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Review |

Medical Management After Coronary Stent Implantation:  A Review FREE

Emmanouil S. Brilakis, MD, PhD1; Vishal G. Patel, MD1; Subhash Banerjee, MD1
[+] Author Affiliations
1VA North Texas Health Care System and University of Texas Southwestern Medical Center at Dallas
JAMA. 2013;310(2):189-198. doi:10.1001/jama.2013.7086.
Text Size: A A A
Published online

Importance  Percutaneous coronary intervention (PCI) with stents is currently the most commonly performed coronary revascularization procedure; hence, optimizing post-PCI outcomes is important for all physicians treating such patients.

Objective  To review the contemporary literature on optimal medical therapy after PCI.

Evidence Review  We performed a comprehensive search of the PubMed and Cochrane Library databases for manuscripts on medical therapy after PCI, published between 2000 and February 2013. Bibliographies of the retrieved studies were searched by hand for other relevant studies. Priority was given to data from large randomized controlled trials, systematic reviews, and meta-analyses. Of the 6852 publications retrieved, 91 were included.

Findings  Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor (eg, ticlopidine, clopidogrel, prasugrel, ticagrelor) reduces the risk of stent thrombosis and subsequent cardiovascular events post-PCI (number needed to treat, 33-53) and is the current standard of care. Aspirin should be continued indefinitely and low dose (75-100 mg daily) is preferred over higher doses. A P2Y12 inhibitor should be administered for 12 months after PCI, unless the patient is at high risk for bleeding; however, ongoing studies are assessing the value of shorter or longer duration of P2Y12 inhibitor administration. In patients with acute coronary syndromes, prasugrel and ticagrelor further reduce cardiovascular ischemic events compared with clopidogrel but are associated with higher bleeding risk. If possible, noncardiac surgery should be delayed until 12 months after coronary stenting. Patients receiving coronary stents who require warfarin are at high risk for bleeding if they also receive dual antiplatelet therapy. Omission of aspirin may be advantageous in such patients. Routine platelet function or genetic testing is currently not recommended to tailor antiplatelet therapy after PCI.

Conclusions and Relevance  Dual antiplatelet therapy remains the cornerstone of medical therapy after PCI. Continuous advances in pharmacotherapy can further enhance our capacity to improve outcomes in this high-risk patient group.

Percutaneous coronary intervention (PCI) is commonly performed for coronary revascularization in patients with stable angina or acute coronary syndromes (ACS),1 with approximately 600 000 procedures performed in the United States during 2009.2 Coronary stents are metallic scaffolds that prevent vessel recoil and reduce the risk for restenosis. Stents are currently used in more than 90% of patients undergoing PCI3 because they significantly improve procedural success and subsequent clinical outcomes.4,5 Two types of coronary stents are available in the United States: bare-metal (BMS) and drug-eluting (DES). DESs elute an antiproliferative drug and are commonly classified into first generation (sirolimus-eluting and paclitaxel-eluting) and second generation (everolimus-eluting and zotarolimus-eluting). First-generation DESs had stainless-steel platforms, whereas second-generation DESs have cobalt-chrome or platinum-chrome platforms with thinner strut thickness and more biocompatible, durable polymer coatings.6 The main complications after stent implantation are in-stent restenosis and stent thrombosis. Stent thrombosis usually presents as ST-segment elevation acute myocardial infarction (MI) and is associated with high mortality.7Compared with BMSs, DESs decrease the risk of restenosis8 but may be associated with slightly increased risk of very late stent thrombosis (0.6% per year for first-generation DESs) because of delayed vessel healing.9

The goal of medical treatment after coronary stenting is to prevent stent thrombosis, slow the progression of coronary artery disease, and prevent major adverse cardiac events. The risk for stent thrombosis is highest within the first 30 days after stenting but continues at a lower rate for at least 3 years in patients receiving first-generation DES.9Several clinical factors are associated with increased stent thrombosis risk, such as presentation with an ACS, depressed left ventricular ejection fraction, diabetes, renal failure, treatment of bifurcation lesions, longer stent length, and use of stents other than the everolimus-eluting stent.1013 Dual antiplatelet therapy (DAPT) is currently recommended for all patients receiving coronary stents to reduce the risk of stent thrombosis and will be the main focus of the present review.

