Ticagrelor-based Dual Antiplatelet Therapy Research Articles

Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials.

In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. PROSPERO (ID: CRD42023476470).

Clinical Impact of Dyspnea after Ticagrelor Treatment and the Effect of Switching to Clopidogrel in Patients with Myocardial Infarction.

Dyspnea is frequent during ticagrelor-based dual antiplatelet therapy (DAPT) for acute myocardial infarction (AMI). However, its clinical characteristics or management strategy remains uncertain. The study assessed 2,617 AMI patients from the Ticagrelor versus Clopidogrel in Stabilized Patients with AMI (TALOS-AMI) trial. Dyspnea during 1-month ticagrelor-based DAPT and following DAPT strategies with continued ticagrelor or de-escalation to clopidogrel from 1 to 12 months were evaluated for drug adherence, subsequent dyspnea, major adverse cardiovascular events (MACE), and bleeding events. Dyspnea was reported by 538 patients (20.6%) during 1 month of ticagrelor-based DAPT. Adherence to allocated DAPT over the study period was lower in the continued ticagrelor arm than the de-escalation to clopidogrel, particularly among the dyspneic population (81.1% vs. 91.5%, p < 0.001). Among ticagrelor-treated patients with dyspnea, those switched to clopidogrel at 1 month had a lower frequency of dyspnea at 3 months (34.3% vs. 51.7%, p < 0.001) and 6 months (25.5% vs. 38.4%, p = 0.002) than those continued with ticagrelor. In patients with dyspnea in their 1-month ticagrelor-based DAPT, de-escalation was not associated with increased MACE (1.3% vs. 3.9%, hazard ratio [HR]: 0.31, 95% confidence interval [CI]: 0.08-1.11, p = 0.07) or clinically relevant bleeding (3.2% vs. 6.2%, HR: 0.51, 95% CI: 0.22-1.19, p = 0.12) at 1 year. Dyspnea is a common side effect among ticagrelor-based DAPTs in AMI patients. Switching from ticagrelor to clopidogrel after 1 month in AMI patients may provide a reasonable option to alleviate subsequent dyspnea in ticagrelor-relevant dyspneic patients, without increasing the risk of ischemic events (NCT02018055).

Dual Antiplatelet Therapy De-Escalation in Stabilized Myocardial Infarction With High Ischemic Risk

In patients with acute myocardial infarction (AMI) who have high ischemic risk, data on the efficacy and safety of the de-escalation strategy of switching from ticagrelor to clopidogrel are lacking. To evaluate the outcomes of the de-escalation strategy compared with dual antiplatelet therapy (DAPT) with ticagrelor in stabilized patients with AMI and high ischemic risk following percutaneous coronary intervention (PCI). This was a post hoc analysis of the Ticagrelor vs Clopidogrel in Stabilized Patients With Acute Myocardial Infarction (TALOS-AMI) trial, an open-label, assessor-blinded, multicenter, randomized clinical trial. Patients with AMI who had no event during 1 month of ticagrelor-based DAPT after PCI were included. High ischemic risk was defined as having a history of diabetes or chronic kidney disease, multivessel PCI, at least 3 lesions treated, total stent length greater than 60 mm, at least 3 stents implanted, left main PCI, or bifurcation PCI with at least 2 stents. Data were collected from February 14, 2014, to January 21, 2021, and analyzed from December 1, 2021, to June 30, 2022. Patients were randomly assigned to either de-escalation from ticagrelor to clopidogrel or ticagrelor-based DAPT. Ischemic outcomes (composite of cardiovascular death, myocardial infarction, ischemic stroke, ischemia-driven revascularization, or stent thrombosis) and bleeding outcomes (Bleeding Academic Research Consortium type 2, 3, or 5 bleeding) were evaluated. Of 2697 patients with AMI (mean [SD] age, 60.0 [11.4] years; 454 [16.8%] female), 1371 (50.8%; 684 assigned to de-escalation and 687 assigned to ticagrelor-based DAPT) had high ischemic risk features and a significantly higher risk of ischemic outcomes than those without high ischemic risk (1326 patients [49.2%], including 665 assigned to de-escalation and 661 assigned to ticagrelor-based DAPT) (hazard ratio [HR], 1.74; 95% CI, 1.15-2.63; P = .01). De-escalation to clopidogrel, compared with ticagrelor-based DAPT, showed no significant difference in ischemic risk across the high ischemic risk group (HR, 0.88; 95% CI, 0.54-1.45; P = .62) and the non-high ischemic risk group (HR, 0.65; 95% CI, 0.33-1.28; P = .21), without heterogeneity (P for interaction = .47). The bleeding risk of the de-escalation group was consistent in both the high ischemic risk group (HR, 0.64; 95% CI, 0.37-1.11; P = .11) and the non-high ischemic risk group (HR, 0.42; 95% CI, 0.24-0.75; P = .003), without heterogeneity (P for interaction = .32). In stabilized patients with AMI, the ischemic and bleeding outcomes of an unguided de-escalation strategy with clopidogrel compared with a ticagrelor-based DAPT strategy were consistent without significant interaction, regardless of the presence of high ischemic risk.

