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Hindawi Journal of Interventional Cardiology Volume 2022, Article ID 3895205, 15 pages https://doi.org/10.1155/2022/3895205 Research Article Thrombotic vs. Bleeding Events of Interruption of Dual Antiplatelet Therapy within 12 Months among Patients with Stent-Driven High Ischemic Risk Definition following PCI 1 2 1 2 2 Hao-Yu Wang , Bo Xu, Chen-Xi Song, Chang-Dong Guan, Li-Hua Xie, 3 1 1 1 Yan-Yan Zhao, Zhong-Xing Cai, Sheng Yuan, and Ke-Fei Dou Department of Cardiology, Cardiometabolic Medicine Center, Coronary Heart Disease Center, Fuwai Hospital, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Catheterization Laboratories, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Medical Research and Biometrics Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China Correspondence should be addressed to Ke-Fei Dou; drdoukefei@126.com Received 21 July 2021; Accepted 22 December 2021; Published 13 January 2022 Academic Editor: &ach N. Nguyen Copyright © 2022 Hao-Yu Wang et al. &is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. &ere is a paucity of real-world data regarding the clinical impact of dual antiplatelet therapy (DAPT) interruption (temporary or permanent) among patients at high ischemic risk. &e aim of this study was to assess the risk of cardiovascular events after interruption of DAPT in high-risk PCI population. Methods. &is study used data from the Fuwai PCI registry, a large, prospective cohort of consecutive patients who underwent PCI. We assessed 3,931 patients with at least 1 high ischemic risk criteria of stent-related recurrent ischemic events proposed in the 2017 ESC guidelines for focused update on DAPT who were free of major cardiac events in the first 12 months. &e primary ischemic endpoint was 30-month major adverse cardiac and ce- rebrovascular events, and the key safety endpoints were BARC class 2, 3, or 5 bleeding and net adverse clinical events. Results. DAPT interruption within 12 months occurred in 1,122 patients (28.5%), most of which were due to bleeding events or patients’ noncompliance to treatment. A multivariate Cox regression model, propensity score (PS) matching, and inverse probability of treatment weighting (IPTW) based on the propensity score demonstrated that DAPT interruption significantly increased the risk of primary ischemic endpoint compared with prolonged DAPT (3.9% vs. 2.2%; Cox-adjusted hazard ratio (HR): 1.840; 95% confidence interval (CI): 1.247 to 2.716; PS matching-HR: 2.049 [1.236–3.399]; IPTW-adjusted HR: 1.843 [1.250–2.717]). &is difference was driven mainly by all-cause death (1.8% vs. 0.7%) and MI (1.3% vs. 0.5%). Furthermore, the rate of net adverse clinical events (4.9% vs. 3.2%; Cox-adjusted HR: 1.581 [1.128–2.216]; PS matching-HR: 1.639 [1.075–2.499]; IPTW-adjusted HR: 1.554 [1.110–2.177]) was also higher in patients with DAPT interruption (≤12 months), whereas no significant differences between groups were observed in terms of BARC 2, 3, or 5 bleeding. &ese findings were consistent across various stent-driven high- ischemic risk subsets with respect to the primary ischemic endpoints, with a greater magnitude of harm among patients with diffuse multivessel diabetic coronary artery disease. Conclusions. In patients undergoing high-risk PCI, interruption of DAPT in the first 12 months occurred infrequently and was associated with a significantly higher adjusted risk of major adverse car- diovascular events and net adverse clinical events. 2017 ESC stent-driven high ischemic risk criteria may help clinicians to discriminate patient selection in the use of long-term DAPT when the ischemic risk certainly overcomes the bleeding one. 2 Journal of Interventional Cardiology 12 months. We excluded patients who had a major adverse 1. Introduction cardiac or cerebrovascular event (the composite of all-cause Dual antiplatelet therapy (DAPT) of aspirin and a P2Y 12 death, MI, or stroke), repeat revascularization, stent inhibitor has been a therapeutic cornerstone after percu- thrombosis, or Bleeding Academic Research Consortium taneous coronary intervention (PCI) or acute coronary (BARC) type 3 or 5 bleeding at 12-month follow-up. De- syndrome (ACS); however, its optimal duration in different mographic and clinical characteristics, angiographic and clinical scenarios is currently a matter of debate [1,2]. After procedural information, and in-hospital and follow-up PCI with drug-eluting stent (DES) implantation, DAPT is outcomes were systematically collected and were prospec- generally recommended for 12 months in ACS patients and tively entered into the dedicated database. Institutional for 6 months in patients with stable coronary artery disease review board approval was granted for this research by the (CAD) [3]. Although DAPT is continued beyond 12 months ethics committee of Fuwai hospital, and written informed after stenting to offer a broader atherothrombotic risk consent was obtained for all participants for participation in protection, this risk reduction comes at the cost of an in- this prospective registry. &is study was conducted in ac- creased risk of bleeding [4]. Based on lower rates of late stent cordance with the Declaration of Helsinki. thrombosis with newer-generation DES, the risk of thrombotic events is not increased even with 1 to 6 months 2.2. Procedures and Follow-Up. &e PCI procedure, in- of DAPT [5]. Many clinical trials (most of which were cluding device selection and revascularization strategy, and relatively small and open-label noninferiority trials) have related management followed standard guidelines at the suggested that the benefits of lower risk of bleeding events discretion of the treating physician [16,17]. Aspirin 300 mg with abbreviated DAPT followed by aspirin-based single and a loading dose of a P2Y inhibitor (clopidogrel 300 or antiplatelet therapy (SAPT) were counterbalanced by higher 600 mg or ticagrelor 180 mg) were given before intervention. rates of stent thrombosis [6–9], while an individual par- After PCI, patients were prescribed 100 mg/day aspirin ticipant data meta-analysis showed that P2Y inhibitor indefinitely and P2Y inhibitor (clopidogrel 75 mg once monotherapy after short DAPT was associated with lower daily or ticagrelor 90 mg twice daily) for 12 months. Detailed major bleeding and similar risks of fatal and ischemic events information on procedures is shown in the supplementary compared with traditional DAPT [10]. materials. Clinical follow-up was prospectively conducted Considering populations in the trials investigating the via office visit or telephone contact at 30 days, 6 months, optimal minimal duration of DAPT followed by aspirin 12 months, and annually thereafter. At follow-up, data about monotherapy mostly constituted of selected patients un- patients’ clinical status, all interventions received, and dergoing elective noncomplex PCI [11], limited and con- outcome events were documented by independent research troversial evidence is available on the value of aspirin-based personnel. Information regarding time of DAPT cessation, SAPT after shortened DAPT in intermediate-to-high-risk which drug (aspirin or P2Y inhibitor) was stopped, and the patients. Observational studies have reported increased risk reason for stopping treatment was collected. Other possible of myocardial infarction (MI) and adverse cardiac outcomes follow-up information was obtained from hospital read- for patients with DAPT interruptions within 6 months after mission, outpatient records, the referring physician and PCI [12–15]. In that respect, the prognostic significance of relatives, and external medical records from other hospitals, interruption or any nonadherence to DAPT in the first as necessary. 