We performed a comprehensive search of the PubMed and Cochrane Library databases for articles on medical therapy post-PCI. Search terms included coronary stent(s), drug-eluting stent(s), medical therapy, aspirin, clopidogrel, prasugrel, ticagrelor, and DAPT. Bibliographies of the retrieved studies and previous reviews were searched by hand for other relevant studies. Human studies in English published between 2000 and February 2013 were included if they reported on medical treatment and outcomes post-PCI. Priority was given to data from large randomized controlled trials, systematic reviews, and meta-analyses. Of the 6852 publications retrieved, 91 were included in the present review.

Antiplatelet Therapy After Stent Implantation

Dual antiplatelet therapy with aspirin and an oral P2Y12 adenosine diphosphate receptor inhibitor is the standard treatment after coronary stenting. Compared with warfarin, DAPT reduces cardiac events (such as stent thrombosis, MI, and cardiac death), major bleeding, and vascular access complications after coronary stenting.1416 However, approximately 1 in 7 patients may discontinue adenosine diphosphate P2Y12 inhibitor within 30 days post-PCI, which is associated with higher mortality during the ensuing 11 months (adjusted hazard ratio, 9.0; 95% CI, 1.3 to 60.6), emphasizing the importance of careful patient selection and counseling after coronary stent implantation (especially DESs).17

Aspirin Dose

Aspirin should be administered indefinitely after PCI.1 A systematic review of various aspirin doses (30 -1300 mg/d) for coronary and cerebrovascular disease reported similar efficacy but higher bleeding risk with high- compared with low-dose aspirin.18 In the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE), Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb, and Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trials, the incidence of death, MI, and stroke in patients with ACS was similar with various aspirin doses.19,20 The CURE trial randomized 12 562 patients with non–ST-segment elevation ACS to receive clopidogrel (300 mg immediately, followed by 75 mg once daily) or placebo in addition to aspirin for 3 to 12 months and demonstrated significant reduction in the composite of death from cardiovascular causes, nonfatal MI, or stroke in the clopidogrel group.21 Among 2658 patients in CURE who underwent PCI, the incidence of cardiovascular death, MI, or stroke was similar with low- (<100 mg), moderate- (100-199 mg), or high-dose (≥200 mg daily) aspirin, whereas major bleeding was 2.05-fold higher (95% CI, 1.20-3.50; P = .009) in the high-dose compared with the low-dose group (3.9% vs 1.9%).22 The Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events–Seventh Organization to Assess Strategies in Ischemic Syndromes (CURRENT-OASIS 7) trial prospectively compared low-dose (75-100 mg daily) vs high-dose (300-325 mg daily) aspirin in patients with ACS and found similar 30-day incidence of cardiovascular death, MI, or stroke with both aspirin doses.23

Types, Mechanisms of Action, and Clinical Efficacy of P2Y12 Receptor Inhibitors

The P2Y12 receptor is the main platelet receptor responsible for adenosine diphosphate–induced platelet aggregation.24 Four P2Y12 inhibitors are available for clinical use in the United States: ticlopidine, clopidogrel, prasugrel, and ticagrelor (Table 1).

