The common misconception that seafood allergies and contrast reactions are cross-reactions to iodine probably arose from a survey published in 1975 in which 15% of patients with a history of contrast reaction reported a personal history of shellfish allergy, but nearly identical proportions of patients reported allergies to other foods, such as milk and egg, in the same survey.287 Pretreatment of patients with steroids based only on a history of seafood or shellfish allergy has a small but non-zero risk of adverse effect (eg, hyperglycemia in a patient with diabetes) without any demonstrated benefit.288,289 4.6. Statin Treatment: Recommendation Class IIa 1. Administration of a high-dose statin is reasonable before PCI to reduce the risk of periprocedural MI. (Level of Evidence: A for statin-na ve patients290 296; (Level of Evidence: B for those on chronic statin See Online Data Supplement 19 for additional data regarding preprocedural statin treatment. Statins have long-term benefits in patients with CAD343,344 and ACS.345,346 The benefits of statins in ACS begin early, before substantial lipid lowering has oc- curred,345,347 suggesting pleiotropic effects of statins. These might include anti-inflammatory effects, improve- ment of endothelial function, decrease of oxidative stress, or inhibition of thrombogenic responses.348 Statins were beneficial when pretreatment was started from 7 days to 4.7. Bleeding Risk: Recommendation Class I 1. All patients should be evaluated for risk of bleeding before PCI. (Level of Evidence: C) Periprocedural bleeding is now recognized as a major risk factor for subsequent mortality.265,266 Bleeding may lead to mortality directly (because of the bleeding event) or through ischemic complications that occur when antiplatelet or anti- coagulant agents are withdrawn in response to the bleeding. Bleeding may also be a marker of comorbidities associated with worse prognosis (eg, occult cancer). The risk of bleeding is associated with a number of patient factors (eg, advanced age, low body mass index, CKD, baseline anemia), as well as the degree of platelet and thrombin inhibition, vascular access site, and sheath size.267 269 The overall approach to PCI should be individualized to minimize both ischemic and bleeding risks. Measures to minimize the risks of bleeding complica- tions are discussed in several sections of this guideline. These include use of anticoagulation regimens associated with a lower risk of bleeding, weight-based dosing of heparin and other agents, use of activated clotting times to guide unfractionated heparin (UFH) dosing, avoidance of excess anticoagulation,349 dosing adjustments in patients with CKD (eg, eptifibatide, tirofiban, bivalirudin),350 use of radial artery access site,255 and avoidance of femoral vein cannulation when possible. Vascular closure devices have not been clearly demonstrated to decrease bleeding complications and are discussed in detail in Section 5.11. 4.8. PCI in Hospitals Without On-Site Surgical Backup: Recommendations Class IIa 1. Primary PCI is reasonable in hospitals without on-site cardiac surgery, provided that appropriate planning for program development has been accom- plished.351,352 (Level of Evidence: B) Class IIb 1. Elective PCI might be considered in hospitals with- out on-site cardiac surgery, provided that appropri- ate planning for program development has been accomplished and rigorous clinical and angiographic criteria are used for proper patient selection.352 354 (Level of Evidence: B) Class III: HARM 1. Primary or elective PCI should not be performed in hospitals without on-site cardiac surgery capabilities without a proven plan for rapid transport to a cardiac surgery operating room in a nearby hospital or without appropriate hemodynamic support capa- bility for transfer. (Level of Evidence: C) See Online Data Supplement 20 for additional data regarding hospitals without on-site surgical backup. Primary and elective PCI can be performed at hospitals without on-site cardiac surgical backup with a high success rate, low in-hospital mortality rate, and low rate for emer- gency CABG.351,353,354 The best outcomes for patients with STEMI are achieved at hospitals with 24/7 access to primary PCI.355 Criteria for the performance of PCI without on-site surgical backup have been proposed in an SCAI expert consensus document.352 Consideration of elective PCI with- out on-site cardiac surgical backup is thought to be appropri- ate only when performed by experienced operators with complication rates and outcomes equivalent or superior to national benchmarks. Accurate assessment of complication rates and patient outcomes via a regional or national data registry, so that outcomes can be compared with established benchmarks, is an important quality control component of any PCI program. Desires for personal or institutional finan- cial gain, prestige, market share, or other similar motives are not appropriate considerations for initiation of PCI programs without on-site cardiac surgery. It is only appropriate to consider initiation of a PCI program without on-site cardiac surgical backup if this program will clearly fill a void in the healthcare needs of the community. Competition with another PCI program in the same geographic area, particularly an established program with surgical backup, may not be in the best interests of the community. Tables 5 and 6 list the SCAI expert consensus document requirements for PCI programs without on-site surgical backup. Table 7 gives the requirements for primary PCI and emergency CABG at hospitals without on-site cardiac sur- gery, and Table 8 lists the requirements for patient and lesion selection and backup strategy for nonemergency PCI.352 5. Procedural Considerations 5.1. Vascular Access: Recommendation Class IIa 1. The use of radial artery access can be useful to decrease access site complications.255,260,356 362 (Level of Evidence: A) See Online Data Supplement 21 for additional data regarding radial access. Femoral artery access remains the most commonly used approach in patients undergoing PCI in the United States. Choosing a femoral artery puncture site is facilitated by fluoroscopic landmark identification or ultrasound guidance. Low punctures have a high incidence of peripheral artery complications, whereas high punctures have an increased risk of retroperitoneal hemorrhage. In patients with a synthetic graft, arterial access is possible after the graft is a few months old and complication rates are not increased.254 Radial site access is used frequently in Europe and Canada but not in the United States.260 A learning curve exists for the radial approach that will affect procedure time and radiation dose, with a trend toward lower procedural success rates for radial versus femoral access.255 However, compared with femoral access, radial access decreases the rate of access- Table 5. SCAI Expert Consensus Document Personnel and Facility Requirements for PCI Programs Without On-Site Surgical Backup Experienced nursing and technical laboratory staff with training in interventional laboratories. Personnel must be comfortable treating acutely ill patients with hemodynamic and electrical instability. On-call schedule with operation of laboratory 24 h/d, 365 d/y.