Enhanced Long-Term Antiplatelet Therapy after Coronary Stenting

Since the introduction of coronary stenting to interventional cardiology in 1989, improvements in stent implantation techniques and antiplatelet drug therapy have dramatically improved the short-term and long-term outcomes of percutaneous intervention, and stenting is now routinely performed in 90% of all percutaneous coronary interventions (PCI). Coronary stenting was initially approved for treatment of the acute complications of balloon angioplasty: by providing a mechanical scaffold for the vessel wall, sealing dissections and preventing elastic recoil, stents reduce the risk of abrupt vessel closure¹ (Figure 1). As a result, emergency coronary artery bypass graft (CABG) surgery is now required in fewer than 1% of stent procedures compared with 5% of conventional balloon angioplasty procedures.^2,3 The demonstration in the mid-1990s that coronary stenting reduced angiographic restenosis rates in large-diameter vessels from the 30–40% rate seen with balloon angioplasty to 10–20%^4,5 — primarily by eliminating elastic recoil and negative vascular remodeling⁶ — heralded the present era of elective stenting. The benefits of stenting over balloon angioplasty in reducing angiographic restenosis, target vessel revascularization and clinical event rates are now well established for small-vessel,⁷ saphenous graft,⁸ and restenotic⁹ lesions, as well as for chronic coronary artery occlusion^10,11 and acute myocardial infarction.^12–15 Increasing use of stents for more complex lesion types (diffuse, small-vessel and bifurcated lesions) and in high-risk settings (e.g., diabetic patients) has, however, highlighted the problem of in-stent restenosis.^16,17 Two recent breakthrough technologies — brachytherapy (intracoronary radiation) for the treatment of in-stent restenosis¹⁸ and drug-eluting stents for (primarily) the prevention of restenosis^19,20 — have largely resolved this issue. By allowing controlled release of antiproliferative agents directly to the injured endothelium, drug-eluting stents offer the prospect of virtually eradicating in-stent restenosis, especially of the diffuse variety.²¹ Two drug-eluting stents — the sirolimus-eluting CYPHER™ stent (Cordis/Johnson & Johnson, Miami, Florida) and the paclitaxel-eluting TAXUS™ stent (Boston Scientific Corporation, Natick, Massachusetts) are currently approved in the U.S. by the Food and Drug Administration (FDA) for prevention of restenosis in native coronary arteries. From its inception, PCI has been intended as a focal treatment of flow-limiting coronary stenosis associated with discrete culprit lesions. However, in addition to providing lasting improvement in luminal patency, the ultimate goal of percutaneous coronary revascularization is to prevent morbidity and mortality arising from ongoing atherosclerosis in nonstenotic coronary segments. Coronary atherosclerosis is a diffuse, multifocal disease process that affects the entire coronary arterial tree,^22–24 and patients with acute coronary syndromes are likely to have multiple sites of coronary plaque ulceration.^25–27 Recurrent ischemic events after PCI are often due to atherosclerotic disease progression at sites removed from the culprit lesion, and serial angiographic studies indicate that most myocardial infarctions occur at sites previously associated with only mild or moderate luminal stenosis.^28,29 This extensive, pan-coronary deterioration in non-culprit lesions may reflect a diffuse destabilization of atherosclerotic plaques after the initial ischemic event.²⁵ Moreover, plaque vulnerability and liability for ischemicevents are determined more by the biological properties of the coronary plaque than by the degree of vessel stenosis.³⁰ Indeed, vulnerable plaques are frequently not severely stenotic prior to rupture, as the accumulating atheroma is accommodated by positive vascular remodeling, thereby offsetting the reduction in lumen size.³¹ The detrimental effects of progressive atherosclerosis on the long-term efficacy of PCI are seen in the frequent need for repeat revascularization in patients with multivessel disease³² and the high ratio of new lesion-to-target lesion restenosis in those with saphenous vein grafts.³³ Accumulating evidence of the diffuse nature of coronary artery disease, coupled with the inherent difficulties involved in identifying and treating multiple individual lesions, underlines the importance of adjunctive systemic pharmacotherapy and risk factor modification post-PCI in stabilizing atherosclerotic plaques throughout the coronary vasculature and reducing the likelihood of further ischemic events.³⁴Platelet activation associated with coronary intervention. Platelets are integrally involved in the thrombotic complications of atherosclerosis. Atherosclerotic plaque disruption results in exposure of the subendothelial matrix and its constituent platelet-adhesive proteins (von Willebrand factor, collagen and thrombospondin) to circulating blood.