12 months in higher-risk routine practice populations re- mains unclear. &erefore, using prospective data from a contemporary real-world group of patients undergoing PCI, 2.3. Definitions and Outcomes. Interruptions of DAPT we focused on a subset of patients who satisfied high is- within 12 months were defined as either a temporary in- chemic risk criteria based on patient-related clinical and terruption of aspirin and/or P2Y12 inhibitor (interruption of angiographic characteristics and PCI-related features (using at least 1 days) or a permanent discontinuation (>30 days). the 2017 ESC updates for DAPT guidelines) to estimate the Permanent DAPT discontinuation was considered if DAPT incidence of DAPT interruption (temporary or permanent) was never resumed 30 days after discontinuation. Patients in the first 12 months after PCI and evaluate the efficacy and were defined as high ischemic risk if they met at least 1 of the safety of DAPT interruption ≤12 months as compared with following characteristics according to 2017 ESC guidelines longer than 12 months of DAPT for these high-risk patients. for focused update on DAPT in CAD: diabetes with diffuse multivessel CAD, chronic kidney disease, at least 3 lesions treated, at least 3 stents implanted, a total stent length of 2. Methods more than 60 mm, a bifurcation lesion treated with two 2.1. Study Population. &e Fuwai PCI registry database, stents, and treatment of chronic total occlusion [3]. which involves prospective recruitment of consecutive pa- Adapting the criteria to fit the available information, a subset tients undergoing PCI with DES placement between January of patients with at least 1 modified ESC high ischemic risk 2013 to December 2013 at the Fuwai Hospital (National criteria (without information on previous stent thrombosis Center for Cardiovascular Diseases, Beijing, China), was on antiplatelet therapy and last patent vessel) was defined. used for the current retrospective analysis. &e present Given that the clinical variables evaluated in the present analysis included patients with high ischemic risk defined by analysis were collected at a time when the Academic Research 2017 ESC DAPT guidelines who were event free at Consortium for High Bleeding Risk (ARC-HBR) definition Journal of Interventional Cardiology 3 included in the PSM models are presented in Supplementary was not yet available, Supplementary Table 1 illustrates the list of major and minor ARC-HBR criteria and their respective Table 2. &ird, we used the inverse probability of treatment weighting (IPTW) Cox proportional hazard regression definitions adapted to the current study database. Patients were defined as HBR if they met at least 1 major or 2 minor model to estimate the average treatment effects. In this criteria [18]. Conversely, those not meeting any ARC-HBR approach, the weights for patients treated with interruptions criterion or patients with only 1 minor criterion were con- (≤12 months) of DAPT were the inverse of (1-propensity sidered non-HBR. score), and the weights for patients treated with DAPT> 12 &e primary ischemic endpoint was major adverse cardiac months were the inverse of propensity score. Balance be- and cerebrovascular events, defined as a composite of all- tween the two groups after PSM and IPTW was evaluated by cause death, MI, or stroke. &e key secondary endpoint was the standardized difference, using a threshold of less than clinically relevant bleeding defined by BARC 2-, 3-, or 5-type 10% to indicate a balance. Sensitivity analysis was performed with the entire population (n � 4,430), including patients bleedings [19] and net adverse clinical events, defined as a composite of clinically relevant bleeding and major adverse who were followed up for <12 months or presented with adverse events within 12 months after PCI in patients who cardiac and cerebrovascular events. Secondary end points included all-cause death, cardiac death, MI, definite or satisfied high ischemic risk criteria. &e consistency of effects probable ST, and stroke. Cardiac mortality was defined on primary ischemic endpoint was also explored across the according to Academic Research Consortium (ARC) criteria individual components of the ESC high ischemic risk def- as any death because of an immediate cardiac cause, deaths inition, the number of high ischemic risk criteria fulfilled (1, related to the procedure, or undetermined cause of death [20]. 2, or 3 or more features), and major subgroups. P< 0.05 was &e diagnosis of MI was based on the &ird Universal considered significant for all analyses. Statistical analyses were conducted using SPSS version 24 (SPSS Inc., Chicago, Definition of MI [21]. Stent thrombosis was defined as definite or probable stent thrombosis based on the ARC classification IL, USA) and R version 3.2.0 (R Foundation for Statistical Computing, Vienna, Austria). [20]. Stroke was defined as a focal loss of neurologic function caused by an ischemic or hemorrhagic event, with residual symptoms lasting at least 24 hours or leading to death [22]. 3. Results Source documents were obtained for any adverse events or any DAPTcessation. All clinical events were adjudicated by an 3.1. Cohort Characteristics. A total of 10,167 consecutive independent clinical event committee, composed of members patients undergoing PCI with DES were eligible for who did not participate in patient enrollment for this study. evaluation. Based on the adapted high ischemic risk All endpoints were evaluated at 30 months. Median follow-up criteria defined by the 2017 ESC DAPT guidelines, 4,430 was 877 days (interquartile range: 808 to 944 days). patients satisfied at least 1 criterion and were, thus, considered to be at high ischemic risk. Of these, 479 patients with adverse clinical events during the 12-month 2.4. Statistical Analysis. Categorical data are described as follow-up after PCI and 20 patients with incomplete frequency and percentages and continuous data as means follow-up on clinical outcomes within 12 months were with standard deviations. Statistical significance of differ- excluded. &e final cohort consisted of 3,931 patients who ences in continuous variables between patient groups was were at high ischemic risk and survived the first year after tested with the use of two-sample Student’s t-test; the chi- PCI without a major ischemic or bleeding event, of whom square or Fisher exact test was used for categorical variables. 