Dual Antiplatelet Therapy Trial Research Articles

Dual Antiplatelet Therapy in the Management of Acute Minor Ischemic Stroke and High-Risk Transient Ischemic Attack: An Expert Consensus Statement From Taiwan Stroke Society and Taiwan Society of Emergency Medicine.

The aim of this review is to achieve a consensus between Taiwan Stroke Society (TSS) and Taiwan Society of Emergency Medicine (TSEM) to manage acute non-cardioembolic minor ischemic stroke (MIS) and high-risk transient ischemic attack (TIA). The methodology is to review the recent findings from clinical trials of dual antiplatelet therapy (DAPT) from 2010 to 2021 and updates in clinical practice guidelines from 2018 to 2022 for non-cardioembolic MIS/TIA management at the acute stage. Four leading clinical studies, CHANCE, POINT, THALES, and CHANCE-2 along with other relevant studies introducing DAPT, are discussed in this review. The risk-benefit profile between stroke recurrence reduction and major bleeding increase is also elucidated. TSS and TSEM concluded that for patients presenting with non-cardioembolic MIS or high-risk TIA who did not receive intravenous alteplase, initiation of DAPT within 24 hours after stroke onset and continued up to 21 days, followed by antiplatelet monotherapy, is effective in reducing recurrent ischemic stroke for a period of up to 90 days.

Abbreviated Antiplatelet Therapy After Coronary Stenting in Patients With Myocardial Infarction at High Bleeding Risk

BackgroundThe optimal duration of antiplatelet therapy (APT) after coronary stenting in patients at high bleeding risk (HBR) presenting with an acute coronary syndrome remains unclear. ObjectivesThe objective of this study was to investigate the safety and efficacy of an abbreviated APT regimen after coronary stenting in an HBR population presenting with acute or recent myocardial infarction. MethodsIn the MASTER DAPT trial, 4,579 patients at HBR were randomized after 1 month of dual APT (DAPT) to abbreviated (DAPT stopped and 11 months single APT or 5 months in patients with oral anticoagulants) or nonabbreviated APT (DAPT for minimum 3 months) strategies. Randomization was stratified by acute or recent myocardial infarction at index procedure. Coprimary outcomes at 335 days after randomization were net adverse clinical outcomes events (NACE); major adverse cardiac and cerebral events (MACCE); and type 2, 3, or 5 Bleeding Academic Research Consortium bleeding. ResultsNACE and MACCE did not differ with abbreviated vs nonabbreviated APT regimens in patients with an acute or recent myocardial infarction (n = 1,780; HR: 0.83; 95% CI: 0.61-1.12 and HR: 0.86; 95% CI: 0.62-1.19, respectively) or without an acute or recent myocardial infarction (n = 2,799; HR: 1.03; 95% CI: 0.77-1.38 and HR: 1.13; 95% CI: 0.80-1.59; Pinteraction = 0.31 and 0.25, respectively). Bleeding Academic Research Consortium 2, 3, or 5 bleeding was significantly reduced in patients with or without an acute or recent myocardial infarction (HR: 0.65; 95% CI: 0.46-0.91 and HR: 0.71; 95% CI: 0.54-0.92; Pinteraction = 0.72) with abbreviated APT. ConclusionsA 1-month DAPT strategy in patients with HBR presenting with an acute or recent myocardial infarction results in similar NACE and MACCE rates and reduces bleedings compared with a nonabbreviated DAPT strategy. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020)

Impact of Medication Nonadherence in a Clinical Trial of Dual Antiplatelet Therapy

