Procedure

Vascular access is obtained either through the femoral or radial artery, where a sheath is introduced with the use of local anesthesia. A 5F to 8F guiding catheter is advanced through the sheath to the ostium of the coronary artery to be dilated. Once the guiding catheter is positioned in the coronary ostium, angiography of the diseased artery is performed to visualize the stenosis and the arterial segments proximal and distal to it; intracoronary infusion of nitrates is mandatory for the diagnosis and accurate sizing of the lesions and the choice of stent (Figure 77-1, A). A flexible guidewire is advanced through the guiding catheter, navigated across the stenosis by rotating and advancing its angulated tip, and positioned in the distal arterial segment. The deflated balloon angioplasty catheter is advanced over the wire and positioned at the stenosis. The positions of the guidewire and balloon catheter are confirmed periodically by injecting contrast medium into the coronary artery through the guiding catheter. Once it is positioned, the balloon is usually inflated with a mixture of saline and contrast medium so the inflation can be visualized (see Figure 77-1, B and C). Most often, a stent is implanted after balloon angioplasty (Figure 77-2). Balloon-expandable stents are most commonly used. The stent-balloon device is positioned on the predilated site (see Figure 77-1, D), and the stent is implanted in the coronary artery wall by a short balloon inflation (see Figure 77-1, E). The balloon catheter is deflated and pulled out. The result is evaluated by injecting contrast medium (see Figure 77-1, F). If the result is satisfactory, the guidewire is removed. If the angiographic result is unsatisfactory, the guidewire remains in place. The balloon catheter can be replaced by a larger one, or another stent can be implanted. At the end of the procedure, a final angiogram is obtained to confirm that the result is satisfactory.

Figure 77-1 Coronary angioplasty procedure.

A, Critical stenosis in midsegment of a right coronary artery. B, Inflation of a 3.5-mm-diameter angioplasty balloon. C, Angiographic control after balloon inflation. D, Placement of a 3.5-mm-diameter, 18-mm-long metal stent. E, Inflation of the balloon. F, Final result.

Figure 77-2 Implantation of a coronary stent.

A, Placement of balloon catheter. B, Predilation with balloon catheter. C, Balloon is withdrawn. D, Placement of coronary stent, which has been crimped on a balloon catheter. E, Inflation of balloon and expansion of stent. F, Withdrawal of balloon catheter and final result.

In noncalcified lesions, direct stent implantation without prior balloon dilation is often performed. Direct stenting shortens the duration of the procedure and reduces costs and is used in approximately 30% to 50% of cases.⁵

Preprocedure and Postprocedure Management and Medications

The combination of low-dose aspirin (75-325 mg) and clopidogrel has been shown to reduce the incidence of acute stent occlusion after PTCA and is considered essential therapy before coronary interventions.^6,7 If patients are not treated chronically or if there is doubt about medication compliance, a dose of aspirin (500 mg orally) should be given more than 3 hours prior, or at least 300 mg intravenously (IV) directly prior to the procedure. For chronic use, there is no need for doses higher than 100 mg daily.⁸ Current guidelines recommend a loading dose of clopidogrel, 300 mg, administered at least 6 hours before the procedure. Higher loading doses (600 mg) lead to more rapid (around 2 hours) and long-lasting inhibition of platelet aggregation. The CURRENT-OASIS 7 trial compared 300-mg and 600-mg clopidogrel loading doses and demonstrated fewer adverse events with a loading dose of 600 mg of clopidogrel, followed by 150 mg daily for a week, and 75 mg daily for at least 3 weeks.⁹

