Explore the vast range of titles available.

In this placebo-controlled trial, 7119 patients were randomly assigned at 3 months after PCI to either receive ticagrelor alone or continue dual therapy with ticagrelor plus aspirin. The trial evaluated bleeding and ischemic end points at 1 year.

A randomized trial involving patients with acute coronary syndromes showed that prasugrel was superior to ticagrelor with regard to the incidence of death, myocardial infarction, or stroke within 1 year, with no increased risk of bleeding.

In a trial in China, patients with a minor stroke or transient ischemic attack with CYP2C19 loss-of-function alleles as determined by point-of-care testing had modestly fewer second strokes with ticagrelor than with clopidogrel but also had more total bleeding events.

A trial involving 11,016 patients showed that the combination of ticagrelor and aspirin after a stroke or high-risk transient ischemic attack was better than aspirin alone in preventing a stroke or death within 30 days. Severe bleeding was rare but occurred more frequently in the dual antiplatelet group.

In patients with acute myocardial infarction receiving potent antiplatelet therapy, the bleeding risk remains high during the maintenance phase. We sought data on a uniform unguided de-escalation strategy of dual antiplatelet therapy (DAPT) from ticagrelor to clopidogrel after acute myocardial infarction. In this open-label, assessor-masked, multicentre, non-inferiority, randomised trial (TALOS-AMI), patients at 32 institutes in South Korea with acute myocardial infarction receiving aspirin and ticagrelor without major ischaemic or bleeding events during the first month after index percutaneous coronary intervention (PCI) were randomly assigned in a 1:1 ratio to a de-escalation (clopidogrel plus aspirin) or active control (ticagrelor plus aspirin) group. Unguided de-escalation without a loading dose of clopidogrel was adopted when switching from ticagrelor to clopidogrel. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or bleeding type 2, 3, or 5 according to Bleeding Academic Research Consortium (BARC) criteria from 1 to 12 months. A non-inferiority test was done to assess the safety and efficacy of de-escalation DAPT compared with standard treatment. The hazard ratio (HR) for de-escalation versus active control group in a stratified Cox proportional hazards model was assessed for non-inferiority by means of an HR margin of 1·34, which equates to an absolute difference of 3·0% in the intention-to-treat population and, if significant, a superiority test was done subsequently. To ensure statistical robustness, additional analyses were also done in the per-protocol population. This trial is registered at ClinicalTrials.gov, NCT02018055. From Feb 26, 2014, to Dec 31, 2018, from 2901 patients screened, 2697 patients were randomly assigned: 1349 patients to de-escalation and 1348 to active control groups. At 12 months, the primary endpoints occurred in 59 (4·6%) in the de-escalation group and 104 (8·2%) patients in the active control group (pnon-inferiority<0·001; HR 0·55 [95% CI 0·40–0·76], psuperiority=0·0001). There was no significant difference in composite of cardiovascular death, myocardial infarction, or stroke between de-escalation (2·1%) and the active control group (3·1%; HR 0·69; 95% CI 0·42–1·14, p=0·15). Composite of BARC 2, 3, or 5 bleeding occurred less frequently in the de-escalation group (3·0% vs 5·6%, HR 0·52; 95% CI 0·35–0·77, p=0·0012). In stabilised patients with acute myocardial infarction after index PCI, a uniform unguided de-escalation strategy significantly reduced the risk of net clinical events up to 12 months, mainly by reducing the bleeding events. ChongKunDang Pharm, Medtronic, Abbott, and Boston Scientific.