* Experienced coronary care unit nursing staff comfortable with invasive hemodynamic monitoring, operation of temporary pacemaker, and management of IABP. Personnel capable of endotracheal intubation and ventilator management both on-site and during transfer if necessary. Full support from hospital administration in fulfilling the necessary institutional requirements, including appropriate support services (eg, respiratory care, blood bank). Written agreements for emergency transfer of patients to a facility with cardiac surgery. Transport protocols should be developed and tested a minimum of 2 times per year. Well-equipped and maintained cardiac catheterization laboratory with high-resolution digital imaging capability and IABP equipment compatible with transport vehicles. The capability for real-time transfer of images and hemodynamic data (via T-1 transmission line) as well as audio and video images to review terminals for consultation at the facility providing surgical backup support is ideal. Appropriate inventory of interventional equipment, including guide catheters, balloons, and stents in multiple sizes; thrombectomy and distal protection devices; covered stents; temporary pacemakers; and pericardiocentesis trays. Pressure wire device and IVUS equipment are optimal but not mandatory. Rotational or other atherectomy devices should be used cautiously in these facilities because of the greater risk of perforation. Meticulous clinical and angiographic selection criteria for PCI (Tables 6 and 7). Performance of primary PCI as the treatment of first choice for STEMI to ensure streamlined care paths and increased case volumes. Door-to-balloon times should be tracked, and 90 min outlier cases should be carefully reviewed for process improvement opportunities. On-site rigorous data collection, outcomes analysis, benchmarking, quality improvement, and formalized periodic case review. Participation in a national data registry where available, such as the ACC NCDR in the United States. *Required for US facilities but may not be possible for all facilities worldwide. ACC indicates American College of Cardiology; IABP, intra-aortic balloon pump; IVUS, intravascular ultrasound; NCDR, National Cardiovascular Data Registry; PCI, percutaneous coronary intervention; SCAI, Society for Cardiovas- cular Angiography and Interventions; and STEMI, ST-elevation myocardial infarction. Adapted with permission from Dehmer et al.352 Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e595 related bleeding and complications.255,260,363 In a recent large RCT comparing radial and femoral access in patients with ACS undergoing PCI, there was no difference in the primary composite endpoint (death, MI, stroke, major bleeding), although there was a lower rate of vascular complications with the use of radial access.362 Radial artery access is particularly appealing in patients with coagulopathy, elevated international normalized ratio due to warfarin, or morbid obesity. 5.2. PCI in Specific Clinical Situations 5.2.1. UA/NSTEMI: Recommendations Class I 1. An early invasive strategy (ie, diagnostic angiogra- phy with intent to perform revascularization) is indicated in UA/NSTEMI patients who have refrac- tory angina or hemodynamic or electrical instability (without serious comorbidities or contraindications to such procedures).207,364,365 (Level of Evidence: B) 2. An early invasive strategy (ie, diagnostic angiography with intent to perform revascularization) is indicated in initially stabilized UA/NSTEMI patients (without serious comorbidities or contraindications to such pro- cedures) who have an elevated risk for clinical events.207,365 367 (Level of Evidence: A) 3. The selection of PCI or CABG as the means of revascularization in the patient with ACS should generally be based on the same considerations as those without ACS.53,156,207,368 (Level of Evidence: B) Class III: NO BENEFIT 1. An early invasive strategy (ie, diagnostic angiogra- phy with intent to perform revascularization) is not recommended in patients with extensive comorbidi- ties (eg, liver or pulmonary failure, cancer) in whom (Level of Evidence: C) a. The risks of revascularization and comorbid con- ditions are likely to outweigh the benefits of revascularization, b. There is a low likelihood of ACS despite acute chest pain, or c. Consent to revascularization will not be granted regardless of the findings. The goals of coronary angiography and revascularization in UA/NSTEMI patients are to reduce the risk of death and MI and provide symptom relief. To improve prognosis, early risk stratification is essential for selection of medical and/or invasive treatment strategies. Indications for revasculariza- tion depend on the patient s clinical risk characteristics and coronary anatomy and are in general stronger in the presence of high-risk clinical presentation (eg, dynamic electrocardio- Table 6. SCAI Expert Consensus Document Requirements for Off-Site Surgical Backup 1. Interventional cardiologists establish a working relationship with cardiac surgeons at the receiving facility. 2. Cardiac surgeon must have privileges at the referring facility to allow review of treatment options as time allows. 3. Cardiac surgeon and receiving hospital agree to provide cardiac surgical backup for urgent cases at all hours and for elective cases at mutually agreed hours. 4. Surgeon and receiving facility ensure that patients will be accepted based on medical condition, capacity of surgeon to provide services at the time of request, and availability of resources. If this cannot be ensured before the start of an elective procedure, the case should not be done at this time. 5. Interventional cardiologists must review with surgeons the immediate needs and status of any patient transferred for urgent surgery. 6. Hospital administrations from both facilities endorse transfer agreement. 7. Transferring and receiving facilities establish a rigorous protocol for rapid transfer of patients, including the proper personnel with appropriate experience. 8. A transport provider is available to begin transport within 20 min of the request and provide vehicle/helicopter with necessary life-sustaining equipment, including IABP and monitoring capability. 9. Transferring physician obtains consent for surgery from patient or appropriate surrogate. 10. Initial informed consent for PCI discloses that the procedure is being done without on-site surgical backup and acknowledges the possibility of risks related to transfer. The consent process should include the risk of urgent surgery (approximately 0.3%) and state that a written plan for transfer exists. 11. As part of the local continuous quality improvement program, a regular review of all patients transferred for emergency surgery with the outcome of surgery and identification of any improvement opportunities. IABP indicates intra-aortic balloon pump; PCI, percutaneous coronary interven- tion; and SCAI, Society for Cardiovascular Angiography and Interventions. Adapted with permission from Dehmer et al.352 Table 7. SCAI Expert Consensus Document Requirements for Primary PCI and Emergency Aortocoronary Bypass Surgery at Hospitals Without On-Site Cardiac Surgery Avoid intervention in patients with 50% diameter stenosis of left main artery proximal to infarct-related lesion, especially if the area in jeopardy is relatively small and overall LV function is not severely impaired Long, calcified, or severely angulated target lesions at high risk for PCI failure with TIMI flow grade 3 present during initial diagnostic angiography Lesions in other than the infarct artery (unless they appeared to be flow limiting in patients with hemodynamic instability or ongoing symptoms) Lesions with TIMI flow grade 3 that are not amenable to stenting in patients with left main or 3-vessel disease that will require coronary bypass surgery Culprit lesions in more distal branches jeopardizing only a modest amount of myocardium when there is more proximal disease that could be worsened by attempted intervention Transfer emergently for coronary bypass surgery patients with High-grade left main or 3-vessel coronary disease with clinical or hemodynamic instability after successful or unsuccessful PCI of an occluded vessel and preferably with IABP support Failed or unstable PCI result and ongoing ischemia, with IABP support during transfer IABP indicates intra-aortic balloon pump; LV, left ventricular; PCI, percuta- neous coronary intervention; SCAI, Society for Cardiovascular Angiography and Interventions; and TIMI, Thrombolysis in Myocardial Infarction. Adapted with permission from Dehmer et al.352 gram [ECG] changes, elevated troponin, high Global Registry of Acute Coronary Events score), recurrent symptoms, threat- ened viable myocardium, CKD, and larger ischemic burden (Appendix 4E). For choice of revascularization technique, the anatomical considerations are generally those used for stable CAD, although PCI may initially be performed in the index lesion to stabilize the patient (Section 2). Contemporary studies variably comparing strategies of very early (within hours of admission), early (within 24 hours of admission), and delayed (1 to 7 days after admission) cardiac catheterization and revascularization support a strat- egy of early angiography and revascularization to reduce the risk of recurrent ischemia and MI, particularly among those at high risk (eg, Global Registry of Acute Coronary Events score 140),367,369,370 whereas a delayed approach is reason- able in low-intermediate