1,122 (28.5%) had an interruption or discontinued DAPT Time-to-event data were plotted using the Kaplan–Meier in the first 12 months (Figure 1). Source documents in- method and compared using the log-rank test. In an attempt dicated BARC type 1 or 2 bleeding as the most commonly to reduce the impact of treatment selection bias inherent to identified reason for the DAPT cessation (42%), followed an observational study, three sensitivity analyses were by nonadherence (31%), need for surgery (12%), other performed to adjust for confounding factors as much as specified reasons (6%), and unknown (9%). possible. First, a multivariable Cox proportional hazard Mean patient age was 59.1 years; 76.5% were men, 47.2% regression model was used to estimate the independent had diabetes mellitus, and 57.1% presented with acute effect of DAPT duration on clinical outcome. Factors in- coronary syndromes (ACS). Nearly 90% of patients had cluded in multivariable models were based on variables with multivessel CAD, and the left main or left anterior P< 0.10 in the univariate analyses, along with traditional descending artery lesion was treated in about 85% of pa- cardiac risk factors. &e variables selected appear in the full tients. &e mean number of ESC high ischemic risk criteria model shown in Table 1. Second, the propensity score per patient was 2.0; a total of 2,188 of 3,931 patients (55.7%) matching (PSM) method was performed. Propensity scores met 2 or more criteria. &e most common high ischemic risk were created by a multivariable logistic regression model qualifying features were at least 3 stents implanted and with the dependent variable of DAPT duration and a list of diffuse multivessel diabetic CAD patients (Figure 2). Patient- covariates as the independent variables. We matched pa- level clinical, angiographic and procedural data in the DAPT tients with prolonged DAPT (>12-month) to those with interruption ≤12 months and DAPT maintenance> 12 discontinued DAPT within 12 months using the 1 : 1 nearest months groups are summarized in Tables 2 and 3. Patients neighbor approach without replacement with a caliper width with DAPT interruption≤12 months more often had ACS as of 0.2 SD of the logit of the propensity score. Variables the indication for PCI and had higher rates of ARC for High 4 Journal of Interventional Cardiology Table 1: 30-month ischemic and bleeding outcomes by DAPT interruption status. Propensity score Multivariable adjusted IPTW adjusted Unadjusted matching DAPT interruption DAPT maintenance ≤12 months (n � 1122) >12 months (n � 2809) P P P P HR (95% CI) HR (95% CI) HR (95% CI) HR (95% CI) value value value value Major adverse cardiac and 1.840 2.049 1.843 1.963 44 (3.9) 62 (2.2) 0.002 0.005 0.002 0.001 cerebrovascular events (1.247–2.716) (1.236–3.399) (1.250–2.717) (1.334–2.887) 2.510 2.679 2.513 2.505 All-cause death 20 (1.8) 21 (0.7) 0.003 0.019 0.003 0.003 (1.353–4.653) (1.177–6.096) (1.357–4.653) (1.356–4.627) 4.597 5.711 4.786 4.685 Cardiac death 16 (1.4) 9 (0.3) <0.001 0.006 <0.001 <0.001 (2.011–10.509) (1.660–19.646) (2.098–10.914) (2.067–10.622) 2.486 3.133 2.636 2.636 Myocardial infarction 15 (1.3) 15 (0.5) 0.013 0.027 0.009 0.008 (1.209–5.113) (1.137–8.633) (1.279–5.435) (1.287–5.399) Stent thrombosis (definite/ 2.979 3.204 3.175 3.031 9 (0.8) 8 (0.3) 0.026 0.081 0.017 0.023 probable) (1.141–7.783) (0.865–11.869) (1.227–8.213) (1.166–7.879) 1.275 1.349 1.317 1.329 Stroke 19 (1.7) 38 (1.4) 0.393 0.387 0.326 0.312 (0.730–2.224) (0.684–2.662) (0.761–2.280) (0.766–2.309) 0.922 0.796 0.864 0.926 Clinically relevant bleeding 11 (1.0) 32 (1.1) 0.818 0.568 0.681 0.827 (0.462–1.840) (0.365–1.740) (0.430–1.736) (0.466–1.841) 1.581 1.639 1.554 1.613 Net adverse clinical events 55 (4.9) 91 (3.2) 0.008 0.022 0.010 0.005 (1.128–2.216) (1.075–2.499) (1.110–2.177) (1.153–2.257) Values are number of events (Kaplan–Meier estimated event rates), unless otherwise indicated. Adjusted variables included age, sex, body mass index, current smoking, hypertension, diabetes mellitus, left ventricular ejection fraction, peripheral artery disease, prior coronary artery bypass grafting, prior myocardial infarction, prior PCI, prior major bleeding, acute coronary syndrome presentation, transradial approach, use of intravascular ultrasound, drug-eluting stent type, and total stent length. Major adverse cardiac and cerebrovascular events included the composite of all-cause mortality, myocardial infarction, or b c stroke; clinically relevant bleeding was defined as BARC type 2, 3, or 5 bleeding; net adverse clinical events included the composite of all-cause mortality, myocardial infarction, stroke, or clinically relevant bleeding. CI, confidence interval; CABG, coronary artery bypass grafting; DAPT, dual antiplatelet therapy; HR, hazard ratio; PCI, percutaneous coronary intervention. Journal of Interventional Cardiology 5 10,167 consecutive patients who underwent PCI using DES were prospectively enrolled (From Fuwai PCI registry, Jan. 2013 to Dec. 2013) Definition of patients with stent-driven high ischemic risk criteria as endorsed by 2017 ESC DAPT Guidelines At least 1 of the following clinical and angiographic characteristics: Diffuse (lesion length≥20 mm) multivessel disease in diabetic patients Chronic kidney disease ≥3 stents implanted ≥3 lesions treated Bifurcation with 2 stents implanted Total stent length>60 mm Treatment of chronic total occlusion Patients with high ischemic risk criteria (n=4,430) Excluded patients (n=499) 20 were lost to follow-up during 12 months 479 had events* during 12 months 27 died 101 had myocardial infarction 35 had stroke 31 had stent thrombosis 316 had revascularization 70 had BARC type 3 or 5 bleeding 3,931 patients without events at 12 months aer the index procedure DAPT interruption DAPT maintenance ≤12-month >12-month (n=1,122) (n=2,809) Figure 1: Study flow diagram. BARC � Bleeding Academic Research Consortium; DES � drug-eluting stent; DAPT �dual antiplatelet therapy; ESC � European Society of Cardiology; HIR � high ischemic risk; and PCI � percutaneous coronary intervention. Subjects may have >1 event. ≥3 stents implanted 53.6% 9.7% Total stent length>60 mm 46.1% Diffuse multivessel diabetic CAD patients 42.6% 19.2% 44.3% Treatment of chronic total occlusion 18.7% ≥3 lesions treated 16.5% 26.7% Bifurcation stenting with 2 stents 9.7% CKD 9.0% 1 × HIR criteria 0 102030405060 2 × HIR criteria 3 × HIR criteria ≥4 × HIR criteria (a) (b) Figure 2: &e distribution and prevalence of the ESC stent-driven high ischemic risk criteria components among patients fulfilling high ischemic risk definition. (a) &e sum of high ischemic risk criteria satisfied by