Table Graphic Jump LocationTable 1.  P2Y12 Inhibitors Currently in Clinical Use After Percutaneous Coronary Intervention

Ticlopidine is used infrequently because of increased risk of hematologic complications (neutropenia and thrombotic thrombocytopenic purpura), allergic exanthema, and diarrhea compared with clopidogrel.25 Neutropenia occurs in 0.5% to 0.8% of patients treated with ticlopidine vs 0.1% of patients treated with clopidogrel.16,26 Thrombotic thrombocytopenic purpura occurs in approximately 1 in 1600 to 5000 patients treated with ticlopidine, whereas the incidence with clopidogrel is at least an order of magnitude less than that observed with ticlopidine and is likely similar to its frequency in the general population.25,27

Ticlopidine, clopidogrel, and prasugrel are thienopyridine prodrugs that require conversion to an active metabolite that irreversibly binds to the P2Y12 receptor.24 Conversion of clopidogrel to its active metabolite requires at least 2 cytochrome-dependent steps, and mutations of enzymes involved in this pathway (especially cytochrome 2C19 and cytochrome 3A4) are largely responsible for significant interindividual variability in clopidogrel responsiveness.24 In contrast, prasugrel is more rapidly and reliably converted to its active metabolite with little interindividual variability, resulting in a faster and more potent inhibition of platelet activity compared with clopidogrel.28 Ticagrelor belongs to a new family of antiplatelet agents, cyclopentyl-triazolo-pyrimidines, which directly and reversibly bind to the P2Y12 receptor, also resulting in more rapid and potent inhibition of platelet activity compared with clopidogrel.24,28 A few key trials have examined the efficacy of clopidogrel, along with the new P2Y12 receptor inhibitors, prasugrel and ticagrelor.

Clopidogrel

Although early studies demonstrated a benefit for short-term (2 to 4 weeks) thienopyridine in addition to aspirin after stenting with BMSs primarily to prevent stent thrombosis, 2 key trials suggested that longer duration of clopidogrel after PCI may be beneficial (Table 2).

Table Graphic Jump LocationTable 2.  Pivotal P2Y12 Inhibitor Trials Post–Coronary Stent Implantation

Among the 2658 ACS patients in the CURE trial who underwent PCI with BMSs, continuing clopidogrel after the first 4 weeks post-PCI for a mean of 8 months was associated with 31% reduction (from 12.6% to 8.8%; relative risk, 0.69 [95% CI, 0.54-0.87]; P = .002) in the incidence of cardiovascular death, MI, or revascularization without an increase in major bleeding.29 The Clopidogrel for the Reduction of Events During Observation (CREDO) trial evaluated prolonged clopidogrel administration after PCI in a lower-risk population, with approximately one third undergoing PCI for non-ACS indications.30 In CREDO, compared with clopidogrel for 28 days after PCI, continuing clopidogrel for 1 year resulted in a 26.9% relative reduction in the 12-month incidence of death, MI, and stroke.30 The benefit was consistent across multiple subgroups, including those with and without ACS and those with and without stent implantation.30 When only events that occurred after the first month were evaluated with a landmark analysis, prolonged clopidogrel administration was associated with a non–statistically significant benefit in PCI-CURE and a small benefit in CREDO.33 However, only patients who received clopidogrel pretreatment were included in the long-term clopidogrel arm, making it impossible to separate the benefit of clopidogrel loading from that of prolonged clopidogrel administration.

The PCI-CURE and CREDO trials did not examine the optimal clopidogrel dose. A number of small randomized trials demonstrated greater platelet inhibition with higher loading (600 mg vs 300 mg)3436 and maintenance (150 mg vs 75 mg daily)37,38 clopidogrel dosing but were not powered for clinical end points. The CURRENT-OASIS 7 trial randomized 25 086 ACS patients to high-dose (600 mg loading followed by 150 mg daily for 6 days, followed by 75 mg daily thereafter) vs low-dose (300 mg loading followed by 75 mg daily) clopidogrel.23 The 30-day incidence of the primary ischemic endpoint (cardiovascular death, MI, or stroke) was similar in both groups, whereas major bleeding was higher in the high-dose clopidogrel group.23 In the subgroup of 17 263 patients undergoing PCI, high-dose clopidogrel was associated with a 15% reduction in the incidence of the primary ischemic endpoint; however, this analysis did not meet the prespecified threshold of significance for a test of interaction.23 As a result, after the initial loading dose most patients currently receive 75 mg of clopidogrel daily.