risk patients (based on clinical course). There is no evidence that incremental benefit is derived by angiography and PCI performed within the first few hours of hospital admission.207,367,371 378 5.2.2. ST-Elevation Myocardial Infarction 5.2.2.1. Coronary Angiography Strategies in STEMI: Recommendations Class I 1. A strategy of immediate coronary angiography with intent to perform PCI (or emergency CABG) in patients with STEMI is recommended for a. Patients who are candidates for primary PCI.351,379 382 (Level of Evidence: A) b. Patients with severe heart failure or cardiogenic shock who are suitable candidates for revascular- ization.383,384 (Level of Evidence: B) Class IIa 1. A strategy of immediate coronary angiography (or transfer for immediate coronary angiography) with intent to perform PCI is reasonable for patients with STEMI, a moderate to large area of myocardium at risk, and evidence of failed fibrinolysis.385,386 (Level of Evidence: B) 2. A strategy of coronary angiography (or transfer for coronary angiography) 3 to 24 hours after initiating fibrinolytic therapy with intent to perform PCI is reasonable for hemodynamically stable patients with STEMI and evidence for successful fibrinolysis when angiography and revascularization can be per- formed as soon as logistically feasible in this time frame.387 391 (Level of Evidence: A) Class IIb 1. A strategy of coronary angiography performed be- fore hospital discharge might be reasonable in stable patients with STEMI who did not undergo cardiac catheterization within 24 hours of STEMI onset. (Level of Evidence: C) Class III: NO BENEFIT 1. A strategy of coronary angiography with intent to perform PCI is not recommended in patients with STEMI in whom the risks of revascularization are likely to outweigh the benefits or when the patient or designee does not want invasive care. (Level of Evidence: C) The historical reperfusion strategies of primary PCI, imme- diate PCI, rescue PCI, deferred PCI, facilitated PCI, and the pharmacoinvasive strategy have evolved in parallel with advances in antithrombotic therapy and STEMI prehospital and hospital systems of care. The clinical challenge in primary PCI is achieving rapid time to treatment and increasing patient access to this preferred reperfusion strategy. The clinical challenge in patients treated with fibrinolytic therapy is deciding for whom and when to perform coronary angiography. In unstable patients (eg, severe heart failure or cardiogenic shock, hemodynamically compromising ventricular arrhyth- Table 8. SCAI Expert Consensus Document Requirements for Patient and Lesion Selection and Backup Strategy for Nonemergency PCI by Experienced Operators at Hospitals Without On-Site Cardiac Surgery Patient risk: expected clinical risk in case of occlusion caused by procedure High patient risk: Patients with any of the following Decompensated congestive heart failure (Killip Class 3) without evidence for active ischemia, recent CVA, advanced malignancy, known clotting disorders LVEF 25% Left main stenosis ( 50% diameter) or 3-vessel disease unprotected by prior bypass surgery ( 70% stenoses in the proximal segment of all major epicardial coronary arteries) Single-target lesion that jeopardizes 50% of remaining viable myocardium Lesion risk: probability that procedure will cause acute vessel occlusion Increased lesion risk: lesions in open vessels with any of the following characteristics Diffuse disease ( 2 cm in length) and excessive tortuosity of proximal segments More than moderate calcification of a stenosis or proximal segment Location in an extremely angulated segment ( 90%) Inability to protect major side branches Degenerated older vein grafts with friable lesions Substantial thrombus in the vessel or at the lesion site Any other feature that may, in the operator s judgment, impede successful stent deployment Aggressive measures to open CTOs are also discouraged because of an increased risk of perforation Strategy for surgical backup based on lesion and patient risk High-risk patients with high-risk lesions should not undergo nonemergency PCI at a facility without on-site surgery. High-risk patients with non high-risk lesions: Nonemergency patients with this profile may undergo PCI, but confirmation that a cardiac surgeon and operating room are immediately available is necessary. Non high-risk patients with high-risk lesions require no additional precautions. Non high-risk patients with non high-risk lesions require no additional precautions. Best scenario for PCI without on-site surgery. CTO indicates chronic total occlusion; CVA, cerebrovascular accident; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention; and SCAI, Society for Cardiovascular Angiography and Interventions. Adapted with permission from Dehmer et al.352 Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e597 mias) not treated initially with primary PCI, a strategy of immediate coronary angiography with intent to perform PCI is implemented unless invasive management is considered futile or unsuitable given the clinical circumstances.383,384 In stable patients treated with fibrinolytic therapy and clinical suspicion of reperfusion failure, a strategy of imme- diate coronary angiography followed by PCI improves out- come in those at high risk.385,386 Such a strategy is also implemented in patients with evidence for infarct artery reocclusion (Table 9). The clinical diagnosis of failed fibri- nolysis is difficult but is best made when there is 50% ST-segment resolution 90 minutes after initiation of therapy in the lead showing the greatest degree of ST-segment elevation at presentation. Given the association between bleeding events and adverse cardiac events, a reasonable approach is to select moderate- and high-risk patients for PCI and treat low-risk patients with medical therapy. ECG and clinical findings of anterior MI or inferior MI with right ventricular involvement or precordial ST-segment depression, as well as ongoing pain, usually predicts increased risk and the greatest potential benefit.392 Conversely, patients with symptom resolution, improving ST-segment elevation, or inferior MI localized to 3 ECG leads probably gain little benefit. In stable patients treated with fibrinolytic therapy and clinical evidence for successful reperfusion, an early invasive strategy with cardiac catheterization performed within 24 hours de- creases reinfarction and recurrent ischemic events.388,390,391 Be- cause of the associated increased bleeding risk, very early ( 2 to 3 hours) catheterization after administration of fibrinolytic ther- apy with intent to perform revascularization should be reserved for patients with evidence of failed fibrinolysis and significant myocardial jeopardy for whom immediate angiography and revascularization would be appropriate.393 5.2.2.2. Primary PCI of the Infarct Artery: Recommendations Class I 1. Primary PCI should be performed in patients within 12 hours of onset of STEMI.379 382 (Level of Evidence: A) 2. Primary PCI should be performed in patients with STEMI presenting to a hospital with PCI capability within 90 minutes of first medical contact as a systems goal.394,395 (Level of Evidence: B) 3. Primary PCI should be performed in patients with STEMI presenting to a hospital without PCI capa- bility within 120 minutes of first medical contact as a systems goal.396 398 (Level of Evidence: B) 4. Primary PCI should be performed in patients with STEMI who develop severe heart failure or cardio- genic shock and are suitable candidates for revascu- larization as soon as possible, irrespective of time delay.383,384 (Level of Evidence: B) 5. Primary PCI should be performed as soon as possi- ble in patients with STEMI and contraindications to fibrinolytic therapy with ischemic symptoms for less than 12 hours.399,400 (Level of Evidence: B) Class IIa 1. Primary PCI is reasonable in patients with STEMI if there is clinical and/or electrocardiographic evi- dence of ongoing ischemia between 12 and 24 hours after symptom onset.401 403 (Level of Evidence: B) Class IIb 1. Primary PCI might be considered in asymptomatic patients with STEMI and higher risk presenting between 12 and 24 hours after symptom onset. (Level of Evidence: C) Class III: HARM 1. PCI should not be performed in a noninfarct artery at the time of primary PCI in patients with STEMI without hemodynamic compromise.404 408 (Level of Evidence: B) Primary PCI is preferred to fibrinolytic therapy when time- to-treatment delays are short and the patient presents to a high-volume, well-equipped center staffed with expert inter- ventional cardiologists and skilled support staff. Compared with fibrinolytic therapy in RCTs, primary PCI produces higher rates for infarct artery patency, TIMI flow grade 3, and Table 9. Indications for Coronary Angiography in STEMI Indications COR LOE References Immediate coronary angiography Candidate for primary PCI I A 351,379 382 Severe heart failure or cardiogenic shock (if suitable revascularization candidate) I B 383,384 Moderate to large area of myocardium at risk and evidence of failed fibrinolysis IIa B 385,386 Coronary angiography 3 to 24 h after fibrinolysis Hemodynamically stable patients with evidence for successful fibrinolysis IIa A 387 391 Coronary angiography before hospital discharge Stable patients IIb C N/A Coronary angiography at any time Patients in whom the risks of revascularization are likely to outweigh the benefits or the patient or designee does not want invasive care III: No Benefit C N/A COR indicates class of recommendation; LOE, level of evidence; N/A, not applicable; PCI, percutaneous coronary intervention; and STEMI, ST-elevation myocardial infarction. lower rates for recurrent ischemia, reinfarction, emergency repeat revascularization procedures, intracranial hemorrhage, and death.379 Early, successful PCI also greatly decreases the complications of STEMI that result from longer ischemic times or unsuccessful fibrinolytic therapy, allowing earlier hospital discharge and resumption of daily activities. The greatest mortality benefit of primary PCI is in high-risk patients. PCI outcomes may not be as successful with prolonged time-to-treatment or low-volume hospitals and operators (Table 10). Several reports have shown excellent outcomes for patients with STEMI undergoing interhospital transfer where first med- ical contact to-door balloon time modestly exceeded the sys- tematic goal of 90 minutes.396 398,409 In these reports, the referring hospital and the receiving hospital established a transfer protocol that minimized transfer delays, and out- comes were similar to those of direct-admission patients. On the basis of these results, the PCI and STEMI guideline writing committees have modified the first medical contact to-device time goal from 90 minutes to 120 minutes for interhospital transfer patients,397 while empha- sizing that systems should continue to strive for times 90 minutes. Hospitals that cannot meet these criteria should use fibrinolytic therapy as their primary reperfusion strategy. PCI of a noninfarct artery at the time of primary PCI in stable patients is associated with worse clinical outcomes unless the patient is in cardiogenic shock where PCI of a severe stenosis in a coronary artery supplying a large territory of myocardium might improve hemodynamic stabil- ity.404,406,408 Delayed PCI can be performed in noninfarct arteries at a later time if clinically indicated.410 412 5.2.2.3. Delayed or Elective PCI in Patients With STEMI: Recommendations Class IIa 1. PCI is reasonable in patients with STEMI and clinical evidence for fibrinolytic failure or infarct artery reocclusion.385,386 (Level of Evidence: B) 2. PCI is reasonable in patients with STEMI and a patent infarct artery 3 to 24 hours after fibrinolytic therapy.390,391 (Level of Evidence: B) 3. PCI is reasonable in patients with STEMI who demonstrate ischemia on noninvasive testing.410,411 (Level of Evidence: B) Class IIb 1. PCI of a hemodynamically significant stenosis in a patent infarct artery greater than 24 hours after STEMI may be considered as part of an invasive strategy.413 417 (Level of Evidence: B) Class III: NO BENEFIT 1. PCI of a totally occluded infarct artery greater than 24 hours after STEMI should not be performed in asymptomatic patients with 1- or 2-vessel disease if patients are hemodynamically and electrically stable and do not have evidence of severe ischemia.418 420 (Level of Evidence: B) Studies and meta-analyses suggest potential benefit for PCI in fibrinolytic failure.385,386 In stable patients treated with fi- brinolytic therapy and clinical evidence for successful reper- fusion, an early invasive strategy with cardiac catheterization performed within 24 hours decreases reinfarction and recur- rent ischemic events.388,390,391 Table 10. Indications for PCI in STEMI Indications COR LOE References Primary PCI* STEMI symptoms within 12 h I A 379 382 Severe heart failure or cardiogenic shock I B 383,384 Contraindications to fibrinolytic therapy with ischemic symptoms 12 h I B 399,400 Clinical and/or electrocardiographic evidence of ongoing ischemia between 12 and 24 h after symptom onset IIa B 401 403 Asymptomatic patients presenting between 12 and 24 h after symptom onset and higher risk IIb C N/A Noninfarct artery PCI at the time of primary PCI in patients without hemodynamic compromise III: Harm B 404 408 Delayed or elective PCI in patients with STEMI Clinical evidence for fibrinolytic failure or infarct artery reocclusion IIa B 385,386 Patent infarct artery 3 to 24 h after fibrinolytic therapy IIa B 390,391 Ischemia on noninvasive testing IIa B 410,411 Hemodynamically significant stenosis in a patent infarct artery 24 h after STEMI IIb B 413 417 Totally occluded infarct artery 24 h after STEMI in a hemodynamically stable asymptomatic patient without evidence of severe ischemia III: No Benefit B 418 420 *Systems goal of performing primary PCI within 90 min of first medical contact when the patient presents to a hospital with PCI capability394,395 (Class I; LOE: B) and within 120 min when the patient presents to a hospital without PCI capability396 398 (Class I; LOE: B). COR indicates class of recommendation; LOE, level of evidence; N/A, not applicable; PCI, percutaneous coronary intervention; and STEMI, ST-elevation myocardial infarction. Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e599 PCI for a hemodynamically significant stenosis in a patent infarct artery 24 hours after STEMI as part of a revascu- larization strategy improves outcome.410,411,413 417 PCI of an occluded infarct artery 1 to 28 days after MI in asymptomatic patients without evidence of myocardial ischemia has no incremental benefit beyond optimal medical therapy with aspirin, beta blockers, angiotensin-converting enzyme inhib- itors, and statins in preserving LV function and preventing subsequent cardiovascular events.418 420 It is important to note that elective PCI of an occluded infarct artery has not been studied in patients with New York Heart Association functional class III or IV heart failure, rest angina, serum creatinine 2.5 mg/dL, left main or 3-vessel CAD, clinical instability, or severe inducible ischemia on stress testing in an infarct zone that is not akinetic or dyskinetic. 5.2.3. Cardiogenic Shock: Recommendations Class I 1. PCI is recommended for patients with acute MI who develop cardiogenic shock and are suitable candi- dates.384,421 423 (Level of Evidence: B) 2. A hemodynamic support device is recommended for patients with cardiogenic shock after STEMI who do not quickly stabilize with pharmacological ther- apy.384,424 427 (Level of Evidence: B) See Online Data Supplement 22 for additional data regarding cardiogenic shock. Cardiogenic shock is the leading cause of in-hospital mortality complicating STEMI. Revascularization is the only treatment proven to decrease mortality rates.384,421 423 Al- though revascularization is almost always accomplished through PCI, selected patients with severe 3-vessel or left main disease can benefit from emergency CABG. Revascu- larization attempts may be futile and not indicated in cases of severe multiorgan failure.427 Patient selection for revascular- ization is more important in the elderly, but several observa- tional reports demonstrate acceptable outcomes in patients with few comorbidities and a reasonable potential for sur- vival.428 431 Patients who present to hospitals without PCI capability are usually emergently transported to a PCI center, because mortality without transfer is markedly elevated.432 5.2.3.1. Procedural Considerations for Cardiogenic Shock Patients with cardiogenic shock should receive standard pharmacological therapies, including aspirin, a P2Y12 recep- tor antagonist, and anticoagulation.427,433 Inotropic and vaso- pressor