each patient was used to stratify patients according to the number of times they fulfilled the 2017 ESC DAPT guideline stent-driven high ischemic risk definition. &e pie chart shows the distribution of HIR patients with increasing numbers of multiple coexisting criteria (1 × HIR to≥4 × HIR). (b) Bars indicate the overall prevalence of each high ischemic risk criterion among patients qualified as being at high ischemic risk. HIR � high ischemic risk. Other abbreviations are as in Figure 1. Bleeding Risk (ARC-HBR) compared with DAPT> 12 3.2. Impact of ESC High Ischemic Risk Criteria on Very Late months. After PSM and IPTW, the absolute standardized Clinical Events (12 to 30 Months after PCI). At 12 to differences for all the baseline patient characteristics be- 30 months after stenting, the rate of major adverse cardiac tween the two groups were less than 0.1 (Supplementary and cerebrovascular events was higher in patients with Table 2). versus without ESC high ischemic risk criteria (2.7% vs. 6 Journal of Interventional Cardiology Table 2: Baseline characteristics. groups. After multivariate adjustment, the presence of ESC high ischemic risk remained independently associated with Interruption of DAPT within increased 30-month risks for major adverse cardiac and 12 months after PCI value cerebrovascular events, cardiac death, and stroke, with a No (n � 2809) Yes (n � 1122) trend toward an increased risk for MI and stent thrombosis. Age, years 59.05± 10.00 59.33± 10.48 0.445 Male 2155 (76.7) 854 (76.1) 0.687 Hyperlipidemia 1954 (69.6) 751 (66.9) 0.108 3.3. Major Adverse Coronary Events and Safety According to Hypertension 1926 (68.6) 764 (68.1) 0.773 the DAPT Treatment Strategy (12 to 30 Months after PCI). Diabetes mellitus 1309 (46.6) 545 (48.6) 0.263 Among patients who satisfied high ischemic risk criteria Chronic kidney disease 248 (8.8) 104 (9.3) 0.662 using the 2017 ESC updates for DAPT guidelines, DAPT Current smoker 1601 (57.0) 627 (55.9) 0.525 interruption ≤12 months, compared with extended-term Heart failure 69 (2.5) 22 (2.0) 0.351 (>12 months) DAPT, had higher crude 30-month rates of Peripheral artery disease 89 (3.2) 38 (3.4) 0.727 major adverse cardiac and cerebrovascular events, all-cause History of myocardial 607 (21.6) 240 (21.4) 0.880 death, cardiac death, MI, and stent thrombosis with similar infarction rates of BARC-defined bleeding type 2, 3, or 5, thereby Prior PCI 630 (22.4) 256 (22.8) 0.792 resulting in an increase in the net adverse clinical events Prior CABG 139 (4.9) 53 (4.7) 0.768 History of stroke 331 (11.8) 152 (13.5) 0.128 (Figure 3). After multivariable adjustment, cessation of History of major DAPT within 12 months significantly increased the 30- 17 (0.6) 12 (1.1) 0.124 bleeding month risk of major adverse cardiac and cerebrovascular Body mass index, kg/m 26.10± 3.14 25.97± 3.28 0.279 events when compared with continued DAPT beyond LVEF, % 62.42± 7.63 62.42± 7.46 0.991 12 months (adjusted HR: 1.840, 95% CI: 1.247–2.716; Clinical presentation 0.010 P � 0.002; Table 1 and Supplementary Table 4), whereas Stable coronary artery 1241 (44.2) 445 (39.7) there were no statistically significant differences in BARC 2-, disease 3-, or 5-type bleedings between the 2 groups (adjusted HR: Acute coronary 1568 (55.8) 677 (60.3) 0.922, 95% CI: 0.462–1.840; P � 0.818). Similar trends were syndrome observed for cardiac death (adjusted HR: 4.597, 95% CI: UA/NSTEMI 1234 (43.9) 527 (46.9) 0.084 STEMI 334 (11.9) 150 (13.4) 0.203 2.011–10.509; P< 0.001), MI (adjusted HR: 2.486, 95% CI: White blood cell count, 1.209–5.113; P � 0.013), and stent thrombosis (adjusted HR: 6.80± 1.64 6.84± 1.63 0.482 10 /L 2.979, 95% CI: 1.141–7.783; P � 0.026). &e net adverse Hemoglobin, g/dL 14.25± 1.58 14.18± 1.56 0.220 clinical events occurred in 91 patients (3.2%) who received Platelet count, 10 /L 204.08± 53.91 205.22± 53.21 0.550 DAPT maintenance >12 months and in 55 patients (4.9%) ARC-HBR 573 (20.4) 264 (23.5) 0.032 who received DAPT interruption≤12 months (adjusted HR: Discharge medication 1.581, 95% CI: 1.128–2.216; P � 0.008). Aspirin 2778 (98.9) 1112 (99.1) 0.554 Clopidogrel 2766 (98.5) 1110 (98.9) 0.266 Ticagrelor 9 (0.3) 8 (0.7) 0.107 3.4. Sensitivity and Subgroup Analyses. Consistent results β-blocker 2584 (92.0) 1033 (92.1) 0.935 were observed when sensitivity analyses using PSM and ACEI/ARB 1731 (61.6) 694 (61.9) 0.893 IPTW were conducted. In the PSM and IPTW propensity CCB 1408 (50.1) 550 (49.0) 0.531 score-adjusted cohort, interruption of DAPT within 12 Statin 2701 (96.2) 1068 (95.2) 0.168 months remained independently associated with increased Values are mean± SD for continuous variables and n (%) for categorical risks for primary ischemic endpoint (matched HR: 2.049, variables. ACS indicates acute coronary syndrome; ACEI, angiotensin- 95% CI: 1.236–3.399; IPTW-HR: 1.843, 95% CI: converting enzyme inhibitors; ARB, angiotensin II receptor antagonists; ARC-HBR, Academic Research Consortium-High Bleeding Risk; CCB, 1.250–2.717), cardiac death (matched HR: 5.711, 95% CI: calcium channel blockers; CABG, coronary artery bypass grafting; DAPT, 1.660–19.646; IPTW-HR: 4.786, 95% CI: 2.098–10.914), MI dual antiplatelet therapy; LVEF, left ventricular ejection fraction; NSTEMI, (matched HR: 3.133, 95% CI: 1.137–8.633; IPTW-HR: 2.636, non-ST-segment elevation myocardial infarction; PCI, percutaneous cor- 95% CI: 1.279–5.435), and stent thrombosis (matched HR: onary intervention; STEMI, ST-segment elevation myocardial infarction; 3.204, 95% CI: 0.865–11.869; IPTW-HR: 3.175, 95% CI: and UA, unstable angina. Chronic kidney disease was defined as an es- timated glomerular filtration rate of less than 60 mL/min/1.73 m of body 1.227–8.213). &ere was no significant association between surface area. Spontaneous (nonintracranial) bleeding requiring hospital- DAPT interruption and BARC type 2, 3, or 5 bleeding ization or transfusion. (matched HR: 0.796, 95% CI: 0.365–1.740; IPTW-HR: 0.864, 95% CI: 0.430–1.736). A higher risk of net adverse clinical 1.6%; adjusted HR: 1.533, 95% CI: 1.150–2.044, P � 0.004), a events was identified in subjects with interruptions com- difference driven by higher rates of all-cause death (1.0% vs. pared with subjects without (matched HR: 1.639, 95% CI: 0.6%), MI (0.8% vs. 0.5%), and stroke (1.5% vs. 0.6%) 1.075–2.499; IPTW-HR: 1.554, 95% CI: 1.110–2.177). Sen- (Supplementary Table 3). Very late cardiac death was more sitivity analyses conducted for the entire population with frequent in patients with versus without ESC high ischemic stent-driven high ischemic risk definition (n � 4,430) risk criteria (0.6% vs. 0.3%; HR: 2.405, 95% CI: 1.250–4.626, exhibited consistent results for the primary and secondary endpoints (Supplementary Tables 5–7), confirming the ro- P � 0.009). &ere were no significant differences in the rates of 12- to 30-month clinically relevant bleeding between two bustness of the primary analysis. In the entire study Journal