^30,35,36 Platelets are attracted to the site of vascular injury and adhere to the exposed subendothelium, where they are activated by locally generated thrombin, collagen, epinephrine and adenosine diphosphate (ADP). Platelet activation in turn triggers changes in platelet morphology, platelet degranulation and the release of various agonists (ADP, thromboxane A2 and platelet activating factor) that promote further platelet recruitment^30,37 (Figure 2). The final process of platelet aggregation involves the binding of circulating fibrinogen and von Willebrand factor to the glycoprotein (GP) IIb/IIIa receptor on the platelet surface, leading to cross-linkage of adjacent platelets into a platelet-rich thrombus.³⁸ In addition to promoting platelet aggregation and thrombus formation, platelet activation may contribute to the chronic inflammatory and fibroproliferative response that is central to atherosclerosis. Activated platelets bind to leukocytes via surface receptor-ligand interactions to cause the release of proinflammatory cytokines such as tissue necrosis factor-a, monocyte-chemotactic factor-1 and CD-40 ligand.³⁹ These platelet-leukocyte interactions may be relevant to the development of the late ischemic complications and vessel restenosis that follow angioplasty.^40,41Procedure-related platelet activation and its complications. Percutaneous coronary revascularization causes mechanical laceration and fracture of atherosclerotic plaque, frequently extending through the internal elastic lamina into the media, and denudation of the arterial endothelium.⁴² The platelet appears to be a pivotal mediator of the ensuing pathophysiological response to vascular injury: the physical insult triggers thrombin generation, platelet deposition, mural thrombosis and (through the release of platelet-derived cytokines and growth factors) smooth muscle cell proliferation and neointimal hyperplasia.^43–45 The degree of platelet deposition and thrombosis is governed by the extent of arterial wall injury and by local shear forces caused by the stenosis.^46,47 The platelet-rich mural thrombus initially acts as a hemostatic plug, sealing the vascular injury site; the subsequent healing process involves intense cellular (monocyte/macrophage) infiltration of the thrombus, resulting in its gradual resorption and replacement by neointimal tissue.⁴⁸ Balloon dilatation of the coronary artery produces transient (~48 hours) local platelet activation,^49–53 which forms part of a broader systemic inflammatory response characterized by leukocyte and platelet activation and elevation of C-reactive protein levels.^54,55 Coronary stenting amplifies platelet activation compared to angioplasty alone,^52,56,57 presumably on account of the heightened vessel trauma associated with stent placement and the added presence of thrombogenic surfaces (i.e., bare metal struts). Platelet-rich thrombi appear on stent struts within the first 3 days of stenting, and peak in number during the following week.⁴² Despite the use of intensive anticoagulant therapy (aspirin, heparin and phenprocoumon), coronary stenting results in sustained platelet activation, as indicated by increased surface expression of activated fibrinogen receptors and P-selectin, with the effect peaking 3–6 days after stenting.⁵⁸ Stent design also appears to be relevant, with an open-cell structure producing more pronounced platelet activation over the first 30 days post-stenting than a closed-cell design.⁵⁹ Vascular injury and the accompanying platelet activation contribute to the two major drawbacks of coronary stenting — stent thrombosis and in-stent restenosis. Preprocedural platelet activation, as indicated by enhanced surface expression of the platelet membrane proteins CD62, CD63 and thrombospondin, confers an increased risk of acute ischemic events after balloon angioplasty,⁶⁰ while platelet fibrinogen receptor expression is an independent predictor of subacute stent thrombosis.⁶¹ Subacute thrombotic occlusion of coronary stents, which usually occurs within the first few days to weeks of stent deployment, is a catastrophic complication which manifests itself as acute transmural myocardial infarction in 60% of cases and has a 25% mortality rate.^62,63 In the present era of dual antiplatelet therapy with aspirin and a thienopyridine, the incidence of subacute thrombosis with bare metal stents ranges from a low of 0.4% with intravascular ultrasound guidance to a high of 2.8% after multivessel stenting,⁶⁴ although in the early trials with aspirin and coumadin, it occurred in up to 24% of patients.⁶⁵ In-stent restenosis, characterized by neointimal hyperplasia and collagen deposition within the stent struts, affects 15–25% of de novo lesions in large vessels following bare-metal stent placement; this rate easily doubles in diabetic patients, long diffuse lesions and/or small vessels or bifurcations.