Despite administration of dual antiplatelet therapy combining aspirin and clopidogrel, a small percentage (0.4-1.1%) still suffer subacute stent thrombosis. Variability in response to clopidogrel may account for some of these events,^10–12 and more potent antiplatelet agents have been investigated. Prasugrel, a novel oral thienopyridine, has a more rapid onset and predictable and potent antiplatelet effects.^13,14 In the TRITON-TIMI 38 trial,¹⁵ 13,608 moderate to high-risk ACS patients were randomized to prasugrel (60-mg loading dose followed by 10 mg daily) or clopidogrel (300-mg loading dose followed by 75 mg daily). Follow-up was up to 15 months. Prasugrel was associated with a 19% reduction in the primary efficacy endpoint of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke. This was accompanied by a 32% increase of major bleeding, especially in subgroups of patients with cerebrovascular accident, weight less than 60 kg, and older than 75 years of age. Ticagrelor, a reversible and direct-acting oral antagonist of the adenosine diphosphate receptor P2Y12, provides faster, greater, and more consistent platelet inhibition than clopidogrel. PLATO,¹⁶ a multicenter double-blind, randomized trial compared ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter) for the prevention of cardiovascular events in 18,624 patients with an ACS. At 12 months, ticagrelor significantly reduced the occurrence of the primary endpoint, a composite of death from vascular causes, MI, or stroke—9.8% of patients receiving ticagrelor as compared with 11.7% of those receiving clopidogrel (hazard ratio, 0.84; 95% confidence interval [CI], 0.77 to 0.92; P < 0.001). No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups (11.6% and 11.2%, respectively; P = 0.43), but ticagrelor was associated with a higher rate of major bleeding unrelated to coronary artery bypass grafting (CABG) (4.5% versus 3.8%, P = 0.03), including more instances of fatal intracranial bleeding and fewer fatal bleeding of other types.

Intracoronary nitrates are given at the beginning of and during the procedure to prevent vasospasm. Unfractionated heparin (typically 5000 to 10,000 units) is administered IV during PTCA to decrease the incidence of coronary artery thrombosis,¹⁷ but it is usually not continued after the procedure. Low-molecular-weight heparin has been suggested as an accepted alternative to unfractionated heparin.¹⁸

Although the mainstay of antiplatelet and anticoagulation therapy for PTCA is the combination of clopidogrel and aspirin before and after the procedure and heparin during it, the use of platelet glycoprotein IIb/IIIa inhibitors or the direct thrombin inhibitor, bivalirudin, have emerged as powerful adjunctive therapies. The platelet glycoprotein IIb/IIIa receptor binds fibrinogen to cross-link platelets and can be blocked irreversibly by inhibitors such as abciximab, eptifibatide, and tirofiban. Several multicenter randomized studies have compared heparin and aspirin to an additional treatment with platelet glycoprotein IIb/IIIa receptor inhibitors in patients undergoing PTCA and showed a significant reduction in major clinical events.^19–21 The greatest treatment benefit of platelet glycoprotein IIb/IIIa inhibitors appears to be in procedures on high-risk lesions or in patients with severe clinical patterns, such as ACS with ST-segment changes or elevation of biological markers of myocardial necrosis.^22–24 Bivalirudin, when used instead of heparin plus glycoprotein IIb/IIIa inhibitors, has been shown in large-scale randomized trials to reduce major and minor bleeding and thrombocytopenia while resulting in similar rates of ischemia after percutaneous intervention (PCI) in patients with stable angina or ACS.²⁵

The femoral arterial sheath is usually removed immediately after PTCA. Hemostasis is obtained by either manual compression or use of closure devices. Patients with stable angina and an uncomplicated procedure are usually discharged the day after removal of the sheath. Medications prescribed at the time of discharge depend on the underlying condition. Most often, the post-PTCA regimen includes low-dose aspirin, clopidogrel, a beta-blocker or a calcium antagonist, and a statin.

Although the femoral artery remains the most widely used approach in the United States for diagnostic and therapeutic procedures, the radial artery is used increasingly to reduce the local complication rate and increase the patient’s comfort. The sheath is pulled out immediately after the procedure, and hemostasis is obtained by applying a pressure dressing for several hours.²⁶ Immediate ambulation is feasible, and hospital discharge on the same day is possible in selected cases.²⁷

Efficacy of the Procedure

PTCA of a nonoccluded coronary artery is successful in more than 97% of patients. In the remaining patients, PTCA is unsuccessful because the stenosis cannot be crossed with either the guidewire or the balloon catheter, or because the stenosis is not adequately dilated despite the use of an appropriately sized balloon and stents. In 2% to 3% of cases, the vessel abruptly occludes (abrupt closure) during or immediately after the procedure. Reopening of the artery is attempted with repeat balloon inflations and multiple stent implantations. Stenting for abrupt closure (bailout stenting) has virtually eliminated the need for urgent coronary bypass surgery after failed PTCA. The most challenging lesions (long, angulated, calcified, or associated with intraluminal thrombus) carry a lower success rate.²⁸ PTCA also has a lower initial success rate (50%-70%) in patients with chronically occluded arteries, because it may be difficult to manipulate the guidewire through a chronically occluded region.^29,30 In patients with recurrent angina after bypass surgery, the success rate of PTCA performed for properly selected stenosis of saphenous and arterial bypass grafts is close to that of native arteries, but the incidence of late events (MI, repeat PTCA, or other surgery) is higher.^31,32

