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. Prasugrel is not recommended for patients 75 years of age because of the increased risk of fatal and intracranial bleeding and lack of benefit, except in patients with diabetes or a history of prior MI. Prasugrel should not be started in patients likely to undergo urgent CABG. Prasugrel has not been studied in elective PCI, and thus no recommen- dation can be made regarding its use in this clinical setting. Ticagrelor reversibly binds the P2Y12 receptor. Unlike clopidogrel or prasugrel, ticagrelor is not a thienopyridine. It also does not require metabolic conversion to an active metabolite. Compared with clopidogrel in patients with ACS in the PLATO (Platelet Inhibition and Patient Outcomes) trial, ticagrelor was associated with a significant 1.9% reduc- tion in absolute risk and a 16% reduction in relative risk in the primary composite endpoint of vascular death, nonfatal MI, or nonfatal stroke.568 Importantly, a significant reduction in vascular mortality and all-cause mortality was observed. Although CABG-related bleeding was not significantly in- creased with ticagrelor compared with clopidogrel, a signif- icantly greater incidence of major bleeding was observed in patients not undergoing CABG. Ticagrelor was associated with higher rates of transient dyspnea and bradycardia com- pared with clopidogrel, although only a very small percentage of patients discontinued the study drug because of dyspnea. Based on post hoc analysis of the PLATO study, specifically the results in the US patient cohort, a black box warning states that maintenance doses of aspirin above 100 mg reduce the effectiveness of ticagrelor and should be avoided. After any initial dose, ticagrelor should be used with aspirin 75 mg to 100 mg per day.583 Given the twice-daily dosing and reversible nature of the drug, patient compliance may be a particularly important issue to consider and emphasize. Ti- cagrelor has not been studied in elective PCI or in patients who received fibrinolytic therapy; thus, no recommendations about its use in these clinical settings can be made. 5.7.3. IV Antiplatelet Therapy: Recommendations STEMI Class IIa 1. In patients undergoing primary PCI treated with UFH, it is reasonable to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-bolus dose tirofiban), whether or not patients were pretreated with clopidogrel.584 590 (For GP IIb/IIIa inhibitor administration in patients not pre- treated with clopidogrel, Level of Evidence: A; for GP IIb/IIIa inhibitor administration in patients pretreated with clopidogrel, Level of Evidence: C) Class IIb 1. In patients undergoing primary PCI with abcix- imab, it may be reasonable to administer intracoro- nary abciximab.589,591 604 (Level of Evidence: B) Class III: NO BENEFIT 1. Routine precatheterization laboratory (eg, ambu- lance or emergency department) administration of GP IIb/IIIa inhibitors as part of an upstream strat- egy for patients with STEMI undergoing PCI is not beneficial.605 612 (Level of Evidence: B) UA/NSTEMI Class I 1. In UA/NSTEMI patients with high-risk features (eg, elevated troponin level) not treated with bivalirudin and not adequately pre-treated with clopidogrel, it is useful at the time of PCI to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-bolus dose tirofiban) in patients treated with UFH.613 618 (Level of Evidence: A) Class IIa 1. In UA/NSTEMI patients with high-risk features (eg, elevated troponin level) treated with UFH and ade- quately pretreated with clopidogrel, it is reasonable at the time of PCI to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-bolus dose tirofiban).616,619 (Level of Evidence: B) SIHD Class IIa 1. In patients undergoing elective PCI treated with UFH and not pretreated with clopidogrel, it is reasonable to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-bolus dose tirofiban).619 621 (Level of Evidence: B) Class IIb 1. In patients undergoing elective PCI with stent im- plantation treated with UFH and adequately pre- treated with clopidogrel, it might be reasonable to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-bolus dose tiro- fiban).619,622 624 (Level of Evidence: B) See Online Data Supplement 24 for additional data regarding IV antiplatelet therapy. In the era before DAPT, trials of adequately dosed GP IIb/IIIa inhibitors in patients undergoing balloon angioplasty and coronary stent implantation demonstrated a reduction in the incidence of composite ischemic events with GP IIb/IIIa treatment, primarily through a reduction of enzymatically defined MI.613,615,618,620,621 Earlier RCTs of GP IIb/IIIa inhib- itors were generally conducted in patients treated with UFH. In some trials, use of GP IIb/IIIa inhibitors are associated with some increased bleeding risk, and trials of these agents have generally excluded patients at high risk of bleeding (eg, tions about use of GP IIb/IIIa inhibitors are best construed as applying to those patients not at high risk of bleeding complications. Abciximab, double-bolus eptifibatide (180 mcg/kg bolus followed 10 minutes later by a second 180 mcg/kg bolus), and high-bolus dose tirofiban (25 mcg/kg) all result in a high degree of platelet inhibition,627 629 have been demonstrated to reduce ischemic complications in patients undergoing PCI,608,609,613,615,618 621 and appear to lead to comparable angiographic and clinical outcomes.630,631 Trials of GP IIb/IIIa inhibitors in the setting of STEMI and primary PCI were conducted in the era before routine stenting and DAPT. The results of these and more recent trials, as well as several meta-analyses, have yielded mixed results.584 590 Therefore, it is reasonable to administer GP IIb/IIIa inhibitors in patients with STEMI undergoing PCI, although these agents cannot be definitively recommended as routine ther- apy. These agents might provide more benefit in selective use, such as in patients with large anterior MI and/or large thrombus burden. Trials of precatheterization laboratory (eg, ambulance or emergency room) administered GP IIb/IIIa inhibitors in patients with STEMI undergoing PCI, with or without fibrinolytic therapy, have generally shown no clinical benefit, and GP IIb/IIIa inhibitor use in this setting may be associated with an increased risk of bleeding.605 610,612 Stud- ies of intracoronary GP IIb/IIIa inhibitor administration (predominantly using abciximab) consist of several small RCTs, retrospective analyses, retrospective and prospec- tive registries, cohort analyses, and case