Repeat coronary revascularization in high-risk patients treated with ticagrelor monotherapy after PCI: Insights from the randomized TWILIGHT trial

Abstract Background Repeat revascularization after percutaneous coronary intervention (PCI) remains a major concern, even though its impact on mortality is limited. The effect of ticagrelor monotherapy vs. standard dual antiplatelet therapy (DAPT) on this outcome is unclear. Aim To assess the impact of ticagrelor monotherapy vs. DAPT on repeat revascularization after PCI. Methods In the TWILIGHT trial, high-risk patients who were event-free and adherent to a ticagrelor-based DAPT for 3 months after PCI were randomized to ticagrelor plus aspirin or ticagrelor plus placebo for 12 additional months. In this post-hoc analysis, the primary endpoint was repeat revascularization due to recurrent or persistent symptomatic myocardial ischemia. Secondary endpoints included target lesion revascularization (TLR), target vessel revascularization (TVR) and major adverse cardiac and cerebrovascular events (MACCE) and net adverse clinical events (NACE) (Figure). All endpoints were adjudicated and assessed at 12 months after randomization in the per-protocol population. Results Among 6,759 patients, ticagrelor monotherapy and ticagrelor plus aspirin were associated with a similar risk of repeat revascularization (7.1% vs 6.7%, HR 1.07, 95% CI 0.89-1.29), TLR, TVR and MACCE (Figure), while NACE was lower with ticagrelor monotherapy. Conclusion In high-risk patients undergoing PCI, ticagrelor monotherapy after 3 months of ticagrelor plus aspirin was associated with similar rates of recurrent coronary revascularization and MACCE and a lower risk of NACE compared with continued DAPT.

Clinically Driven Revascularization in High-Risk Patients Treated With Ticagrelor Monotherapy After PCI: Insights from the Randomized TWILIGHT Trial

Repeat coronary revascularization is a common adverse event after successful percutaneous coronary intervention. This analysis aimed to assess the effects of ticagrelor monotherapy on repeat clinically driven revascularization (CDR). In the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, after 3months of ticagrelor plus aspirin, high-risk patients were maintained on ticagrelor and randomly allocated to aspirin or placebo for 1year. The primary end point of this analysis was CDR within 12months after randomization. The key secondary end points were major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, stroke, or CDR, and net adverse clinical events (NACEs), including the individual components of MACCEs and clinically relevant bleeding. The analysis was performed in the per-protocol population. CDR occurred in 473 of 7,039 patients and was associated with a significantly higher risk of subsequent all-cause death, myocardial infarction, or stroke (adjusted hazard ratios [HRs] 2.92, 95% confidence interval [CI] 1.82 to 4.67). Ticagrelor monotherapy was associated with a similar 12-month risk of CDR (7.1% vs 6.6%; HR 1.09, 95% CI 0.90 to 1.30, p=0.363) and MACCEs (8.9% vs 8.6%; HR 1.04, 95% CI 0.89 to 1.22, p=0.619), and a lower risk of NACEs (12.2% vs 14.6%; HR 0.83 95% CI 0.73 to 0.94, p=0.004) than ticagrelor plus aspirin. In conclusion, among high-risk patients who underwent percutaneous coronary intervention, ticagrelor monotherapy after 3months of ticagrelor-based dual antiplatelet therapy was associated with a similar risk of CDR and MACCEs and a decrease of NACEs (TWILIGHT: NCT02270242).

Influence of early dose reduction of ticagrelor on clinical outcomes following percutaneous coronary intervention for complex lesions

Ticagrelor-based dual antiplatelet therapy (DAPT) provides potent antiplatelet inhibition but may increase the bleeding risk in Asian populations. We investigated the influence of early ticagrelor dose reduction (120 mg) on clinical outcomes in Korean patients undergoing percutaneous coronary intervention (PCI). A multicenter prospective clinical cohort study was conducted with patients who received standard-dose ticagrelor-based DAPT (180 mg) after PCI for complex lesions. Major adverse cardiovascular event (MACE: a composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization), bleeding, and net adverse clinical events (NACE: a composite of MACE and bleeding) were assessed. Among the 772 patients on standard-dose ticagrelor-based DAPT, 115 (14.8%) switched to low-dose ticagrelor-based DAPT (120 mg) within 6 months. Common reasons for the regimen changes were switching as planned (38.8%), dyspnea (25.5%), and bleeding (23.6%). A multivariable Cox proportional hazard model (CPH) showed that the risks of MACE, bleeding, and NACE were not different between the low-dose and standard-dose groups throughout the entire follow-up period and the period beyond 6 months post-PCI. Time-varying multivariable CPH models of the ticagrelor dose reduction yielded similar results. A reduction of the ticagrelor dose within 6 months after PCI is feasible and safe even in patients with complex lesions harboring a high ischemic event risk.