of Interventional Cardiology 7 Table 3: Lesion and procedural characteristics. Interruption of DAPT within 12 months after PCI P value No (n � 2809) Yes (n � 1122) Lesion characteristics Multivessel CAD 2525 (89.9) 998 (88.9) 0.382 Location of the lesion treated LM 140 (5.0) 50 (4.5) 0.486 LAD 2386 (84.9) 964 (85.9) 0.436 LCx 835 (29.7) 348 (31.0) 0.426 RCA 959 (34.1) 371 (33.1) 0.520 Bypass graft 7 (0.2) 3 (0.3) 0.919 Target lesion morphology Heavy calcified lesion 143 (5.1) 55 (4.9) 0.807 In-stent restenosis lesion 128 (4.6) 49 (4.4) 0.796 Bifurcation lesion 569 (20.3) 221 (19.7) 0.693 Bifurcation with two stents implanted 283 (10.1) 98 (8.7) 0.200 &rombotic lesion 116 (4.1) 52 (4.6) 0.480 Chronic total occlusion 541 (19.3) 194 (17.3) 0.153 Type B2 or C lesion 2510 (89.4) 1020 (90.9) 0.146 SYNTAX score 14.67± 8.46 14.51± 8.26 0.629 Total lesion length, mm 57.22± 30.35 55.76± 27.88 0.163 Procedural characteristics Number of vessels treated 1.49± 0.60 1.50± 0.59 0.566 Number of lesions treated 1.75± 0.81 1.75± 0.81 1.000 1 1241 (44.1) 501 (44.7) 0.787 2 1111 (39.6) 432 (38.5) 0.543 ≥3 458 (16.3) 189 (16.8) 0.680 Number of stents implanted 2.66± 1.16 2.59± 1.13 0.105 1 429 (15.3) 189 (16.8) 0.221 2 863 (30.7) 343 (30.6) 0.926 ≥3 1517 (54.0) 590 (52.6) 0.420 Total stent length, mm 61.00± 29.34 59.99± 27.90 0.327 Total stent length> 60 mm 1280 (45.9) 523 (46.6) 0.666 Mean stent diameter, mm 2.92± 0.52 2.91± 0.54 0.640 Vascular access site 0.459 Radial approach 2538 (90.4) 1005 (89.6) Femoral approach 271 (9.6) 117 (10.4) Use of intravascular ultrasound 214 (7.6) 91 (8.1) 0.602 Use of glycoprotein IIb/IIIa inhibitors 520 (18.5) 223 (19.9) 0.324 Drug-eluting stent type 0.949 First-generation DES 286 (10.2) 115 (10.2) Second-generation DES 2523 (89.8) 1007 (89.8) Values are mean± SD for continuous variables and n (%) for categorical variables. CAD indicates coronary artery disease; DES, drug-eluting stent; LM, left main coronary artery; LAD, left anterior descending coronary artery; LCx, left circumflex coronary artery; RCA, right coronary artery; and SYNTAX, Synergy between PCI with Taxus and Cardiac Surgery. population, interruption of DAPT in the first 12 months P � 0.307) and to permanent DAPT discontinuation was after PCI was associated with a significantly higher adjusted 1.906 (1.269–2.864; P � 0.002) (Figure 4(a)). In supple- risk of not only primary ischemic outcome but also the mentary analyses, the entire study population (n � 4,430) clinically relevant bleeding and net adverse clinical com- yielded associations for temporary and permanent DAPT posite outcomes over a 30-month period. discontinuation that were qualitatively similar in direction and magnitude with our overall findings (Supplementary &e differential effect of temporary or permanent DAPT interruption within the first 12 months after PCI compared Figure 1(a)). A similar pattern was observed for net adverse with DAPT maintenance >12 months on primary ischemic clinical events (Figure 4(c) and Supplementary Figure 1(c)). and key secondary endpoints is shown in Figure 4 and For clinically relevant bleeding events, patients who had Supplementary Figure 1. In the patients that were event free temporary and permanent DAPT discontinuations were not after the first year (n � 3,931), in contrast to patients who associated with increased risk of major bleeding between 12 remained on DAPT, the adjusted HR for major adverse and 30 months (Figure 4(b)), while major bleeding cardiac and cerebrovascular events and due to temporary throughout the 30-month follow up period was increased DAPT interruption was 1.556 (95% CI 0.666–3.633; only after DAPT interruption on a permanent (>30 days) 8 Journal of Interventional Cardiology 8 6 HR (95% CI): 1.963 (1.334-2.887) HR (95% CI): 2.505 (1.356-4.627) Log-rank P = 0.001 Log-rank P = 0.003 3.9% 1.8% 2 2.2% 0.7% 0 0 12 15 18 21 24 27 30 12 15 18 21 24 27 30 Time since procedure (months) Time since procedure (months) Number at risk Number at risk DAPT≤12-month 1122 1118 1109 1103 1097 767 279 DAPT≤12-month 1122 1120 1117 1105 1111 780 286 DAPT>12-month 2809 2800 2794 2780 2760 1913 1143 DAPT>12-month 2809 2803 2802 2796 2786 1937 1157 DAPT maintenance >12-month DAPT interruption ≤12-month DAPT interruption12-month DAPT maintenance >12-month (a) (b) 6 6 HR (95% CI): 4.685 (2.067-10.622) HR (95% CI): 2.636 (1.287-5.399) Log-rank P < 0.001 Log-rank P = 0.006 4 4 2 2 1.4% 1.3% 0.5% 0.3% 0 0 12 15 18 21 24 27 30 12 15 18 21 24 27 30 Time since procedure (months) Time since procedure (months) Number at risk Number at risk DAPT≤12-month 1122 1120 1117 1115 1111 780 286 DAPT≤12-month 1122 1120 1116 1113 1108 778 283 DAPT>12-month 2809 2803 2802 2796 2786 1937 1157 DAPT>12-month 2809 2803 2801 2793 2783 1934 1154 DAPT maintenance >12-month DAPT interruption ≤12-month DAPT interruption ≤12-month DAPT maintenance >12-month (c) (d) 6 6 HR (95% CI): 3.031 (1.166-7.879) HR (95% CI): 1.329 (0.766-2.309) Log-rank P = 0.017 Log-rank P = 0.309 4 4 2 2 1.7% 1.4% 0.8% 0.3% 0 0 12 15 18 21 24 27 30 12 15 18 21 24 27 30 Time since procedure (months) Time since procedure (months) Number at risk Number at risk DAPT≤12-month 1122 1120 1116 1114 1109 778 284 DAPT≤12-month 1122 1118 1110 1105 1100 769 282 DAPT>12-month 2809 2803 2802 2794 2784 1934 1155 DAPT>12-month 2809 2801 2795 2783 2762 1915 1146 DAPT interruption ≤12-month DAPT interruption ≤12-month DAPT maintenance >12-month DAPT maintenance >12-month (e) (f ) Figure 3: Continued. Cardiac death (%) MACCE (%) Definite/probable ST (%) All-cause death (%) Stroke (%) Myocardial infarction (%) Journal of Interventional Cardiology 9 6 8 HR (95% CI): 0.926 (0.466-1.841) HR (95% CI): 1.613 (1.153-2.257) Log-rank P = 0.837 Log-rank P = 0.005 4.9% 3.2% 1.1% 1.0% 0 0 12 15 18 21 24 27 30 12 15 18 21 24 27 30 Time since procedure (months) Time since procedure (months) Number at risk Number at risk DAPT≤12-month 1122 1118 1112 1108 1103 773 285 DAPT≤12-month 1122 1116 1103 1096 1089 760 278 DAPT>12-month 2809 2799 2785 2776 2753 1923 1152 DAPT>12-month 2809 2796 2777 2760 2727 1900 1138 DAPT interruption ≤12-month DAPT maintenance >12-month DAPT maintenance >12-month DAPT interruption ≤12-month (g) (h) Figure 3: Time-to-event curves in patients with versus without interruption of DAPT within 12 months. (a) Major adverse cardiac and cerebrovascular events; (b) all-cause death; (c) cardiac death; (d) myocardial infarction; (e) stent thrombosis; (f ) stroke; (g) BARC type 2, 3, or 5 bleeding; and (h) net adverse clinical events. Numbers at risk are shown below the chart. basis (adjusted HR: 1.706, 95% CI: 1.133–2.596; P � 0.111) the most common reason of DAPT interruption was (Supplementary Figure 1(b)). bleeding or noncompliance; (2) DAPT interruption signif- To evaluate the differential effects of DAPT interruption icantly increased the risk of primary ischemic endpoint ≤12 months compared with prolonged treatment with (including death, MI, or