^16,66 Restenosis is triggered by mechanical arterial injury and a foreign body response to the device, resulting in acute and chronic inflammation in the arterial wall, platelet activation and proliferation of smooth muscle cells.^67–70 Neointimal hyperplasia peaks during the first three months following stenting,⁷¹ and may be distributed either focally within the stent at the proximal and distal margins or diffusely over the entire stent length, occasionally extending beyond the stent margins.⁷² Animal models of angioplasty have directly implicated the platelet in the intimal proliferation that results from arterial injury: levels of platelet-derived growth factor (PDGF), a potent mitogen and chemoattractant released by activated platelets, correlate with vascular smooth muscle cell proliferation.73 Clinical studies indicate that platelet hyperreactivity is an important factor in the development of restenosis,⁷⁴ and that increased surface GP IIb/IIIa ligand binding increases the likelihood of in-stent restenosis.⁵⁷ Catheter-based brachytherapy is effective in inhibiting recurrent in-stent restenosis,^75,76 but its use is limited by the appearance of late stent thrombosis, which typically occurs > 30 days postintervention.⁷⁷ By inhibiting neointimal proliferation, brachytherapy may delay endothelial regrowth and leave thrombogenic stent surfaces exposed for prolonged periods, thereby promoting platelet deposition and thrombosis⁷⁸ (Figure 3). Platelet involvement in the pathogenesis of late stent thrombosis is suggested by the observation that prolonged (> 3 months) antiplatelet therapy (aspirin plus clopidogrel) reduces the risk of this complication following brachytherapy (see below).⁷⁷ In view of the antiproliferative effects of paclitaxel and sirolimus, late stent thrombosis is also a potential concern with drug-eluting stents, especially in complex lesion subsets.⁷⁹Disease-related platelet activation. In patients with acute coronary syndromes, the short-term platelet activation associated with PCI occurs against a background of persistent platelet hyperreactivity and thrombin generation.^80,81 Platelets remain active long after these patients have been stabilized clinically. In the TIMI-12 trial, patients continued to show elevated platelet activity one month after experiencing an acute coronary syndrome, despite receiving continuous oral treatment with a potent GP IIb/IIIa receptor antagonist.⁸² This would suggest that the prothrombotic environment is maintained for months (possibly longer) after clinical stabilization, possibly contributing to the recurrence of ischemic events over the long term.⁸³ The role of antiplatelet therapy in coronary stenting. Optimal treatment strategies to minimize thrombotic complications following stenting involve aggressive anticoagulation with heparin and combination antiplatelet therapy. Unfractionated heparin is the most widely used antithrombin agent in PCI. Novel alternatives to heparin under clinical investigation include the direct thrombin inhibitors (e.g., bivalirudin), which unlike heparin, have little effect on thrombin generation but are potent inhibitors of preformed thrombin and platelet activation. The thienopyridines (ticlopidine and clopidogrel) exhibit synergistic antiplatelet activity with aspirin⁸⁴ and the aspirin-thienopyridine combination shows evidence of being more effective than aspirin alone in reducing recurrent ischemia following PCI;^85,86 the potential bleeding risk with this combination can be lessened by reducing the daily aspirin dose to less than 100 mg.⁸⁷ Periprocedural use of intravenous GP IIb/IIIa receptor antagonists in conjunction with heparin, aspirin and clopidogrel, further reduces thrombotic complications and improves clinical outcomes post-PCI, albeit at the expense of an increased risk of bleeding complications.⁸⁸ However, routine use of GP IIb/IIIa receptor antagonists in all stent procedures is questionable, largely because of the associated cost and the lack of a demonstrated efficacy advantage over dual antiplatelet therapy.⁸⁹Prevention of periprocedural and acute complications. Pharmacological prevention of subacute thrombosis after stent implantation is crucial, since this complication, which usually occurs in the first month after stenting (i.e., following hospital discharge), almost invariably results in myocardial infarction. Early clinical trials of elective coronary stenting were marked by a high incidence of subacute stent thrombosis (3.5%) despite intensive anticoagulation with aspirin, dipyridamole, heparin and warfarin,^4,5 prompting refinement of implantation techniques and a search for more effective antithrombotic regimens. Replacement of warfarin with ticlopidine was found to halve the risk of subacute thrombosis (1.6%), irrespective of whether or not intravascular ultrasound guidance was used for stent placement.