Comparison of Clinical Outcomes Between Ticagrelor and Clopidogrel in East-Asian Patients with Acute Coronary Syndrome: Large Cohort Study.

A high risk of bleeding is observed in East Asian patients with acute coronary syndrome (ACS). Therefore, the choice between two antiplatelet therapy drugs, ticagrelor and clopidogrel, remains controversial in this population with ACS. This study aimed to use a large cohort database to assess the clinical outcomes of ticagrelor and clopidogrel therapy, including major bleeding, recurrent ACS, and mortality, in this population. Between January 2009 and December 2019, 43,696 patients were diagnosed with ACS based on the medical history (International Classification of Diseases [ICD] code) of the Chang Gung Research Database. After excluding patients without percutaneous coronary intervention, with concurrent medical problems, and on non-standard dual antiplatelet therapy (DAPT) or a single antiplatelet agent, 18,046 patients were recruited for analysis. Ticagrelor- and clopidogrel-based DAPT were administered to 3666 patients and 14,380 patients, respectively. Baseline characteristics and clinical outcomes were compared between the two groups. A total of 4225 patients were defined as a high-bleeding-risk subgroup according to Academic Research Consortium for High Bleeding Risk (ARC-HBR) score (met one major or two minor criteria), of which 466 and 3759 patients received ticagrelor- and clopidogrel-based DAPT, respectively. Before propensity score matching (PSM), younger age, higher prevalence of male sex, and higher body mass index were noted in the ticagrelor-based DAPT group in the whole cohort and high-bleeding-risk subgroup. After PSM, no difference in baseline characteristics and comorbidities between ticagrelor-based and clopidogrel-based DAPT groups in the whole cohort and high-bleeding-risk subgroup was noted. The Kaplan-Meier curves of recurrent ACS and major bleeding were significantly lower in the ticagrelor-based DAPT group than in the clopidogrel-based DAPT group, and that of cardiovascular (CV) and all-cause mortality showed no significant differences. After PSM, in the high-bleeding-risk subgroup, the Kaplan-Meier curve of recurrent ACS was significantly lower in the ticagrelor-based DAPT group than in the clopidogrel-based DAPT group, and that of major bleeding, CV, and all-cause mortality showed no significant differences. In this large cohort study, patients receiving ticagrelor-based DAPT were at lower risk of recurrent ACS compared to those receiving clopidogrel-based DAPT, especially in the patients with myocardial infarction. Ticagrelor-based DAPT did not result in a higher risk of major bleeding in the whole ACS population and high-bleeding-risk subgroup. The rate of CV and all-cause mortality were similar between both the groups.

Association of ADP-Induced Whole-Blood Platelet Aggregation with Serum Low-Density Lipoprotein Cholesterol in Patients with Coronary Artery Disease When Receiving Maintenance Ticagrelor-Based Dual Antiplatelet Therapy.

The degree of platelet inhibition in patients undergoing dual antiplatelet therapy (DAPT) affects cardiovascular outcomes after acute coronary syndromes (ACS) and/or percutaneous coronary intervention. Our aim was to search for correlates of residual ex vivo platelet reactivity and circulating soluble P-selectin (sP-selectin), an index of in vivo platelet activation, in patients being treated by DAPT with ticagrelor. Adenosine diphosphate (ADP)-induced platelet aggregability (by multiple electrode aggregometry) and plasma sP-selectin were estimated in 62 stable post-ACS subjects (46 men and 16 women; mean age: 64 ± 10 years; 30 with type 2 diabetes (T2DM)) undergoing maintenance DAPT with ticagrelor and aspirin. These patients did not exhibit heart failure or other relevant coexistent diseases except for properly controlled T2DM, mild renal insufficiency, and hypertension. We also assessed this in 64 subjects on clopidogrel-based DAPT matched for age, sex, and T2DM status. ADP-induced platelet aggregation was below the optimal levels (190-460 arbitrary units (AU) * min) in most patients receiving ticagrelor-based DAPT, especially in those with below-median (<1.9 mmol/L) serum concentrations of low-density lipoprotein cholesterol (LDL-c) (128 ± 61 vs. 167 ± 73 AU * min for below-median and above-median LDL-c, respectively, p = 0.025). In contrast, platelet reactivity did not differ by LDL-c on clopidogrel-based DAPT (246 ± 101 vs. 268 ± 108 AU * min for below-median and above-median LDL-c, respectively, p > 0.4). Plasma sP-selectin was found to be unrelated to serum LDL-c when receiving DAPT with ticagrelor (p > 0.4) or clopidogrel (p > 0.8). In conclusion, our preliminary observational study suggests the association of lower residual ex vivo platelet aggregability with better LDL-c control in patients undergoing ticagrelor-based maintenance DAPT, which does not appear to be reflected by plasma sP-selectin. Whether the serum LDL-c level should be considered among the factors affecting the degree of platelet inhibition for those treated with ticagrelor-based DAPT needs to be investigated in larger studies.