therapy improves perfusion pressure. Historically, negative inotropes and vasodilators are avoided. IV GP IIb/IIIa inhibitors have been shown to provide benefit in observational studies but not in 1 small RCT.433 Endotracheal intubation and mechanical ventilation with positive end-expiratory pressure is usually necessary in pa- tients with respiratory failure. Placement of a temporary pacemaker is indicated for patients with bradycardia or high-degree atrioventricular heart block. A pulmonary artery catheter can provide information to dose and titrate inotropes and pressors. Further hemodynamic support is available with IABP counterpulsation or percutaneous LV assist devices, although no data support a reduction in mortality rates.434 Contrast medium injections should be minimized. Orthog- onal angiograms of the left coronary artery and a left anterior oblique angiogram of the right coronary artery are usually sufficient to identify the infarct artery.435 Although most patients undergoing revascularization will receive a stent as part of the procedure, there are conflicting data on the impact of stenting over balloon angioplasty. Some studies reveal lower mortality rates,436 438 whereas others reveal no bene- fit439 or higher mortality rates.440 There are no data comparing the choice of BMS versus DES in cardiogenic shock; how- ever, BMS are often used because compliance with long-term DAPT is often unclear in the emergency setting. In patients with multivessel disease, revascularization of the noninfarct artery may be necessary to maximize myocar- dial perfusion. Alternatively, in patients with multivessel disease and particularly left main disease, emergency CABG as a primary reperfusion strategy may be preferred.50,441 Refractory cardiogenic shock unresponsive to revasculariza- tion may necessitate institution of more intensive cardiac support with a ventricular assist device or other hemodynam- ic support devices to allow for myocardial recovery or subsequent cardiac transplantation in suitable patients. 5.2.4. Revascularization Before Noncardiac Surgery: Recommendations Class IIa 1. For patients who require PCI and are scheduled for elective noncardiac surgery in the subsequent 12 months, a strategy of balloon angioplasty, or BMS implantation followed by 4 to 6 weeks of DAPT, is reasonable.442 448 (Level of Evidence: B) 2. For patients with DES who must undergo urgent surgical procedures that mandate the discontinua- tion of DAPT, it is reasonable to continue aspirin if possible and restart the P2Y12 inhibitor as soon as possible in the immediate postoperative period.444 (Level of Evidence: C) Class III: HARM 1. Routine prophylactic coronary revascularization should not be performed in patients with stable CAD before noncardiac surgery.449,450 (Level of Evidence: B) 2. Elective noncardiac surgery should not be per- formed in the 4 to 6 weeks after balloon angio- plasty or BMS implantation or the 12 months after DES implantation in patients in whom the P2Y12 inhibitor will need to be discontinued periopera- tively.208,447, 451,452 (Level of Evidence: B) The 2007 and 2009 ACC/AHA Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery gave detailed recommendations for the evaluation of patients undergoing noncardiac surgery.444 Patients with evidence of ACS should receive standard therapy, including early revas- cularization, to minimize the risk of adverse events. Patients with known significant left main or 3-vessel CAD who would otherwise benefit from revascularization in terms of survival or symptomatic relief also generally undergo revasculariza- tion before elective noncardiac surgery. Two RCTs449,450 found no benefit with routine preopera- tive revascularization before noncardiac surgery. Noncardiac surgery early after coronary stenting, particularly in the first 4 weeks, is associated with a high risk of stent thrombosis and death.444,446,448 When emergency surgery is necessary, the patient should proceed to surgery without prior PCI. When surgery is required within 30 days and coronary revascular- ization is required before surgery, many clinicians perform balloon angioplasty alone to avoid the need for DAPT. In situations where preoperative revascularization is required and surgery can be deferred for at least 30 days, many clinicians use BMS and discontinue DAPT after 30 days. If surgery is elective and can be deferred for 1 year, most clinicians would consider DES to reduce the long-term risk of restenosis. A dilemma occurs when a patient has undergone PCI and then unexpectedly requires noncardiac surgery. Many patients can undergo surgery on DAPT, where the risk-benefit ratio will favor continued dual antiplatelet inhi- bition. If it is necessary to hold P2Y12 inhibitor therapy, most clinicians will still continue aspirin uninterrupted during the perioperative period if the bleeding risk is not prohibitive. When the risk of delaying surgery or performing surgery while the patient is on DAPT exceeds the risk of stent thrombosis from stopping DAPT, the P2Y12 inhibitor is stopped before surgery and resumed as soon as possible afterward. No P2Y12 inhibitor bridging strategy (eg, GP IIb/IIIa inhibitor, antithrombin therapy) has been validated. 5.3. Coronary Stents: Recommendations Class I 1. Before implantation of DES, the interventional car- diologist should discuss with the patient the need for and duration of DAPT and the ability of the patient to comply with and tolerate DAPT.212 (Level of Evidence: C) 2. DES are useful as an alternative to BMS to reduce the risk of restenosis in cases in which the risk of restenosis is increased and the patient is likely to be able to tolerate and comply with prolonged DAPT (Level of Evidence: A for elective PCI453,453a,454 456; Level of Evidence: C for UA/NSTEMI453; Level of Evidence: A for STEMI453,456 459). 3. Balloon angioplasty or BMS should be used in patients with high bleeding risk, inability to com- ply with 12 months of DAPT, or anticipated invasive or surgical procedures within the next 12 months, during which time DAPT may be inter- rupted.208,460 462 (Level of Evidence: B) Class III: HARM 1. PCI with coronary stenting should not be performed if the patient is not likely to be able to tolerate and comply with DAPT.208 211 (Level of Evidence: B) 2. DES should not be implanted if the patient is not likely to be able to tolerate and comply with prolonged DAPT or this cannot be determined before stent im- plantation.208,460 462 (Level of Evidence: B) Coronary stent implantation is commonly performed during PCI to prevent recoil, abrupt closure, and late restenosis.463,464 BMS are composed of either stainless steel or cobalt chro- mium alloys. Because the risk of stent thrombosis is greatest within the first 30 days after implantation, the use of DAPT is required for 30 days after implantation of BMS.208 In the United States, 4 types of DES are currently ap- proved: sirolimus-eluting stents, paclitaxel-eluting stents, zotarolimus-eluting stents, and everolimus-eluting stents. DES vary according to stent scaffold material and design, drug content, and the polymer used for drug elution; however, several common clinical features are present. First, sirolimus- eluting stents, paclitaxel-eluting stents, and zotarolimus- eluting stents have been demonstrated in RCTs to be associ- ated with a reduced need for repeat revascularization and no increase in death or MI compared with BMS at 4 years follow-up.465 Everolimus-eluting stents have been demon- strated in RCTs to be associated with a lower need for repeat revascularization than paclitaxel-eluting stents, and, by infer- ence, a lower risk for repeat revascularization than BMS,466,467 with no increase in death or MI at 2-year follow-up.468 Second, each of these stents is presumed to be associated with delayed healing based on pathologic studies and longer periods of risk for thrombosis compared with BMS and require longer duration of DAPT.469 In the RCTs that led to the US Food and Drug Administration (FDA) approval of these stents, the recommended minimum duration of DAPT therapy was 3 to 6 months. Recently, the consensus of clinical practice has been 12 months of DAPT following DES implantation to avoid late (after 30 days) thrombosis,208 based on observational studies of paclitaxel-eluting stents and sirolimus-eluting stents that indicate lower risk of late stent thrombosis with 6 