Prasugrel

The Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38 study randomized 13 608 patients with moderate- to high-risk ACS (ST-segment elevation MI, or unstable angina or non–ST segment elevation MI with ischemic symptoms lasting ≥10 minutes and occurring within 72 hours before randomization, a TIMI risk score of ≥3, and either ST-segment deviation of 1 mm or more or elevated levels of a cardiac biomarker of necrosis) scheduled to undergo PCI to prasugrel or clopidogrel before or up to 1 hour after PCI.31 During a median follow-up of 14.5 months, compared with clopidogrel (with a loading dose of 300 mg) prasugrel reduced the incidence of cardiovascular death, MI, or stroke (9.9% vs 12.1%; P < .001) and stent thrombosis39 but also increased the risk for TIMI major and fatal bleeding.31 Patients with ST-segment elevation MI40 and diabetes41 had greater reduction in the primary ischemic endpoint without an increase with non–coronary artery bypass graft–related TIMI major bleeding. Prasugrel was associated with harm among patients with previous transient ischemic attack or stroke (hazard ratio, 1.54; 95% CI, 1.02-2.32 for the composite of death, nonfatal MI, nonfatal stroke, or non–coronary artery bypass graft–related nonfatal TIMI major bleeding) and provided no benefit among patients aged 75 years or older or with weight less than 60 kg.31

Ticagrelor

The Study of Platelet Inhibition and Patient Outcomes (PLATO) trial randomized 18 624 patients with ACS to ticagrelor or clopidogrel and followed them for a median of 277 days.32 Percutaneous coronary intervention was performed in 61% of patients. Ticagrelor reduced the 12-month incidence of vascular death, MI, or stroke compared with clopidogrel (9.8% vs 11.7%; P < .001), as well as all-cause mortality (4.5% vs 5.9%; P < .001)32 and stent thrombosis.42 Patients with decreased renal function derived greater absolute (4.7% vs 1.0%) and relative (23% vs 10%) risk reduction.43 Ticagrelor was associated with a higher rate of non–coronary artery bypass graft-related major bleeding, dyspnea (13.8% vs 7.8%), and ventricular pauses lasting greater than or equal to 3 seconds (but not requiring specific treatment). Significant geographic differences in the effect of ticagrelor were observed (no benefit in North American patients vs benefit in the rest of the world) and were attributed to coadministration of greater than 100 mg daily aspirin dose, which was more common in North America.44 Hence, patients receiving ticagrelor should receive low-dose aspirin (75-100 mg daily).

Optimal Duration of P2Y12 Inhibitor Administration

According to the results of the CURE, CREDO, TRITON-TIMI 38, and PLATO trials, 12-month administration of a P2Y12 inhibitor is recommended for patients presenting with ACS, especially those undergoing PCI. Compared with BMSs, patients receiving DESs may be at increased risk for very late (>1 year post-PCI) stent thrombosis, raising the question of whether prolonged DAPT beyond 1 year could be beneficial. Several observational studies suggested benefit with prolonged DAPT duration.12,45,46 However, 2 recent randomized trials did not demonstrate reduction in death or MI with prolonged DAPT and one study demonstrated harm (increased rates of bleeding) (Table 3).47,48 A meta-analysis of 4 randomized controlled trials testing a variety of DAPT durations after DES4750 confirmed that extended DAPT did not provide clinical benefit (no difference in mortality [odds ratio, 1.15; 95% CI, 0.85 to1.54], MI [odds ratio, 0.95; 95% CI, 0.66 to1.36], and stent thrombosis [odds ratio, 0.88; 95% CI, 0.43 to 1.81]) but increased the risk for TIMI major bleeding (odds ratio, 2.64; 95% CI, 1.31 to 5.30).51 These studies challenge the traditional paradigm of 12 months of DAPT after DES and highlight the paucity of data behind the current recommendation. Dual antiplatelet therapy for less than or greater than 12 months is currently being examined in 2 large ongoing clinical trials.52,53 Shorter duration of DAPT may be beneficial for patients receiving everolimus-eluting stents who are at lower risk of stent thrombosis compared with other DESs.10