reports. Although most of these published studies have reported some benefit of intracoronary administration in terms of acute angio- graphic parameters, infarct size, left ventricle myocardial salvage, and composite clinical endpoints, several other studies have not detected any benefit with intracoronary Trials of GP IIb/IIIa inhibitors in patients with UA/ NSTEMI undergoing PCI demonstrated reduced ischemic outcomes, particularly in those with high-risk features such as positive biomarkers. Most trials were conducted in a prior PCI era and without P2Y12 inhibitor pretreat- ment,613,615,618,632,633 although several trials have also demon- strated benefit in patients with high-risk features pretreated with clopidogrel.616,619 In most older studies of stable patients undergoing balloon angioplasty or coronary stenting, treat- ment with GP IIb/IIIa inhibitors resulted in a reduction of composite ischemic events, primarily enzymatically defined MI.613 618,620,621,634,635 More contemporary trials of patients pretreated with a thienopyridine have not demonstrated any benefit with GP IIb/IIIa inhibitor therapy in patients with stable symptoms undergoing elective PCI.619,622 624 5.7.4. Anticoagulant Therapy 5.7.4.1. Use of Parenteral Anticoagulants During PCI: Recommendation Class I 1. An anticoagulant should be administered to patients undergoing PCI. (Level of Evidence: C) Anticoagulant therapy prevents thrombus formation at the site of arterial injury, on the coronary guidewire, and in the catheters used for PCI.8 With rare exceptions,636 all PCI studies have used some form of anticoagulant. It is the consensus of the writing committee that PCI be performed with the use of some form of anticoagulant therapy. Sug- gested dosing regimens of parenteral agents used in PCI are given in Table 12. Recommendations for antiplatelet and antithrombin pharmacotherapy in PCI are given in Table 13. 5.7.4.2. UFH: Recommendation Class I 1. Administration of IV UFH is useful in patients undergoing PCI. (Level of Evidence: C) As the only anticoagulant available for PCI for many years, UFH became the standard of care by default.8 The dose of UFH for PCI has been based on empiricism and experience from RCTs. Suggested UFH dosing regimens are given in Table 12. When UFH is used during PCI, most cardiologists assess the degree of anticoagulation by measuring the acti- vated clotting time. Although measurements are useful to show that an anti-IIa anticoagulant has been given, the value of the activated clotting time in current practice has been questioned. Although studies in the balloon angioplasty era did demonstrate a relationship between activated clotting time levels and ischemic complications,653 655 more recent analyses from the coronary stent era have not found a clear relationship between activated clotting time and out- comes.349,656,657 There may, however, be a modest relation between bleeding and activated clotting time levels.349,657 In addition, not only are there differences between activated clotting time levels measured by Hemochron and HemoTec devices, but both devices have less than optimal precision.658 Thus, although traditional target activated clotting time levels are included in this document, the utility of measured acti- vated clotting time levels in current practice should be considered uncertain. Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e607 Most cardiologists remove femoral sheaths when the acti- vated clotting time falls to 150 to 180 seconds or when the activated partial thromboplastin time falls to 50 seconds. Full-dose anticoagulation is no longer used after successful PCI procedures. Almost all large clinical trials have enrolled patients who underwent transfemoral PCI, but recent small studies assessing the transradial approach have used similar doses of UFH659 and similar activated clotting time target 5.7.4.3. Enoxaparin: Recommendations Class I 1. An additional dose of 0.3 mg/kg IV enoxaparin should be administered at the time of PCI to patients who have received fewer than 2 therapeutic subcu- taneous doses (eg, 1 mg/kg) or received the last subcutaneous enoxaparin dose 8 to 12 hours before PCI.649,661 664 (Level of Evidence: B) Class IIb 1. Performance of PCI with enoxaparin may be rea- sonable in patients either treated with upstream subcutaneous enoxaparin for UA/NSTEMI or who have not received prior antithrombin therapy and are administered IV enoxaparin at the time of PCI.646 650 (Level of Evidence: B) Class III: HARM 1. UFH should not be given to patients already receiving therapeutic subcutaneous enoxa- parin.649,665 (Level of Evidence: B) Trials of enoxaparin relevant to PCI include both studies in which patients with UA/NSTEMI were started on upstream subcutaneous enoxaparin therapy that was continued up to the time of PCI and trials in which patients who had received no prior antithrombin therapy were treated with IV enoxaparin at the time of PCI.646 650,661 663,666 In the SYNERGY (Superior Yield of the New strategy of Enoxa- parin, Revascularization and Glycoprotein IIb/IIIa Inhibi- tors) trial, there was an increased incidence of bleeding in those treated with upstream enoxaparin, later attributed at least in part to the fact that some patients being treated with enoxaparin were also administered UFH at the time of PCI (so-called stacking ).649,665 Almost all patients un- dergoing elective PCI who are administered enoxaparin (0.5 mg/kg IV) will have a peak anti-Xa level 0.5 IU/mL.647 Most clinical studies have used a regimen of 0.5 to 0.75 mg IV.667 Several studies have used this regimen in elective patients and those with STEMI.646 Patients who have received multiple doses of subcutaneously adminis- tered enoxaparin who undergo PCI within 8 hours of the last subcutaneous dose generally have adequate degrees of anticoagulation to undergo PCI, but the degree of antico- agulation may diminish in the 8- to 12-hour period after the last subcutaneous dose. In such patients, as well as in patients who have received only 1 subcutaneous dose of enoxaparin, the addition of enoxaparin (0.3 mg/kg IV) at the time of PCI provides an additional degree of antico- agulation and has become standard practice.648,661 664 Pa- tients who undergo PCI 12 hours after the last subcuta- neous dose are usually treated with full-dose de novo anticoagulation using an established regimen (eg, full-dose UFH or bivalirudin). 