Dataset Information

'Ticagrelor alone vs. dual antiplatelet therapy from 1 month after drug-eluting coronary stenting among patients with STEMI': a post hoc analysis of the randomized GLOBAL LEADERS trial.

ABSTRACT:

Aim

To evaluate the efficacy and safety of ticagrelor monotherapy beyond 1 month and up to 24 months vs. standard 12-month dual antiplatelet therapy (DAPT) with aspirin and ticagrelor followed by aspirin monotherapy among ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI) in the GLOBAL LEADERS trial.

Methods and results

We performed a post hoc analysis of STEMI patients in the GLOBAL LEADERS trial comparing experimental ticagrelor monotherapy (1062 patients) with standard 12-month DAPT (1030 patients). We evaluated predefined primary and secondary endpoints in both treatment arms. Rates of net adverse clinical events (NACE), patient-oriented composite endpoints (POCE), and bleeding academic research consortium (BARC)-defined bleeding Type 3 or 5 were also evaluated. At 2 years, there were no significant differences in rates of primary endpoints in patients who had STEMI [0.89 (0.61-1.31)]. There were similar rates of NACE and POCE in both experimental and reference treatment groups at 2 years post-PCI [hazard ratio (HR) 0.96 (0.77-1.20) and 0.96 (0.77-1.21), respectively]. BARC 3 or 5 bleeding events were numerically less in experimental compared to reference treatment groups at 1 year [HR 0.55 (0.27-1.13)] and 2 years [0.61 (0.32-1.16)].

Conclusion

Presentation with STEMI has not influenced the incidence of GLOBAL LEADERS defined primary endpoints. There were no significant differences in rates of NACE, POCE, and BARC bleeding between the two treatment groups up to 2 years of follow-up. Although these findings should be viewed as exploratory, they expand the evidence on potential safety of aspirin-free antiplatelet strategies after PCI in STEMI.

SUBMITTER: Gamal AS

PROVIDER: S-EPMC8483765 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceA significant number of patients receive bare-metal stents (BMSs) instead of drug-eluting stents (DESs) to shorten the duration of dual antiplatelet therapy (DAPT). Emerging evidence suggests that new-generation DESs, particularly those optimized for biocompatibility, may be more efficacious and safer than BMSs, even with a single month of DAPT after stent implantation.ObjectiveTo evaluate the efficacy and safety of DESs compared with BMSs for coronary intervention with a single month of DAPT.Data sourcesHuman studies found in PubMed, the Cochrane databases through April 2018, and reference lists of selected articles.Study selectionRandomized clinical trials were included if they enrolled patients undergoing percutaneous coronary intervention and randomly assigned each patient to treatment with either DESs or BMSs. The additional inclusion criterion was use of only 1 month of DAPT poststent implantation.Data extraction and synthesisTwo reviewers independently extracted the data. Odds ratios (ORs) were calculated using random-effects models.Main outcomes and measuresThe efficacy end points were major adverse cardiac events, myocardial infarction, target vessel revascularization, ischemia-driven target lesion revascularization, cardiac mortality, and all-cause mortality at 1 year. The safety outcomes were stent thrombosis and bleeding complications.ResultsData from 3 randomized clinical trials involving 3943 patients were included (2457 men [62.3%]; mean [SD] age ranging from 75.7 [9.3] years to 81.4 [4.3] years per trial subgroup). Coronary intervention with DESs reduced the rates for major adverse cardiac events (OR, 0.68 [95% CI, 0.57-0.82]; P < .001), target lesion revascularization (OR, 0.38 [95% CI, 0.22-0.67]; P = .001), target vessel revascularization (OR, 0.50 [95% CI, 0.38-0.65]; P < .001), and myocardial infarction (OR, 0.51 [95% CI, 0.31-0.83]; P = .01) compared with BMSs at 1 year. The incidence of stent thrombosis was also lower with DESs compared with BMSs (1.8% vs 2.8%), but this difference was not statistically significant in the random-effects model. Additionally, the 2 stent types did not differ in the risks of all-cause mortality, cardiac mortality, and bleeding.Conclusions and relevanceIn the limited number of randomized clinical trials comparing DESs with BMSs with shortened DAPT durations in patients who have high bleeding risk or are uncertain candidates for prolonged DAPT, coronary intervention with specific DESs optimized for biocompatibility is not only safe but also efficacious, even with only 1 month of DAPT.

