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INTRODUCTION — In patients with obstructive coronary artery disease who undergo percutaneous coronary intervention (PCI) to improve symptoms, stents, and in particular drug-eluting stents (DES), are used in the majority. There are some countries and regions where bare metal stents (BMS) are used more commonly.
Stent thrombosis is an uncommon but serious complication of coronary artery stenting that often presents as death and is almost always accompanied by myocardial infarction (MI), usually with ST-segment elevation. (See "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Definitions'.)
Long-term dual antiplatelet therapy (DAPT; aspirin plus platelet P2Y12 receptor blocker) significantly lowers the risk of stent thrombosis. In addition, there is some evidence to support the idea that it also prevents ischemic events remote from the stented area.
This topic will discuss the use of antiplatelet therapy to reduce the risk of adverse outcomes after PCI in patients with stable coronary artery disease. Related topics include:
OUR APPROACH TO TREATMENT DURATION — For most patients with stable coronary artery disease who have undergone percutaneous coronary intervention (PCI) with stenting (either bare metal stent [BMS] or drug-eluting stent [DES]), we recommend aspirin 75 to 100 mg daily plus clopidogrel 75 mg daily for at least 12 months. For many individuals who have tolerated this therapy, we continue this dual antiplatelet therapy (DAPT) for an additional 18 months. (See 'Duration' below.)
However, the decision regarding the duration of DAPT must be individualized, taking into account the benefits (prevention of ischemic events) and risks (bleeding):
Patients who may be reasonable candidates for less than one year of DAPT include those at relatively high bleeding risk: a history of transient ischemic attack or stroke, age ≥75 years, propensity to bleed (eg, recent trauma or surgery, recent or recurrent gastrointestinal bleeding, active peptic ulcer disease, severe hepatic impairment), body weight <60 kg, or concomitant use of medications that increase risk (oral anticoagulants or nonsteroidal antiinflammatory drugs [NSAIDs]).
●For patients who have successfully completed one year of DAPT, we discuss with them benefits and risks of continuing therapy. We use clinical judgment as well as the DAPT risk calculator to determine if DAPT beyond 12 months is reasonable (DAPT score). For patients with a score of <2, we generally stop at 12 months. For patients with a score of 2 or greater, we generally continue therapy for an additional 18 months. (See 'Decision tools' below.)
RATIONALE — The benefit from indefinite antiplatelet therapy with aspirin in patients with atherosclerotic cardiovascular disease (secondary prevention) is well established. (See "Benefits and risks of aspirin in secondary and primary prevention of cardiovascular disease", section on 'Efficacy'.)
All patients who undergo percutaneous coronary intervention (PCI), including those treated with balloon angioplasty without stenting, receive dual antiplatelet therapy (DAPT), which is the combination of aspirin and a P2Y12 receptor blocker to reduce the risk of myocardial infarction (MI) or cardiovascular death. DAPT likely decreases the risk of these ischemic events by preventing stent thrombosis and by lowering the risk of adverse events consequent to plaque rupture at sites remote from the stented location.
The rationale for the use of DAPT, as opposed to antiplatelet monotherapy, is derived from the known tendency of circulating blood to clot in the presence of many metals. This period of risk decreases after the metal portion of the stent is endothelialized [1-4]. More intense antiplatelet therapy (DAPT) lowers the risk of stent thrombosis compared with aspirin alone. (See "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Early and late stent thrombosis' and "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Risk factors' and "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Mechanisms'.)
In early studies of patients who received bare metal stents (BMS), the rate of stent thrombosis was significantly lower with aspirin plus ticlopidine than with aspirin alone (or aspirin plus warfarin) [5-9]. For example, the efficacy of combined antiplatelet therapy was demonstrated in the STARS trial in which 1653 patients were randomly assigned to aspirin alone or in combination with warfarin or ticlopidine . The primary end point included all clinical events reflecting stent thrombosis within 30 days: death, revascularization of the target lesion, angiographically documented thrombosis, or MI. The rate of the primary end point was significantly lower with aspirin plus ticlopidine than with aspirin plus warfarin or aspirin alone (0.5 versus 2.7 or 3.6 percent, respectively). After one randomized trial demonstrated similar efficacy between ticlopidine and clopidogrel but a better side effect profile with the latter, the use of ticlopidine declined dramatically; it is now rarely used . (See "Antithrombotic therapy for elective percutaneous coronary intervention: General use", section on 'P2Y12 receptor blockers'.)
