis and target-vessel revascularization rate as compared to baremetal stents (BMS) [11–13]. Putative differences in terms of early systemic inflammatory response among patients treated with DES versus BMS have been put forward as a plausible explanation for the DES superiority. Literature associates DES either with a decrease [14, 15] or no effect [16, 17] in the early systemic inflammatory response compared to BMS. The reasons for these unclear results are unknown, but the same limitations as described above Cardiovasc Drugs Ther (2009) 23:103–105 DOI 10.1007/s10557-008-6158-z