Table Graphic Jump LocationTable 3.  Clinical Trial Evaluating the Duration of P2Y12 Inhibitor Administration After Stent Implantation
Special Scenarios
Noncardiac Surgery After Stent Implantation

Approximately 4% to 7% of patients who receive coronary stents require noncardiac surgery each year after stent implantation.5456 Noncardiac surgery poststenting carries risk for perioperative stent thrombosis because of a combination of surgery-induced prothrombotic state and antiplatelet therapy discontinuation. This risk is highest early after stenting for up to 6 weeks after BMS and at least up to 6 months after DES implantation.5759 If possible, noncardiac surgery after DES should be postponed until after a 12-month course of DAPT with aspirin and clopidogrel is completed. If, however, surgery needs to be performed earlier, continuation of dual (or at least single) oral antiplatelet therapy may help minimize the stent thrombosis risk.60 For patients who require surgery early after stenting and for whom all antiplatelet therapy needs to be discontinued (for example, patients undergoing intracranial or spine surgery), preoperative administration of a short-acting intravenous agent (such as glycoprotein IIb/IIIa inhibitor, heparin, or cangrelor) has been proposed; however, the efficacy and safety of such a treatment have been poorly studied. Moreover, the highest-risk period for stent thrombosis is immediately after surgery, not before.61 Given these risks, noncardiac surgery should be performed at centers with primary PCI capacity to enable rapid treatment if stent thrombosis occurs. In addition, communication and collaboration between the surgeon, cardiologist, and anesthesiologist are important to help optimize the management of such patients.

Patients Who Require Oral Anticoagulation

Patients requiring oral anticoagulation (for example, for atrial fibrillation or mechanical heart valve) who undergo coronary stenting present a challenging clinical dilemma. As discussed earlier, DAPT therapy significantly reduces cardiac events after coronary stenting compared with oral anticoagulation.14,15,62 However, coadministration of DAPT and oral anticoagulation (“triple therapy”) is associated with high bleeding risk.63 In a meta-analysis of 18 studies aggregating data from 4138 patients, the rate of major bleeding with triple therapy was 2- to 3-fold higher than that observed with DAPT both at 30 days in 2791 patients and at 6 months in 2550 patients. Triple therapy is generally discouraged for patients with an indication for oral anticoagulation after stenting unless the bleeding risk is low or the thromboembolic risk is sufficiently high.63

An alternative strategy was tested in the What Is the Optimal Antiplatelet and Anticoagulant Therapy in Patients With Oral Anticoagulation and Coronary Stenting (WOEST) trial that randomized 573 patients to dual therapy with oral anticoagulation and clopidogrel (75 mg daily) or to triple therapy with oral anticoagulation, clopidogrel, and aspirin 80 mg daily.64 Treatment was continued for 1 month after BMS (35% of patients) and 1 year after DES (65% of patients). At 1-year follow-up, bleeding was significantly reduced in the dual-therapy group, without an increase in MI, target vessel revascularization, stroke, or stent thrombosis.64 There was also a statistically significant reduction in mortality in the dual-therapy group compared with triple therapy. According to the WOEST trial, omitting aspirin may be an attractive option for patients requiring oral anticoagulation, although more clinical trials are needed to confirm those findings.