There are no studies that have compared dual with single antiplatelet therapy in stable patients who received drug-eluting stents (DES). However, we believe the rationale for DAPT (as opposed to antiplatelet monotherapy) after DES implantation is strong based on biologic plausibility, evidence of benefit in patients with BMS, and observations of adverse outcomes, including stent thrombosis, when DAPT is discontinued during the period of time when incomplete endothelialization is possible or probable. (See "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Risk factors'.)
In addition to lowering the risk of stent thrombosis, we believe DAPT prevents adverse events consequent to plaque rupture at sites remote from the stented location (events not related to stent placement). Evidence supporting the role of DAPT in this regard is suggested by the following:
●In patients with acute coronary syndromes treated medically (no PCI), DAPT, compared with aspirin alone, reduces the rate of MI (figure 1). (See "Antiplatelet agents in acute non-ST elevation acute coronary syndromes", section on 'Specifics of P2Y12 therapy'.)
●In the PEGASUS-TIMI 54 trial, which compared ticagrelor with placebo in patients who were one to three years away from their MI, a composite end point of cardiovascular death, MI, or stroke occurred less often with ticagrelor than with placebo at three years. However, the risk of major bleeding was increased. (See 'Drug-eluting stents' below.)
●In the DAPT trial (see 'Drug-eluting stents' below), which showed that overall ischemic event rates and stent thrombosis were lower with 30 rather than 12 months of DAPT after stenting, the rate of MI not related to stenting was also lower (1.8 versus 2.9 percent; hazard ratio [HR] 0.59; p<0.001). This difference accounted for 55 percent of the total reduction in MI with prolonged DAPT. However, the risk of bleeding was increased.
DURATION — For most stable patients (and for acute coronary syndrome patients as well) treated with either drug-eluting stents (DES) or bare metal stents (BMS) in whom surgery is not anticipated and the bleeding risk is not excessive (discussed in the next paragraph), we prescribe DAPT for 12 months. After 12 months, we re-evaluate the patient. For patients who have not had clinically significant bleeding and who continue to be at low risk for bleeding, we continue DAPT for at least an additional 18 months. Each practitioner and his/her patients must weigh the decrease in the risk of ischemic events with the increase in the rate of major bleeding prior to deciding on continuing DAPT after 12 months.
Patients at high bleeding risk started on DAPT are considered for treatment of less than 12 months duration . In these patients, we individualize care (duration) taking into account the relative risks and benefits of DAPT. These patients include those with a history of transient ischemic attack or stroke, age ≥75 years, propensity to bleed (eg, recent trauma or surgery, recent or recurrent gastrointestinal bleeding, active peptic ulcer disease, severe hepatic impairment, body weight <60 kg [for prasugrel], or concomitant use of medications that increase risk [oral anticoagulants or nonsteroidal antiinflammatory drugs (NSAIDs)]) . (See "NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity", section on 'Risk factors' and 'Patients taking anticoagulants' below and "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Risk factors'.)
Occasionally, patients may unexpectedly need to stop DAPT prior to 12 months. We believe the minimum duration of uninterrupted therapy (ie, before which every effort to not stop therapy should be made) is 30 days. (See 'Patients needing temporary discontinuation' below.)
These recommendations are based in large part on the randomized trials discussed below. It should be kept in mind that the trials did not demonstrate a difference in relative benefit based on risk factors for stent thrombosis. This does not exclude the possibility that some patient groups may derive greater benefit, such as those with :
●Complex percutaneous coronary intervention (PCI; bifurcation or left main stenting, long lesions, saphenous vein grafts)
●Less than optimal stenting result (eg, stent malapposition, residual stenosis)
●Reduced left ventricular systolic function
●Prior stent thrombosis or a cardiovascular ischemic event within the first 12 months of DAPT (see "Coronary artery stent thrombosis: Clinical presentation and management", section on 'Long-term antiplatelet therapy')
Drug-eluting stents — The optimal duration of dual antiplatelet therapy (DAPT) after placement of intracoronary drug-eluting (and bare metal) stents is not known and it likely depends on patient-specific ischemic and bleeding risks. For most patients, we recommend at least 12 months of DAPT. For patients who remain free of major (table 2) or moderate (need for transfusion) severity bleeding events after 12 months and who are able to continue this therapy, we continue DAPT for at least an additional 18 months. We individualize this important decision, taking into account predictors of bleeding or ischemic events. However, we prescribe DAPT for less than one year if a bleeding event occurs or the bleeding risk is very high.