BackgroundNonadherence to antiplatelet therapy after percutaneous coronary intervention (PCI) is common, even in clinical trials. ObjectivesThe purpose of this study was to investigate the impact of nonadherence to study protocol regimens in the MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen) trial. MethodsAt 1-month after PCI, 4,579 high bleeding risk patients were randomized to single antiplatelet therapy (SAPT) for 11 months (or 5 months in patients on oral anticoagulation [OAC]) or dual antiplatelet therapy (DAPT) for ≥2 months followed by SAPT. Coprimary outcomes included net adverse clinical events (NACE), major adverse cardiac and cerebral events (MACE), and major or clinically relevant nonmajor bleeding (MCB) at 335 days. Inverse probability-of-censoring weights were used to correct for nonadherence Academic Research Consortium type 2 or 3. ResultsIn total, 464 (20.2%) patients in the abbreviated-treatment and 214 (9.4%) in the standard-treatment groups incurred nonadherence Academic Research Consortium type 2 or 3. At inverse probability-of-censoring weights analyses, NACE (HR: 1.01; 95% CI: 0.88-1.27) or MACE (HR: 1.07; 95% CI: 0.83-1.40) did not differ, and MCB was lower with abbreviated compared with standard treatment (HR: 0.51; 95% CI: 0.60-0.73) consistently across OAC subgroups; among OAC patients, SAPT discontinuation 6 months after PCI was associated with similar MACE and lower MCB (HR: 0.47; 95% CI: 0.22-0.99) compared with SAPT continuation. ConclusionsIn the MASTER DAPT adherent population, 1-month compared with ≥3-month DAPT was associated with similar NACE or MACE and lower MCB. Among OAC patients, SAPT discontinuation after 6 months was associated with similar MACE and lower MCB than SAPT continuation (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020)

Impact of one-month DAPT followed by aspirin monotherapy in patients undergoing percutaneous coronary intervention according to clinical presentation: a post hoc analysis of the randomised One-Month DAPT trial.

The impact of 1-month dual antiplatelet therapy (DAPT) followed by aspirin monotherapy according to clinical presentation has not been elucidated. This study aimed to compare the impact of 1-month DAPT followed by aspirin monotherapy after polymer-free drug-coated stent (PF-DCS) implantation (1-month DAPT after PF-DCS) vs 6-12-month DAPT followed by aspirin monotherapy after biodegradable polymer drug-eluting stent (BP-DES) implantation (6-12-month DAPT after BP-DES) according to clinical presentation. This is a post hoc analysis of the One-Month DAPT trial. The primary outcome was the composite of major adverse cardiac and cerebrovascular events (MACCE; a composite of cardiac death, non-fatal myocardial infarction, target vessel revascularisation, and stroke) and major bleeding. Among 1,828 patients with stable coronary artery disease (CAD), 1-month DAPT after PF-DCS resulted in lower rates of the primary outcome than 6-12-month DAPT after BP-DES (3.9% vs 6.5%; hazard ratio [HR] 0.59, 95% confidence interval [CI]: 0.39-0.90; p=0.012). However, among 1,192 patients with acute coronary syndrome (ACS), the rates of the primary outcome were not significantly different between the two therapy groups (5.6% vs 3.6%; HR 1.57, 95% CI: 0.91-2.70; p=0.102) and a significant interaction was observed between therapy and clinical presentation regarding the primary outcome (Pint=0.005). A significant interaction was observed in MACCE (Pint=0.016), but not in major bleeding (Pint=0.276). In patients undergoing drug-eluting stent implantation for non-complex lesions, the benefits of 1-month DAPT followed by aspirin monotherapy for a composite of ischaemic and bleeding outcomes were found in patients with stable CAD, but not in those with ACS. gov: NCT02513810.

Duration of antiplatelet therapy after complex percutaneous coronary intervention in patients at high bleeding risk: a MASTER DAPT trial sub-analysis

To assess the effects of 1- or ≥3-month dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients who received biodegradable-polymer sirolimus-eluting stents for complex percutaneous coronary intervention (PCI) and/or acute coronary syndrome (ACS). In the MASTER DAPT trial, 3383 patients underwent non-complex (abbreviated DAPT, n = 1707; standard DAPT, n = 1676) and 1196 complex (abbreviated DAPT, n = 588; standard DAPT, n = 608) PCI. Co-primary outcomes at 335 days were net adverse clinical events [NACE; composite of all-cause death, myocardial infarction, stroke, and bleeding academic research consortium (BARC) 3 or 5 bleeding events]; major adverse cardiac or cerebral events (MACCE; all-cause death, myocardial infarction, and stroke); and Types 2, 3, or 5 BARC bleeding. Net adverse clinical events and MACCE did not differ with abbreviated vs. standard DAPT among patients with complex [hazard ratio (HR): 1.03, 95% confidence interval (CI): 0.69-1.52, and HR: 1.24, 95% CI: 0.79-1.92, respectively] and non-complex PCI (HR: 0.90, 95% CI: 0.71-1.15, and HR: 0.91, 95% CI: 0.69-1.21; Pinteraction = 0.60 and 0.26, respectively). BARC 2, 3, or 5 was reduced with abbreviated DAPT in patients with and without complex PCI (HR: 0.64; 95% CI: 0.42-0.98, and HR: 0.70; 95% CI: 0.55-0.89; Pinteraction = 0.72). Among the 2816 patients with complex PCI and/or ACS, NACE and MACCE did not differ and BARC 2, 3, or 5 was lower with abbreviated DAPT. In HBR patients free from recurrent ischaemic events at 1 month, DAPT discontinuation was associated with similar NACE and MACCE and lower bleeding rates compared with standard DAPT, regardless of PCI or patient complexity. This trial is registered with ClinicalTrials.gov, number NCT03023020, and is closed to new participants, with follow-up completed.

