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Patients benefit from antiplatelet therapy after coronary-artery bypass grafting (CABG) for an acute coronary syndrome. Whether the addition of ticagrelor to aspirin, as compared with aspirin alone, further reduces the risk of adverse cardiovascular outcomes is unclear. In this open-label, registry-based, clinical trial conducted at 22 Nordic cardiothoracic surgery centers, we randomly assigned patients in a 1:1 ratio to receive either ticagrelor plus aspirin or aspirin alone for 1 year after CABG for an acute coronary syndrome. The primary outcome was a composite of death, myocardial infarction, stroke, or repeat revascularization, evaluated at 1 year. A key secondary outcome was net adverse clinical events, defined as a primary-outcome event or major bleeding. A total of 2201 patients were randomly assigned to receive ticagrelor plus aspirin (1104 patients) or aspirin alone (1097 patients). The mean age of the patients was 66 years, and 14.4% were women. A primary-outcome event occurred in 53 patients (4.8%) in the ticagrelor-plus-aspirin group and 50 (4.6%) in the aspirin-alone group (hazard ratio, 1.06; 95% confidence interval [CI], 0.72 to 1.56; P = 0.77). Net adverse clinical events occurred in 9.1% of patients in the ticagrelor-plus-aspirin group and 6.4% in the aspirin-alone group (hazard ratio, 1.45; 95% CI, 1.07 to 1.97). Major bleeding occurred in 4.9% of patients in the ticagrelor-plus-aspirin group and 2.0% in the aspirin-alone group (hazard ratio, 2.50; 95% CI, 1.52 to 4.11). Among patients who underwent CABG for an acute coronary syndrome, ticagrelor plus aspirin did not result in a lower incidence of death, myocardial infarction, stroke, or repeat coronary revascularization than aspirin alone at 1 year. (Funded by the Swedish Research Council and others; TACSI ClinicalTrials.gov number, NCT03560310; EudraCT number, 2017-001499-43; EU Clinical Trials number, 2023-508551-40-00.).

In patients with an acute coronary syndrome, stopping aspirin early after PCI and using P2Y12 inhibitor monotherapy was not noninferior to dual therapy with respect to the risk of death or ischemic events but did reduce bleeding events.

In low-risk patients with MI and early complete revascularization, stopping aspirin after 1 month and continuing P2Y12 monotherapy was noninferior to dual antiplatelet therapy for ischemic outcomes and led to reduced bleeding at 1 year.

Background The CD4/CD8 ratio has been associated with the risk of AIDS and non-AIDS events. We describe trends in immunological parameters in people who underwent a switch to monotherapy or dual therapy, compared to a control group remaining on triple antiretroviral therapy (ART). Methods We included patients in Icona who started a three-drug combination ART regimen from an ART-naïve status and achieved a viral load ≤ 50 copies/mL; they were subsequently switched to another triple or to a mono or double regimen. Standard linear regression at fixed points in time (12-24 months after the switch) and linear mixed model analysis with random intercepts and slopes were used to compare CD4 and CD8 counts and their ratio over time according to regimen types (triple vs. dual and vs. mono). Results A total of 1241 patients were included; 1073 switched to triple regimens, 104 to dual (72 with 1 nucleoside reverse transcriptase inhibitor (NRTI), 32 NRTI-sparing), and 64 to monotherapy. At 12 months after the switch, for the multivariable linear regression the mean change in the log 10 CD4/CD8 ratio for patients on dual therapy was −0.03 (95% confidence interval (CI) –0.05, –0.0002), and the mean change in CD8 count was +99 (95% CI +12.1, +186.3), taking those on triple therapy as reference. In contrast, there was no evidence for a difference in CD4 count change. When using all counts, there was evidence for a significant difference in the slope of the ratio and CD8 count between people who were switched to triple (points/year change ratio = +0.056, CD8 = −25.7) and those to dual regimen (ratio = −0.029, CD8 = +110.4). Conclusions We found an increase in CD8 lymphocytes in people who were switched to dual regimens compared to those who were switched to triple. Patients on monotherapy did not show significant differences. The long-term implications of this difference should be ascertained.