5.7.4.4. Bivalirudin and Argatroban: Recommendations Class I 1. For patients undergoing PCI, bivalirudin is useful as an anticoagulant with or without prior treatment with UFH.625,637 645 (Level of Evidence: B) Table 12. Dosing of Parenteral Anticoagulants During PCI Drug Patient Has Received Prior Anticoagulant Therapy Patient Has Not Received Prior Anticoagulant Therapy UFH IV GPI planned: additional UFH as needed (eg, 2000 to 5000 U) to achieve an ACT of 200 to 250 s IV GPI planned: 50 to 70 U/kg bolus to achieve an ACT of 200 to 250 s No IV GPI planned: additional UFH as needed (eg, 2000 to 5000 U) to achieve an ACT of 250 to 300 s for HemoTec, 300 to 350 s for Hemochron No IV GPI planned: 70 to 100 U/kg bolus to achieve target ACT of 250 to 300 s for HemoTec, 300 to 350 s for Hemochron Enoxaparin For prior treatment with enoxaparin, if the last SC dose was administered 8 to 12 h earlier or if only 1 SC dose of enoxaparin has been administered, an IV dose of 0.3 mg/kg of enoxaparin should be given. 0.5 to 0.75 mg/kg IV bolus If the last SC dose was administered within the prior 8 h, no additional enoxaparin should be given. Bivalirudin For patients who have received UFH, wait 30 min, then give 0.75 mg/kg IV bolus, then 1.75 mg/kg per h IV infusion. 0.75 mg/kg bolus, 1.75 mg/kg per h IV infusion Fondaparinux For prior treatment with fondaparinux, administer additional IV treatment with an anticoagulant possessing anti-IIa activity, taking into account whether GPI receptor antagonists have been administered. N/A Argatroban 200 mcg/kg IV bolus, then 15 mcg/kg per min IV infusion 350 mcg/kg bolus, then 25 mcg/kg per min IV infusion ACT indicates activated clotting time; IV, intravenous; GPI, glycoprotein inhibitor; N/A, not applicable; PCI, percutaneous coronary intervention; SC, subcutaneous; and UFH, unfractionated heparin. 2. For patients with heparin-induced thrombocytopenia, it is recommended that bivalirudin or argatroban be used to replace UFH.668,669 (Level of Evidence: B) Bivalirudin is being increasingly used in clinical practice670 as evidence emerges from clinical trials across the spectrum of CAD.638 644 In individual trials and meta-analyses, the use of bivalirudin has been associated with reduced bleeding compared with UFH plus a GP IIb/IIIa inhibitor, although concerns about ischemic events have emerged in individual studies.625,637 645 Longer-term follow-up of the major bivali- rudin trials, however, suggests that small or nominal in- creases in ischemic events have not translated into long-term consequences and that treatment at or before the time of PCI with clopidogrel may mitigate any increased early ischemic risk.637 645 Thus, a treatment strategy of bivalirudin compared with heparin (or enoxaparin) plus GP IIb/IIIa inhibitor ap- pears to lower the risk of bleeding complications. The lower bleeding rates associated with bivalirudin (compared with UFH plus a GP IIb/IIIa inhibitor) are mitigated when used concomitantly with a GP IIb/IIIa inhibitor.639 A strategy of use of provisional GP IIb/IIIa inhibitor in patients treated with bivalirudin is widely accepted.639,643,644 In patients with heparin-induced thrombocytopenia,671,672 a direct-thrombin inhibitor (argatroban) has been approved as an alternative parenteral anticoagulant to be used during PCI.668 The use of bivalirudin for heparin-induced thrombo- cytopenia has been reported as well.669 5.7.4.5. Fondaparinux: Recommendation Class III: HARM 1. Fondaparinux should not be used as the sole antico- agulant to support PCI. An additional anticoagulant Table 13. Recommendations for Antiplatelet and Antithrombin Pharmacotherapy at the Time of PCI COR LOE References Relevant Caveats/Comments Oral antiplatelet agents Aspirin I B 301 304,560 563 N/A P2Y12 inhibitors I A 564 568 A loading dose of a P2Y12 inhibitor should be given to patients undergoing PCI with stenting. Clopidogrel I B 564 566 600-mg loading dose now recommended. Prasugrel I B 567 Contraindicated in patients with prior TIA/CVA: Class III: Harm; LOE: B. Generally not recommended in patients 75 y of age (Section 5.7.2). Consideration of using a lower maintenance dose in patients weighing 60 kg suggested by FDA (Section 5.7.2). Ticagrelor I B 568 Issues of patient compliance may be especially important. GP IIb/IIIa inhibitors (abciximab, double-bolus eptifibatide, high-bolus dose tirofiban) No clopidogrel pretreatment STEMI: IIa A 584 590 UA/NSTEMI recommendation applies to those with high-risk features. GPI use in STEMI may be most appropriate in those with large anterior MI and/or large thrombus burden. IC abciximab administration in STEMI: Class IIb; LOE: B. Precatheterization laboratory GPI administration in STEMI: Class III: No Benefit; LOE: B. Recommendations apply to those not at high risk for bleeding complications. UA/NSTEMI: I A 613 618 SIHD: IIa B 619 621 Clopidogrel pretreatment STEMI: IIa C 584 590 UA/NSTEMI: IIa B 616,619 SIHD: IIb B 619,622 624 Antithrombin agents UFH I C N/A Dosing based on whether or not GPI was administered. Bivalirudin I B 625,637 645 Lower bleeding rates associated with bivalirudin are mitigated when used concomitantly with a GPI. Enoxaparin IIb B 646 650 Recommendations apply to administration of IV enoxaparin at the time of PCI for those who have not received prior antithrombin therapy or who have received upstream SC enoxaparin therapy for UA/NSTEMI. An additional dose of 0.3 mg/kg IV enoxaparin should be administered at the time of PCI to patients who have received 2 therapeutic SC doses (eg, 1 mg/kg) or received the last SC enoxaparin dose 8 to 12 h before PCI: Class I; LOE: B. Patients treated with SC enoxaparin within 12 h of PCI should not receive additional treatment with UFH during PCI ( stacking ): Class III: Harm; LOE: B. Anti-Xa inhibitors Fondaparinux III: Harm C 651,652 PCI should not be performed with fondaparinux as the sole antithrombin agent in patients treated with upstream fondaparinux. An additional anticoagulant with anti-IIa activity should be administered. ACT indicates activated clotting time; COR, class of recommendation; CVA, cerebrovascular accident; FDA, US Food and Drug Administration; GP, glycoprotein; GPI, glycoprotein IIb/IIIa inhibitor; IC, intracoronary; IV, intravenous; LOE, level of evidence; MI, myocardial infarction; N/A, not applicable; PCI, percutaneous coronary intervention; SC, subcutaneous; SIHD, stable ischemic heart disease; STEMI, ST-elevation myocardial infarction; TIA, transient ischemic attack; UA/NSTEMI, unstable angina/non ST-elevation myocardial infarction; and UFH, unfractionated heparin. Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e609 with anti-IIa activity should be administered be- cause of the risk of catheter thrombosis.651,652 (Level of Evidence: C) Fondaparinux, a pentasaccharide, is an indirect factor Xa inhibitor but has no effect on thrombin. On the basis of reports of catheter thrombosis when fondaparinux is used alone during primary PCI,651,652 the writing committee rec- ommends that an anticoagulant with anti-IIa activity be used in patients undergoing PCI.651,652 One study suggested that clinical outcomes were better when fondaparinux was re- placed during PCI by a standard dose of UFH (85 U/kg, 60 U/kg with GP IIb/IIIa inhibitors) rather than by a low dose 5.7.5. No-Reflow Pharmacological Therapies: Recommendation Class IIa 1. Administration of an intracoronary vasodilator (adenosine, calcium channel blocker, or nitroprus- side) is reasonable to treat PCI-related no-reflow that occurs during primary or elective PCI.674 689 (Level of Evidence: B) See Online Data Supplement 25 for additional data regarding no-reflow therapies. No-reflow is a broad term used to describe 2 distinct entities. The first is interventional no-reflow attributed to vasospasm and downstream embolization of debris dislodged during PCI, usually in the setting of atherectomy, thrombus, or degenerated SVGs. The second entity is suboptimal reperfusion of an infarct artery, attributed to endothelial injury in addition to embolization and vasospasm. Angio- graphic no-reflow is the most obvious sequela of the same pathophysiology that produces abnormal TIMI frame counts and TIMI blush scores, so these measures are often used interchangeably. The principal clinical sequela of no-reflow is myonecrosis. Efforts to prevent no-reflow overlap with strategies to reduce MI size and prevent periprocedural MI. In the setting of MI, several drugs have been shown to reduce the incidence of no-reflow. Evidence for a beneficial effect on no-reflow exists for abciximab, adenosine, nic- orandil, and nitroprusside.674,675,680,682,683,685,687,688,690 How- ever, their adoption into clinical practice has depended on their effect on hard clinical endpoints such as infarct size and mortality. These benefits, and consequentially the use of these agents, have been limited. For interventional no-reflow, several therapies have proven effective after no-reflow has started. These include adeno- sine, calcium channel blockers, and nitroprus- side.676,678,679,681,684,686,689,691 There are fewer data to support the use of epinephrine.692 No-reflow after rotational atherec- tomy was less common with nicorandil compared with verapamil infusions in 3 studies,693 695 and an infusion of nicorandil/adenosine during rotational atherectomy prevented no-reflow in 98% of patients.677 Trials of pre-PCI intracoro- nary verapamil, nicardipine, and adenosine have reported them to be safe but have not demonstrated reductions in post-PCI no-reflow.696 698 Mechanical devices to prevent interventional and myocardial infarct reperfusion no-reflow are also covered in Section 5.5.5. 5.8. PCI in Specific Anatomic Situations 5.8.1. CTOs: Recommendation Class IIa 1. PCI of a CTO in patients with appropriate clinical indications and suitable anatomy is reasonable when performed by operators with appropriate exper- tise.699 703 (Level of Evidence: B) See Online Data Supplements 26 to 28 for additional data regarding CTOs. Approximately one third of patients with suspected CAD who undergo coronary angiography have 1 CTO (defined as occlusion of a duration 3 months).704 Although stress- induced ischemia can be elicited in the majority of patients with CTO despite the presence of collaterals,706,707 only 8% to 15% of these patients undergo PCI.708,709 The disparity between the frequency of CTOs and percutaneous treatment underscores not only the technical and procedural complex- ities of this lesion subtype but also the clinical uncertainties regarding which patients benefit from CTO revascularization. Studies suggest that patients who undergo successful, rather than failed, recanalization of CTOs fare better in terms of symptom status and need for CABG,699 as well as LV function.710 However, the impact of successful CTO recana- lization on long-term survival remains unsettled.701,711,712 The decision to try PCI for a CTO (versus continued medical therapy or surgical revascularization) requires an individual- ized risk-benefit analysis encompassing clinical, angio- graphic, and technical considerations. Consultation with a cardiothoracic surgeon and use of the Heart Team approach in cases of CTO in which a large territory is subtended and/or multivessel CAD is present are frequently done. From a technical perspective, successful recanalization of CTOs has steadily increased over the years because of adoption of dedicated wires, novel techniques, and increased operator experience.702 In patients who undergo successful CTO recanalization, use of DES significantly reduces the need for repeated target-vessel revascularization, compared with BMS and balloon angioplasty, without compromising 5.8.2. SVGs: Recommendations Class I 1. EPDs should be used during SVG PCI when techni- cally feasible.532 535 (Level of Evidence: B) Class III: NO BENEFIT 1. Platelet GP IIb/IIIa inhibitors are not beneficial as adjunctive therapy during SVG PCI.212,571,720,721 (Level of Evidence: B) Class III: HARM 1. PCI is not recommended for chronic SVG occlu- sions.722 724 (Level of Evidence: C) See Online Data Supplement 29 for additional data regarding SVG. Adverse cardiac event rates are doubled after SVG PCI compared with native-artery PCI.536 A distal balloon occlu- sion EPD decreased the 30-day composite outcome of death, MI, emergency CABG, or target-lesion revascularization (9.6% versus 16.5%) in the only RCT comparing embolic protection with no embolic protection.532 Subsequent nonin- feriority comparisons have demonstrated similar benefit with proximal occlusion and distal filter EPDs, with benefit limited to reduction in periprocedural MI.534,535 PCI in chronic SVG occlusion is associated with low success rates, high complication rates, and poor long-term patency rates.722,723 Restenosis and target-vessel revascularization rates are lower with DES compared with BMS, although mortality and stent thrombosis rates are similar.725 The use of covered stents is limited to the treatment of the uncommon complication of SVG perforation. Balloon angioplasty for distal SVG anastomotic stenoses has low restenosis rates,724 so stenting is commonly reserved at this location for subop- timal balloon angioplasty results or restenosis. Routine GP IIb/IIIa inhibitor therapy has not proven beneficial in SVG PCI.720 Fibrinolytic therapy is no longer used for thrombus- containing lesions, but rheolytic or manual aspiration throm- bectomy is sometimes employed. 