Efficacy and Safety of Ticagrelor and Aspirin in Patients With Moderate Ischemic Stroke

Prior trials of dual antiplatelet therapy excluded patients with moderate ischemic stroke. These patients were included in the Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death (THALES) trial, but results have not been reported separately, raising concerns about safety and efficacy in this subgroup. To evaluate the efficacy and safety of ticagrelor plus aspirin in patients with moderate ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 4 to 5). The THALES trial was a randomized trial conducted at 414 hospitals in 28 countries in January 2018 and December 2019. This exploratory analysis compared patients with moderate stroke (baseline NIHSS score of 4 to 5) with patients with less severe stroke (NIHSS score of 0 to 3). A total of 9983 patients with stroke were included in the present analysis, after excluding 2 patients with NIHSS scores greater than 5 and 1031 patients with transient ischemic attack. Data were analyzed from March to April 2021. Ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily on days 2 to 30) or placebo within 24 hours after symptom onset. All patients received aspirin, 300 to 325 mg, on day 1 followed by aspirin, 75 to 100 mg, daily on days 2 to 30. Patients were observed for 30 additional days. The primary outcome was time to stroke or death within 30 days. The primary safety outcome was time to severe bleeding. In total, 3312 patients presented with moderate stroke and 6671 presented with less severe stroke. Of those in the moderate stroke group, 1293 (39.0%) were female, and the mean (SD) age was 64.5 (10.8) years; of those in the less severe stroke group, 2518 (37.7%) were female, and the mean (SD) age was 64.8 (11.2) years. The observed primary outcome event rate in patients with moderate stroke was 7.6% (129 of 1671) for those in the ticagrelor group and 9.1% (150 of 1641) for those in the placebo group (hazard ratio, 0.84; 95% CI, 0.66-1.06); the primary outcome event rate in patients with less severe stroke was 4.7% (158 of 3359) for those in the ticagrelor group and 5.7% (190 of 3312) for those in the placebo group (hazard ratio, 0.82; 95% CI, 0.66-1.01) (P for interaction = .88). Severe bleeding occurred in 8 patients (0.5%) in the ticagrelor group and in 4 patients (0.2%) in the placebo group in those with moderate stroke compared with 16 patients (0.5%) and 3 patients (0.1%), respectively, with less severe stroke (P for interaction = .26). In this study, patients with a moderate ischemic stroke had consistent benefit from ticagrelor plus aspirin vs aspirin alone compared with patients with less severe ischemic stroke, with no further increase in the risk of intracranial bleeding or other severe bleeding events. ClinicalTrials.gov Identifier: NCT03354429.

Trials of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention Lack Strategies to Ensure Appropriate Gastroprotection.

Gastrointestinal bleeding is a morbid complication of dual antiplatelet therapy (DAPT). We evaluated the extent to which contemporary trials of DAPT included steps to ensure appropriate use of proton pump inhibitor (PPI) gastroprotection and reported rates of PPI use. A methodological review of randomized trials comparing varying durations of DAPT after percutaneous coronary intervention. Among 21 trials, none incorporated protocol procedures or guidance for prescribing PPIs. Five reported rates of PPI use (range 25.6-69.1%). PPI gastroprotection is overlooked in major trials of DAPT. Appropriate use of PPI gastroprotection represents an important opportunity to improve patient safety.