The consistent observation of a risk for stent thrombosis for as long as one year (and longer) after placement of a DES led to an early recommendation for at least one year of DAPT. (See "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Drug-eluting stents'.)
Our approach to long-term antiplatelet therapy in patients who have undergone elective stenting is based on the following evidence.
The DAPT trial randomly assigned 9961 patients with DES implantation, who had been successfully treated with 12 months of aspirin and a P2Y12 receptor blocker (either clopidogrel or prasugrel), to continue receiving the P2Y12 receptor blocker or placebo for another 18 months (randomization was performed one year after the index hospitalization); all patients continued aspirin . Enrolled patients had either stable (38 percent) or unstable disease. Exclusion criteria included a major adverse cardiovascular or cerebrovascular event, repeat revascularization, or moderate or severe bleeding within the first 12 months after the index procedure. The new-generation everolimus-eluting XIENCE stent was used in approximately half of patients, whereas first-generation stents were used in the remainder. The following findings were reported:
●The rates for each of the co-primary end points of stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death from any cause, myocardial infarction [MI], or stroke) were lower with continued P2Y12 therapy (0.4 versus 1.4 percent; hazard ratio [HR] 0.29, 95% CI 0.17-0.48 and 4.3 versus 5.9 percent; HR 0.71, 95% CI 0.59-0.85, respectively). The reduction in events with continued DAPT was mostly attributable to a lower rate of MI (2.1 versus 4.1 percent; HR 0.47, p<0.001), which represents 20 fewer MIs per 1000 treated patients per year.
●The rate of the primary safety end point of moderate or severe bleeding applying the GUSTO criteria (table 2) was increased with continued DAPT (2.5 versus 1.6 percent, p = 0.001), which represents nine more major bleeds per 1000 treated patients per year.
●The rate of death from any cause was higher in the DAPT group (2.0 versus 1.5 percent; HR 1.36, 95% CI 1.00-1.85). This increase was due to an increase in noncardiac deaths (1.0 versus 0.5 percent, p = 0.002), which represents five more deaths per 1000 treated patients per year.
●Regarding the primary end point, a prespecified sub-group analysis suggested a greater benefit of longer duration of DAPT in patients with an MI compared with those without an MI (3.9 versus 6.8 percent compared with 4.4 versus 5.3 percent; p-interaction = 0.03) .
●In a post-hoc analysis of 4703 patients treated with the second generation everolimus eluting stent, the results were similar to the results of the overall DAPT trial . Continued P2Y12 therapy reduced the rate of stent thrombosis (0.3 versus 0.7 percent; HR 0.38, 95% CI 0.15-0.97) and MI (2.1 versus 3.2 percent; HR 0.63, 95% CI 0.44-0.91), while the rate of moderate/severe bleeding was increased (2.5 versus 1.3 percent, HR 1.79, 95% CI 1.15-2.80).
As new-generation stents are used in the majority of cases, the results in this subgroup are particularly important. Given the smaller (compared with the entire study group) absolute reductions in ischemic events, significant consideration to the relative hazards of ischemic events and bleeding events is warranted before determining a long-term DAPT strategy in the individual patient receiving everolimus-eluting stents.
The DAPT trial is the largest of the randomized trials that have compared longer- with shorter-duration DAPT after DES placement. Other randomized trials such as PRODIGY, DES-LATE, and ARCTIC-Interruption did not show a decrease in ischemic events with longer therapy [15-17]. However, they had design limitations that may have prevented the demonstration of benefit.
Multiple meta-analyses of randomized trials with patients have been performed [18-22]. The largest of these was published in 2016 and included 10 trials with 33,051 patients who received predominantly newer-generation DES . The following findings were noted in this meta-analysis:
●Comparing 12 with 3 to 6 months, there were no significant differences in the incidence of death (odds ratio [OR] 1.17, 95% CI 0.85-1.63), major hemorrhage (OR 1.65, 95% CI 0.97-2.82), MI (OR 0.87, 95% CO 0.65-0.1.18), or stent thrombosis (OR 0.86, 95% 0.49-1.55).