Despite the wide variety of antiplatelet regimens and durations, the optimal treatment approach for chronic coronary syndrome (CCS) patients remains a subject of ongoing debate. While current guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and clopidogrel, the development of drug-eluting stents (DES) and more potent agents has sparked interest in shorter DAPT regimens, followed by P2Y12 inhibitor monotherapy, as a potential alternative. Recent trials and meta-analyses have shown that this approach may provide similar protection against thrombotic events with reduced bleeding risk. Despite promising data, the safety and efficacy of Ticagrelor monotherapy specifically in CCS patients have not been rigorously tested in randomized trials. TICALONE is a non-inferiority, two-arm, double-blinded, randomized controlled clinical trial designed to evaluate the safety and efficacy of ticagrelor monotherapy compared to DAPT in CCS patients following PCI. Eligible patients undergoing PCI with drug-eluting stents will be randomly assigned to receive either conventional DAPT (aspirin and clopidogrel) or ticagrelor monotherapy for six months. Follow-up visits will be conducted at 1, 3, 6, and 12 months post-PCI to assess efficacy and safety endpoints. The primary efficacy endpoint is a composite endpoint of cardiac death, myocardial infarction, stroke, stent thrombosis, and the need for revascularization. The primary safety endpoint is the occurrence of Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding events. The secondary endpoints include components of the primary efficacy endpoint, any bleeding event (BARC type 1-5), and all-cause mortality. Ancillary endpoints are other adverse events including dyspnea, drug adherence, and reaction. All endpoints will be monitored by a Data Safety Monitoring Board (DSMB) and Trial Management Committee (TMC). Statistical analysis and reporting of trial results will follow the estimand framework. Kaplan-Meier estimates will be used to assess event rates, while the log-rank test and Cox regression analysis will be employed to compare safety and efficacy outcomes between the groups. This trial may serve as a crucial step toward eliminating aspirin from post-PCI regimens, specifically in CCS patients. By comparing the safety and efficacy of Ticagrelor monotherapy with the conventional DAPT regimen and addressing potential risks of aspirin-free therapy and adverse events like dyspnea, this study could offer valuable insights into the possibility of P2Y12 monotherapy's safe adoption in this population. TICALONE is registered at https://clinicaltrials.gov/ with the identifier NCT06509893.

•We report the design and rationale of an investigator-initiated randomized controlled trial.•2700 STEMI and non-STEMI patients at high bleeding risk are considered for inclusion after PCI.•This multiarm trial tests CYP2C19 genotype-guided de-escalation to clopidogrel and abbreviated DAPT.•One-year coprimary outcomes are NACE and major and minor bleeding.•This trial seeks to improve the safety without compromising efficacy of DAPT in high-risk patients. Approximately one-third of patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) are at high risk of bleeding side-effects when on dual antiplatelet therapy (DAPT). High bleeding risk is often accompanied by high ischemic risk, thus challenging the choice of P2Y12 inhibitor and duration of DAPT. The optimal DAPT strategy for these patients remains debated, and it is unknown whether genotype-guided DAPT de-escalation to clopidogrel and aspirin, with or without abbreviation of DAPT to 3 months, is noninferior in terms of net adverse clinical events (NACE) and superior in reducing bleeding side-effects compared with standard DAPT for 6 months. The DAN-DAPT trial is an investigator-initiated, open-label, multicenter, multiarm, randomized controlled trial conducted at all Danish hospitals performing PCI. From 2022 to 2029, we planned to randomize 2,700 patients with MI and high bleeding risk in a 1:1:1 ratio to 1 of 3 groups: CYP2C19-genotyping and 6 months DAPT (experimental group 1), CYP2C19-genotyping and 3 months DAPT (experimental group 2), and 6 months DAPT with prasugrel (or ticagrelor) and aspirin (control group). The coprimary outcomes are NACE defined as the composite of all-cause mortality, recurrent MI, definite stent thrombosis, stroke, and BARC type 3-5 bleeding (Bleeding Academic Research Consortium), and major and minor bleedings defined as the composite of BARC type 2-5 bleedings at 1 year. DAN-DAPT trial is an open-label, multicenter, randomized controlled trial comparing genotype-guided DAPT de-escalation to clopidogrel - with or without DAPT abbreviation to 3 months - and standard DAPT for 6 months after PCI in high bleeding risk patients with MI. As of March 2025, 36% of the planned 2,700 patients have been enrolled in the study. ClincialTrials.gov (NCT05262803) and EU number (2022-500125-32-00).

•Developed a liposomal carrier using nanotechnology for low-dose dual antiplatelet drugs (clopidogrel and aspirin).•Demonstrated high drug encapsulation efficiency and sustained release properties of the liposomal carriers.•Conducted a randomized controlled trial comparing the nanoparticle drug delivery system with traditional therapy in CHD patients.•Found superior efficacy and lower incidence of complications with the novel delivery system.•Suggested the nanoparticle drug delivery approach as a promising therapeutic strategy for managing CHD, with potential for further validation through larger studies. Coronary heart disease (CHD) is a leading cause of global mortality, and antiplatelet drugs are crucial in its treatment. Traditional therapy, however, often faces issues like inconsistent efficacy, frequent dosing, and high complication rates. This study aimed to develop a liposomal carrier for low-dose dual antiplatelet drugs (clopidogrel and aspirin) using nanotechnology and evaluate its efficacy and safety in CHD patients. The study first prepared drug carriers for clopidogrel and aspirin using a liposomal approach, and the characteristics and in vitro drug release properties of these carriers were evaluated using various techniques. Subsequently, a randomized controlled trial was conducted with 270 patients diagnosed with CHD, who were divided into the control group (receiving 75 mg of clopidogrel and 100 mg of aspirin daily) and the treatment group (receiving the same regimen as the control group, with the addition of a nanoparticle drug delivery system), with 135 patients in each group. The efficacy and safety of the two interventions were then evaluated. The liposomal carriers demonstrated high drug encapsulation efficiency and sustained release. Clinical trials showed superior efficacy and fewer complications with the nanoparticle drug delivery system compared to traditional antiplatelet therapy. The nanoparticle drug delivery system for low-dose dual antiplatelet drugs shows promise as a novel therapeutic strategy for CHD patients. Further validation through larger sample sizes and long-term follow-up studies is necessary.

