BACKGROUND: Results from multiple randomized clinical trials comparing outcomes after intravascular ultrasound (IVUS)– and optical coherence tomography (OCT)–guided percutaneous coronary intervention (PCI) with invasive coronary angiography (ICA)–guided PCI as well as a pivotal trial comparing the 2 intravascular imaging (IVI) techniques have provided mixed results. METHODS: Major electronic databases were searched to identify eligible trials evaluating at least 2 PCI guidance strategies among ICA, IVUS, and OCT. The 2 coprimary outcomes were target lesion revascularization and myocardial infarction. The secondary outcomes included ischemia-driven target lesion revascularization, target vessel myocardial infarction, death, cardiac death, target vessel revascularization, stent thrombosis, and major adverse cardiac events. Frequentist random-effects network meta-analyses were conducted. The results were replicated by Bayesian random-effects models. Pairwise meta-analyses of the direct components, multiple sensitivity analyses, and pairwise meta-analyses IVI versus ICA were supplemented. RESULTS: The results from 24 randomized trials (15 489 patients: IVUS versus ICA, 46.4%, 7189 patients; OCT versus ICA, 32.1%, 4976 patients; OCT versus IVUS, 21.4%, 3324 patients) were included in the network meta-analyses. IVUS was associated with reduced target lesion revascularization compared with ICA (odds ratio [OR], 0.69 [95% CI, 0.54–0.87]), whereas no significant differences were observed between OCT and ICA (OR, 0.83 [95% CI, 0.63–1.09]) and OCT and IVUS (OR, 1.21 [95% CI, 0.88–1.66]). Myocardial infarction did not significantly differ between guidance strategies (IVUS versus ICA: OR, 0.91 [95% CI, 0.70–1.19]; OCT versus ICA: OR, 0.87 [95% CI, 0.68–1.11]; OCT versus IVUS: OR, 0.96 [95% CI, 0.69–1.33]). These results were consistent with the secondary outcomes of ischemia-driven target lesion revascularization, target vessel myocardial infarction, and target vessel revascularization, and sensitivity analyses generally did not reveal inconsistency. OCT was associated with a significant reduction of stent thrombosis compared with ICA (OR, 0.49 [95% CI, 0.26–0.92]) but only in the frequentist analysis. Similarly, the results in terms of survival between IVUS or OCT and ICA were uncertain across analyses. A total of 25 randomized trials (17 128 patients) were included in the pairwise meta-analyses IVI versus ICA where IVI guidance was associated with reduced target lesion revascularization, cardiac death, and stent thrombosis. CONCLUSIONS: IVI-guided PCI was associated with a reduction in ischemia-driven target lesion revascularization compared with ICA-guided PCI, with the difference most evident for IVUS. In contrast, no significant differences in myocardial infarction were observed between guidance strategies.

P2Y₁₂ inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) may balance ischemic and bleeding risks in patients with acute coronary syndrome (ACS). However, it remains uncertain how different P2Y₁₂ inhibitors used as monotherapy affect outcomes. Randomized controlled trials comparing P2Y₁₂ inhibitor monotherapy after a short course of DAPT (≤3 months) versus 12-month DAPT in ACS were included. The primary endpoint was major adverse cardiovascular events (MACE). All analyses included an interaction term for the P2Y₁₂ inhibitor used as monotherapy. Trial sequential analysis were run to explore whether the effect estimate of each outcomes may be affected by further studies. Seven trials encompassing 27,284 ACS patients were included. Compared with 12-month DAPT, P2Y₁₂ inhibitor monotherapy after a short course of DAPT was associated with no difference in MACE (OR 0.92, 95% CI 0.76-1.12) and a significant reduction in net adverse clinical events (NACE) (OR 0.75; 95% CI 0.60-0.94), any bleeding (OR 0.54, 95% CI 0.43-0.66) and major bleeding (OR 0.47, 95% CI 0.37-0.60). Significant interactions for subgroup difference between ticagrelor and clopidogrel monotherapy were found for MACE (p_int=0.016), all-cause death (p_int=0.042), NACE (p_int=0.018), and myocardial infarction (p_int=0.028). Trial sequential analysis showed conclusive evidence of improved NACE with ticagrelor, but not with clopidogrel monotherapy, compared with standard DAPT. In patients with ACS, P2Y₁₂ inhibitor monotherapy after short DAPT halves bleeding without increasing ischemic events compared with standard DAPT. Ticagrelor, but not clopidogrel monotherapy, reduced MACE, NACE and mortality compared with standard DAPT, supporting its use after aspirin discontinuation. Protocol registration: This study is registered in PROSPERO (CRD42023494797).

The evolution of anticoagulation therapy, from vitamin K antagonists to the advent of direct oral anticoagulants (DOACs) almost two decades ago, marks significant progress. Despite improved safety demonstrated in pivotal trials and post-marketing observations, persistent concerns exist, particularly regarding bleeding risk and the absence of therapeutic indications in specific subgroups or clinical contexts. Factor XI (FXI) has recently emerged as a pivotal contributor to intraluminal thrombus formation and growth, playing a limited role in sealing vessel wall injuries. Inhibiting FXI presents an opportunity to decouple thrombosis from haemostasis, addressing concerns related to bleeding events while safeguarding against thromboembolic events. Notably, FXI inhibition holds promise for patients with end-stage renal disease or cancer, where clear indications for DOACs are currently lacking. Various compounds have undergone design, testing, and progression to phase 2 clinical trials, demonstrating a generally favourable safety and tolerability profile. However, validation through large-scale phase 3 trials with sufficient power to assess both safety and efficacy outcomes is needed. This review comprehensively examines FXI inhibitors, delving into individual classes, exploring their pharmacological properties, evaluating the latest evidence from randomized trials, and offering insights into future perspectives.