Comparing dual antiplatelet therapy strategies post-acute coronary syndrome: network meta-analysis

Abstract Background Various approaches to dual antiplatelet therapy (DAPT) management exist to balance thrombotic and bleeding risks following acute coronary syndrome (ACS). Purpose The aim of this study was to compare and rank different DAPT management strategies in patients with ACS with or without percutaneous coronary interventions. Methods We conducted a systematic review with network meta-analysis of randomized controlled trials comparing DAPT strategies in patients with ACS using MEDLINE, Embase, and CENTRAL (2007-July 2021). The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included all-cause death and major bleeding. We performed Bayesian network meta-analyses to compare all interventions simultaneously using the Markov-chain Monte Carlo method, conducted under the assumption of transitivity. We generated odds ratios (ORs) with 95% credible intervals (CrI) from the medians and 2.5th and 97.5th percentiles of the posterior distributions using a hierarchical Bayesian framework, using a random-effects model with informative priors for between-study heterogeneity based on pharmacological interventions with semi-objective outcomes (MACE or bleeding) or death. To rank interventions for each outcome, we calculated the mean surface under the cumulative ranking (SUCRA) curve. Results From 5941 articles, we included 24 trials (89,620 patients). Both clopidogrel- and ticagrelor-based DAPT increased MACE compared with pharmacogenomics-guided P2Y12 inhibitor selection (odds ratio [OR] 1.37, 95% credible interval [CrI] 1.08–1.74 and 1.35, 1.05–1.79, respectively) and empiric P2Y12 inhibitor de-escalation (OR 1.53, 95%CrI 1.00–2.30 and 1.51, 1.00–2.27, respectively). Compared with short-duration DAPT, standard DAPT duration with all P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) and pharmacogenomics-guided P2Y12 inhibitor selection increased major bleeding. Ticagrelor-based DAPT increased major bleeding compared with platelet function testing-guided DAPT (OR 1.60, 95%CrI 1.00–2.55). Empiric P2Y12 inhibitor de-escalation ranked best for MACE (SUCRA 0.89), whereas short-duration DAPT ranked best for death (SUCRA 0.89) and major bleeding (SUCRA 0.93). Conclusions In patients with ACS, empiric P2Y12 inhibitor de-escalation was most efficacious whereas short-duration DAPT was the safest compared to other DAPT strategies. Funding Acknowledgement Type of funding sources: None.

Platelet P2Y12 inhibiting therapy in adjunct to vascular dose of rivaroxaban or aspirin: a pharmacodynamic study of dual pathway inhibition vs. dual antiplatelet therapy.

Dual pathway inhibition (DPI) by adding a vascular dose of rivaroxaban to a single antiplatelet agent has emerged as a promising antithrombotic strategy. However, in most studies the antiplatelet agent of choice used in adjunct to a vascular dose of rivaroxaban was aspirin, and data on a P2Y12 inhibitor and how this DPI regimen compares with standard dual antiplatelet therapy (DAPT) are limited. This investigation was a substudy analysis conducted in selected cohorts of patients with stable atherosclerotic disease enrolled from a larger prospective, open-label, parallel-group pharmacodynamic (PD) study. We analysed data from 40 patients treated with either clopidogrel- or ticagrelor-based DAPT first, and clopidogrel- or ticagrelor-based DPI thereafter. PD measures explored key pathways involved in thrombus formation and included markers of (1) P2Y12 reactivity, (2) platelet-mediated global thrombogenicity, (3) cyclooxygenase-1 activity, (4) thrombin receptor-activating peptide (TRAP)-induced platelet aggregation, (5) tissue factor (TF)-induced platelet aggregation, and (6) thrombin generation. Compared with DAPT, on a background of the same P2Y12 inhibitor (clopidogrel or ticagrelor), DPI was associated with reduced thrombin generation, increased markers of cyclooxygenase-1 activity and TRAP-induced platelet aggregation, and no differences in markers of P2Y12 signalling, platelet-mediated global thrombogenicity, and TF-induced platelet aggregation. In an analysis according to P2Y12 inhibitor type, ticagrelor reduced markers of platelet-mediated global thrombogenicity, P2Y12 signalling, and rates of high platelet reactivity compared with clopidogrel. Compared with DAPT with aspirin and a P2Y12 inhibitor, the use of a P2Y12 inhibitor in adjunct to a vascular dose of rivaroxaban as part of a DPI strategy is associated with similar effects on platelet-mediated global thrombogenicity but reduced thrombin generation. A DPI strategy with ticagrelor is associated with enhanced antithrombotic efficacy, the clinical implications of which warrant larger scale investigations. ClinicalTrials.gov identifier: NCT03718429.