months of therapy.212 Extending DAPT beyond 1 year is considered reasonable by some practitioners based on observational data analysis,212 but RCTs to deter- mine whether longer DAPT is associated with reduction in stent thrombosis risk have not been completed. Finally, DES therapy is more expensive than BMS. Cost-effectiveness analysis has shown a reduction in total cost associated with DES because of avoidance of repeat procedures, yet it may be reasonable to consider use of BMS in patient subsets in which the risk of restenosis is low.470 This risk-benefit profile is most favorable for DES over BMS when the risk of restenosis with BMS is high (Table 11). Pooled and meta-analyses have demonstrated that in patients with diabetes, use of DES decreases the risk of restenosis compared with BMS.471,472 DES may be more appealing for unprotected left main PCI, given the rate and clinical consequences of restenosis in this location.473 475 The risk of stent thrombosis is higher in populations or lesion types excluded from RCTs of DES (eg, STEMI, smaller arteries [ 2.5 mm diameter], longer lesions, bifurca- tions).210,465 Importantly, these features also predict both stent thrombosis476 and restenosis in BMS.477 The greatest risk of stent thrombosis is within the first year, ranging from 0.7% to 2.0%, depending on patient and lesion complexity. Late stent thrombosis risk after 1 year with DES is observed at a rate of Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e601 Compared with balloon angioplasty, routine BMS implan- tation during primary PCI decreases risk for target-vessel revascularization and possibly reduces MI rates but does not reduce mortality rates.479 More recent primary PCI studies and meta-analyses have demonstrated lower restenosis rates without increased risk of adverse stent outcome with DES compared with BMS. Although stent thrombosis rates in trials of STEMI are higher than in trials of elective PCI, the rates of stent thrombosis are not higher with DES compared with BMS in STEMI.453,456 459 The greatest risk for DES thrombosis is early discontinu- ation of DAPT.208,460 462 It is therefore important to deter- mine that the patient will likely be able to tolerate and comply with DAPT before implantation of DES. Therefore, DES should not be used in the presence of financial barriers to continuing prolonged DAPT, social barriers that may limit patient compliance, or medical issues involving bleeding risks or the need for invasive or surgical procedures in the following year that would interrupt antiplatelet therapy. The need for use of long-term warfarin and the associated in- creased risk of bleeding with long-term triple therapy is also a consideration in deciding on DES versus BMS.480 Patients implanted with most contemporary coronary stents can undergo magnetic resonance imaging (MRI) examination any time after implantation.481,482 The effect of the MRI examination on heating of the drug or polymer coating used in DES is unknown. There is no indication for antibiotic prophylaxis before dental or invasive procedures in patients with coronary stents.483 5.4. Adjunctive Diagnostic Devices 5.4.1. FFR: Recommendation Class IIa 1. FFR is reasonable to assess angiographic intermedi- ate coronary lesions (50% to 70% diameter stenosis) and can be useful for guiding revascularization decisions in patients with SIHD.12,97,484 486 (Level of Evidence: A) See Online Data Supplement 23 for additional data regarding FFR. The limitations of coronary angiography for determination of lesion severity have been well described. Angiography may under- or overestimate lesion stenosis. Various physio- logic measurements can be made in the catheterization laboratory, including coronary flow reserve and FFR. The correlation of ischemia on stress testing with FFR values of 0.75 has been established in numerous comparative studies with high sensitivity (88%), specificity (100%), positive predictive value (100%), and overall accuracy (93%).487 The 5-year outcomes for patients with medical therapy based on an FFR 0.75 were superior compared with PCI in the DEFER (Deferral Versus Performance of Balloon Angio- plasty in Patients Without Documented Ischemia) study.485 The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study identified the benefit for deferring PCI in patients with multivessel disease and lesion FFR 0.80, with reduced rates of cardiac events at both 1 and 2 years.97,486 Whereas both FFR and IVUS have been used for assessment of intermediate angiographic stenosis with favor- able outcomes, FFR may reduce the need for revasculariza- tion when compared with IVUS.488 Although IVUS is often considered in the assessment of equivocal left main stenosis, FFR may be similarly effective.484 5.4.2. IVUS: Recommendations Class IIa 1. IVUS is reasonable for the assessment of angio- graphically indeterminant left main CAD.489 491 (Level of Evidence: B) 2. IVUS and coronary angiography are reasonable 4 to 6 weeks and 1 year after cardiac transplantation to exclude donor CAD, detect rapidly progressive car- diac allograft vasculopathy, and provide prognostic information.492 494 (Level of Evidence: B) 3. IVUS is reasonable to determine the mechanism of stent restenosis.495 (Level of Evidence: C) Class IIb 1. IVUS may be reasonable for the assessment of non left main coronary arteries with angiographi- cally intermediate coronary stenoses (50% to 70% diameter stenosis).489,496,497 (Level of Evidence: B) 2. IVUS may be considered for guidance of coronary stent implantation, particularly in cases of left main coronary artery stenting.490,495,498 (Level of Evidence: B) 3. IVUS may be reasonable to determine the mecha- nism of stent thrombosis.495 (Level of Evidence: C) Class III: NO BENEFIT 1. IVUS for routine lesion assessment is not recom- mended when revascularization with PCI or CABG is not being contemplated. (Level of Evidence: C) IVUS provides a unique coronary artery assessment of lesion characteristics, minimal and maximal lumen diameters, cross- sectional area, and plaque area. Diagnostic uses for IVUS include the assessment of angiographic indeterminant coro- nary artery stenoses, determination of the mechanism of stent restenosis or thrombosis, and postcardiac transplantation surveillance of CAD.488,490 492,499 For left main coronary artery stenoses, a minimal lumen diameter of 2.8 mm or a Table 11. Clinical Situations Associated With DES or BMS Selection Preference DES Generally Preferred Over BMS (Efficacy Considerations) BMS Preferred Over DES (Safety Considerations) Left main disease Small vessels In-stent restenosis Bifurcations Diabetes Long lesions Multiple lesions Saphenous vein grafts Unable to tolerate or comply with DAPT Anticipated surgery requiring discontinuation of DAPT within High risk of bleeding BMS indicates bare-mental stent(s); DAPT, dual antiplatelet therapy; and DES, drug-eluting stent(s). minimal lumen area of 6 mm2 suggests a physiologically significant lesion for which patients may benefit from revas- cularization. A minimal lumen area 7.5 mm2 suggests that revascularization may be safely deferred.490 A minimal lumen requires further physiological assessment, such as measurement of FFR.487,500 For non left main stenoses, minimal lumen diameter 2.0 mm and min- imal lumen area 4.0 mm2 correlate with low event rates.489 However, in smaller-diameter arteries (minimal lumen area ), measurement of FFR may more accurately reflect a significant stenosis.488 Studies correlating IVUS measures with ischemia have not specified the size of coronary arteries for which such correlations are IVUS assessment after stent thrombosis may serve to identify stent underexpansion or malapposition.499 IVUS is superior to angiography in the early detection of the diffuse, immune-mediated, cardiac allograft vasculopathy; recom- mendations about the use of IVUS for this purpose were published in 2010 by the International Society of Heart and Lung Transplantation.492 Whereas IVUS has been an impor- tant research tool in interventional cardiology, most clinical studies of IVUS have not been able to demonstrate that its routine use results in a reduction of MACE or restenosis rates.498,501,502 IVUS has been inappropriately used in clinical practice to justify implanting stents in mildly diseased seg- ments that may require no intervention.503 5.4.3. Optical Coherence Tomography Compared with IVUS, optical coherence tomography has greater resolution (10 to 20 micronmeter axially) but more limited depth of imaging (1 to 1.5 mm).504,505 Unlike IVUS, optical coherence tomography requires that the artery be perfused with saline solution or crystalloid during image acquisition and therefore does not permit imaging of ostial lesions. Clinical studies have shown low optical coherence tomography complication rates,506,507 similar to those of IVUS.508 The excellent resolution of optical coherence to- mography permits detailed in vivo 2-dimensional imaging of plaque morphological characteristics (eg, calcification, lipid, thrombus, fibrous cap thickness, and plaque ulceration or rupture)508 510 and evaluation of the arterial response to stent implantation (eg, stent strut neointimal thickness and appo- sition)511 513 and may be of value in clinical research. The appropriate role for optical coherence tomography in routine clinical decision making has not been established. 