Future Directions

Novel therapeutic strategies are in development or have been examined in the setting of ACS and PCI to address inflammation. The Immunosuppressive Therapy for Prevention of Restenosis after Coronary Artery Stent Implantation (IMPRESS) study demonstrated a benefit to prednisone therapy in patients with elevated CRP after elective PCI with respect to clinical end points at 12 months and angiographic restenosis at 6 months.82 Although this was one of the only studies demonstrating a benefit to steroid therapy initiated after PCI, the duration of treatment (45 days) was considerably longer than in other studies.

P38 mitogen-activated protein kinase (p38 MAPK) inhibitors have recently garnered attention for potential anti-inflammatory actions in the context of ACS as well. Studies have shown that p38 MAPK inhibitors reduce CRP-mediated inflammatory cytokine production.83 Preliminary data have demonstrated the ability of p38 MAPK inhibitors to reduce inflammation in patients with ACS. Although large-scale clinical randomized data are not yet available, the promise of targeting inflammation remains exciting.

The issue of late stent thrombosis with DES is an important one, reviewed in Chapter 31, which occurs in low frequency but has serious late sequelae, including sudden death. It is possible that markers of arterial inflammation may be useful in predicting this uncommon event, for the selective use of long-term dual antiplatelet therapy or more aggressive prevention.

The most effective method of treatment will rely heavily on early identification of those at risk for either potent inflammatory underpinnings in ACS or robust inflammatory responses after PCI. Molecular biomarkers representative of inflammation, as discussed, will play a vital role in the diagnosis. Molecular imaging is also likely to become a formidable player in the process of early identification of inflammation. The ability to noninvasively quantify the degree of inflammation at the level of the endothelial cell using VCAM targeting peptides with magnetic resonance imaging84 may help identify patients at higher risk earlier on and allow for more aggressive medical anti-inflammatory therapy to improve efficacy of standard interventional therapy.

In the setting of both elective PCI and emergent PCI for ACS, modulation of inflammation will affect post-PCI outcomes, in both the short and the long term. In the setting of elective PCI, it is imperative that patients be pretreated with adjuvant medical therapy before the procedure, so as to derive the maximal anti-inflammatory benefit from these drugs to prevent postprocedural complications related to inflammation. In the setting of ACS, rapid action, in terms of "door to balloon" time, is necessary to ensure optimal outcomes. The price of acting quickly is the inability to adequately modulate inflammation in ACS. Often, it is unrealistic to expect longer duration of pretreatment with statins or clopidogrel in this setting, and therefore it is unlikely that patients truly derive the maximum potential benefit from these drugs in this setting. The answer to this problem may lie in other medications with faster onset of action. One such drug on the horizon is cangrelor, a potent, reversible intravenous PY12 inhibitor with a short half-life and a rapid onset of action. Small phase II clinical studies have shown safety and efficacy in the setting of PCI.85 Although more data are necessary, particularly in the context of PCI for ACS, it remains an attractive alternative to achieve more rapid platelet inhibition and potentially anti-inflammatory benefit in the setting of emergent PCI for ACS.

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