stroke) up to 30 months; and (3) DAPT beyond 12 months for various high ischemic risk there was also a modest but statistically significant increase in 30-month net adverse clinical events in those who dis- features according to the 2017 ESC updates for DAPT guidelines, we additionally performed a subgroup analysis continued DAPT prematurely. Importantly, the main driver according to the components of 2017 ESC high ischemic risk of the difference was an increase in all-cause death and MI definition (Figure 5(a)). &e relationship between DAPT without resulting in fewer bleeding events. Taken together, interruption ≤12 months and primary ischemic endpoint patients who stop DAPT prematurely may require more was consistent across various clinical or angiographic sub- intensive surveillance to prevent long-term adverse events. sets of high ischemic risk factors. &e greatest increased risk &e current study provided evidence favoring extended- in primary ischemic endpoint associated with interruption term DAPT therapy for ischemic events, which may be of DAPT within 12 months was found in patients with appropriate for certain patients who are at a higher risk of diffuse multivessel diabetic CAD (HR: 2.48; 95% CI: cardiovascular events after PCI and low risk of bleeding, 1.40–4.38; P � 0.002). Relative treatment effects of DAPT such as those presenting with stent-driven high ischemic risk interruption≤12 months were consistent independent of the criteria. progressive number of high ischemic risk criteria fulfilled Prescribers of DAPT are confronted with a number of (Figure 5(b)). challenges for optimal clinical decision making of DAPT We calculated the results of the subgroup analyses type and duration with the scope of minimizing the risk of comparing the association between DAPT cessation within ischemic and bleeding events in light of each patient’s 12 months and major adverse cardiac and cerebrovascular atherothrombotic and hemorrhagic risk and clinical char- events for each key subgroup (Table 4 and Supplementary acteristic and circumstance [1,2]. Although previous studies Table 8). In general, the associations were similar in di- showed no significant differences in antithrombotic efficacy rection and magnitude across key subgroups, and results of between short- and long-term DAPT, longer DAPT treat- formal interaction testing were not significant. ment was associated with an increased risk for bleeding [6–9]. In most studies, patients had a relatively low risk of recurrent ischemia (mostly patients with chronic coronary 4. Discussion syndrome or low-risk ACS). However, whether this short DAPT protects sufficiently against ischemic events and To our knowledge, the present analysis is the first study to date to examine the efficacy and safety of DAPT interruption adequately reduces bleeding events among patients at high ≤12 months versus DAPT maintenance >12 months after risk of future stent-driven ischemic events is still unclear PCI in real-world patients at stent-driven high ischemic risk because of limited statistical power of the individual trials criteria undergoing PCI with DES, using data from a con- and mixed results [23]. Of note, evidence regarding deci- temporary prospective cohort. &e principal findings of this sions about the duration of DAPT for patients at high is- study are as follows: (1) interruption (temporary or per- chemic risk undergoing PCI in real-world clinical practice is manent) with the prescribed 1 year of DAPT (28.5%) was scarce. To address this complex issue, we analyzed the risk of frequent within 12 months of stent implantation, in which major adverse cardiac and cerebrovascular events in subjects BARC type 2, 3, or 5 bleeding (%) Net adverse clinical events (%) 10 Journal of Interventional Cardiology Events rate Adjusted HR P Value MACCE % (n/N) (95% CI) 1.5% (62/2809) reference DAPT maintenance>12-month - Temporary DAPT interruption (within 12 months) 2.8% (6/211) 1.556 (0.666-3.633) 0.307 1.906 (1.269-2.864) 0.002 Permanent DAPT discontinuation (within 12 months) 4.2% (38/911) 0.1 1 10 (a) Events rate Adjusted HR Clinically relevant bleeding P Value % (n/N) (95% CI) 1.1% (32/2809) reference DAPT maintenance>12-month - Temporary DAPT interruption (within 12 months) 0.5% (1/211) 0.508 (0.069-3.751) 0.506 1.1% (10/911) 1.016 (0.498-2.074) 0.965 Permanent DAPT discontinuation (within 12 months) 0.01 0.1 1 10 (b) Events rate Adjusted HR P Value Net adverse clinical events % (n/N) (95% CI) 3.2% (91/2809) reference DAPT maintenance>12-month - Temporary DAPT interruption (within 12 months) 3.3% (7/211) 1.254 (0.577-2.724) 0.568 5.3% (48/911) 1.654 (1.163-2.351) 0.005 Permanent DAPT discontinuation (within 12 months) 0.1 1 10 (c) Figure 4: &e differential effect of temporary or permanent DAPT interruption within the first 12 months after PCI compared with DAPT maintenance>12 months on primary ischemic and key secondary endpoints. MACCE � major adverse cardiac and cerebrovascular events. Journal of Interventional Cardiology 11 DAPT interruption DAPT maintenance Total population HR (95% CI) P value ≤12−month (n=1122) >12−month (n=2809) Diffuse multivessel diabetic CAD 48/1673 (2.9%) 23/479 (4.8%) 25/1194 (2.1%) 2.48 (1.40−4.38) 0.002 Chronic kidney disease 24/352 (6.8%) 10/104 (9.6%) 14/248 (5.6%) 1.75 (0.78−3.94) 0.176 At least 3 stents implanted 56/2107 (2.7%) 24/590 (4.1%) 32/1517 (2.1%) 2.05 (1.21−3.49) 0.008 At least 3 lesions treated 16/647 (2.5%) 6/189 (3.2%) 10/458 (2.2%) 1.46 (0.53−4.06) 0.469 Bifurcation with 2 stents implanted 7/381 (1.8%) 2/98 (2.0%) 5/283 (1.8%) 1.32 (0.25−6.88) 0.511 Total stent length >60 mm 46/1811 (2.5%) 21/523 (4.0%) 25/1288 (1.9%) 2.24 (1.25−4.01) 0.007 Treatment of chronic total occlusion 20/735 (2.7%) 9/194 (4.6%) 11/541 (2.0%) 2.47 (1.02−5.96) 0.045 Ove rall 106/3931 (2.7%) 44/1122 (3.9%) 62/2809 (2.2%) 1.96 (1.33−2.89) 0.001 0.1 1.0 10.0 DAPT>12–month DAPT≤12–month (a) DAPT interruption DAPT maintenance Total population HR (95% CI) P for interaction ≤12−month (n=1122) >12−month (n=2809) 1 ESC−HIR criterion 46/1743 (2.6%) 15/491 (3.1%) 31/1251 (2.5%) 1.26 (0.68−2.35) 2 ESC−HIR criteria 28/1050 (2.7%) 15/308 (4.9%) 13/742 (1.8%) 2.88 (1.37−6.06) 0.226 ≥3 ESC−HIR criteria 32/1138 (2.8%) 14/323 (4.3%) 18/815 (2.2%) 2.14 (1.06−4.31) 0.1 1.0 10.0 DAPT>12–month DAPT≤12–month (b) Figure 5: Comparison of long-term risk of primary ischemic endpoint between DAPT interruption ≤12 months and DAPT main- tenance> 12 months according to subgroups. &e cumulative incidence and hazard ratio with 95% confidence interval of primary efficacy endpoint are presented between DAPT> 12 months and DAPT≤ 12 months according to the components of the ESC stent-driven high ischemic risk definition (a) and number of ESC stent-driven high ischemic risk criteria fulfilled (b). CAD � coronary artery disease; HIR � high ischemic risk; and other abbreviations are as in Figure 1. who interrupt temporarily or permanently DAPT in the