5.5. Adjunctive Therapeutic Devices 5.5.1. Coronary Atherectomy: Recommendations Class IIa 1. Rotational atherectomy is reasonable for fibrotic or heavily calcified lesions that might not be crossed by a balloon catheter or adequately dilated before stent implantation.514,515 (Level of Evidence: C) Class III: NO BENEFIT 1. Rotational atherectomy should not be performed routinely for de novo lesions or in-stent resteno- sis.516 519 (Level of Evidence: A) Rotational atherectomy in RCTs was associated with higher rates of MACE at 30 days and no reduction in restenosis. It has a limited role in facilitating the dilation or stenting of lesions that cannot be crossed or expanded with PCI.520,521 Devices for directional coronary atherectomy are no longer marketed in the United States. 5.5.2. Thrombectomy: Recommendation Class IIa 1. Aspiration thrombectomy is reasonable for patients undergoing primary PCI.522 524 (Level of Evidence: B) The benefit of thrombectomy in patients with STEMI appears to be dependent on the type of thrombectomy technique used.522 526 No clinical benefit for routine rheolytic throm- bectomy (AngioJet device, MEDRAD Interventional, Minne- apolis, MN and Pittsburgh, PA) has been demonstrated in support the use of manual aspiration thrombectomy during primary PCI to improve microvascular reperfusion and de- crease MACE. It is not known whether a strategy of selective thrombus aspiration in patients with a large thrombus burden might be equivalent to routine thrombus aspiration. 5.5.3. Laser Angioplasty: Recommendations Class IIb 1. Laser angioplasty might be considered for fibrotic or moderately calcified lesions that cannot be crossed or dilated with conventional balloon angioplasty.527 (Level of Evidence: C) Class III: NO BENEFIT 1. Laser angioplasty should not be used routinely dur- ing PCI.516,518,528 (Level of Evidence: A) RCTs of laser angioplasty have not demonstrated improved clinical or angiographic PCI outcomes, although some prac- titioners think that laser angioplasty may be of use in the treatment of lesions that are difficult to dilate with balloon 5.5.4. Cutting Balloon Angioplasty: Recommendations Class IIb 1. Cutting balloon angioplasty might be considered to avoid slippage-induced coronary artery trauma dur- ing PCI for in-stent restenosis or ostial lesions in side branches.529 (Level of Evidence: C) Class III: NO BENEFIT 1. Cutting balloon angioplasty should not be per- formed routinely during PCI.516,529,530 (Level of Evi- dence: A) Although some small, single-center trials have suggested that cutting balloon angioplasty was more efficacious than bal- Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e603 loon angioplasty, it was not found to be safer or more effective in several large trials.516,529,531 When balloon dila- tion is required for in-stent restenosis, however, cutting balloons are less likely to slip and may offer a technical advantage over conventional balloons.529 Scoring balloons have been used by some cardiologists as an alternative to cutting balloons, but no RCTs have been reported.531 5.5.5. Embolic Protection Devices: Recommendation Class I 1. Embolic protection devices (EPDs) should be used during saphenous vein graft (SVG) PCI when tech- nically feasible.532 535 (Level of Evidence: B) The incidence of MACE doubles in SVG PCI compared with native-artery PCI.536 A distal balloon occlusion EPD de- creased the 30-day composite outcome of death, MI, emer- gency CABG, or target-lesion revascularization (9.6% versus 16.5%) in the only RCT.532 Subsequent noninferiority com- parisons have demonstrated similar benefit with proximal occlusion and distal filter EPDs, with benefit limited to reduction in periprocedural MI534,535 (Section 5.10). Distal EPDs do not improve survival or reinfarction rates in patients undergoing native-artery PCI.524,537 5.6. Percutaneous Hemodynamic Support Devices: Recommendation Class IIb 1. Elective insertion of an appropriate hemodynamic support device as an adjunct to PCI may be reason- able in carefully selected high-risk patients. (Level of Evidence: C) IABP counterpulsation is frequently used as an adjunct to PCI in hemodynamically unstable patients.538,539 In single-center series, the routine prophylactic use of IABP during PCI in high-risk patients was associated with lower mortality and fewer major complications compared with rescue use of IABP.540,541 In the only RCT in high-risk PCI patients (BCIS-1 [Balloon Pump-Assisted Coronary Intervention Study]),542 there was no difference in the primary composite outcome between routine and provisional use of IABP. There were also no differences in major secondary endpoints except major procedural complications (eg, prolonged hypotension, ventricular tachycardia/fibrillation, cardiopulmonary arrest), which were lower in the routine IABP group. Bleeding and access site complication rates tended to be higher in the routine IABP group. The bailout rate of IABP insertion in the provisional IABP group was 12%, mostly for procedural hypotension.542 A meta-analysis of IABP therapy in patients with STEMI did not show improved outcomes with the use of The Impella Recover LP 2.5 System (Abiomed, Aachen, Germany/Danvers, Massachusetts) is a 12.5 Fr catheter that is inserted percutaneously through a 13 Fr femoral artery sheath and placed across the aortic valve into the left ventricle, through which a transaxial blood pump provides flows of up to 2.5 L/min. This has been used in patients with cardiogenic shock543,544 as well as elective PCI.545 The hemodynamic effects of the Impella 2.5 have been studied in high-risk PCI patients, demonstrating beneficial LV unloading effect (de- creased end-diastolic pressure and wall stress) with no change in global or systolic LV function.546 The PROTECT I (A Prospective Feasibility Trial Investigating the Use of the IMPELLA Recover LP 2.5 System in Patients Undergoing High-Risk PCI) trial in 20 patients undergoing high-risk PCI with the Impella 2.5 system concluded that this device was safe, easy to implant, and hemodynamically effective.547 The Europella Registry included 144 patients undergoing high- risk PCI and reported the safety, feasibility, and potential usefulness of the device and that RCTs were warranted.548 The randomized PROTECT II (A Prospective, Multicenter, Randomized Controlled Trial of the IMPELLA Recover LP 2.5 System Versus Intra Aortic Balloon Pump in Patients Undergoing Non Emergent High Risk PCI) trial, which was designed to demonstrate superiority of Impella over IABP in terms of 1-month adverse events, was halted for futility after interim analysis of study results.549 The TandemHeart (CardiacAssist, Inc, Pittsburgh, PA) is a left atrial to aorta catheter-based system that includes a centrifugal blood pump providing flows of up to 4 L/min. This device uses a 21 Fr cannula percutaneously inserted into the femoral vein for transseptal access of the left atrium with a 15 Fr catheter placed in the contralateral femoral artery and positioned above the aortic bifurcation. An extracorporeal pump then returns oxygenated blood from the left atrium to the arterial system, thereby unloading the left ventricle.550,551 The hemodynamic effects have been studied in patients undergoing high-risk PCI.552 Several small studies have addressed the clinical efficacy of the TandemHeart in high- risk patients undergoing PCI.551,553 556 In a single-center report of 68 patients undergoing high-risk PCI using either TandemHeart or Impella Recover 2.5, success rates ( 90%) and vascular complications (7%) were similar.553 High-risk patients may include those undergoing unpro- tected left main or last-remaining-conduit PCI, those with severely depressed EF undergoing PCI of a vessel supplying a large territory, and/or those with cardiogenic shock. Patient risk, hemodynamic support, ease of application/removal, and operator and laboratory expertise are all factors involved in consideration of use of these devices. With devices that require large cannula insertion, the risk of vascular injury and related complications are important considerations regarding necessity and choice of device. 