Utility of the dual antiplatelet therapy score to guide antiplatelet therapy: A systematic review and meta‐analysis

The dual antiplatelet therapy (DAPT) score, one of the first prediction tools to attempt to uncouple bleeding and ischemic risk following percutaneous coronary intervention, can help guide antiplatelet duration after coronary intervention. Evaluating the generalizability of the score is important to understand its utility in clinical practice. We conducted a systematic review and meta-analysis of studies that validated the DAPT score. A random effect meta-analysis was performed of ischemic and bleeding risk based on DAPT score. A secondary analysis assessed the risk of longer versus shorter P2Y12 inhibitor duration on ischemic and bleeding risk in randomized controlled trials of DAPT duration. We identified 10 patient cohorts involving 88,563 patients. Compared with a low DAPT score, a high DAPT score was associated with increased ischemic risk (RR: 1.62, 95% CI: 1.41-1.87) and reduced bleeding risk (RR: 0.80, 95% CI: 0.70-0.92). In three randomized trials of DAPT duration that contained information on the DAPT score, the relative risk of net adverse clinical events (combined ischemic and bleeding events) with longer duration of DAPT was 1.56 (95% CI: 0.77-3.19) for low DAPT score patients, and 0.86 (95% CI: 0.61-1.21) for high DAPT score patients (pinteraction = .14). In this large meta-analysis, the DAPT score consistently stratified bleeding and ischemic risk in opposing directions across several different study populations. More evaluation is needed to understand if the effect of longer DAPT duration on NACE is modified by the DAPT score in current practice.

Biomarkers of platelet activation and cardiovascular risk in the DAPT trial.

Prolonged use of dual antiplatelet therapy (DAPT) post-percutaneous coronary intervention (PCI) has been shown to reduce the risk of major adverse cardiovascular events (MACE), but with increased bleeding. It remains unknown whether biomarkers of platelet activation may be useful for identifying patients at increased risk of MACE. The DAPT studywas a randomized trial of 12 versus 30months of DAPT in patients who underwent PCI. Serum biomarkers [myeloid-related protein (MRP)-8/14, P-selectin, soluble CD-40 ligand (sCD40L)] were assessed in 1399 patients early post-PCI. On-treatment platelet reactivity index (PRI) using VASP phosphorylation was assessed in 443 patients randomized to continued DAPT at 1year. MACE was defined as CV death, MI, or ischemic stroke. Multivariable models were adjusted for baseline characteristics, index event, and stent type. A stepwise increase in the risk of MACE was observed with increasing tertiles of both MRP-8/14 and P-selectin (p-trend = 0.04 for both). After multivariable adjustment, the adjusted HR (95% CI) for MACE in patients in the top tertile was 1.94 (1.14-3.30) for MRP-8/14 and 1.62 (0.99-2.64) for P-selectin. In contrast, baseline sCD40L was not associated with CV risk. Among patients randomized to continued DAPT, higher on-treatment platelet reactivity was not significantly associated with risk of MACE (p-trend = 0.32; adj-HR T3 vs. T1 1.54, 95% CI 0.20-12.18) or bleeding (P-trend = 0.17; adj-HR 0.25, 95% CI 0.05-1.21). MRP-8/14 and soluble P-selectin may be useful for identifying patients at increased risk of MACE after PCI. The utility of on-treatment platelet function testing requires further study.Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifier NCT00977938.

P2Y12 inhibitors: do they increase cancer risk?

Treatment with dual antiplatelet therapy (DAPT), typically combining a P2Y12 inhibitor with aspirin, is the standard of care for the prevention of coronary stent thrombosis, especially post revascularization and in the setting of acute coronary syndromes (ACS). Determining the appropriate duration has been debated as prolonged courses have been associated with reduced thrombotic complications. Despite proven benefit, there have been reports of a potential cancer risk associated with DAPT following the FDA's review of the TRITON-TIMI 38 trial and the DAPT trial. The latter revealed an increased risk of non-cardiovascular death, which was driven by more bleeding and cancer-related deaths. This further clouds the decision if longer courses of DAPT should be recommended. Several trials and meta-analyses have been conducted to further review this cancer risk with P2Y12 inhibitors. This manuscript intends to evaluate current literature to determine if there is a risk of cancer for patients on DAPT and its consequences in the management of cardiovascular disease.