first however, these strategies had a higher risk of MI and stent 12 months after PCI and in patients who met criteria for ESC thrombosis than extended-term DAPT, in turn raising high ischemic risk and were not at high bleeding risk. concern about broad application of this practice in higher- In our cohort, the rate of any interruption of DAPT was risk routine population [26]. We enrolled patients at stent- driven high ischemic risk criteria that were more akin to 28.5% at 12 months after PCI, which was in line with the post hoc analysis of ADAPT-DES and other registries that assessed real-world PCI practice patterns and showed higher long- the incidence and effect of DAPT cessation on subsequent term risks of cardiac mortality and ischemic events after PCI cardiovascular risk among patients who underwent PCI with among patients who had DAPT cessation within 12 months, DES implantation [24]. A higher incidence of DAPT cessation and these risks persisted even in patients who were free of (30.2%) through 1 year of follow-up has been reported in adverse events in the first year. Recently, Sorrentino et al. patients undergoing extensive and more complex PCI in the [27] demonstrated that disruption of DAPT due to bleeding ADAPT-DES registry [25]. Similarly, any nonadherence to or poor compliance was associated with an increased risk of DAPT occurred frequently in the contemporary PCI setting, major adverse cardiac events and MI at 2 years in patients ranging from 5.1% within 6 months after coronary stents in with history of MI, stroke, or peripheral artery disease. It is the DAPT study [12] and 9.6% during the first 6 months after important to note that the problem of DAPT nonadherence remains inconclusive for the first 6 months after DES second-generation DES placement in the EDUCATE registry [13] to 23.3% over 1 year of follow-up for patients undergoing placement. Data from previous studies also showed that PCI in the PARIS registry [15] and 44.0% in patients who discontinuation of DAPT within 6 months of stenting was discontinued DAPT prematurely (≤12-month) in the Vet- associated with significantly higher risk of thrombotic erans Affairs healthcare system [24]. complications, including death, MI, and stent thrombosis Our findings extended insights from the ongoing debate [12,13,28]. Our registry amplified these findings by identi- regarding the timing and risk of DAPT interruption in fying an independent association of major adverse cardiac patients treated with current-generation DES. Although events with DAPT interruption ≤12 months, reflecting that short-term to midterm (≤6 months) DAPT had similar physicians appropriately continue DAPT beyond 12 months in high-ischemic risk patients, thereby accounting for lower safety and effectiveness in comparison with 12-month DAPT and better safety than extended-term DAPT, ischemic events after adopting an extended DAPT strategy. 12 Journal of Interventional Cardiology Table 4: Primary ischemic endpoint in selected subgroups. DAPT interruption ≤12 months DAPT maintenance >12 months P for HR (95% CI) (n � 1122) (n � 2809) interaction Age 0.570 <65 years 21/765 (2.7%) 34/1983 (1.7%) 1.688 (0.979–2.912) ≥65 years 24/358 (6.7%) 27/825 (3.3%) 2.168 (1.250–3.762) Sex 0.470 Female 12/268 (4.5%) 12/654 (1.8%) 2.454 (1.102–5.466) Male 33/855 (3.9%) 49/2154 (2.3%) 1.829 (1.175–2.849) Diabetes mellitus 0.350 No 20/578 (3.5%) 33/1499 (2.2%) 1.596 (0.914–2.786) Yes 25/545 (4.6%) 28/1309 (2.1%) 2.346 (1.365–4.034) Chronic kidney disease 0.834 No 35/1019 (3.4%) 47/2560 (1.8%) 2.026 (1.306–3.142) Yes 10/104 (9.6%) 14/248 (5.6%) 1.751 (0.778–3.943) Smoking 0.182 No 24/495 (4.8%) 24/1208 (2.0%) 2.577 (1.462–4.542) Yes 21/628 (3.3%) 37/1600 (2.3%) 1.545 (0.903–2.644) Acute coronary 0.310 syndrome No 18/446 (4.0%) 22/1240 (1.8%) 2.479 (1.326–4.635) Yes 27/677 (4.0%) 39/1568 (2.5%) 1.632 (0.996–2.673) Previous MI 0.440 No 31/882 (4.0%) 46/2202 (2.1%) 1.767 (1.120–2.788) Yes 14/241 (5.8%) 15/606 (2.5%) 2.531 (1.212–5.287) Multivessel disease 0.284 3.683 No 6/125 (4.8%) 4/283 (1.4%) (1.037–13.083) Yes 39/998 (3.9%) 57/2525 (2.3%) 1.813 (1.206–2.728) Generation of DES 0.889 First-generation DES 4/115 (3.5%) 6/286 (2.1%) 2.030 (0.562–7.340) Second-generation 41/1008 (4.1%) 55/2522 (2.2%) 1.965 (1.310–2.946) DES ARC-HBR 0.699 No 24/858 (2.8%) 39/2236 (1.7%) 1.695 (1.018–2.823) Yes 20/264 (7.6%) 23/573 (4.0%) 1.977 (1.085–3.602) DES indicates drug-eluting stent. A careful assessment of both bleeding and ischemic risks Previous studies attempted to evaluate the effect of different modes of DAPT cessation on cardiac events after of the individual patient represents the foundation towards personalized medicine in the field of antiplatelet therapy. In PCI [15,29]. &e Xience V coronary stent system trials suggested that the rate of definite and probable ST after the field of managing bleeding vs. ischemic outcomes, we cobalt chromium everolimus-eluting stents in patients need to optimize therapies for those at HBR after PCI as a interrupting DAPT at any point was similar to that of pa- post-PCI bleeding event confers an adverse prognosis tients who never interrupted DAPT during the 2-year fol- similar to post-PCI myocardial infarction [30]. Recently, the low-up period, whereas permanent DAPT discontinuation ARC-HBR criteria were established to standardize the before 3 months was strongly associated with ST in a large, definition of HBR and promote consistency across trials pooled sample of real-world patients [29]. Additionally, evaluating this vulnerable subset of patients [31]. A number Mehran et al. [15] detected no significant increase in of studies have reported on the predictive value of the ARC- HBR definition in identifying patients at increased risk not thrombotic events in patients who had temporary DAPT interruption lasting up to 14 days. &e present study con- only for bleeding but also for thrombotic events [18,32–34], firms and extends these findings by demonstrating that as well as validated the clinical usefulness of the ARC-HBR DAPT interruption on a permanent (>30 days) basis within criteria in relation to clinical presentation and sex [35,36]. 