There is limited experience with use of DAPT with novel oral anticoagulants, such as dabigatran, rivaroxaban, and apixaban, and such a combination is avoided because of concerns for increased risk of bleeding.65 In the Apixaban for Prevention of Acute Ischemic Events 2 (APPRAISE-2) trial, compared with standard DAPT, the addition of full-dose apixaban (5 mg twice daily) administration in high-risk ACS patients did not reduce the incidence of ischemic outcomes but increased the risk for major bleeding.66 In contrast, in the Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome 2–Thrombolysis in Myocardial Infarction 51 (ATLAS ACS 2–TIMI 51) trial, low-dose twice-daily rivaroxaban at doses of 2.5 and 5 mg reduced cardiac and all-cause mortality and the incidence of stent thrombosis when administered in addition to aspirin and clopidogrel in ACS patients.67

Use of Genetic and Functional Platelet Testing to Determine the Intensity of Antiplatelet Therapy

Genetic polymorphisms such as the cytochrome 2C19 loss of function allele result in decreased response to clopidogrel and have been associated with increased risk of cardiovascular events in some68 but not all69 studies. Given the significant interindividual variability in the degree of platelet inhibition achieved with clopidogrel,70 tailoring of antiplatelet therapy according to functional platelet activity is theoretically an appealing strategy. In 2010 the FDA issued a black box warning for clopidogrel suggesting that cytochrome 2C19 genetic testing may identify individuals who are poor metabolizers of clopidogrel, which can be used to adjust the dosing of clopidogrel or consider alternative antiplatelet agents. However, tailoring antiplatelet therapy according to platelet function testing did not improve clinical outcomes in 2 large clinical trials (Gauging Responsiveness With A VerifyNow Assay–Impact on Thrombosis and Safety [GRAVITAS] and Assessment by a Double Randomization of a Conventional Antiplatelet Strategy vs a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption vs Continuation One Year After Stenting [ARCTIC]).71,72

Aspirin or P2Y12 Inhibitor Allergy

Allergic reactions to aspirin are mediated either through inhibition of the cyclooxygenase 1 enzyme or through aspirin-specific immunoglobulin E production and can manifest as aspirin-exacerbated respiratory tract disease, urticaria/angioedema, or anaphylaxis.73 Given the importance of aspirin after PCI in preventing adverse cardiovascular events, patients with a true aspirin reaction (except for those with chronic idiopathic urticaria) are usually treated with aspirin desensitization.74 Rapid desensitization protocols completed within 4 hours have been demonstrated to be safe and efficacious in a small series of patients requiring PCI.75 Among 1014 patients admitted for cardiac catheterization, 26 (2.6%) had a history of aspirin sensitivity, and rapid desensitization was successfully achieved in 23 (88.5%). Although the majority of patients were treated before PCI, 4 (0.4%) patients presenting with ST-segment elevation MI underwent successful desensitization after PCI before hospital discharge.76 Alternative treatment strategies for patients who develop aspirin allergy after PCI include administration of newer P2Y12 inhibitors, such as ticagrelor or prasugrel. Patient compliance is central to the success of aspirin desensitization because missing doses for more than 48 hours can result in resensitization.

Compared with ticlopidine, newer P2Y12 receptor inhibitors are better tolerated, although allergic or hypersensitivity reactions still occur in 1.5% to 6% of patients treated with clopidogrel, prasugrel, or ticagrelor.26,31,32,77 The most commonly described hypersensitivity reaction to clopidogrel is a pruritic, macular, erythematous, confluent, predominantly truncal rash (though occasionally involving the extremities and palms/soles).77,78 Less commonly described are localized rashes and angioedema or urticaria.77,79 For most patients ( ≈ 98%) with cutaneous hypersensitivity reactions to clopidogrel, a short course of oral steroids and antihistamines results in complete resolution without interruption of antiplatelet therapy.77 In the remaining patients, successful clopidogrel desensitization has been reported, but these regimens typically require a washout period without clopidogrel, which is not ideal after recent PCI.78 Hence, switching to an alternative P2Y12 inhibitor is the preferred option, although there is 27% cross-reactivity when switching to prasugrel from clopidogrel.77