Role of Gender in Dual Antiplatelet Therapy After Acute Coronary Syndrome.

The effect of gender on use of dual antiplatelet therapy (DAPT) in treatment of acute coronary syndrome (ACS) is not well established. The purpose of this review is to understand gender-based differences in response to DAPT, so that treatment of ACS can be optimized in women to prevent ischemic events while minimizing bleeding risk. There are innate gender differences in platelet reactivity and response. However, it is unknown if this translates into differences in clinical outcomes. In all major studies evaluating the effect of DAPT in ACS, women are underrepresented. Hence, the results from the existing trials cannot be generalizable to women. There is a significant knowledge gap regarding how to balance the bleeding and ischemic risk profile among women with ACS. Currently, there is no recommendation to consider gender as covariate in choosing the type of antiplatelet drug or duration. The existing clinical evidence is limited by under representation of women in DAPT trials. The current literature does not strongly support considering gender in decision making regarding type or duration of DAPT after ACS. Future dedicated trial designs with adequate representation from women and gender specific analysis from large registry data are warranted to enhance our understanding of the interaction of gender with DAPT after ACS.

Is P2Y12 inhibitor therapy associated with an increased risk of cancer?

Antiplatelet therapy is a mainstay of cardiovascular therapy and is well established in clinical routine. Recently, the potential risk of solid cancers with P2Y12 inhibitor therapy has been an issue of growing interest. The alleged association primarily originated from the findings of an US Food and Drug Administration (FDA) review of the randomized controlled TRITON-TIMI 38 trial and the following results of the DAPT trial. The higher risk of cancer was predominately observed with the newer, more potent P2Y12 inhibitors and in the setting of prolonged dual antiplatelet therapy (DAPT). Current European Society of Cardiology (ESC) Guidelines suggest consideration of prolonged DAPT beyond the recommended duration of 6 months in stable coronary artery disease and 12 months in acute coronary syndrome if ischaemic risk prevails over the risk of bleeding. Several trials, studies and meta-analyses have addressed the potential interplay of cancer and P2Y12 inhibition since then. The effect of P2Y12 inhibition on cancer has been investigated extensively in basic research as well. In this review, we summarize current available evidence of cancer risk with P2Y12 inhibitor therapy and discuss the resulting clinical implications.

Prediction of Ischemic and Bleeding Events Using the Dual Antiplatelet Therapy Score in an Unrestricted Percutaneous Coronary Intervention Population.

The dual antiplatelet therapy (DAPT) risk score was developed from the DAPT trial to inform the optimal duration of DAPT after percutaneous coronary intervention. We assessed the performance of the DAPT score in the ADAPT-DES (Assessment of Dual AntiPlatelet Therapy with drug-eluting stents) all-comers registry and tested the utility of additional predictors of adverse events. Outcomes between 1 and 2 years were examined according to DAPT score ≥2 versus <2, adjusted for DAPT continuation as a time-dependent variable. To assess the incremental utility of variables not included in the DAPT score, baseline high platelet reactivity was added to the ischemia model, and high platelet reactivity, baseline hemoglobin, and warfarin use 1 year after percutaneous coronary intervention were added to the bleeding model. Among 8582 patients enrolled in ADAPT-DES, 5397 were event-free after 1 year. Between 1 and 2 years, ischemic (myocardial infarction or stent thrombosis) and bleeding events occurred in 75 (1.5%) and 124 (2.3%) patients, respectively. Patients with higher DAPT scores (≥2 versus <2) had higher rates of myocardial infarction or stent thrombosis (1.9% versus 1.1%; P=0.01) and similar rates of bleeding (2.2% versus 2.4%, respectively; P=0.79). For the prediction of myocardial infarction or stent thrombosis, bleeding and death, DAPT score ≥2 had sensitivities of 57%, 41%, and 56%, respectively; specificities of 58%, 57%, and 58%, respectively; positive predictive values of 1.9%, 2.2%, and 2.1%, respectively; and negative predictive values of 99%, 98%, and 99%, respectively. Addition of baseline high platelet reactivity to the DAPT score did not improve discrimination for ischemic events. Addition of high platelet reactivity and 2 other bleeding covariates to the DAPT score marginally improved discrimination. In ADAPT-DES, the DAPT score was predictive of ischemic events between 1 and 2 years after drug-eluting stents. Prediction of bleeding improved marginally after addition of variables not incorporated in the DAPT score.