●Comparing 18 to 48 to 6 to 12 months, there was no difference in the incidence of all-cause death (OR 1.14, 95% CI -0.92 to 1.42), an increase in major hemorrhage (OR 1.58, 95% CI 1.20-2.09), a decrease in MI (OR 0.67, 95% CI 0.47-0.95), and a decrease in stent thrombosis (OR 0.42, 95% CI 0.24-0.74).
●Post-hoc analysis found a trend toward increased mortality with longer DAPT. This has been noted in other meta-analyses. Although complete explanations are not available, it is possible that the finding is related to complications of observed or unobserved bleeding and modified substantially by the relative risks of ischemic versus bleeding events in individual patients.
●In an analysis of one randomized trial and one post-hoc analysis of a randomized trial, use of DAPT for more than one year after MI reduced the composite risk of cardiovascular death, MI, or stroke (hazard ratio [HR] 0.84, 95% CI 0.74-0.95) but increased major bleeding (HR 2.32, 95% CI 1.68-3.21).
Other evidence to support a recommendation for more than 12 months of DAPT comes from the PEGASUS-TIMI 54 trial. PEGASUS-TIMI 54 randomly assigned 21,162 patients with an MI one to three years earlier (median time 1.7 years) to one of two doses of ticagrelor (90 or 60 mg twice daily) or placebo . The primary efficacy end point (a composite of cardiovascular death, MI, or stroke) occurred less often with ticagrelor than with placebo at three years (7.85, 7.77, and 9.04 percent, respectively; hazard ratios 0.85, 95% CI 0.75-0.96 and 0.84, 95% CI 0.74-0.95). The rate of the primary safety end point of Thrombolysis in Myocardial Infarction (TIMI) major bleeding (table 2) was higher in the ticagrelor 90 and 60 mg groups (2.6, 2.3, and 1.06 percent, respectively; p<0.001 for each dose versus placebo) but there was no difference in the rates of fatal and nonfatal intracranial hemorrhage (0.63, 0.71, and 0.60 percent, respectively). Importantly, there was no difference in the rate of death from any cause (5.15, 4.69, and 5.15 percent, respectively; HR 0.89, 95% CI 0.76-1.04) and a trend toward a lower rate of cardiovascular death. In addition, ticagrelor lowered the risk of any stroke at the lower dose. (See "Antiplatelet agents in acute non-ST elevation acute coronary syndromes", section on 'Duration'.)
We do not recommend DAPT for less than one year except in patients at high bleeding risk. The SECURITY, ITALIC, ISAR-SAFE, OPTIMIZE, EXCELLENT, RESET, and PRODIGY trials compared six months of DAPT with 12 months or longer [24-29]. Each trial had one or more significant limitations, including small sample size and enrollment of lower-risk patients, and there was significant heterogeneity between the trials. In a meta-analysis (n = 8180), which included only studies comparing shorter duration (three to six months) to 12 months of therapy, there was no significant difference in the risk of all-cause death (HR 0.89, 95% CI 0.66-1.20) .
Bioresorbable polymer drug-eluting stents — Bioresorbable (also referred to as biodegradable) polymer DES have been developed in an attempt to minimize the duration of vascular inflammation associated with the polymer. (See "Bioresorbable polymer or scaffold drug-eluting coronary artery stents", section on 'Bioresorbable polymer DES'.)
The optimal duration of DAPT for these newer stents is not known. The I-LOVE-IT 2 trial randomly assigned 1829 patients with an implanted biodegradable polymer sirolimus-eluting stent, with a thin strut design, to receive 6 or 12 months of DAPT . There was no significant difference in the primary outcome of the 12-month target lesion failure rate (a composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization) between the two groups (6.8 versus 5.9 percent, respectively).
Bare metal stents — For patients who have received BMS, our recommendations are the same as for DES. The DAPT trial provided evidence to suggest that the benefit for prolonged DAPT is largely independent of stent type. (See 'Drug-eluting stents' above.)