5.8.3. Bifurcation Lesions: Recommendations Class I 1. Provisional side-branch stenting should be the initial approach in patients with bifurcation lesions when the side branch is not large and has only mild or moderate focal disease at the ostium.726 729 (Level of Evidence: A) Class IIa 1. It is reasonable to use elective double stenting in patients with complex bifurcation morphology involving a large side branch where the risk of side-branch occlusion is high and the likelihood of successful side-branch reaccess is low.730 733 (Level of Evidence: B) Side-branch occlusion or severe stenosis after stenting the main artery in coronary bifurcation PCI occurs in 8% to 80% of unselected patients.732,734 The frequency of side-branch occlusion is related to complex bifurcation morphology (severe and/or long side-branch ostial stenosis, large plaque burden in the side-branch ostium, and/or unfavorable side- branch angulation).732,735,736 Side-branch occlusion after PCI is associated with Q-wave and non Q-wave MI.734,735 There- fore, preservation of physiologic flow in the side branch after PCI is important.736 There are 2 bifurcation PCI strategies: provisional stenting (stenting the main vessel with additional balloon angioplasty or stenting of the side branch only in the case of an unsatisfactory result) and elective double stenting of the main vessel and the side branch. When there is an unsatis- factory result in the side branch from the provisional stent in the main branch, sometimes balloon angioplasty alone in the side branch will improve the result and stenting the side branch is not necessary. Some experts have suggested that using the side- branch balloon alone will distort the main branch stent and thus this always needs to be a kissing balloon inflation. In patients with low-risk bifurcation lesions (minimal or moderate ostial side-branch disease [ 50% diameter steno- sis] of focal length [5 to 6 mm]), provisional stenting yields similar clinical outcome to elective double stenting, with lower incidence of periprocedural biomarker elevation.726 729 Conversely, in patients with high-risk bifurcations, elective double stenting is associated with a trend toward higher angiographic success rates, lower in-hospital MACE, and better long-term patency of the side branch compared with provisional stenting.193 Culotte, Crush, and T-stent techniques have been studied in RCTs.726 729,737 Use of DES yields better outcomes than BMS,738 and sirolimus-eluting stents yield better outcomes than paclitaxel-eluting stents.739 742 Clinical evidence supports the use of final kissing balloon inflation after elective 5.8.4. Aorto-Ostial Stenoses: Recommendations Class IIa 1. IVUS is reasonable for the assessment of angio- graphically indeterminant left main CAD.744,745 (Level of Evidence: B) 2. Use of DES is reasonable when PCI is indicated in patients with an aorto-ostial stenosis.746,747 (Level of Evidence: B) Aorto-ostial stenoses of native coronary arteries (left main coronary artery and right coronary artery) are most com- monly caused by atherosclerosis, but they can also occur in patients with congenital malformations, radiation exposure, vasculitides, and aortic valve replacement. The angiographic diagnosis of aorto-ostial disease is not always straightfor- ward, especially in the ostial left main coronary artery, where eccentricity and angulation can be mistaken for stenosis.490,748 Aorto-ostial disease can be evaluated with IVUS744,745; FFR (with IV adenosine) has also been used.484,749 The treatment of aorto-ostial stenoses with balloon angioplasty has been associated with lower procedural success rates, more frequent in-hospital complications, and a greater likelihood of late restenosis.750 Although atherectomy devices (directional atherectomy, rotational atherectomy, and excimer laser an- gioplasty) have improved acute angiographic results over balloon angioplasty, restenosis has remained a limitation.751 In patients with aorto-ostial stenoses undergoing PCI, use of DES has been shown to reduce restenosis compared with 5.8.5. Calcified Lesions: Recommendation 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.514,515,520 (Level of Evidence: C) The presence of coronary calcification is a marker for significant CAD and increased long-term mortality.753 Calci- fied coronary lesions are not a homogenous entity, and their response to PCI varies according to severity of calcification. Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e611 Severely calcified lesions respond poorly to balloon angio- plasty,230,754 and when stents are implanted in such lesions, an incomplete and asymmetrical stent expansion occurs in the majority of cases.755 Attempts to remedy the underexpanded stents with aggressive high-pressure balloon dilatation may result in coronary artery rupture.756 All the published pro- spective RCTs that evaluated the various catheter-based coronary interventional devices excluded patients with se- verely calcified lesions. Therefore, the evidence base for best PCI practices in patients with severely calcified lesions comes from nonrandomized single-arm studies. Among the various adjunct devices that are used to facilitate PCI in severely calcified lesions, only rotational atherectomy has been shown to have potential utility.514,757 Although rota- tional atherectomy increases the chances of angiographic success in severely calcified lesions, its use as a stand-alone device has not led to a reduction in restenosis.520,521,758 Several retrospective studies have shown that in patients with severely calcified lesions, the use of rotational atherectomy before implantation of BMS514 or DES515 is safe. Intermediate-term patency is more favorable with DES than 5.9. PCI in Specific Patient Populations Several specific patient subsets with higher risks for PCI, and at times higher absolute clinical benefit, have traditionally been underrepresented in RCTs and are described below. The elderly constitute a growing proportion of patients considered for PCI.760 In 1 series examining trends over a 25-year period, the proportion of patients undergoing PCI who were 75 to 84 years of age doubled, and those 85 years of age increased 5-fold.761 Age