Duration of Dual Antiplatelet Therapy in Patients With Ischemic Heart Disease After Implantation of Endovascular Stents

Optimal duration of dual antiplatelet therapy (DAPT) after stent implantation is uncertain. Some patients have an extended risk of thrombotic complications including that of very late stent thrombosis after cessation of recommended course of DAPT (6-12 months). On the other hand, there is a real risk of bleeding on DAPT. In this review, we present and discuss results of clinical trials of long-term DAPT and data of their meta-analyses. The review also contains consideration of some aspects of new AHA/ACC recommendations (2016) on duration of DAPT.

TCT-546 Performance of the Dual AntiPlatelet Therapy (DAPT) Score in the ADAPT-DES Study

The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) remains in dispute, particularly after 12 months. The DAPT Score was developed from the DAPT trial to identify pts who may benefit the most from extended therapy. We sought to assess the

Stent thrombosis and optimal duration of dual antiplatelet therapy after coronary stenting in contemporary practice.

The introduction of drug-eluting stents (DES) in the practice of percutaneous coronary intervention (PCI) has substantially reduced angiographic and clinical restenosis but is associated with an increasing propensity for very late stent thrombosis (ST). Among several clinical, lesion, or procedure-related predictors of ST, early discontinuation of dual antiplatelet therapy (DAPT) is the most important factor for DES-associated late thrombosis; therefore, the optimal duration of DAPT is a major issue to be critically considered in the current DES era. Given that the benefit and risk of longer duration DAPT should be simultaneously considered, the optimal DAPT period following DES implantation has been controversial. Several small-to-medium sized randomized clinical trials and observational registries have indicated that short-term DAPT (< 6 months) is not inferior to 12-month DAPT with fewer bleeding events, whereas prolonged duration of DAPT (> 12 months) failed to prove its superiority. However, compelling evidence from a landmark DAPT trial has clearly demonstrated the efficacy of prolonged DAPT up to 30 months in terms of preventing ST and major cardiovascular adverse events at the expense of major bleeding. In addition, coupled with various risk algorithms, a more individualized approach to balance the efficacy and safety of optimal DAPT duration has been emphasized. In this review article, we systematically summarize the cumulative evidence from key clinical studies and try to help the physician make decisions on the optimal duration of DAPT in contemporary PCI practice.

Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: conceptual evolution based on emerging evidence.

The objective of this article is to review the contemporary literature on optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) implantation. Relevant studies were searched through MEDLINE, the Cochrane database, and the EMBASE database. Of the 6852 publications retrieved, 23 were considered relevant, including 11 randomized controlled trials (RCTs) and 12 meta-analyses. Initially prescribed for 3-6 months after first-generation DES, the recommended duration of DAPT was subsequently prolonged to at least 1 year, a response to reports of late stent thrombosis after DAPT discontinuation. Seven RCTs subsequently suggested that 1-year DAPT may not be necessary after DES implantation, and that a 6-month or even a 3-month course of DAPT may be as effective and safer. In contrast, four RCTs examining the benefit of DAPT beyond 1 year reached conflicting conclusions. In the DAPT trial, 30-month compared with 12-month DAPT after DES resulted in reduced rates of stent thrombosis and major adverse cardiovascular events, but greater rates of major bleeding with increased non-cardiac mortality. Several meta-analyses have subsequently been performed collectively demonstrating increased rates of all-cause mortality with prolonged DAPT compared with shorter DAPT after DES, due to greater non-cardiovascular mortality with prolonged DAPT not offset by a concomitant reduction in cardiac mortality. The benefit-risk ratio of prolonged DAPT appears to be better in patients with myocardial infarction (MI) than in those without prior MI. On the basis of these findings, a personalized approach is advisable when deciding upon the optimal duration of DAPT after DES, wherein the individualized risks of ischaemic vs. bleeding events are carefully considered for each patient.

Abstract 11515: Does Prolonged Dual Antiplatelet Therapy Increase Mortality After Drug-Eluting Stent Implantation?