If a bleeding event occurs, or the bleeding risk is high, or if the patient needs to undergo noncardiac surgery before one year, we consider limiting therapy to as short as one month. This is based on the fact that the risk of stent thrombosis with BMS is greatest in the first 14 to 30 days, perhaps because the majority of the process of endothelialization has occurred. The best evidence regarding the duration of DAPT for more than 30 days in patients who receive BMS comes from the CREDO trial, in which 2116 patients were randomly assigned to a 300 mg loading dose of clopidogrel or placebo prior to PCI . All patients received clopidogrel 75 mg daily through day 28. From day 29 through 12 months, patients in the initial clopidogrel group received clopidogrel 75 mg daily and those in the control group received placebo. All patients received aspirin throughout the study. At one year, the risk of the composite primary outcome of death, MI, or stroke was significantly lower with continuation of clopidogrel (8.5 versus 11.5 percent; relative risk reduction 26.9, 95% CI 2.9-44.4). Indirect support for the use of DAPT for one year comes from the PCI-CURE trial of patients with acute coronary syndromes who underwent stenting with BMS. After one month of clopidogrel plus aspirin, patients were randomly assigned to aspirin plus clopidogrel or aspirin plus placebo for a mean of nine months . Findings were similar to those in CREDO.
In the PCI-CURE and CREDO trials, the benefit of clopidogrel therapy increased over time, with no evidence of a plateau at one year (figure 2 and figure 3). Although neither trial assessed the specific outcome of stent thrombosis, both provide some evidence in favor of clopidogrel therapy for at least one year in patients with BMS.
In an analysis of the 1687 patients in the DAPT trial treated with BMS, there were no significant differences in the rates of stent thrombosis, major adverse cardiovascular and cerebrovascular events (a composite of death from any cause, MI, or stroke), or major/severe bleeding (0.5 versus 1.11 percent [HR 0.49, 95% CI 0.15-1.64], 4.04 versus 4.69 [HR 0.92, 95% CI 0.57-1.47], and 2.01 versus 0.90 [p = 07]) . There was no interaction in the analysis between DES and BMS, suggesting that the therapeutic benefit is similar independent of stent type.
Bleeding risk — DAPT lowers the rate of ischemic events after PCI (see 'Rationale' above). However, its use is associated with an increased risk of bleeding, which is the most important common major side effect associated with platelet P2Y12 receptor blocker therapy. The combination of clopidogrel plus aspirin, compared with aspirin alone, in the CURE trial (see "Antiplatelet agents in acute non-ST elevation acute coronary syndromes", section on 'P2Y12 inhibitors for all patients') was associated with a significant increase in major (3.7 versus 2.7 percent), minor (5.1 versus 2.4 percent), and gastrointestinal bleeding (1.3 versus 0.7 percent), but not life-threatening bleeding events at 12 months . (See "Antithrombotic therapy for elective percutaneous coronary intervention: Clinical studies", section on 'P2Y12 receptor blockers'.)
Compared with clopidogrel, both ticagrelor and prasugrel increase non-coronary artery bypass graft surgery (CABG) bleeding, although the magnitude of that increase appears less with ticagrelor. CABG-related bleeding and reoperations are substantially increased by prasugrel, but not by ticagrelor, relative to clopidogrel. In general, holding clopidogrel or ticagrelor is recommend five days pre-CABG, and seven days for prasugrel.
Risk factors for bleeding with a P2Y12 receptor blocker include a history of transient ischemic attack or stroke, age ≥75 years, propensity to bleed (eg, recent trauma or surgery, recent or recurrent gastrointestinal bleeding, active peptic ulcer disease, severe hepatic impairment), body weight <60 kg, or concomitant use of medications that increase risk (oral anticoagulants or NSAIDs). A history of active gastrointestinal bleeding presents a challenge to the care of the patient with acute coronary syndrome. The discussion of the incidence, risk factors, outcomes, prevention, and treatment of periprocedural gastrointestinal bleeding is found elsewhere. (See "Periprocedural and long-term gastrointestinal bleeding in patients undergoing percutaneous coronary intervention".)
Decision tools — Although other tools are available to guide patients and practitioners in the process of deciding whether DAPT should be continued for more than 12 months, we prefer the DAPT score.
Using data from 11,648 patients who received either a drug-eluting or a bare metal stent in the DAPT trial (see 'Drug-eluting stents' above), the investigators developed a decision tool (prediction rule) to identify which patients would likely benefit from continuing dual antiplatelet therapy from 12 to 30 months . The DAPT Score (http://www.daptstudy.org/for-clinicians/score_calculator.htm) predicts the combined ischemic and bleeding risks and includes the following factors: age, cigarette smoking within the last two years, prior MI or PCI, history of heart failure or left ventricular ejection fraction <30 percent, MI at presentation, stenting of a vein graft, type of stent, diabetes, or stent diameter <3 mm. Of these, age ≥75 years was the most important determinant of a worse outcome with longer therapy.