5.7. Interventional Pharmacotherapy 5.7.1. Procedural Sedation The term conscious sedation is falling out of favor with the recognition that there is a spectrum of procedural sedation levels. Most patients undergoing PCI fall under the definition of either minimal sedation (anxiolysis) or moderate sedation (depressed consciousness with the ability to respond purpose- fully to verbal commands).557 Nonetheless, an underlying principle of procedural sedation is that the physician should be prepared to manage one level of sedation deeper than the level intended. Thus, cardiologists should be cognizant of the principles of managing deep sedation (depressed conscious- ness without easy arousal that may require assistance in maintaining airway patency or spontaneous ventilation). A full review of procedural sedation is beyond the scope of this document, but practice guidelines for sedation and analgesia by nonanesthesiologists, along with The Joint Commission standards, provides a reasonable framework. These guidelines outline several general principles.558,559 Before the procedure the patient should be assessed for predictors of difficult intubation or a history of prior difficult intubation. The patient should be monitored by someone dedicated to observing the level and effects of sedation. Level of consciousness, respiratory rate, blood pressure, cardiac rhythm, and oxygen saturation by pulse oximetry should be monitored. Available equipment should include a high-flow oxygen source, suction, airway management equipment, a defibrillator, resuscitation drugs, and reversal agents appro- priate for the drugs being used. A free-flowing IV line should be established. Supplemental oxygen is usually administered, even in the absence of preexisting hypoxia, to provide a margin of safety. Agents used for sedation are best given in incremental doses, allowing adequate time for the development and assessment of peak effect. The most commonly used agents are listed in Appendix 4F. 5.7.2. Oral Antiplatelet Therapy: Recommendations Class I 1. Patients already taking daily aspirin therapy should take 81 mg to 325 mg before PCI.301 304 (Level of Evidence: B) 2. Patients not on aspirin therapy should be given nonenteric aspirin 325 mg before PCI.301,303,304 (Level of Evidence: B) 3. After PCI, use of aspirin should be continued indef- initely.560 563 (Level of Evidence: A) 4. A loading dose of a P2Y12 receptor inhibitor should be given to patients undergoing PCI with stenting564 568 (Level of Evidence: A). Options include a. Clopidogrel 600 mg (ACS and non-ACS pa- tients)564 566 (Level of Evidence: B) b. Prasugrel 60 mg (ACS patients)567 (Level of Evi- dence: B) c. Ticagrelor 180 mg (ACS patients)568 (Level of Evidence: B) 5. The loading dose of clopidogrel for patients under- going PCI after fibrinolytic therapy should be 300 mg within 24 hours and 600 mg more than 24 hours after receiving fibrinolytic therapy.565,569 (Level of Evidence: C) 6. Patients should be counseled on the need for and risks of DAPT before placement of intracoronary stents, especially DES, and alternative therapies should be pursued if patients are unwilling or unable to comply with the recommended duration of DAPT.208 (Level of Evidence: C) 7. The duration of P2Y12 inhibitor therapy after stent implantation should generally be as follows: a. In patients receiving a stent (BMS or DES) dur- ing PCI for ACS, P2Y12 inhibitor therapy should be given for at least 12 months. Options include (Level of Evidence: B) b. In patients receiving DES for a non-ACS indica- tion, clopidogrel 75 mg daily should be given for at least 12 months if patients are not at high risk of bleeding.208,212,571 (Level of Evidence: B) c. In patients receiving BMS for a non-ACS indica- tion, clopidogrel should be given for a minimum of 1 month and ideally up to 12 months (unless the patient is at increased risk of bleeding; then it should be given for a minimum of 2 weeks).208,572 (Level of Evidence: B) Class IIa 1. After PCI, it is reasonable to use aspirin 81 mg per day in preference to higher maintenance doses.302,573 576 (Level of Evidence: B) 2. If the risk of morbidity from bleeding outweighs the anticipated benefit afforded by a recommended du- ration of P2Y12 inhibitor therapy after stent implan- tation, earlier discontinuation (eg, <12 months) of P2Y12 inhibitor therapy is reasonable. (Level of Evidence: C) Class IIb 1. Continuation of DAPT beyond 12 months may be considered in patients undergoing DES implanta- tion.567,568 (Level of Evidence: C) Class III: HARM 1. Prasugrel should not be administered to patients with a prior history of stroke or transient ischemic attack.567 (Level of Evidence: B) Aspirin reduces the frequency of ischemic complications after PCI. Although the minimum effective aspirin dosage in the setting of PCI has not been established, aspirin 325 mg given at least 2 hours, and preferably 24 hours, before PCI is recommended,302,303 after which aspirin 81 mg daily should be continued indefinitely. Several investigations have explored various loading doses of clopidogrel before or during PCI. Compared with a 300-mg loading dose, doses of either 600 mg or 900 mg achieve greater degrees of platelet inhibition with fewer low responders.577 A meta-analysis of 7 studies that included 25,383 patients undergoing PCI demonstrated that intensified loading of clopidogrel with 600 mg reduces the rate of MACE without an increase in major bleeding compared with 300 mg.578 Another study suggested that a 600-mg loading dose of clopidogrel is associated with improvements in procedural angiographic endpoints and 1-year clinical out- comes in patients with STEMI who undergo primary PCI compared with a 300-mg dose.579 There is no benefit with increasing the loading dose to 900 mg compared with 600 mg.577 Clopidogrel 75 mg daily should be given for a minimum of 4 weeks after balloon angioplasty or BMS Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e605 implantation (a minimum of 2 weeks if increased bleeding risk is present)580 and for at least 12 months after DES implantation (unless the risk of bleeding outweighs the anticipated benefit). Patients should be counseled on the need for and risks of DAPT before stent implantation, especially DES implantation, and alternative therapies pursued (BMS or balloon angioplasty) if they are unwilling or unable to comply with the recommended duration of DAPT. The efficacy of clopidogrel pretreatment remains contro- versial. Although some studies have suggested that pretreat- ment with clopidogrel is associated with decreased platelet aggregation and a significantly lower incidence of periproce- dural MI after elective PCI, others have suggested no benefit to pretreatment compared with administration of the drug in the catheterization laboratory.572,581,582 When prasugrel was compared with clopidogrel in patients with ACS in TRITON TIMI 38 (Trial to Assess Improve- ment in Therapeutic Outcomes by Optimizing Platelet Inhi- bition with Prasugrel Thrombolysis In Myocardial Infarc- tion), prasugrel was associated with a significant 2.2% reduction in absolute risk and a 19% reduction in relative risk in the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke, and a significant increase in the rate of TIMI major hemorrhage (1.8% versus 2.4%).567 Prasugrel is contraindicated in patients with a history of transient ische- mic attack or stroke. Patients weighing 60 kg have an increased risk of bleeding on the 10 mg daily maintenance dose. The package insert suggests that consideration should be given to lowering the maintenance dose to 5 mg daily, although the effectiveness and safety of the 5-mg dose has not been studied. 