Mechanisms of Coronary Artery Dilatation

The mechanisms by which PTCA increases the size of the arterial lumen have been studied in animals and cadavers.^33–36 Balloon-induced barotrauma causes endothelial denudation, cracking and disruption of the atherosclerotic plaque, and stretching or tearing of the media and adventitia (Figure 77-3). These brutal and profound changes account for the postballoon inflation angiographic features of intraluminal haziness, intimal flap, or dissection (Figure 77-4). Intracoronary ultrasound imaging, which provides a cross-sectional view of the artery within the lumen, detects dissection of the arterial wall—sometimes extensive—in 50% to 80% of patients who have undergone successful PTCA.^37,38 These morphologic alterations open up new pathways for blood flow, leading to an increased luminal size. Balloon inflation may be deleterious, however, causing plaque hemorrhage, extensive dissection resulting in luminal compromise, platelet deposition, and thrombus formation.

Figure 77-3 Pathologic specimen after coronary angioplasty. Balloon inflation has created plaque rupture with hemorrhage.

Figure 77-4 Arterial dissection (arrow) after balloon inflation in midsegment of a right coronary artery.

In the weeks after successful PTCA, favorable remodeling of the disrupted plaque and endothelialization at the sites of intimal injury result in an increased luminal size. Angiographic studies indicate that intimal disruption usually resolves within 1 month after successful PTCA.³⁹

Restenosis

In patients who have undergone successful PTCA, recurrence of the stenosis, or restenosis, was the main limitation to long-term, event-free survival. Restenosis occurs in about 30% to 50% of patients in whom a coronary artery stenosis has been dilated by balloon alone.^40–42 Restenosis typically occurs 1 to 6 months after PTCA.⁴⁰

The process of restenosis is multifactorial. Injury of the vessel initiates release of thrombogenic, vasoactive, and mitogenic factors.⁴³ Endothelial and deep-vessel injury leads to platelet aggregation, thrombus formation, inflammation, and activation of macrophages. These events induce the production and release of growth factors and cytokines, which in turn may promote their own synthesis and release from target cells.⁴⁴ A self-perpetuating process is initiated that results in the migration of smooth muscle cells from their usual location in the arterial media to the intima, where they change to a synthetic phenotype, produce extracellular matrix, and proliferate, thereby resulting in a stenosis within the vessel lumen. Intimal thickening accounts for about 30% of the loss in lumen diameter 6 months after coronary interventions. In addition, arterial remodeling occurs in the weeks after PTCA and can be evaluated using serial intravascular ultrasound imaging to measure the reduction in the cross-sectional area of the vessel.^45,46

Coronary stenting with bare metal stents significantly reduces the incidence of restenosis, because it produces large lumens and staves off pathologic remodeling.^47,48 Several multicenter randomized trials showed that the incidence of restenosis is 25% to 50% lower after coronary stenting than after balloon angioplasty. Drug-eluting stents have been developed to further reduce the restenosis rate. Stents are covered with a polymer that allows progressive delivery of antiproliferative drugs such as sirolimus, paclitaxel, or everolimus that inhibit smooth muscle cell proliferation. The restenosis rate has been virtually abolished with drug-eluting stents, with no increase in the acute complication rate.⁴⁹ Currently, drug-eluting stents are used in the majority of procedures.

An annual rate of 0.4 to 0.6% of late stent thrombosis has been noted after implantation of sirolimus- or paclitaxel-eluting stents, with no increase of death or MI.⁵⁰ Incomplete endothelial coverage of the stent and a prolonged inflammatory reaction to the polymer have been suggested as causal factors. Current guidelines recommend dual antiplatelet therapy for 12 months after implantation of drug-eluting stents, although no randomized trial has proved the efficacy of this strategy to prevent late stent thrombosis.^8,51 Interruption of clopidogrel administration after implantation of a drug-eluting stent is associated with acute stent thrombosis, especially during the first 6 months.⁵²