Ticagrelor vs. Clopidogrel in Acute Coronary Syndrome Patients With Chronic Kidney Disease After New-Generation Drug-Eluting Stent Implantation.

Background: The impact of ticagrelor-based dual antiplatelet therapy (DAPT) on acute coronary syndrome (ACS) in patients with chronic kidney disease (CKD) remains unclear.Methods: Data on a total of 1,067 ACS patients with CKD including end-stage renal disease (ESRD) who underwent new-generation drug-eluting stent implantation were extracted from a multicenter registry. This study aimed to compare outcomes of patients treated with ticagrelor- (n = 449) and those treated with clopidogrel-based (n = 618) DAPT. Outcomes of interest included major adverse cardiac and cerebrovascular events (MACCEs) and bleeding (Bleeding Academic Research Consortium grade 3 or 5) at 12 months. Propensity-score matching (346 pairs) analysis was performed.Results: The patients with ESRD showed the highest MACCE and bleeding rates (P < 0.001). There was no difference in the rate of MACCEs between the treatment groups (7.8% vs. 8.4%; hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.56–1.61, P = 0.855); however, a trend toward an increased bleeding rate was observed in the ticagrelor-based DAPT group (6.8% vs. 3.8%, HR = 1.84, 95% CI = 0.93–3.63, P = 0.079). Among patients with CKD stage III/IV but without ESRD (277 pairs), the ticagrelor-based DAPT group showed a reduced MACCE rate (3.6% vs. 8.7%, HR = 0.41, 95% CI = 0.19–0.86, P = 0.018) and a similar bleeding rate (5.1% vs. 3.2%, HR = 1.61, 95% CI = 0.70–3.71, P = 0.267), compared with those of the clopidogrel-based DAPT group.Conclusion: The effects of ticagrelor-based DAPT on ischemic and bleeding outcomes of ACS patients with CKD varied according to CKD stage; in ACS patients with CKD without ESRD, ticagrelor-based DAPT reduced MACCE risk without increasing bleeding risks, relative to those observed with clopidogrel-based DAPT.

745 Meta-analysis comparing the safety and efficacy of ticagrelor monotherapy after a short course of ticagrelor-based dual antiplatelet therapy versus standard therapy in complex percutaneous coronary interventions

Abstract Aims Current guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor for 6–12 months after percutaneous coronary intervention (PCI). A shorter duration ticagrelor-based DAPT followed by ticagrelor monotherapy can significantly reduce bleeding events while preserving anti-ischaemic effects in patients undergoing conventional PCI. Whether this strategy can be safely and effectively applied to those patient that undergo ‘complex’ PCI is uncertain. Methods We performed a systematic search of randomized controlled trials comparing a short course of ticagrelor-based DAPT vs. standard DAPT in patients undergoing complex PCI. A mixed-effects Poisson regression model with random intervention effects was used to estimate the pooled incidence rate ratios (IRR) with 95% confidence intervals (CI). Results Out of 10 689 studies screened, three were identified for a total of 4176 participants on ticagrelor monotherapy after a short course of ticagrelor based DAPT, and 4209 on standard DAPT. Overall, the pooled analysis showed a strong evidence that compared to standard treatment, ticagrelor monotherapy after a short course of ticagrelor-based DAPT (1–3 months) reduced the risk of cardiovascular death [IRR 0.52; CI (0.28–0.96); P = 0.04; I2 = 0%], all-cause death [IRR 0.65; CI (0.49–0.86); P = 0.003; I2 = 0%], and any bleeding events [IRR 0.62; CI (0.47–0.81); P &amp;lt; 0.001; I2 = 44%]. Weak evidence was found of an association between the experimental strategy and a lower risk of myocardial infarction [IRR 0.79; CI (0.61–1.01); P = 0.06; I2 = 0%]. Instead, no significant difference in the risk of major bleeding [IRR 0.72; CI (0.48–1.08); P = 0.11; I2 = 61%], definite or probable stent thrombosis [IRR 0.77; CI (0.34–1.75); P = 0.53; I2 = 0%] and ischaemic stroke [IRR 0.83; CI (0.25–2.73); P = 0.76; I2 = 0%] was observed. We speculate that the observed mortality benefits might be related to the reduction of any bleeding events, mainly dictated by minor bleeding reduction, since major bleeding did not seem to be decreased in the shorter regimen group. Conclusion Among patients undergoing complex PCI, ticagrelor monotherapy after a short course of ticagrelor-based DAPT significantly reduced bleeding risk without increasing ischaemic risk. As complex PCI procedures are being increasingly performed nowadays, and more comorbid patients are being treated, more studies are required to confirm and explain these findings. This could lead to optimization of antiplatelet therapy across a broad spectrum of patients.

Walking the Line with Ticagrelor: Meta-Analysis Comparing the Safety and Efficacy of Ticagrelor Monotherapy after a Short Course of Ticagrelor-Based Dual Antiplatelet Therapy versus Standard Therapy in Complex Percutaneous Coronary Intervention.