is one of the strongest predictors of mortality after PCI,762 and elderly patients present with a substantially higher clinical risk profile760 Nonetheless, the angiographic success rates and clinical benefits of PCI in elderly patients are similar to younger patients.763 In fact, the absolute benefit is typically greater because of higher absolute risk of adverse outcomes in these patients.764 However, increased risks of complications such as major bleeding and stroke mandate careful consideration of the benefits and risks of PCI in elderly patients.373 Patients with diabetes represent approximately one third of patients undergoing PCI in the United States. Restenosis, which had been a major limitation of PCI, is significantly reduced in patients with diabetes treated with DES compared with BMS.471 However, there are no definitive data from RCTs supporting different clinical outcomes for different types of DES,765 with a recent meta-analysis of 35 RCTs involving 3852 patients with diabetes unable to find major differences between patients receiving sirolimuseluting stents or paclitaxel-eluting stents.472 Numerous analyses and clini- cal studies have evaluated how the presence of diabetes may impact the clinical outcome of patients undergoing PCI and decisions about PCI or CABG.14,116,163,164,186 These studies and the approach to revascularization decisions in diabetes are addressed in Section 4. Diabetes is an important risk factor for the development of contrast-induced AKI. Strategies to reduce the risk of contrast-induced AKI in patients with diabetes are discussed in Section 4.4. Cardiovascular disease is the leading cause of death in women in the United States and Europe,766 and an estimated 35% of PCIs in the United States are performed in women.767,768 Women undergoing PCI usually have more risk factors (including hypertension, advanced age, elevated cho- lesterol, and more significant and diffuse CAD) compared with men.769 Women with STEMI are also less likely to receive early medical treatments and experience longer de- lays to reperfusion therapy.770,771 In subgroup analyses of clinical trials, use of DES appears to be similarly efficacious in women and men.772 5.9.4. CKD: Recommendation Class I 1. In patients undergoing PCI, the glomerular filtration rate should be estimated and the dosage of renally cleared medications should be adjusted.298 300 (Level of Evidence: B) CKD is an independent risk factor for the development and progression of CAD,773,774 and is also associated with worse prognosis after MI or PCI.369,775 A glomerular filtration rate of body surface area should be considered abnormal. Patients with CKD undergoing PCI have a higher risk of complications, including bleeding,776 AKI, and death,236,777 but CKD is not a strong predictor of restenosis after BMS or DES.778 Strategies to reduce the risk of contrast-induced AKI in patients with CKD are discussed in Section 4.4. Platelet dysfunction and overdosing of anti- platelet and antithrombin drugs350 in patients with CKD contribute to the increased risk of bleeding. The Cockcroft- Gault formula is commonly used as a surrogate marker for estimating creatinine clearance, which in turn estimates glomerular filtration rate.298,299,779,780 Medications that require dosage adjustments in patients with CKD include eptifibatide, tirofiban, bivalirudin, enoxaparin, and fondaparinux.781 5.9.5. Cardiac Allografts Cardiac allograft vasculopathy is a major cause of death in cardiac transplant recipients after their first year of sur- vival.782 In general, revascularization for cardiac allograft vasculopathy with PCI is only palliative, with no evidence supporting benefit in regard to long-term survival or avoid- ance of retransplantation. The restenosis rate after PCI in patients with cardiac allograft vasculopathy is high, although stent implantation reduces early and midterm restenosis compared with balloon angioplasty. DES have been shown to have a tendency to lower restenosis rates compared with BMS.783,784 Thus, many clinicians perform stenting with DES or BMS in cardiac transplant patients with discrete lesions who have an abnormal stress test or symptoms suggestive of myocardial ischemia. 5.10. Periprocedural MI Assessment: Recommendations Class I 1. In patients who have signs or symptoms suggestive of MI during or after PCI or in asymptomatic patients with significant persistent angiographic complications (eg, large side-branch occlusion, flow-limiting dissec- tion, no-reflow phenomenon, or coronary thrombosis), creatine kinase-MB and/or troponin I or T should be measured. (Level of Evidence: C) Class IIb 1. Routine measurement of cardiac biomarkers (crea- tine kinase-MB and/or troponin I or T) in all pa- tients after PCI may be reasonable. (Level of Evi- dence: C) Major events leading to ischemia or MI after PCI include acute closure, embolization and no-reflow, side-branch oc- clusion, and acute stent thrombosis. Issues surrounding the routine assessment of cardiac biomarkers after PCI are complex, especially given that the definition of PCI-related MI has evolved over the years and most events are asymp- tomatic. The most recent consensus definition of MI consid- ers troponin elevations of 3 times the upper limit of normal as a PCI-related MI in patients with normal baseline levels; this is further classified as a type 4a MI.240 This definition is supported by studies with delayed-enhancement MRI con- firming that there is irreversible injury in the myocardium associated with biomarker elevations and that the size of this injury correlates with the degree of elevation.785 Furthermore, a meta-analysis of 15 observational studies found that tro- ponin elevations at any level were linked with worse in- hospital and long-term outcomes; elevations 3 times the upper limit of normal predicted even worse outcomes.242 Other observational data, however, have raised concerns about whether the relationship is causal.786,787 A recent study found creatinine kinase-MB to correlate better with MRI- detected MI than troponin level.788 Definitions of PCI-related MI are being reevaluated by the Task Force for the Redefi- nition of Myocardial Infarction. Although there may be value for individual operators and hospitals to routinely measure cardiac biomarkers to track rates of PCI-related MI, at present there are not compelling data to recommend this for all PCI procedures. 