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As our understanding of the pathophysiology of adverse cardiovascular events evolves, the central role of platelets has become increasingly recognized. Plaque rupture, platelet activation, aggregation, and thrombus formation occur as a result of complex interactions between platelets, vascular endothelium, inflammatory cells, and circulating proteins and red blood cells. These processes can lead to vascular occlusion, ischaemia, and infarction in the native circulation consequent on plaque erosion or disruption. Similarly, during percutaneous coronary intervention and stent implantation, coronary vessel trauma and inflammation, as well as delayed stent endothelialization with ongoing exposure of the platelet-atttrative metal stent struts, combine to make some patients susceptible to adverse thrombotic events, including the potentially fatal stent thrombosis. This chapter will review key components of the processes and determine how therapeutic strategies can attenuate potential adverse cardiovascular events.

Congestive heart failure (CHF) is a major source of morbidity, mortality, and health-care resource consumption. However, the incidence of symptomatic CHF after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) has rarely been fully reported. We therefore examined the early and late incidence, predictors, and implications of CHF in the large-scale, prospective, randomized HORIZONS-AMI trial.New York Heart Association (NYHA) functional classification was prospectively collected from patient-level data at baseline, 30 days, 6 months, and at 1 and 2 years from 3,343 patients with STEMI undergoing PCI at 123 centers in 11 countries. The baseline incidence of CHF (before the index STEMI) was 2.6%, increasing to 4.6% 1 month after primary PCI (P.0001), 4.7% at 1 year, and 5.1% at 2 years. The incidence of NYHA class III/IV symptoms was 0.4% at baseline and 0.8% at 2 years (P = .03). CHF at 1 year was associated with diabetes (P.0001), dyslipidemia (P = .009), previous MI (P.0001), previous revascularization (P = .01), anterior STEMI (P = .02), and baseline TIMI grade 0 flow (P = .01) but not procedural anticoagulation with bivalirudin versus heparin + GPIIb/IIIa inhibitors (P = .93) or use of drug-eluting versus bare metal stents (P = .66). Among patients in whom CHF was not present at baseline but developed after PCI, the rate of all-cause mortality was significantly higher during 2-year follow-up (7.3% vs 2.0%, P.0001), as was cardiac mortality (2.4% vs 0.8%, P = .004), reinfarction (9.4% vs 5.2%, P = .0009), stent thrombosis (7.0% vs 3.8%, P = .007), and ischemic target vessel revascularization (19.4% vs 11.8%, P.0001).In the HORIZONS-AMI trial, the development of new-onset CHF within 2 years after contemporary PCI, although infrequent, was associated with significantly increased rates of mortality and major adverse ischemic events.

Accepting that the adhesion, activation, and aggregation of platelets plays a central role in the initial formation and subsequent propagation of intracoronary thrombi, antiplatelet therapy (APT) has become central to the management of a number of manifestations of cardiovascular (CV) disease; not least in preventing the deleterious effects of stent thrombosis (ST) that can follow percutaneous coronary intervention (PCI) with stent deployment. PCI causes significant local trauma to the vessel wall leading to exposure of the subendothelium and release of its thrombogenic constituents into the intravascular environment resulting in an increased risk of vaso-occlusive complications. Exposure of the stent struts can further stimulate platelet adherence to the non-endothelialized vessel wall and accelerate activation and aggregation. Furthermore, PCI can also potentiate the release of vasoactive agents from the platelet-rich thrombus. This may be of particular importance when PCI is undertaken in those presenting with acute coronary syndromes (ACS) where plaque disruption has already locally activated platelets by exposing the flowing blood constituents to thrombogenic plaque contents.

Over the past three decades, new strategies have rapidly evolved to achieve coronary reperfusion of ischaemic myocardium in patients with coronary artery disease (CAD). Studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) have shown that the long-term rates of death and/or myocardial infarction (MI) are substantially the same, justifying the increasing and widespread use of PCI. PCI is the dominant reperfusion therapy for such patients with the ratio of numbers of PCIs undertaken to CABG performed being 4:1 in the United Kingdom and up to 8:1 in other parts of Europe. A recurrent issue during the evolution of PCI has been the difference between PCI and CABG in the percentage of patients requiring a repeat procedure (reintervention). To date, the need of reintervention has been less with CABG and this is due to the development of in-stent restenosis that occurs after PCI. Restenosis is the re-narrowing of the vessel, which requires a repeat procedure. The rate of restenosis with early balloon angioplasty has been high. The implantation of bare metal stents (BMS) and then drug-eluting stents (DES) has reduced significantly the incidence of restenosis. While such improved overall clinical outcomes with DES has supported the use of these in preference to BMS, another long-term complication has somewhat tempered the enthusiasm for their use: the possibility that implantation of DES would result in an excess of occlusive stent thrombosis (ST). This chapter will analyse the data on the incidence, causes, and clinical consequences of ST, and will outline the ongoing and future preventive and therapeutic initiatives. Finally, the risk/benefit of DES will be addressed.

Major changes in the management of symptomatic obstructive coronary artery disease have been seen in the past 10 years with a substantial shift towards percutaneous coronary intervention (PCI). In the UK in 2005, for example, 73 000 PCIs were performed compared with 22 000 isolated coronary artery bypass grafting (CABG) procedures.1 Recently, there has been much debate about which of these two revascularisation options is “better” as measured by clinical outcome and overall cost effectiveness. This editorial will attempt to redress the balance on the use of PCI versus medical treatment in stable angina and its use in multivessel disease. Some have interpreted the recently published COURAGE trial,2 which randomised ( after coronary angiography) 2287 patients with positive non-invasive tests to either optimal medical treatment (OMT) or PCI, as indicating that OMT is equivalent to PCI for stable coronary artery disease and suggested that PCI is an overcostly, overused procedure. The 4.6-year composite of death/non-fatal myocardial infarction was 19.0% for PCI with OMT and 18.5% for OMT alone (p = 0.62). The relevance of this study to UK practice is doubtful since angioplasty in the UK is generally reserved for patients who have continuing symptoms despite OMT, although clearly there are patients who undergo PCI where there is clear evidence on objective non-invasive testing of silent ischaemia and a significant lesion in the same territory. It has never been the interventionist’s claim that PCI has an impact on mortality. Given that patients with left main stem disease and important left ventricular dysfunction (the very patients who may benefit prognostically from revascularisation) were excluded from this trial it seems highly likely that a similar trial comparing CABG with OMT would also show no difference. It is important to note that >40% of patients had little or no angina at trial entry. At follow-up 32.6% …

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