(1) Shorter-duration dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy has been shown to significantly reduce bleeding events while preserving anti-ischemic effects in patients undergoing conventional percutaneous coronary interventions (PCI). Whether this strategy is also safe and effective in complex PCI remains elusive; (2) A systematic search of randomized controlled trials comparing a short course of ticagrelor-based DAPT versus standard DAPT in patients undergoing complex PCI was performed; (3) Of 10,689 studies screened, 3 were identified for a total of 4176 participants on ticagrelor monotherapy after a short course of ticagrelor-based DAPT, and 4209 on standard DAPT. The pooled analysis revealed no difference in the outcomes of major bleeding, myocardial infarction, definite or probable stent thrombosis and ischemic stroke. A significant reduction in the risk of cardiovascular death (incidence rate ratio (IRR) 0.52; 95% CI 0.28–0.96; p = 0.04), all-cause death (IRR 0.65; 95% CI 0.49–0.86; p = 0.003), and any bleeding events (IRR 0.62; 95% CI 0.47–0.81; p < 0.001) was seen in the shorter DAPT group; (4) Among patients undergoing complex PCI, ticagrelor monotherapy after a short course of ticagrelor-based DAPT significantly reduced bleeding risk without increasing ischemic risk. More data are needed to definitively explain mortality benefits.

Abstract 15223: Comparison of Net Clinical Benefit Between Clopidogrel-based and Ticagrelor-based Dual Antiplatelet Therapy in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention in China

Introduction: Dual antiplatelet therapy (DAPT) increases the bleeding risk, which might outweigh the benefits of reduction in ischemic events in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI). This study aimed to evaluate the difference in net clinical benefits of clopidogrel-based DAPT compared with ticagrelor-based DAPT in ACS patients undergoing PCI in a real-world setting in China. Method: This study was conducted on three pre-existing PCI patient databases, two were from nation-wide studies with similar prospective designs and time-span: the BRIC-ACS(I) study and the COSTIC study, and other was from a tertiary hospital-maintained PCI patient database. The primary endpoint was net adverse clinical and cerebral event (NACCE), which was a composite of all-cause death, non-fatal myocardial infarction (MI), non-fatal stroke and BARC ≥ 2 (excluding BARC 4) bleeding within 12 months after discharge. The efficacy outcome, major adverse cardiovascular events (MACE), was defined as a composite of all-cause death, non-fatal MI, and non-fatal stroke. The safety outcome was defined as BARC ≥ 2 (excluding BARC 4) bleeding. Kaplan-Meier survival curves, and Cox regression were applied to analyze the difference between the two groups after propensity score matching (PSM). Results: A total of 7,236 adult ACS patients who underwent PCI in the period of Jan 2014 to Oct 2017 were analyzed. Of them, 4,330 patients were included in post-PSM analyses. Patients prescribed clopidogrel and aspirin had a significant lower risk of NACCE within 12 months after discharge relative to those prescribed ticagrelor and aspirin [5.4% vs. 8.3%, hazard ratio (HR) = 0.63, 95% CI: 0.50 - 0.80]. While the two groups did not vary significantly in the risk of MACE (2.9% vs. 3.1%, HR = 0.91, 95% CI: 0.64 - 1.28), clopidogrel-based DAPT was associated with a significant lower risk of BARC ≥ 2 (excluding BARC 4) bleeding (2.9% vs. 5.5%, HR = 0.50, 95% CI: 0.37 - 0.68) compared to ticagrelor-based DAPT. Conclusion: In this real-world study, post-PCI ACS patients prescribed clopidogrel-based DAPT were associated with a reduction in NACCE and bleeding events without significant difference in MACE, compared to patients treated with ticagrelor-based DAPT.

Management of Acute Coronary Syndromes Beyond the First Year: A Canadian Clinical Practice Survey

BackgroundAntithrombotic management following acute coronary syndromes (ACSs) has evolved significantly. However, given lingering uncertainty as to when an ACS may be considered stable, there is the possibility of practice divergence beyond the first year. MethodsAn online adaptive survey describing patients with varying cardiac and extracardiac ischemic risk was developed in order to asses self-reported physician practice intentions pertaining to the antithrombotic management of ACS patients who lack a formal indication for therapeutic anticoagulation. Provincial “champions” (Prince Edward Island not represented) were identified to ensure dissemination of the survey within their jurisdictions via 3 coordinated e-mailings; the survey was made available in French and English from November 2018 through January 2019. ResultsA total of 135 practitioners responded to the survey (response rate 15%). Surveys were fully completed in all cases. Nearly all respondents (97%) were cardiologists; 76% worked at an academic center, and 54% had been in practice ≥ 10 years. Most respondents (81%-90%, depending on the scenario) preferred ticagrelor-based dual antiplatelet therapy as the initial ACS treatment. However, beyond 12 months, management decisions differed significantly according to the balance of cardiac and extracardiac risk. ConclusionsThis study provides a first look at how the introduction of rivaroxaban 2.5 mg might be integrated into the clinical management of ACS patients beyond the first year in Canada. Whether to pursue dual antiplatelet therapy or transition early to low-dose rivaroxaban plus acetylsalicylic acid will likely be driven by patient clinical characteristics and perceived cardiac vs extra-cardiac ischemic risk.

