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.

Atherosclerotic cardiovascular disease is a major health concern worldwide and requires effective preventive measures. Lp(a) (lipoprotein [a]) has recently garnered attention as an independent risk factor for astherosclerotic cardiovascular disease, with proinflammatory and prothrombotic mechanisms contributing to its atherogenicity. On an equimolar basis, Lp(a) is ~5 to 6 times more atherogenic than particles that have been widely associated with adverse cardiovascular outcomes, such as LDL (low-density lipoprotein). Lp(a) can enter the vessel wall, leading to the accumulation of oxidized phospholipids in the arterial intima, which are crucial for initiating plaque inflammation and triggering vascular disease progression. In addition, Lp(a) may cause atherothrombosis through interactions between apoA (apolipoprotein A) and the platelet PAR-1 (protease-activated receptor 1) receptor, as well as competitive inhibition of plasminogen. Because Lp(a) is mostly determined on genetic bases, a 1-time assessment in a lifetime can suffice to identify patients with elevated levels. Mendelian randomization studies and post hoc analyses of randomized trials of LDL cholesterol–lowering drugs showed a causal link between Lp(a) concentrations and cardiovascular outcomes, with therapeutic reduction of Lp(a) expected to contribute to estimated cardiovascular risk mitigation. Many Lp(a)-lowering drugs, including monoclonal antibodies, small interfering ribonucleic acids, antisense oligonucleotides, small molecules, and gene editing compounds, are at different stages of clinical investigation and show promise for clinical use. In particular, increased Lp(a) testing and treatment are expected to have a substantial impact at the population level, enabling the identification of high-risk individuals and the subsequent prevention of a large number of cardiovascular events. Ongoing phase 3 trials will further elucidate the cardiovascular benefits of Lp(a) reduction over the long term, offering potential avenues for targeted interventions and improved cardiovascular outcomes.

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).

Despite advances in secondary prevention, adverse cardiovascular events still occur after acute myocardial infarction (AMI). Contributing to residual cardiovascular risk, acute and persistent inflammation is a stronger predictor of recurrent events and mortality than low-density lipoprotein cholesterol. The inflammatory response following AMI is a finely regulated, multiphase process, beginning with a proinflammatory phase followed by a reparative phase. Disruptions in its regulation lead to persistent low-grade inflammation and worse clinical outcomes. Modulating inflammation has emerged as a promising secondary prevention strategy, with several drugs being tested with conflicting results regarding their efficacy and safety. Recently, novel approaches have reignited the interest in anti-inflammatory strategies after AMI. However, key knowledge gaps remain regarding potential class effects, drug choice, patient selection, and the optimal administration timing. This review provides an updated and comprehensive overview of inflammatory mechanisms after AMI and critically appraises the evolving clinical evidence surrounding anti-inflammatory therapies for secondary cardiovascular prevention.

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.

Efforts to enhance risk stratification in patients with coronary artery disease have driven the pursuit of early detection of rupture-prone plaques—before destabilization and the onset of life-threatening thrombosis—giving rise to the concept of the vulnerable plaque (VP). Invasive diagnostic modalities closely mirror histology and provide instrumental information on VP hallmarks and their prognostic significance. However, limited positive predictive value and invasive nature restrict their use for systematic screening. Noninvasive techniques offer broader application potential, but their specificity and resolution remain inferior to those of invasive techniques. A deeper understanding of the complex interplay between traditional ischemic risk factors, anatomic settings, rheological effects and systemic influences contributing to plaque evolution and rupture has refined our approach to identifying and managing VPs. Systemic therapies have been shown to counteract plaque progression and stabilize VPs by thickening the fibrous cap, decreasing atheroma and necrotic core volumes, and reducing inflammation. In parallel, the hypothesis of sealing and passivating VPs by intravascular imaging-guided preventive stenting is gaining support after the promising results of clinical trials and substantial advances in contemporary device performance and biocompatibility. Upcoming evidence will be instrumental in defining the net benefit of novel diagnostic tools and therapeutic strategies for VPs.