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is the cornerstone for prevention ischemic events in patients with acute coronary syndromes (ACS) and undergoing percutaneous coronary intervention. However, the optimal antiplatelet strategy for ACS patients with both high bleeding and high ischemic risks is unclear. The OPT-BIRISK trial is a multicenter, double-blinded, placebo-controlled randomized study designed to test the superiority of extended antiplatelet therapy with clopidogrel monotherapy compared with aspirin and clopidogrel for reduction of bleeding events in ACS patients with both high bleeding and high ischemic risks (“bi-risk”). A total of 7,700 patients who completed 9- to 12-month dual antiplatelet therapy after new-generation drug-eluting stent implantation for the treatment of ACS will be randomized to receive clopidogrel monotherapy or aspirin plus clopidogrel for 9 months followed by aspirin monotherapy for 3 months. The primary end point is Bleeding Academic Research Consortium type 2, 3, or 5 bleedings at 9 months after randomization. The key secondary end point is major adverse cardiac and cerebral events at 9 months after randomization, defined as a composite of all-cause death, myocardial infarction, stroke, or coronary artery revascularization. OPT-BIRISK is the first large-scale randomized trial aimed to explore the optimal antiplatelet strategy for bi-risk ACS patients after percutaneous coronary intervention in current clinical practice. The results will add evidence regarding de-escalation antiplatelet therapy for patients at special risk.

To compare adherence to once-daily umeclidinium/vilanterol (UMEC/VI), a long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA), and twice-daily inhaled corticosteroids (ICS)/LABA single-inhaler dual therapy in patients with chronic obstructive pulmonary disease (COPD) in a primary care cohort in England.PurposeTo compare adherence to once-daily umeclidinium/vilanterol (UMEC/VI), a long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA), and twice-daily inhaled corticosteroids (ICS)/LABA single-inhaler dual therapy in patients with chronic obstructive pulmonary disease (COPD) in a primary care cohort in England.Active comparator, new-user, retrospective cohort study using CPRD-Aurum primary care data and linked Hospital Episode Statistics secondary care administrative data. Patients without exacerbations in the previous year were indexed on first/earliest pre0% difference between treatment groups.In total, 6815 eligible patients were included (UMEC/VI:1623; ICS/LABA:5192). At 12 months post-index, weighted odds of a patient being adherent were significantly greater with UMEC/VI versus ICS/LABA (odds ratio [95% CI]: 1.71 [1.09, 2.66]; p=0.0185), demonstrating superiority of UMEC/VI. Patients taking UMEC/VI were statistically significantly more adherent than those taking ICS/LABA at 6, 18, and 24 months post-index (p<0.05). Differences in time-to-triple therapy, time-to-moderate COPD exacerbations, HCRU, and direct medical costs were not statistically significant between treatments after IPTW was applied.ResultsIn total, 6815 eligible patients were included (UMEC/VI:1623; ICS/LABA:5192). At 12 months post-index, weighted odds of a patient being adherent were significantly greater with UMEC/VI versus ICS/LABA (odds ratio [95% CI]: 1.71 [1.09, 2.66]; p=0.0185), demonstrating superiority of UMEC/VI. Patients taking UMEC/VI were statistically significantly more adherent than those taking ICS/LABA at 6, 18, and 24 months post-index (p<0.05). Differences in time-to-triple therapy, time-to-moderate COPD exacerbations, HCRU, and direct medical costs were not statistically significant between treatments after IPTW was applied.At 12 months post-treatment initiation, once-daily UMEC/VI was superior to twice-daily ICS/LABA in medication adherence among patients with COPD without exacerbations in the previous year, newly initiating dual maintenance therapy in England. The finding was consistent at 6, 18, and 24 months.ConclusionAt 12 months post-treatment initiation, once-daily UMEC/VI was superior to twice-daily ICS/LABA in medication adherence among patients with COPD without exacerbations in the previous year, newly initiating dual maintenance therapy in England. The finding was consistent at 6, 18, and 24 months.

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 study was a randomized trial of 12 versus 30 months 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 1 year. 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 Registrationhttps://www.clinicaltrials.gov. Unique identifier NCT00977938.