Current guidelines recommend potent platelet inhibition with ticagrelor or prasugrel in patients after an acute coronary syndrome. However, data about optimal platelet inhibition in older patients are scarce. We aimed to investigate the safety and efficacy of clopidogrel compared with ticagrelor or prasugrel in older patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). We did the open-label, randomised controlled POPular AGE trial in 12 sites (ten hospitals and two university hospitals) in the Netherlands. Patients aged 70 years or older with NSTE-ACS were enrolled and randomly assigned in a 1:1 ratio using an internet-based randomisation procedure with block sizes of six to receive a loading dose of clopidogrel 300 mg or 600 mg, or ticagrelor 180 mg or prasugrel 60 mg, and then a maintenance dose for the duration of 12 months (clopidogrel 75 mg once daily, ticagrelor 90 mg twice daily, or prasugrel 10 mg once daily) on top of standard care. Patient and treating physicians were aware of the allocated treatment strategy, but the outcome assessors were masked to treatment allocation. Primary bleeding outcome consisted of PLATelet inhibition and patient Outcomes (PLATO; major or minor bleeding [superiority hypothesis]). Co-primary net clinical benefit outcome consisted of all-cause death, myocardial infarction, stroke, PLATO major and minor bleeding (non-inferiority hypothesis, margin of 2%). Follow-up duration was 12 months. Analyses were done on intention-to-treat basis. This trial is registered with the Netherlands Trial Register (NL3804), ClinicalTrials.gov (NCT02317198), and EudraCT (2013–001403–37). Between June 10, 2013, and Oct 17, 2018, 1002 patients were randomly assigned to clopidogrel (n=500) or ticagrelor or prasugrel (n=502). Because 475 (95%) patients received ticagrelor in the ticagrelor or prasugrel group, we will refer to this group as the ticagrelor group. Premature discontinuation of the study drug occurred in 238 (47%) of 502 ticagrelor group patients randomly assigned to ticagrelor, and in 112 (22%) of 500 patients randomly assigned to clopidogrel. Primary bleeding outcome was significantly lower in the clopidogrel group (88 [18%] of 500 patients) than in the ticagrelor group (118 [24%] of 502; hazard ratio 0·71, 95% CI 0·54 to 0·94; p=0·02 for superiority). Co-primary net clinical benefit outcome was non-inferior for the use of clopidogrel (139 [28%]) versus ticagrelor (161 [32%]; absolute risk difference −4%, 95% CI −10·0 to 1·4; p=0·03 for non-inferiority). The most important reasons for discontinuation were occurrence of bleeding (n=38), dyspnoea (n=40), and the need for treatment with oral anticoagulation (n=35). In patients aged 70 years or older presenting with NSTE-ACS, clopidogrel is a favourable alternative to ticagrelor, because it leads to fewer bleeding events without an increase in the combined endpoint of all-cause death, myocardial infarction, stroke, and bleeding. Clopidogrel could be an alternative P2Y12 inhibitor especially for elderly patients with a higher bleeding risk. ZonMw.

Patients with stable coronary artery disease and diabetes were randomly assigned to receive either ticagrelor plus aspirin or placebo plus aspirin. At 40 months, the incidence of the composite efficacy outcome of cardiovascular death, myocardial infarction, or stroke was lower with ticagrelor than with placebo; the frequency of major bleeding was higher with ticagrelor.

Many studies evaluated the efficacy and safety of ticagrelor versus clopidogrel in patients with ischemic stroke; none of these trials included North African participants, and all of these trials comprised only participants who experienced transient ischemic attack (TIA) or minor stroke. We compared the efficacy and safety of ticagrelor versus clopidogrel in patients with first-ever noncardioembolic moderate or moderate-to-severe ischemic stroke. Our trial involved 900 first-ever noncardioembolic patients with acute ischemic stroke (AIS) who randomly received either loading and maintenance doses of ticagrelor or clopidogrel within the first 24 h of stroke onset. We involved 900 patients in the intention-to-treat analysis. A total of 39 (8.7%) patients in ticagrelor arm and 62 (13.8%) in clopidogrel arm experienced a new stroke [hazard ratio (HR) 0.46; 95% confidence interval (CI) 0.34-0.83; P value = 0.006]. A total of 57 (12.7%) patients in ticagrelor group and 80 (17.8%) patients in clopidogrel group experienced composite of new stroke, myocardial infarction (MI), or death due to vascular insults (HR 0.51; 95% CI 0.43-0.82; P value = 0.004). Participants who received ticagrelor experienced less frequent unfavorable outcomes. We found no significant variation between our study's two arms concerning the hemorrhagic and non-hemorrhagic complications. Patients with noncardioembolic moderate or moderate-to-severe ischemic stroke who received ticagrelor within the first 24 h after ischemic stroke had better clinical outcomes based on recurrent stroke rates and unfavorable modified Rankin Scale (mRS) rates compared with those who received clopidogrel. There were no significant variations between ticagrelor and clopidogrel regarding hemorrhagic and non-hemorrhagic complications. ClinicalTrials.gov identifier number NCT05553613.