No Differences in Gastrointestinal Bleeding Risk among Clopidogrel-, Ticagrelor-, or Prasugrel-Based Dual Antiplatelet Therapy.

The risk for gastrointestinal bleeding from dual antiplatelet therapy (DAPT) with new antiplatelets (prasugrel/ticagrelor) compared to clopidogrel is unclear. Aim: To determine the risk and type of major (gastrointestinal bleeding requiring hospitalization) and minor (anemia and iron deficiency) gastrointestinal events with different types of DAPT. Methods: Retrospective observational cohort study of patients who started DAPT after percutaneous coronary intervention. Follow-up was censored after 12 months of DAPT, when a major gastrointestinal event occurred, or when DAPT was discontinued. Results: Among 1,327 patients (54.03% were treated with clopidogrel-based DAPT, 38.13% with ticagrelor-based DAPT, and 7.84% with prasugrel-based DAPT), 29.5% had at least one gastrointestinal event. Patients taking clopidogrel-DAPT were older, with more comorbidities, and higher gastrointestinal risk compared to those taking other DAPT regimens. Adjusted hazard ratios (HRs) showed no between-group differences in the risk for major (clopidogrel vs. new antiplatelets: HR 0.996; 95% confidence interval 0.497–1.996) and minor (HR 0.920; 0.712–1.189) gastrointestinal events. Most patients received proton pump inhibitors while on DAPT (93.3%) and after withdrawal (83.2%). Conclusion: Prasugrel- or ticagrelor-based DAPT was not associated with increased gastrointestinal bleeding risk when compared to clopidogrel-DAPT. New antiplatelets do not necessarily need to be restricted to patients with low gastrointestinal risk.

A Meta-Analysis Comparing Aspirin Alone Versus Dual Antiplatelet Therapy for the Prevention of Venous Graft Failure Following Coronary Artery Bypass Surgery

BackgroundAspirin (ASA) monotherapy is the current standard of care after coronary artery bypass grafting (CABG) to prevent saphenous vein graft (SVG) failure. Several small, randomized clinical trials (RCTs) have suggested that dual antiplatelet therapy (DAPT) may be more effective at preventing SVG failure than ASA alone; however, it is unclear whether some P2Y12 inhibitors are more effective than others for the prevention of SVG failure. MethodsScientific databases and websites were searched to find RCTs. Both traditional pairwise meta-analysis using random-effect model and network meta-analysis using mixed-treatment comparison models were performed to compare the efficacy of various anti-platelet strategies for the prevention of SVG failure. ResultsNine RCTs, which included a total of 1677 patients, were analyzed. Compared to ASA alone, DAPT decreased the risk of graft failure by 37% (RR: 0.63, 95% CI: 0.47–0.86; p = 0.003). In the moderator analysis, the decreased risk of graft failure with DAPT was not significantly different in the ASA + clopidogrel group than in the ASA + ticagrelor group (P-interaction = 0.17). The results of the network meta-analysis were consistent with those from pairwise analyses. The risk of major bleeding was not statistically significantly different between DAPT and ASA alone (RR: 1.35, 95% CI: 0.62–2.94; p = 0.45). ConclusionIn post-CABG patients, DAPT seems to be more effective at preventing graft failure than ASA alone. This strategy does not seem to significantly increase major bleeding risk. Clopidogrel- and ticagrelor-based DAPT seem to be equally effective for this indication.