Comparing high and low score groups, continued thienopyridine therapy compared with placebo was associated with a larger decrease in ischemic events (2.7 versus 5.7 percent; risk difference [RD] -3 percent, 95% CI -4.1 to -2 percent and 1.7 versus 2.3 percent; RD -0.7 percent, 95% CI -1.4 to 0.09 percent, respectively). In addition, continued therapy was associated with a smaller increase in bleeding in the high score compared with the low score group (1.8 versus 1.4 percent; RD -0.4 percent, 95% CI -1.3 to 1.0 percent and 3 versus 1.4 percent; RD 1.5 percent, 95% CI 0.8-2.3 percent, respectively). Derivation cohort models predicting ischemia and bleeding had modest accuracy with c statistics of 0.70 and 0.68, respectively. In a validation cohort (n = 8136), the c statistics for ischemia and bleeding were 0.64 and 0.64.
At a lower DAPT score, there is a greater increase in bleeding and smaller reduction in ischemia. At a higher score, there is a greater reduction in ischemia and small increase in bleeding. The DAPT investigators concluded that patients with a score <2 have greater harm than good from continued therapy beyond 12 months, while those with a score of 2 or more derive benefit from treatment for an additional 18 months. This tool needs external validation before we can recommend its use widely. This tool needs to be used in conjunction with clinical judgment.
The score is not intended to be applied to patients with the following characteristics: receiving oral anticoagulation, limited life expectancy, stent thrombosis, stroke, repeat revascularization, or bleed, and those not compliant with DAPT during the first year. The score was derived from patients not receiving a paclitaxel-eluting stent (but included patients with BMS), since such stents are no longer commonly used in clinical practice. It was not evaluated in patients receiving ticagrelor.
Potential limitations of the DAPT score are that one-third of patients had an ACS, that the score derivation did not include individuals who had a cardiovascular event while taking DAPT during one year, that it did not include patients taking ticagrelor, and the fact that it was a post-hoc analysis. Some of our experts use the DAPT score as they see it as the best available tool to supplement clinical judgment in decision making. Others await external validation.
Other decision tools, such as one developed from the PARIS registry, have been evaluated . These reinforce the evidence that personalized care may be possible using baseline patient characteristics.
AGENT AND DOSE — In most randomized trials of stent placement for stable coronary artery disease, clopidogrel was the P2Y12 receptor blocker tested. Thus, we prefer clopidogrel to prasugrel or ticagrelor for most stable patients requiring dual antiplatelet therapy (DAPT). We recommend a dose of 75 mg daily, which was the dose used in the clinical trials. (See "Antithrombotic therapy for elective percutaneous coronary intervention: General use", section on 'Evidence regarding timing and dose'.)
We suggest that patients who have undergone elective stenting, irrespective of type of stent, be discharged on 75 to 100 mg/day of aspirin. There have been no randomized trials of differing aspirin doses in stable patients who undergo percutaneous coronary intervention (PCI) in the stent era. The issue of the optimal dose of aspirin was addressed in a prespecified subgroup analysis of the 17,263 acute coronary syndrome patients who underwent early PCI in the CURRENT-OASIS 7 trial. There was no significant difference in the primary outcome (cardiovascular death, myocardial infarction [MI], or stroke at 30 days) between those who were randomly assigned for 30 days to a dose of 300 to 325 mg compared with those given 75 to 100 mg (4.1 versus 4.2 percent, respectively) . While there was no significant difference in the rate of major bleeding, the rate of minor bleeding was significantly higher in those who received the higher dose of aspirin (5.0 versus 4.3 percent; adjusted hazard ratio [HR] 1.18, 95% CI 1.03-1.36). In the analysis of all patients (n = 25,086) enrolled in the study, there was a small but significant increase in the rate of gastrointestinal bleeding with higher-dose aspirin (0.4 versus 0. 2 percent; p = 0.04) .
SPECIFIC PATIENT GROUPS
Patients not likely to comply — Patients who are not likely to comply with a recommendation for one year of dual antiplatelet therapy (DAPT) or who have a planned procedure that requires early cessation of antiplatelet therapy may be better candidates for a bare metal stent (BMS) than a drug-eluting stent (DES) . (See 'Noncardiac surgery or gastrointestinal endoscopy' below and 'Bare metal stents' above.)