^90,91 Subsequent randomized comparisons of antiplatelet and anticoagulant regimens reported a 5- to 9-fold reduction in the rate of subacute stent thrombosis with aspirin plus ticlopidine versus aspirin plus heparin or warfarin and reductions in major adverse cardiac events, including recurrent myocardial infarction and repeat target vessel revascularization, as well as bleeding^92–95 (Figure 4). A pooled analysis of coronary stent trials has confirmed the low incidence of subacute thrombosis (0.9%) in patients undergoing stenting of native coronary artery lesions while receiving aspirin plus ticlopidine.⁶³ Clopidogrel appears to offer comparable efficacy to ticlopidine in preventing subacute stent thrombosis and periprocedural ischemia,^96–99 and has largely replaced ticlopidine on account of its improved hematological safety (ticlopidine is associated with rare but potentially fatal neutropenia and thrombotic thrombocytopenic purpura). The synergistic anti-ischemic effects of aspirin and clopidogrel are reflected in the observation that, in the PCI subset of the Clopidogrel in Unstable angina to prevent Recurrent Events (PCI-CURE) trial, pre-treatment with clopidogrel and aspirin (median 10 days) provided a ~30% reduction relative to aspirin alone in the incidence of cardiovascular death, myocardial infarction or urgent target vessel revascularization in the first month after PCI for acute coronary syndrome.⁸⁵ It is recommended that patients treated with bare-metal stents (non-drug-eluting stents) should receive dual aspirin and clopidogrel therapy for 4 weeks after PCI.¹⁰⁰ Premature discontinuation of clopidogrel within this period increases the risk of subacute thrombosis by approximately 30-fold,⁷⁹ and so it is important that antiplatelet treatment not be interrupted for minor bleeding or elective invasive or surgical procedures. The intravenous GP IIb/IIIa receptor blockers (which inhibit the final common pathway of platelet aggregation) reduce the risk of periprocedural ischemic events associated with PCI.³⁴ Abciximab, eptifibatide and tirofiban have been shown to produce absolute reductions of 1.5% to 6.5% in the combined incidence of death, myocardial infarction and urgent revascularization at 30 days post-PCI,^101–103 with the benefits persisting for up to 6 months.^103,104 In the Evaluation of Platelet IIb/IIIa Inhibition for Stenting (EPISTENT) trial, abciximab reduced the incidence of death, myocardial infarction and urgent revascularization at 30 days post-stenting from 10.8% to 5.3%, primarily through reductions in death and large (creatine kinase-MB isoenzyme elevation 5 times the upper laboratory limit), non-ST-segment elevation myocardial infarction.¹⁰¹ However, the anti-ischemic benefits of intravenous GP IIb/IIIa receptor blockers do not appear to extend to percutaneous revascularization of coronary bypass grafts, where they increase the risk of major bleeding,¹⁰⁵ or to low-to-intermediate risk patients pretreated with high-dose clopidogrel.⁸⁹Prevention of late complications. The pathophysiological role of platelet activation in the late complications of PCI (late stent thrombosis) and recurrent ischemia provides the rationale for continuing dual antiplatelet therapy (clopidogrel plus aspirin) beyond the conventional 4 weeks post-PCI. The risk of late stent thrombosis is increased by the use of vascular brachytherapy for prevention of in-stent restenosis, and possibly also by the use of drug-eluting stents. This thrombotic risk is reduced by prolonged (> 3 months) dual antiplatelet (aspirin plus thienopyridine) therapy.⁷⁷ In the Washington Radiation for In-Stent Restenosis Trial Plus 6 Months of Clopidogrel (WRIST PLUS) trial, which examined the efficacy and safety of prolonged antiplatelet therapy in prevention of late thrombosis, maintenance of dual clopidogrel and aspirin therapy for 6 months after application of brachytherapy for diffuse in-stent restenosis was associated with a rate of late thrombosis (2.5%) similar to that in placebo (no brachytherapy) controls (0.8%), and significantly lower than that in patients who received only one month of clopidogrel treatment after brachytherapy (9.6%).¹⁰⁶ In the more recent WRIST 12 trial, the extension of aspirin and clopidogrel treatment to 12 months post-brachytherapy produced significant reductions in cardiac event and revascularization rates compared to those obtained in the WRIST PLUS trial: at 15-month follow-up, major cardiac event rates were 21% versus 36%, target lesion revascularization rates were 20% versus 39%, and target vessel revascularization rates were 23% versus 39%.