AbstractObjectivesTo investigate whether a less intense antiplatelet regimen could be used for people receiving drug coated balloons.DesignMulticentre, randomised, open label, assessor blind, non-inferiority trial (REC-CAGEFREE II).Setting41 hospitals in China between 27 November 2021 and 21 January 2023.Participants1948 adults (18-80 years) with acute coronary syndrome who received treatment exclusively with paclitaxel-coated balloons according to the international drug coated balloon consensus.InterventionsParticipants were randomly assigned (1:1) to either the stepwise dual antiplatelet therapy (DAPT) de-escalation group (n=975) consisting of aspirin plus ticagrelor for one month, followed by five months of ticagrelor monotherapy, and then six months of aspirin monotherapy, or to the standard DAPT group (n=973) consisting of aspirin plus ticagrelor for 12 months.Main outcome measuresThe primary endpoint was net adverse clinical events (all cause death, stroke, myocardial infarction, revascularisation, and Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding) at 12 months in the intention-to-treat population. Non-inferiority was established if the upper limit of the one sided 95% confidence interval (CI) for the absolute risk difference was smaller than 3.2%.ResultsThe mean age of participants was 59.2 years, 74.9% were men, 30.5% had diabetes, and 20.6% were at high bleeding risk. 60.9% of treated lesions were in small vessels, and 17.8% were in-stent restenosis. The mean drug coated balloon diameter was 2.72 mm (standard deviation 0.49). At 12 months, the primary endpoint occurred in 87 (8.9%) participants in the stepwise de-escalation group and 84 (8.6%) in the standard group (difference 0.36%; upper boundary of the one sided 95% CI 2.47%; Pnon-inferiority=0.013). In the stepwise de-escalation versus standard groups, BARC type 3 or 5 bleeding occurred in four versus 16 participants (0.4% v 1.6%, difference −1.19% (95% CI −2.07% to −0.31%), P=0.008), and all cause death, stroke, myocardial infarction, and revascularisation occurred in 84 versus 74 participants (8.6% v 7.6%, difference 1.05% (95% CI −1.37% to 3.47%), P=0.396). Treated as having hierarchical clinical importance by the win ratio method, more wins were noted with the stepwise de-escalation group (14.4% wins) compared with the standard group (10.1% wins) for the predefined hierarchical composite endpoint of all cause death, stroke, myocardial infarction, BARC type 3 bleeding, revascularisation, and BARC type 2 bleeding (win ratio 1.43 (95% CI 1.12 to 1.83), P=0.004). Results from the per-protocol and the intention-to-treat analysis were similar.ConclusionsAmong participants with acute coronary syndrome who could be treated by drug coated balloons exclusively, a stepwise DAPT de-escalation was non-inferior to 12 month DAPT for net adverse clinical events.Trial registrationClinicaltrials.gov NCT04971356

In healthy volunteers, a monoclonal antibody fragment that binds ticagrelor and its active metabolite led to reversal of the antiplatelet effects of ticagrelor, with very few toxic effects. The presence of low titers of antibody to the active agent had no detectable effect on efficacy.