Project description:BACKGROUND:Patients with both diabetes mellitus (DM) and chronic kidney disease (CKD) are a subpopulation characterized by ultrahigh ischemic and bleeding risk after percutaneous coronary intervention. There are limited data on the impact of ticagrelor monotherapy among these patients. METHODS:In this post hoc analysis of the GLOBAL-LEADERS trial, the treatment effects of the experimental (one-month dual-antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus the reference regimen (12-month DAPT followed by 12-month aspirin alone) were analyzed according to DM/CKD status. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at 2-years. The patient-oriented composite endpoint (POCE) was defined as the composite of all-cause death, any stroke, site-reported MI and any revascularization, whereas net adverse clinical events (NACE) combined POCE with BARC type 3 or 5 bleeding events. RESULTS:At 2 years, the DM?+?/CKD?+?patients had significantly higher incidences of the primary endpoint (9.5% versus 3.1%, adjusted HR 2.16; 95% CI [1.66-2.80], p?<?0.001), BARC type 3 or 5 bleeding events, stroke, site-reported myocardial infraction, all revascularization, POCE, and NACE, compared with the DM-/CKD- patients. Among the DM?+?/CKD?+?patients, after adjustment, there were no significant differences in the primary endpoints between the experimental and reference regimen; however, the experimental regimen was associated with lower rates of POCE (20.6% versus 25.9%, HR 0.74; 95% CI [0.55-0.99], p?=?0.043, pinteraction?=?0.155) and NACE (22.7% versus 28.3%, HR 0.75; 95% CI [0.56-0.99], p?=?0.044, pinteraction?=?0.310), which was mainly driven by a lower rate of all revascularization, as compared with the reference regimen. The landmark analysis showed that while the experimental and reference regimen had similar rates of all the clinical endpoints during the first year, the experimental regimen was associated with significantly lower rates of POCE (5.8% versus 11.0%, HR 0.49; 95% CI [0.29-0.82], p?=?0.007, pinteraction?=?0.040) and NACE (5.8% versus 11.2%, HR 0.48; 95% CI [0.29-0.82], p?=?0.007, pinteraction?=?0.013) in the second year. CONCLUSION:Among patients with both DM and CKD, ticagrelor monotherapy was not associated with lower rates of all-cause death or new Q-wave, or major bleeding complications; however, it was associated with lower rates of POCE and NACE. These findings should be interpreted as hypothesis-generating. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov (NCT01813435).

Project description:Importance:The role of aspirin as part of antiplatelet regimens in acute coronary syndromes (ACS) needs to be clarified in the context of newer potent P2Y12 antagonists. Objective:To evaluate the benefit and risks of aspirin in addition to ticagrelor among patients with ACS beyond 1 month after percutaneous coronary intervention (PCI). Design, Setting, and Participants:This is a nonprespecified, post hoc analysis of GLOBAL LEADERS, a randomized, open-label superiority trial comparing 2 antiplatelet treatment strategies after PCI. The trial included 130 secondary/tertiary care hospitals in different countries, with 15?991 unselected patients with stable coronary artery disease or ACS undergoing PCI. Patients had outpatient visits at 1, 3, 6, 12, 18, and 24 months after index procedure. Interventions:The experimental group received aspirin plus ticagrelor for 1 month followed by 23-month ticagrelor monotherapy; the reference group received aspirin plus either clopidogrel (stable coronary artery disease) or ticagrelor (ACS) for 12 months, followed by 12-month aspirin monotherapy. In this analysis, we examined the clinical outcomes occurring between 31 days and 365 days after randomization, specifically in patients with ACS who, within this time frame, were assigned to receive either ticagrelor alone or ticagrelor and aspirin. Main Outcomes and Measures:The primary outcome was the composite of all-cause death or new Q-wave myocardial infarction. Results:Of 15?968 participants, there were 7487 patients with ACS enrolled; 3750 patients were assigned to the experimental group and 3737 patients to the reference group. Between 31 and 365 days after randomization, the primary outcome occurred in 55 patients (1.5%) in the experimental group and in 75 patients (2.0%) in the reference group (hazard ratio [HR], 0.73; 95% CI, 0.51-1.03; P?=?.07); investigator-reported Bleeding Academic Research Consortium-defined bleeding type 3 or 5 occurred in 28 patients (0.8%) in the experimental group and in 54 patients (1.5%) in the reference arm (HR, 0.52; 95% CI, 0.33-0.81; P?=?.004). Conclusions and Relevance:Between 1 month and 12 months after PCI in ACS, aspirin was associated with increased bleeding risk and appeared not to add to the benefit of ticagrelor on ischemic events. These findings should be interpreted as exploratory and hypothesis generating; however, they pave the way for further trials evaluating aspirin-free antiplatelet strategies after PCI. Trial Registration:ClinicalTrials.gov identifier: NCT01813435.

Dataset Information

'Ticagrelor alone vs. dual antiplatelet therapy from 1 month after drug-eluting coronary stenting among patients with STEMI': a post hoc analysis of the randomized GLOBAL LEADERS trial.

Aim

Methods and results

Conclusion

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