Although DES have been shown to improve outcomes in most patient and lesion subsets, the decision to place a DES rather than a BMS requires careful assessment of the relative benefits and risks [39,40]. The lower rate of repeat target vessel revascularization with a DES must be weighed against the costs of longer-term platelet P2Y12 receptor blocker therapy to prevent stent thrombosis, including an increase in the risk of bleeding while on long-term DAPT and the potentially serious complications of noncompliance, which is often not predictable.
A discussion of the potential difference in the rate of stent thrombosis between stent types is found elsewhere. (See "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Late and cumulative one-year stent thrombosis'.)
Patients taking anticoagulants — Our experts choose either BMS or second generation DES for patients who require long-term anticoagulation. In patients for whom DAPT for longer than one month places the patient at very high risk of bleeding, BMS are preferred, particularly if the risk of restenosis is presumed to be low.
The management of patients taking oral anticoagulant and DAPT is found elsewhere. (See "Triple antithrombotic therapy in patients with cardiovascular disease", section on 'Summary and recommendations'.)
Patients needing temporary discontinuation — Although we recommend DAPT for one year in most patients who have received a coronary stent, temporary discontinuation (interruption) is necessary in some patients. Based on the evidence presented below and clinical experience, temporary discontinuation before 30 days is associated with high risk. We are uncertain of the risk between one and six months and we believe that temporary discontinuation of the P2Y12 receptor blocker after six months may be safe as long as aspirin is continued.
At least four studies have attempted to quantify this risk:
●In the PARIS registry (see 'Prevention of treatment failure' below and "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Early and late stent thrombosis'), the hazard ratio for major adverse cardiovascular events was non-significantly higher for patients with interruption (1.41, 95% CI 0.94-2.12) .
●The ACDC study evaluated 1622 individuals who received a DES and were placed on aspirin and clopidogrel and followed for one year . During this time, 111 patients temporarily discontinued at least one antiplatelet agent: clopidogrel was stopped in 31, aspirin in 27, and both drugs in 53. The median duration of cessation was seven days. The rate of acute coronary syndrome was not significantly different between those who discontinued and those who did not.
●In a pooled analysis of data from 4896 individuals in studies of the Resolute zotarolimus-eluting stent (table 1), 1069 had interruption of DAPT: 166 in the first month and 903 between 1 and 12 months . Among those with interruption in the first month, there were six definite/probable stent thrombosis events (3.61 percent). There was one episode of stent thrombosis between 1 and 12 months, a rate that was comparable to those without interruption.
The causes of and predictors for premature discontinuation are discussed separately. (See "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Early and late stent thrombosis'.)
Noncardiac surgery or gastrointestinal endoscopy — Noncardiac surgery and gastrointestinal endoscopy are situations in which DAPT may need to be interrupted. Except for emergent settings in which surgery cannot be delayed, we recommend that a platelet P2Y12 receptor blocker and aspirin be continued for at least the minimum recommended duration for each stent type and that elective noncardiac surgical procedures requiring discontinuation of DAPT be deferred. For patients who require urgent surgery or endoscopy, we individualize care, taking into account the relative risks of bleeding and stent thrombosis. This issue is discussed in detail elsewhere. (See "Noncardiac surgery after percutaneous coronary intervention", section on 'Our approach'.)
Aspirin should be continued during surgery if possible and not be discontinued without confirming absolute necessity. (See "Perioperative medication management", section on 'Aspirin'.)
Similar issues arise in patients scheduled to undergo gastrointestinal endoscopy. This matter is discussed elsewhere. (See "Management of antiplatelet agents in patients undergoing endoscopic procedures".)
PREVENTION OF TREATMENT FAILURE — The strongest predictor of stent thrombosis between months 1 and 12 is the premature cessation of one or both antiplatelet agents (see 'Rationale' above). Issues related to treatment failure are discussed separately. (See "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Early and late stent thrombosis' and "Coronary artery stent thrombosis: Clinical presentation and management", section on 'Long-term antiplatelet therapy'.)
Clinicians who care for patients treated with dual antiplatelet therapy (DAPT) should pay attention to the following issues in an attempt to minimize the risk of stent thrombosis:
●The risk of noncompliance with recommendations for DAPT must be assessed before the placement of a drug-eluting stent (DES). This should include a discussion in reasonable detail with the patient and relevant caregivers of the pros and cons of DES versus bare metal stents (BMS) and the likelihood of compliance with recommendations for DAPT for a minimum of one year, including issues of cost/insurance coverage, assessment of the likelihood of noncardiac surgery in the next 12 months, and the consequences of premature cessation of therapy. BMS are preferred when compliance with DAPT is uncertain.