5.11. Vascular Closure Devices: Recommendations Class I 1. Patients considered for vascular closure devices should undergo a femoral angiogram to ensure their anatomic suitability for deployment. (Level of Evi- dence: C) Class IIa 1. The use of vascular closure devices is reasonable for the purposes of achieving faster hemostasis and earlier ambulation compared with the use of manual compression.257,789 791 (Level of Evidence: B) Class III: NO BENEFIT 1. The routine use of vascular closure devices is not recommended for the purpose of decreasing vascu- lar complications, including bleeding.256,257,789 792 (Level of Evidence: B) See Online Data Supplement 30 for additional data regarding vascular closure devices. Vascular (arteriotomy) closure devices have been exten- sively reviewed,790 most recently in a 2010 AHA scientific statement,257 which issued several formal recommendations. The results of 4 meta-analyses have found that vascular closure devices decrease time to hemostasis compared with manual compression but do not decrease vascular complica- tions, bleeding complications, or the need for blood transfu- sions.256,789,791,793 Future studies of vascular closure devices need to be randomized, include high-risk patients and high-risk anatomy, use blinded endpoint adjudication as much as possible, use well-defined and comprehensive com- plication endpoints, and be adequately powered to detect clinically important endpoints, particularly bleeding and vas- cular complications. 6. Postprocedural Considerations Postprocedural considerations in patients undergoing PCI are discussed below and summarized in Table 14. Some recom- mendations and text regarding DAPT in Section 5.7.2 are intentionally repeated in this section for reader ease of use. 6.1. Postprocedural Antiplatelet Therapy: Recommendations Class I 1. After PCI, use of aspirin should be continued indef- initely.560 563 (Level of Evidence: A) 2. 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 the patient is 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).572 (Level of Evidence: B) 3. Patients should be counseled on the importance of compliance with DAPT and that therapy should not be discontinued before discussion with their cardi- ologist.208 (Level of Evidence: C) Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e613 Table 14. Postprocedural Recommendations for Patients Undergoing PCI Recommendations COR LOE References Aspirin After PCI, use of aspirin should be continued indefinitely. I A 560 563 After PCI, it is reasonable to use aspirin 81 mg/d in preference to higher maintenance doses. IIa B 302,573 576 In patients receiving a stent (BMS or DES) during PCI for ACS, P2Y12 inhibitor therapy should be given for at least 12 mo. Options include clopidogrel 75 mg/d, prasugrel 10 mg/d, and ticagrelor 90 mg twice daily. I B 567,568,570 In patients receiving DES for a non-ACS indication, clopidogrel 75 mg/d should be given for at least 12 mo if patients are not at high risk of bleeding. I B 208,212,571 In patients receiving BMS for a non-ACS indication, clopidogrel should be given for a minimum of 1 mo and ideally up to 12 mo (unless the patient is at increased risk of bleeding; then it should be given for a minimum of 2 wk). I B 572 Patients should be counseled on the importance of compliance with DAPT and that therapy should not be discontinued before discussion with their cardiologist. I C 208 PPIs should be used in patients with a history of prior GI bleeding who require DAPT. I C 794 If the risk of morbidity from bleeding outweighs the anticipated benefit afforded by a recommended duration of P2Y12 inhibitor therapy after stent implantation, earlier discontinuation (eg, 12 mo) of P2Y12 inhibitor therapy is reasonable. IIa C N/A Use of PPIs is reasonable in patients with an increased risk of GI bleeding (eg, advanced age, concomitant use of warfarin, steroids, NSAIDs, Helicobacter pylori infection) who require DAPT. IIa C 794 Continuation of clopidogrel, prasugrel, or ticagrelor beyond 12 mo may be considered in patients undergoing placement of DES. IIb C N/A Routine use of a PPI is not recommended for patients at low risk of GI bleeding, who have much less potential to benefit from prophylactic therapy. III: No Benefit C 794 Exercise testing For patients entering a formal cardiac rehabilitation program after PCI, treadmill exercise testing is reasonable. IIa C 567,568 Routine periodic stress testing of asymptomatic patients after PCI without specific clinical indications should not be performed. III: No Benefit C 795 Cardiac rehabilitation Medically supervised exercise programs (cardiac rehabilitation) should be recommended to patients after PCI, particularly for patients at moderate to high risk, for whom supervised exercise training is warranted. I A 796 804 Secondary prevention (recommendations included from the 2011 AHA/ACCF Secondary Prevention and Risk Reduction Therapy Guideline)805 Lipid management with lifestyle modification and lipid-lowering pharmacotherapy Lifestyle modification I B 806,807 Statin therapy I A 344,806,808 810,810a Statin therapy which lowers LDL cholesterol to 100 mg/dL and achieves at least a 30% lowering of LDL cholesterol I C 344,806,808 810,810a Statin therapy which lowers LDL cholesterol to 70 mg/dL in very high-risk* patients IIa B 345,808 810,810a,811,812 Blood pressure control (with a blood pressure goal of 140/90 mm Hg) Lifestyle modification I B 813 817 Pharmacotherapy I A 813,818,819 Diabetes management (eg, lifestyle modification and pharmacotherapy) coordinated with the patient s primary care physician and/or endocrinologist I C N/A Complete smoking cessation I A 820 823 *Presence of established cardiovascular disease plus 1) multiple major risk factors (especially diabetes), 2) severe and poorly controlled risk factors (especially continued cigarette smoking), 3) multiple risk factors of the metabolic syndrome (especially high triglycerides 200 mg/dL plus non HDL cholesterol 130 mg/dL with low HDL cholesterol [ 40 mg/dL]), and 4) acute coronary syndromes. ACS indicates acute coronary syndromes; BMS, bare-metal stent(s); COR, class of recommendation; DAPT, dual antiplatelet therapy; DES, drug-eluting stent(s); GI, gastrointestinal; HDL, high-density lipoprotein; LDL, low-density lipoprotein; LOE, level of evidence; N/A, not applicable; NSAID, nonsteroidal anti-inflammatory drug; PCI, percutaneous coronary intervention; and PPI, proton pump inhibitor. Class IIa 1. After PCI, it is reasonable to use aspirin 81 mg per day in preference to higher maintenance dos- es.