Periprocedural myocardial infarction (PMI) and injury, pertinent to both cardiac and non-cardiac procedures, have gained increasing recognition in clinical practice. Over time, diverse definitions for diagnosing PMI have been developed and validated among patient populations undergoing coronary revascularization. However, this variety in definitions presents considerable challenges in clinical settings and complicates both the design and interpretation of clinical trials. The necessity to accurately diagnose PMI has spurred significant interest in establishing universally accepted and prognostically meaningful thresholds for cardiac biomarkers elevation and supportive ancillary criteria. In fact, elevations in cardiac biomarkers in line with the 4th Universal Definition of Myocardial Infarction, have been extensively confirmed to be associated with increased mortality and cardiovascular events. In the context of non-coronary cardiac procedures, such as Transcatheter Aortic Valve Implantation, there is a growing acknowledgment of both the high incidence rates and the adverse impact of PMI on patient outcomes. Similarly, emerging research underscores the significance of PMI and injury in non-cardiac surgery, highlighting the urgent need for effective prevention and risk management strategies in this domain.

Background and Aims: Dual antiplatelet therapy (DAPT) de-escalation strategies improve outcomes after percutaneous coronary intervention (PCI) compared to standard DAPT. However, the potential impact of sex on the safety and efficacy of these strategies is yet to be fully investigated. Methods: Randomized controlled trials comparing de-escalated vs standard DAPT regimens in patients without baseline indication for oral anticoagulation reporting outcomes stratified by sex were included. The co-primary endpoints were trial-defined major adverse cardiovascular events (MACE) and major bleeding. Hazard ratios (HR) with 95% confidence intervals (CI) were computed to account for different follow-up durations. A network meta-analysis including ranking of treatments was performed to explore the comparative effects of different DAPT de-escalation strategies among females and males. Results: Overall, 71 272 patients from 20 trials were included, and 23.3% were female. De-escalation strategies were grouped into (1) DAPT discontinuation, by aspirin or the P2Y12 inhibitor; or (2) P2Y12 inhibitor switch or dose reduction. With DAPT discontinuation vs standard DAPT, a significant interaction between treatment effect and sex was found for both MACE (Pint = .028) and major bleeding (Pint = .015). Indeed, DAPT discontinuation reduced MACE in females (HR, 0.86; 95% CI, 0.75–0.98) but not in males (HR, 1.04; 95% CI 0.93–1.16), while reducing major bleeding in males (HR, 0.60; 95% CI, 0.44–0.82) but not in females (HR, 1.04; 95% CI, 0.76–1.43), compared to standard DAPT. Conversely, no interactions by sex were found with P2Y12 inhibitor switch or dose reduction vs standard DAPT for both MACE (Pint = .668) and major bleeding (Pint = .858). At treatment ranking, aspirin discontinuation ranked best for most outcomes in females, while P2Y12 inhibitor switch to clopidogrel showed the best outcomes in males. Conclusions: Sex may influence the safety and efficacy of antiplatelet de-escalation strategies after PCI, particularly those involving the shortening of DAPT. Aspirin discontinuation may represent the optimal strategy for females, while P2Y12 inhibitor switch to clopidogrel may be most effective for males.

Background and aims: Multiple anti-inflammatory drugs have been tested for secondary prevention after myocardial infarction (MI), giving mixed results and questioning the efficacy of anti-inflammatory therapy. No head-to-head comparisons between anti-inflammatory drugs have been performed. This study aimed to compare the efficacy and safety of anti-inflammatory drugs for secondary prevention after MI and the relative merits of specific drugs and administration strategies. Methods and results: Randomized trials of anti-inflammatory therapy for secondary prevention after MI were identified. Primary efficacy and safety endpoints were trial-defined major adverse cardiovascular events (MACEs) and serious adverse events. Secondary endpoints included all-cause death, individual MACE components, serious infection, cancer, and gastrointestinal adverse events. Pairwise meta-analyses were conducted with interaction analyses for drug type and timing of administration, in addition to network meta-analyses. Multiple sensitivity and meta-regression analyses were conducted to explore potential heterogeneity sources. Twenty-eight studies, involving 44 406 patients with a mean follow-up of 11 months, were included. Anti-inflammatory therapy reduced the incidence of MACEs [incidence rate ratio (IRR): 0.92; 95% confidence interval (CI): 0.86–0.98] compared to control, without increasing serious adverse events. However, it was associated with a higher incidence of gastrointestinal adverse events (IRR: 1.21; 95% CI: 1.07–1.36). No significant interaction was observed between the effects of anti-inflammatory therapy on MACE and the timing of administration. Conclusion: In secondary prevention for MI, anti-inflammatory therapy significantly reduces MACE without increasing serious adverse events, but it is associated with an increased risk of gastrointestinal adverse events.