¹⁰⁷ Despite the longer duration of antiplatelet therapy, the transfusion rate in the WRIST 12 study population was no different from that in the WRIST PLUS populations (2.5% versus 3.3%). In the Scripps Coronary Radiation to Inhibit Proliferation Post-Stenting III (SCRIPPS III) trial, which evaluated the effects of prolonged antiplatelet (aspirin plus clopidogrel) therapy and restriction of new stent placement on the occurrence of late thrombosis after brachytherapy, no cases of late thrombosis were reported after 12-month follow-up of ~500 patients.¹⁰⁸ Accordingly, it is recommended that dual antiplatelet therapy should be maintained for at least 12 months in patients undergoing brachytherapy for in-stent restenosis,¹⁰⁹ although the critical duration of therapy remains to be determined. Concern about delayed vessel healing and re-endothelialization with drug-eluting stents (which likewise reduce neointimal proliferation) has also prompted calls for more prolonged antiplatelet (aspirin plus clopidogrel) therapy to prevent possible late stent thrombosis with these devices. While there is no evidence to suggest that the sirolimus-eluting CYPHER™ stent impairs re-endothelialization,¹¹⁰ animal studies with paclitaxel-eluting stents clearly show delayed re-endothelialization.¹¹¹ Currently, based upon the designs of the pivotal clinical trials that led to approval of the CYPHER™ and TAXUS™ stents, dual antiplatelet therapy is prescribed on an empirical basis for at least 3 months following deployment of the sirolimus-eluting stent and for at least 6 months following deployment of the paclitaxel-eluting stent,¹⁰⁰ with many practitioners extending the treatment duration for complex lesion subsets. Recent reports of late stent thrombosis precipitated by discontinuation of aspirin and clopidogrel therapy 11–15 months after implantation of sirolimus- and paclitaxel-eluting stents¹¹² reinforce the case for maintaining long-term antiplatelet therapy after deployment of a drug-eluting stent. The potential value of antiplatelet drugs as adjuncts or alternatives to drug-eluting stents and catheter-based brachytherapy for treatment of in-stent restenosis is unclear. Abciximab has shown modest benefit in reducing the need for target vessel revascularization at 6 months in diabetic patients undergoing stenting,¹¹³ although other studies have reported no benefit against restenosis.^114–116 Cilostazol, an antiplatelet agent with antithrombotic, antiproliferative and vasodilatory properties, has the potential to slow neointimal proliferation after coronary stenting. However, clinical findings to date have been inconsistent, with significant reductions in angiographic restenosis being reported in some studies^117,118 but not in others.¹¹⁹ Results of the recent Cilostazol for RESTenosis (CREST) trial indicate that orally administered cilostazol, used as an adjunct to aspirin and clopidogrel, significantly reduces the degree of in-stent restenosis compared with standard therapy alone.¹²⁰Prevention of recurrent ischemia. It is important to bear in mind that PCI procedures (including drug-eluting stents) are only palliative measures, and that they do not modify the underlying atherosclerotic disease process. Patients with acute coronary syndromes remain at substantial risk of further ischemic events, as reflected in a 6% incidence of death, myocardial infarction or stroke in the first 6 months after hospital discharge.¹²¹ Despite the use of antithrombotic therapy, coronary thrombi remain detectable for 1 month after an acute ischemic event.¹²² Moreover, once short-term antithrombotic therapy is discontinued, the clinical benefits cease. This suggests that long-term antithrombotic therapy is required to prevent further ischemic events. Findings from two recent large-scale randomized trials highlight the clinical benefits to be gained from sustained antiplatelet therapy (clopidogrel plus aspirin) following PCI.85,86 The PCI-CURE study compared the effects of pretreatment (median 10 days) and long-term (mean 8 months) dual clopidogrel plus aspirin therapy versus aspirin monotherapy in 2,658 patients undergoing PCI for non-ST segment elevation acute coronary syndromes.⁸⁵ Both treatment groups received open-label clopidogrel for 4 weeks after PCI to allow coronary stenting. The overall study results (from randomization to the end of follow-up) revealed a highly significant 31% reduction in the combined incidence of cardiovascular death and myocardial infarction with clopidogrel plus aspirin compared to aspirin alone, reflecting the benefits of pretreatment followed by sustained therapy post-PCI. Over the long term (i.e., from the second month post-PCI to the end of follow-up), significant clinical benefit was also seen with the clopidogrel plus aspirin combination, as indicated by an incremental 21% reduction relative to aspirin in the combined incidence of cardiovascular death/myocardial infarction. This efficacy advantage of dual antiplatelet therapy was not associated with any appreciable increase in the risk of major or life-threatening bleeding. The Clopidogrel for the Reduction of Events During Observation (CREDO) study