COST-EFFECTIVENESS OF SHORTER DURATIONS OF TICAGRELOR-BASED DUAL ANTIPLATELET THERAPY FOLLOWING MYOCARDIAL INFARCTION

Real-world persistence with ticagrelor-based dual antiplatelet therapy (DAPT) following an acute coronary syndrome is lower that of other P2Y12-receptor inhibitors. However, it is not known whether higher than expected rates of patient discontinuation of ticagrelor-DAPT warrants specific intervention. We therefore developed a cost-effectiveness decision analytic model to gauge the clinical impact of shorter durations of ticagrelor-DAPT. Decision trees were created to compare 3, 6, 9, and 12 months of ticagrelor-DAPT to a 12-month regimen of generic clopidogrel-DAPT for patients with myocardial infarction. Clinical outcome probabilities at three-month intervals were generated by estimating the lifetables from relevant landmark clinical trials (PLATO and CURE) and using Dirichlet probability distributions for multiple outcomes. Following ticagrelor discontinuation, patients were assumed to persist with aspirin monotherapy. Clinical outcomes considered in the model included cardiovascular death, myocardial infarction, and major bleeding. Stroke outcomes were not considered as there was no difference in this outcome in the trials. Cost data were derived from a combination of the medical literature and the Régie de l’Assurance-Maladie du Québec medication formulary and is expressed in 2018 Canadian dollars ($CAN). Quality of life weights were derived from the literature. We present our initial analysis of cost-effectiveness at one year (TABLE). Using a willingness-to-pay threshold of $50,000 per quality-adjusted life year (QALY), three months of ticagrelor-DAPT was cost-effective compared to 12 months of clopidogrel-DAPT at one year ($43,496/QALY), 57% probability of cost-effectiveness). Longer regimens of ticagrelor-DAPT were not cost-effective at one year, but are anticipated to be more attractive over a lifetime time horizon. Both cost and effectiveness projections are in line with prior cost-effectiveness models of ticagrelor-DAPT for acute coronary syndromes. Sensitivity analyses showed that the cost-effectiveness of ticagrelor-DAPT was sensitive to both the financial and quality of life costs of major bleeding and myocardial infarction. This analysis shows that even just 3 months of ticagrelor-DAPT is likely to be cost-effective compared to 12 months of clopidogrel-DAPT. As such, we conclude that clinicians should continue to preferentially prescribe ticagrelor-DAPT in appropriate patients and that no specific intervention is warranted at a provincial policy level to improve persistence rates with ticagrelor therapy following myocardial infarction.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Randomized evaluation of ticagrelor monotherapy after 3-month dual-antiplatelet therapy in patients with acute coronary syndrome treated with new-generation sirolimus-eluting stents: TICO trial rationale and design

BackgroundTicagrelor monotherapy after short-term dual-antiplatelet therapy (DAPT) may optimize ischemic and bleeding risks, particularly for acute coronary syndrome (ACS) patients, because its strategy is less potent than ticagrelor-based DAPT but more potent than aspirin or clopidogrel monotherapy. MethodsThe TICO randomized open-label trial will evaluate whether ticagrelor monotherapy following 3-month DAPT is superior to 12-month ticagrelor-based DAPT in terms of net adverse clinical events (NACE) including efficacy and safety in ACS patients treated with ultrathin bioresorbable polymer sirolimus-eluting stents (BP-SES). Patients undergoing BP-SES implantation for ACS treatment will be randomized in a 1:1 fashion to the (1) ticagrelor monotherapy group after 3-month DAPT; or the (2) 12-month DAPT group. The primary endpoint is NACE within 12 months of percutaneous coronary intervention, which includes major adverse cardiac and cerebrovascular events (MACCE) plus major bleeding as defined by Thrombolysis in Myocardial Infarction. MACCE includes the composite of all-cause death, myocardial infarction, stent thrombosis, stroke, and target vessel revascularization. Secondary endpoints included each component of the primary endpoint. ConclusionsThe TICO trial is an ongoing trial evaluating the efficacy and safety of ticagrelor monotherapy following 3-month DAPT exclusively in ACS patients treated with uniform BP-SES. It may provide novel insights regarding the need for adjusted use of DAPT for rebalancing risk–benefit in current practice and changing from the conventional concept of aspirin maintenance to a ticagrelor-based regimen in the management of ACS.

Comparison of Systematic Ticagrelor-Based Dual Antiplatelet Therapy to Selective Triple Antithrombotic Therapy for Left Ventricle Dysfunction Following Anterior STEMI

Antithrombotic management of STEMI patients with apical dysfunction, but without demonstrable thrombus, is controversial. Triple antithrombotic therapy (TATT, defined as the addition of oral anticoagulation to dual antiplatelet therapy, or DAPT) may be associated with increased bleeding, while DAPT alone may not adequately protect against cardio-embolic events. We undertook a dual-center study of anterior STEMI patients treated with primary PCI (pPCI) from 2013 to 2015 and presenting presumed new apical dysfunction. The Centre hospitalier de l’Université de Montréal (CHUM) uses a strategy of selective TATT, whereas the Centre hospitalier universitaire de Sherbrooke (CHUS) has favored ticagrelor-based DAPT for all patients since 2013. The primary composite outcome consisted of death, MI, stroke, revascularization, and BARC 3 to 5 bleeding up to 4-months follow-up. We identified 177 cases (69 CHUM; 108 CHUS). Baseline characteristics were similar and procedural success was high (97%). There was no difference in post-procedure LVEF (39 ± 9% vs 37 ± 9%) or the extent of apical dysfunction. The primary composite outcome occurred in 27% with the selective TATT strategy compared to 19% with ticagrelor-DAPT (p = 0.342). Thus, this retrospective dual-center analysis does not support a strategy of conventional TATT over ticagrelor-based DAPT for patients with apical dysfunction following anterior STEMI treated with pPCI. A pragmatic randomized trial is needed to provide a definitive answer to this clinical conundrum.