1 year after DES implantation was associated with higher 30- Given that bleeding risk was a major reason for discon- month rate of major adverse cardiac and cerebrovascular tinuation of DAPT, we also assessed the effects of DAPT events in patients at increased ischemic risk, while tempo- interruption ≤12 months compared with DAPT mainte- rary interruption of DAPT did not influence the rate of nance >12 months in a contemporary PCI population at ischemic events at 30 months. &ese findings were consistent high ischemic risk and HBR (Table 4). We found that there for patients without experiencing major adverse events of was no significant difference in the primary ischemic end- the first 12 months after PCI and for the total study cohort. point between treatment arms, irrespective of ARC-HBR Journal of Interventional Cardiology 13 to the expanding evidence base for utilizing 2017 ESC stent- status. In aggregate, disruption of DAPT was associated with an increased risk of major adverse cardiac events in high- driven high ischemic risk criteria to guide clinical practice to identify patients who might benefit from prolonging ischemic risk patients irrespective of the underlying bleeding risk. antithrombotic treatment duration. In this contemporary cohort of high-risk patients un- dergoing PCI, the relation between DAPT interruption 4.1. Limitations. Certain limitations were present with the within 12 months and thrombotic risk is multifactorial and analyses presented within this study. First, our data were likely both associative and causative in nature. First, in the derived from a large volume single-center PCI registry and current analysis, the cumulative incidence of DAPT inter- may suffer from limited generalizability. Second, although the ruption within 12 months after PCI was higher in ARC-HBR data were collected prospectively, as for any retrospective patients, and the higher propensity of HBR patients in study, our findings should be considered hypothesis gener- developing hemorrhagic complications lead to permanent ating, and future trials are needed to confirm our findings. We cessation of DAPT. &is finding further emphasizes that performed additional sensitivity analyses, but there is a DAPT interruption per se may represent a marker of patient possibility of unmeasured confounding factors that may lead risk. Interruption of DAPT in the setting of major bleeding to increased risk of ischemic events associated with subjects will inevitably result in permanent and abrupt cessation of who had an interruption or discontinued DAPT. &ird, the antithrombotic therapies, need for blood transfusions, in- decision to discontinue or remain on DAPT after 12 months vasive procedures to manage bleeding, and their clinical was made at the discretion of the patient’s physician (and consequences. Second, more and longer stents implanted possibly influenced by the patient); hence, selection bias was may increase the likelihood of stent size mismatch, stent inevitable in this specific substudy cohort that might have underexpansion, malapposition, and overlapping, all of affected event rates. Fourth, ticagrelor (0.4%) only became which may act as true mediators of delayed endothelization available late during the study recruitment, and prasugrel was and enhancing the stent-related thrombotic risk [37]. In the unavailable in China; as a result, most of patients received current study, up to one-half of patients received at least 3 clopidogrel as a P2Y inhibitor for DAPT. However, owing to stents implanted coexisting with a higher proportion of total 12 the differential propensity for bleeding events with response stent length>60 mm, a fact that suggests that encouraged us to antiplatelet therapy, East Asian populations undergoing to prevent premature discontinuation of DAPT and treat PCI treated with potent P2Y inhibitors did not have a lower them appropriately (e.g., extended DAPT periods). &ird, 12 ischemic outcome, but had higher incidence of clinically given that patients with multivessel CAD represent an ad- significant bleeding compared with clopidogrel [42,43]. In vanced state of atherosclerosis and often leads to incomplete this scenario, our patients were less prone to bleeding and revascularization with a subsequently increased risk of re- were more likely to show a net clinical outcome. Furthermore, current atherothrombotic coronary events and mortality although CYP2C19 genotyping might be used as an optional [38,39], nearly 90% of the population in our cohort com- tool for guiding antiplatelet therapy, it was not available for prised of multivessel CAD and, thus, constitute a high-risk this study. Finally, our study was performed in a Chinese patient group that longer duration of DAPT may be ap- population. Compared with Western population, East Asian propriate to mitigate ischemic risks both within and outside population has a higher prevalence of the CYP2C19 loss-of- of the stented segments. Finally, this large PCI cohort function genotype, which is associated with a higher level of reflecting a real-world setting showed that procedural platelet reactivity during clopidogrel treatment. &rombo- complexity as assessed by ESC stent-driven high ischemic genicity, pharmacogenetics, and susceptibility for bleeding risk definition adequately captures a patient’s cardiovascular complication on P2Y12 inhibitors could be different between and noncardiovascular comorbidities with a greater prob- Asian and Western population. &us, we should be cautious ability of natural plaque progression followed by future about extrapolating these study results outside China. atherothrombotic events, particularly in nontarget lesion events. As reported previously, ischemic events may arise from either stented segments or progressive disease else- 5. Conclusions where in the coronary vasculature >1 year after PCI. Late stent-related events were related to patient age, diabetes, and In this large-scale PCI cohort of patients with stent-driven coronary lesion complexity [40]. In this regard, the fatal high ischemic risk definition, interruption of DAPT (tem- impact of premature discontinuation of DAPT within 1 year porary or permanent) predominantly due to poor compli- in our dataset might be driven by increasing recurrent is- ance or bleeding complications within 12 months was chemic events arising from either from the stented target associated with significantly higher risk for cardiovascular lesion and nonrevascularized atherosclerotic plaques. Of ischemic recurrences at 30 months compared with pro- note in the SWEDEHEART registry, the risk of recurrent MI longed-term (>12 months) DAPT. Patients who had DAPT not originating from a previously stented lesion was twice as interruption may benefit from more intensive surveillance to high as the risk of lesions originating from a previously prevent long-term cardiovascular events. Our findings may stented lesion, emphasizing the importance of preventing inform future considerations for utilizing ESC stent-driven atherothrombotic events from nontreated lesions long term high ischemic risk criteria to help clinicians adopting a and overall coronary disease progression after an initial MI prolonged DAPT course to pursue a best benefit-risk ratio in [41]. Collectively, our findings provided additional insights an individual patient. 14 Journal of Interventional Cardiology Data Availability References [1] D. Cao, R. Chandiramani, M. Chiarito, B. E. Claessen, and &e clinical and procedural data used to support the findings R. 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Journal of Interventional Cardiology – Hindawi Publishing Corporation
Published: Jan 13, 2022
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