compared the benefits of long-term (12 months) dual clopidogrel plus aspirin therapy with those of aspirin monotherapy in 2,116 patients undergoing PCI.86 Patients were pretreated with either aspirin or aspirin plus clopidogrel in the 24 hours preceding PCI, and all patients received aspirin plus clopidogrel for 28 days after PCI before reverting to their original study treatment (i.e., aspirin alone or aspirin plus clopidogrel). At 12 months’ follow-up, dual antiplatelet therapy was associated with a significant 26.9% relative reduction in the combined risk of death, myocardial infarction or stroke [p = 0.02; number needed to treat (NNT) = 33]. Analysis of short-term (day 0 to day 28) and long-term (day 29 to month 12) outcomes revealed that clopidogrel pre-treatment had no significant effect on this composite endpoint at day 28 (relative risk reduction 19.7%; p = 0.21), whereas continuation of clopidogrel beyond the first month resulted in a significant 37.4% relative risk reduction in ischemic events (p = 0.04; NNT = 59). Given the similar findings noted in the PCI-CURE trial, it would appear that long-term clopidogrel therapy provides modest additional efficacy to aspirin in reducing ischemic risk. Accordingly, dual antiplatelet therapy (aspirin plus clopidogrel), which is given as standard therapy for 3 to 6 months after stenting specifically to reduce the risk of stent thrombosis, offers potential additional benefit in preventing recurrent ischemia when continued for 12 months post-stenting.^85,86Long-term adjunctive therapy for secondary prevention. Risk factor modification is critical to reducing the risk of future ischemic events post-PCI, offering the prospect of slower lesion progression, reduced formation of de novo lesions and, possibly, plaque regression.^30,123,124 Accordingly, patients scheduled to undergo cardiac catheterization and PCI should be instructed about necessary lifestyle and risk-factor modifications as well as appropriate medical therapies for secondary prevention prior to hospital discharge. Depending on the risk factors and contraindications present, advice should include antiplatelet (aspirin and clopidogrel) therapy, ACE inhibitor therapy, hypertension control, diabetes management, aggressive control of serum lipids to a target LDL-cholesterol goal of at least 34 Evidence for the use of statins for secondary prevention is compelling: statins initiated immediately after PCI reduce the risk of cardiac events,^125–127 possibly on account of their anti-inflammatory effects.¹²⁵ These agents are effective in reducing mortality and recurrent revascularization rates in patients with elevated cholesterol levels,¹²⁸ normal cholesterol levels (115–174 mg/dl),¹²⁹ and below-normal cholesterol levels (115 mg/dl).¹³⁰ Intensive lipid-lowering provides greater cardiovascular protection than moderate lipid-lowering after acute coronary syndromes.¹³¹ Therefore, all patients should be discharged on statin therapy (unless contraindicated), with supplementary dietary measures and exercise. ACE inhibitors have an important role in the secondary prevention of coronary artery disease, reducing the risk of cardiovascular death, ischemic events and repeat revascularization in both high-risk¹³² and low-risk¹³³ patients, and are appropriate for many patients post-PCI, regardless of systolic function. Long-term‚ b-blocker therapy is indicated in patients with a history of myocardial infarction.¹³⁴ Conclusions Coronary stenting has gained wide popularity over the past decade by providing a better initial angiographic result as well as lower rates of abrupt vessel closure and angiographic and clinical restenosis. Stent technology has advanced significantly, allowing easier stent deployment and access to more difficult types of lesions. At the same time, the shift from warfarin to aspirin and clopidogrel use has reduced the risk of periprocedural complications and stent thrombosis. In elective PCI, the combined balloon/stent/pharmacological approach currently achieves angiographic success rates of 96–99%, with in-hospital mortality rates of 0.5–1.4%, and next-day discharge is now feasible in most cases.³⁴ As acute procedural outcomes improve and restenosis becomes less problematic, interventional cardiology needs to focus on the underlying atherosclerotic disease process and its long-term consequences. PCI is only a palliative procedure and patients require lifelong secondary prevention interventions: aggressive medical management, with control of lipids, hypertension, diabetes, obesity and smoking, should form the foundation of effective long-term care after PCI. Interventional cardiologists in particular should be at the forefront of cardiovascular prevention, ensuring that efforts are made to halt the atherosclerotic disease process after the culprit lesion has been successfully stented.

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