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 clopidogrel, prasugrel, or ticagrelor beyond 12 months may be considered in patients undergoing placement of DES.567,568 (Level of Evi- dence: C) Continued treatment with the combination of aspirin and a P2Y12 inhibitor antagonist after PCI appears to reduce MACE.570,572 On the basis of RCT protocols, secondary prevention measures, and expert consensus opinion, aspirin 81 mg daily should be given indefinitely after PCI. Likewise, P2Y12 inhibitors should be given for a minimum of 1 month after BMS (minimum 2 weeks for patients at significant increased risk of bleeding)580 and for 12 months after DES and ideally in all patients who are not at high risk of bleeding. The 2009 STEMI/PCI guidelines update10 listed the rec- ommendation if the risk of morbidity because of bleeding outweighs the anticipated benefit afforded by thienopyridine therapy, earlier discontinuation should be considered as a Class I recommendation, although the language used, in part, was consistent with a Class IIa recommendation. To clarify the intent of the recommendation, as well as to acknowledge the inherent difficulties in weighing bleeding and stent thrombosis risks, the recommendation is designated a Class IIa recommendation, using the phrase earlier discontinuation is reasonable. Recommendations regarding P2Y12 inhibitor discontinuation before elective or urgent CABG are provided in the 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery. 824 6.1.1. PPIs and Antiplatelet Therapy: Recommendations Class I 1. PPIs should be used in patients with a history of prior gastrointestinal (GI) bleeding who require DAPT.794 (Level of Evidence: C) Class IIa 1. Use of PPIs is reasonable in patients with an in- creased risk of GI bleeding (eg, advanced age, concomitant use of warfarin, steroids, nonsteroidal anti-inflammatory drugs, Helicobacter pylori infec- tion) who require DAPT.794 (Level of Evidence: C) Class III: NO BENEFIT 1. Routine use of a PPI is not recommended for pa- tients at low risk of GI bleeding, who have much less potential to benefit from prophylactic therapy.794 (Level of Evidence: C) See Online Data Supplement 31 for additional data regarding the clopidogrel PPI interaction. PPIs are often prescribed prophylactically when clopidogrel is started to prevent GI complications such as ulceration and bleeding due to DAPT.825 There is pharmacodynamic evidence that omeprazole interferes with clopidogrel metabolism,826,827 but there is no clear evidence implicating other PPIs. However, even with omeprazole, there are no convincing data supporting an important clinical drug drug interaction.826 The FDA com- munication about an ongoing safety review of clopidogrel advises that healthcare providers avoid the use of clopidogrel in patients with impaired CYP2C19 function due to known genetic variation or drugs that inhibit CYP2C19 activity. The FDA notes that there is no evidence that other drugs that reduce stomach acid, such as histamine-2 receptor antagonists (except cimeti- dine) or antacids, interfere with clopidogrel responsiveness. The COGENT (Clopidogrel and the Optimization of Gastrointestinal Events) trial randomized patients with DAPT to clopidogrel and omeprazole or clopidogrel and placebo, and while there was no difference in cardiovascular events between the 2 groups, GI events were halved in those randomized to omeprazole.828 It is reasonable to carefully evaluate the indication for PPI therapy in patients treated with clopidogrel, based on the presence or absence of the risk factors discussed above.794 The need for GI protection increases with the number of risk factors for bleeding. Prior upper GI bleeding is the strongest and most consistent risk factor for GI bleeding on antiplatelet therapy. Patients with ACS and prior upper GI bleeding are at substantial cardiovascular risk, so DAPT with concomitant use of a PPI may provide the optimal balance of risk and benefit. It should be noted that PPIs, by decreasing adverse GI effects related to clopidogrel, might decrease patients discontinuation of clopidogrel. In patients in whom there is a clear indication for PPI therapy, some clinicians may choose to use a PPI other than omeprazole. 6.1.2. Clopidogrel Genetic Testing: Recommendations Class IIb 1. Genetic testing might be considered to identify whether a patient at high risk for poor clinical outcomes is predisposed to inadequate platelet inhi- bition with clopidogrel.829 (Level of Evidence: C) 2. When a patient predisposed to inadequate platelet inhibition with clopidogrel is identified by genetic testing, treatment with an alternate P2Y12 inhibitor (eg, prasugrel or ticagrelor) might be considered.829 (Level of Evidence: C) Class III: NO BENEFIT 1. The routine clinical use of genetic testing to screen patients treated with clopidogrel who are undergoing PCI is not recommended.829 (Level of Evidence: C) On March 12, 2010, the FDA approved a new label for clopidogrel with a boxed warning about the diminished effectiveness of clopidogrel in patients with impaired ability to convert the drug into its active metabolite.829 Patients with decreased CYP2C19 function because of genetic polymor- phisms metabolize clopidogrel poorly and have higher rates of cardiovascular events after ACS and PCI than patients with Levine et al 2011 ACCF/AHA/SCAI PCI Guideline e615 normal CYP2C19 function. The warning also notes that tests are available to identify patients with genetic polymorphisms and that alternative treatment strategies should be considered for patients who are poor metabolizers. The clopidogrel boxed warning leaves the issue of whether to perform CYP2C19 testing up to the individual physician. It does not specifically require genetic testing or other changes in evaluation or treatment and does not imply that there are solid evidence-based reasons for such actions. Rather, it serves to inform clinicians of genetic variations in response to clopidogrel and to emphasize that clinicians should use this knowledge to make decisions about how to treat individual patients. At the present time, the evidence base is insufficient to recommend routine genetic testing in patients undergoing PCI. There may be a potential role for genetic testing for patients undergoing elective high-risk PCI procedures (eg, unprotected left main, bifurcating left main, or last patent coronary artery). 6.1.3. Platelet Function Testing: Recommendations Class IIb 1. Platelet function testing may be considered in pa- tients at high risk for poor clinical outcomes.829 (Level of Evidence: C) 2. 