●Office-based practitioners, such as primary care clinicians or dentists, need to be properly educated about the importance of not discontinuing antiplatelet therapy unless absolutely necessary.
●Placement of BMS should be considered in patients in whom one or more risk factors for bleeding, particularly from the upper gastrointestinal tract, are present. In the event of major bleeding in a noncompressible area that begins in a patient on platelet P2Y12 receptor blocker therapy, the risks of platelet P2Y12 receptor blocker cessation must be weighed against the risk of prolonged bleeding. Consideration should be given to restarting platelet P2Y12 receptor blocker after bleeding has stopped or is controlled and to strategies to decrease the likelihood of bleeding. (See "NSAIDs (including aspirin): Secondary prevention of gastroduodenal toxicity".)
●Rash or other manifestations of a hypersensitivity reaction to clopidogrel may develop in up to four percent of patients and possibly lead to drug discontinuation. This issue is discussed in detail separately. (See "Hypersensitivity reactions to clopidogrel".)
●In the unusual case in which aspirin must be discontinued due to a procedure where there is a significant risk of uncontrollable bleeding, we discuss this decision with the clinician performing the procedure to verify that continuing aspirin is truly a significant risk. There are very few situations that require discontinuing low-dose aspirin. As examples, aspirin can be continued with both coronary artery bypass graft surgery and cataract surgery . (See "Perioperative medication management", section on 'Aspirin'.)
●Cessation of antiplatelet therapy may be required for reasons such as urgent surgery or major bleeding. However, minor bleeding is also a risk factor for antiplatelet therapy cessation. This issue is discussed separately. (See "Antithrombotic therapy for elective percutaneous coronary intervention: General use", section on 'Bleeding'.)
Clopidogrel resistance/nonresponse — Clopidogrel resistance/nonresponse is associated with stent thrombosis. This issue is discussed separately. (See "Clopidogrel resistance and clopidogrel treatment failure".)
RECOMMENDATIONS OF OTHERS — Our recommendations for the prevention of stent thrombosis after coronary artery stenting in stable patients are generally consistent with those made in guidelines from the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) in 2016 and the European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) in 2014 [45,46]. While we prefer 12 months, as opposed to six months as preferred by these guideline organizations, as the minimal duration of therapy in patients not at high risk of bleeding, we acknowledge that the evidence does not allow for a strong recommendation for any particular duration in this range.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient information: Stenting for the heart (The Basics)")
●Beyond the Basics topics (see "Patient information: Angina treatment — medical versus interventional therapy (Beyond the Basics)" and "Patient information: Stenting for the heart (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●The risk of coronary artery stent thrombosis and its consequences of myocardial infarction (MI) or death are diminished by the use of dual antiplatelet therapy (DAPT) with aspirin and a platelet P2Y12 receptor blocker compared with the use of aspirin monotherapy. (See 'Duration' above and "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Comparison of DES and BMS'.)
●For stable patients treated with either drug-eluting or bare metal intracoronary stents (DES/BMS) who are not at high bleeding risk and who do not have planned noncardiac surgery within one year, we recommend aspirin and a platelet P2Y12 receptor blocker for at least 12 months rather than a shorter treatment duration (Grade 1B). (See 'Duration' above.)
●After one year of successful DAPT therapy, practitioners should discuss with their patients the potential benefits and risks of continuing DAPT. We also use the DAPT score to aid in decision-making. (See 'Our approach to treatment duration' above.)
For stable patients who have not had a significant complication with DAPT during the first 12 months, we suggest continuing such therapy for an additional 18 months (Grade 2B). It is reasonable for patients to decide to stop DAPT after 12 months if they are particularly concerned about the increased risk of death or bleeding or due to a hardship associated with continuing DAPT. (See 'Drug-eluting stents' above.)
●For patients treated with BMS at high bleeding risk or who have planned noncardiac surgery within one year, we recommend a minimum of four weeks of uninterrupted DAPT (Grade 1B). For such patients treated with DES, we recommend uninterrupted DAPT for a minimum of six months (Grade 1B). (See 'Bare metal stents' above.)
●We recommend continuing aspirin indefinitely in all stented patients (Grade 1A). (See "Benefits and risks of aspirin in secondary and primary prevention of cardiovascular disease", section on 'Summary and recommendations'.)
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