DAPT and Proton-Pump Inhibitors

Although omeprazole, a proton-pump inhibitor, may decrease the effectiveness of clopidogrel in pharmacodynamic80 observational81 studies, the Clopidogrel and the Optimization of Gastrointestinal Events (COGENT) trial found no difference in the incidence of cardiovascular events between patients receiving clopidogrel and omeprazole or placebo despite a significant reduction in gastrointestinal bleeding with omeprazole.82 Use of proton-pump inhibitors other than omeprazole may be preferred for patients who receive clopidogrel after PCI because there is no clear evidence that other proton-pump inhibitors interfere with metabolism of clopidogrel.80

Cilostazol

Cilostazol is a selective inhibitor of phosphodiesterase III and has antiplatelet and antirestenotic activity. Although observational studies have suggested that addition of cilostazol to aspirin and clopidogrel may decrease the risk of stent thrombosis,83 no such effect was observed in a meta-analysis of randomized controlled trials84 despite a reduction in the need for repeated revascularization with cilostazol.

Other Therapies

Patients who receive coronary stents are at increased risk for recurrent cardiovascular events, emphasizing the need for secondary prevention measures, such as smoking cessation and treating diabetes, dyslipidemia, and hypertension through lifestyle modification and medications. There are several medications of proven benefit to patients with cardiovascular disease, such as statins, β-blockers, and angiotensin-converting enzyme inhibitors. Finally, participation in a cardiac rehabilitation program can be highly beneficial.85,86

The primary finding of our review is that DAPT remains the main medical therapy for optimizing stent-related outcomes after PCI and stent placement. DAPT consists of aspirin and a P2Y12 inhibitor.

Aspirin should be administered indefinitely post-PCI. Because of similar efficacy and higher bleeding risk with higher doses, low-dose aspirin (usually 81 mg daily) is preferred and carries a class IIA recommendation after PCI.1,87,88

Selection of P2Y12 inhibitor depends on the patient’s clinical presentation and comorbidities: non-ACS patients receive clopidogrel, whereas ACS patients may also be treated with ticagrelor or prasugrel, both of which provide superior efficacy compared with clopidogrel but are also associated with increased risk of bleeding. The addition of low-dose rivaroxaban is an appealing emerging strategy,67 but whether dual therapy with aspirin and ticagrelor/prasugrel is similar, superior, or inferior to triple therapy with aspirin, clopidogrel, and rivaroxaban remains to be determined.

The recommended duration of DAPT administration is 12 months for ACS patients and for non-ACS patients receiving DESs if the patients do not have increased risk for bleeding. Non-ACS patients receiving BMSs should be treated with a minimum of 1 month of DAPT, although the American PCI guidelines recommend 12-month DAPT administration to those patients as well, unless they are considered to have high bleeding risk. Whether longer or shorter than 12-month DAPT duration provides benefits is being examined in multiple ongoing clinical trials.32,42 At present, published data do not support routine continuation of DAPT beyond 12 months,51 except possibly for patients at high risk of stent thrombosis (such as patients with diabetes, depressed left ventricular ejection fraction, or renal failure1113,49) or patients in whom stent thrombosis could lead to catastrophic outcomes (such as patients with left main stenting, proximal left anterior descending artery stenting, saphenous vein graft stenting,89 or multivessel stenting).

Dual antiplatelet therapy duration could potentially be tailored to each patient’s unique clinical profile and the type of stent used. Currently, the everolimus-eluting stent and the zotarolimus-eluting stent have CE mark (European conformity) for 3 and 1 months, respectively, DAPT duration.10 Availability of fully bioresorbable stents90 or stents with bioresorbable polymer may allow further reduction in DAPT duration. Careful patient selection and counseling on the importance of DAPT can minimize the risks associated with early DAPT discontinuation.17

Our review findings are in line with the current European91 and US1,87,88 guideline recommendations on DAPT type and duration after coronary stent implantation, which are summarized in Table 4.