Introduction: The Dual Antiplatelet Therapy (DAPT) trial found a borderline increase in the rate of all-cause mortality in patients treated with 30 compared with 12 months of DAPT (2.0% vs. 1.5%, HR 1.36, 95% CI 1.00-1.85, P = 0.05). Hypothesis: A finding of borderline significance in a mega-trial may reflect the play of chance. Methods: We used a Bayesian conjugate-normal approach (Figure A) to update the mortality results from the DAPT trial with an empiric prior probability distribution based on results in 9 smaller randomized controlled trials (RCTs). Results: The empiric prior (blue), which suggests that the odds of mortality in the 9 smaller RCTs could be 6% lower or as much as 40% higher after prolonged than after short DAPT, overlaps with the likelihood (red) from the DAPT trial itself. Bayesian inference (black) affirms a significant increase in mortality with prolonged DAPT (posterior mean odds ratio [OR] 1.21, 95% Bayesian confidence interval [BCI] 1.02-1.44). Sensitivity analysis, which weighs the number of effective events by the proportion of patients with acute coronary syndromes, produces a nearly identical point estimate (OR 1.23, 95% BCI 0.96-1.58). Conclusions: Our analysis provides credible evidence that 30 months of DAPT is associated with higher mortality rates than is 12 months of therapy. The mortality increase in the DAPT trial is predictable from prior RCTs and not likely to be a chance finding.

Abstract 18475: Is There Any End in Sight to This Debate on the Optimal Duration of Dual Antiplatelet Therapy After Drug-eluting Coronary Stent Implantation?

Introduction: There is no end in sight to the ongoing debate on the optimal duration of dual antiplatelet therapy (DAPT) following drug-eluting coronary stent (DES) implantation. Hypothesis: Short-term DAPT is less effective than long-term DAPT in preventing adverse cardiovascular and cerebrovascular outcomes following DES. Methods: MEDLINE, EMBASE, Scopus and CENTRAL were searched for eligible randomized controlled trials (RCTs) that compared short-term (≤ 6 months) DAPT with long-term (≥ 12 months) DAPT following DES implantation. The primary end point was a composite of all cause death, myocardial infarction, target vessel revascularization, stroke or major bleeding. The secondary outcome were the individual components of the primary outcome, cardiovascular death, stent thrombosis and any bleeding episode. Results: A total of 15,378 patients from 7 RCTs were studied. There was no statistically significant difference between the short-term and long-term DAPT groups with respect to the occurrence of the primary outcome {Risk ratio (RR) 1.017 (0.872-1.186), I2 = 0%}, all cause death {RR 0.896 (0.708-1.134)}, cardiovascular death {RR 0.924 (0.668-1.279)}, myocardial infarction {RR 1.139 (0.887-1.461)}, target vessel revascularization {RR 1.174 (0.916-1.505)}, stent thrombosis {RR 1.264 (0.786-2.032)} and stroke {RR 0.876 (0.685-1.611)}. However there was a statistically significant lower risk of major bleeding in the short-term DAPT group {RR 0.57 (0.36-0.90), p 0.02}. There was no statistically significant difference in the sub-group analysis of patients with diabetes and patients presenting with acute coronary syndrome, {RR 1.029 (0.745-1.421)} and {RR 1.062 (0.785-1.438)}, respectively. Conclusion: There was no difference in efficacy outcomes between short-term and long-term DAPT following DES, even among high-risk patients. Longer duration of DAPT was found to be associated with increased risk of major bleeding. These results are contrary to findings from the recently published DAPT trial. However, even though the DAPT trial reported a significant decrease in the incidence of stent thrombosis and major adverse cardiac and cerebrovascular events in the long-term DAPT group, there was a paradoxical increase in mortality.

GW26-e1002 A Meta-analysis of Randomized Clinical Trials of Dual Antiplatelet Therapy in Patients with Drug-Eluting Stent Implantation

The purpose of this study was to perform a meta-analysis comparing short-term versus long-term dual antiplatelet therapy (DAPT) to identify the optimal duration of DAPT in patients with Drug-Eluting Stent (DES) implantation. This study included 15,870 patients from 7 randomized clinical trials (RCT