Table Graphic Jump LocationTable 4.  Medical Therapy After Percutaneous Coronary Intervention With Stent Implantation1

Noncardiac surgery should ideally be postponed until 4 to 6 weeks after BMS implantation or 12 months post-DES implantation to minimize the risk of perioperative stent thrombosis. If surgery is needed earlier, continuation of dual (or at least single) antiplatelet therapy may be beneficial when the surgical bleeding risk is not prohibitive.49,50

Most patients with aspirin allergy are best treated with aspirin desensitization. Patients with P2Y12 inhibitor allergy may be best treated with a different P2Y12 inhibitor, although some cross-reactivity exists between clopidogrel and prasugrel.77 The major adverse events associated with DAPT post-PCI are summarized in Table 5.

Table Graphic Jump LocationTable 5.  Most Common Complications and Challenges Associated With Antiplaletet Therapy After Percutaneous Coronary Intervention

Given the lack of benefit in 2 large randomized controlled trials,65,66 routine genetic or platelet function testing to tailor antiplatelet treatment post-PCI is not currently recommended (class III recommendation).70

Patients who receive coronary stents and also require oral anticoagulation for another indication (such as atrial fibrillation) may be best treated with BMSs followed by 1 month of DAPT. If such patients receive DESs, use of warfarin and clopidogrel without aspirin may be associated with improved outcomes compared with triple therapy.64

Proton-pump inhibitors should be administered to patients who require DAPT after coronary stenting and are at high risk for gastrointestinal bleeding.82

Finally, as with all patients with established coronary artery disease, patients undergoing PCI should receive risk factor and lifestyle modification and antiatherosclerotic therapies to reduce the risk of recurrent ischemic events.1

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor significantly improves the outcomes of patients undergoing coronary stenting. Aspirin should be administered indefinitely, whereas the P2Y12 inhibitor is usually administered for 12 months after stenting. Several ongoing studies will allow further optimization of the medical management of patients who receive coronary stents.

Section Editor: Mary McGrae McDermott, MD, Senior Editor.
Submissions:We encourage authors to submit papers for consideration as a Review. Please contact Mary McGrae McDermott, MD, at mdm608@northwestern.edu.

Corresponding Author: Emmanouil S. Brilakis, MD, PhD, VA North Texas Health Care System, University of Texas Southwestern Medical Center at Dallas, Division of Cardiology (111A), 4500 S Lancaster Rd, Dallas, TX 75216 (emmanouil.brilakis@va.gov).

Author Contributions: Dr Brilakis had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: All authors.

Acquisition of data: Brilakis, Patel.

Analysis and interpretation of data: All authors.

Drafting of the manuscript: All authors.

Criticalrevision of the manuscript for important intellectual content: All authors.

Administrative, technical, or material support: Patel, Banerjee.

Study supervision: Brilakis, Banerjee.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Brilakis reports that his spouse is an employee of Medtronic and reports receiving consulting/speaker honoraria from St Jude Medical, Terumo, Janssen, sanofi-aventis, and Bridgepoint Medical/Boston Scientific; receiving research support from Guerbet; and providing expert testimony for Thompson Coe. Dr Banerjee reports that his spouse has ownership in MDCARE Global and reports receiving research grants from Gilead and the Medicines Company, receiving consultant/speaker honoraria from Covidien and Medtronic, and owning intellectual property in HygeiaTel. No other disclosures were reported.

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Figures

Tables

Table Graphic Jump LocationTable 1.  P2Y12 Inhibitors Currently in Clinical Use After Percutaneous Coronary Intervention
Table Graphic Jump LocationTable 2.  Pivotal P2Y12 Inhibitor Trials Post–Coronary Stent Implantation
Table Graphic Jump LocationTable 3.  Clinical Trial Evaluating the Duration of P2Y12 Inhibitor Administration After Stent Implantation
Table Graphic Jump LocationTable 4.  Medical Therapy After Percutaneous Coronary Intervention With Stent Implantation1
Table Graphic Jump LocationTable 5.  Most Common Complications and Challenges Associated With Antiplaletet Therapy After Percutaneous Coronary Intervention

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