BACKGROUND AND AIMS:Previous literature has suggested that the risk of ischaemic stroke (IS) is lower in patients with atrial flutter (AFL) compared with patients with atrial fibrillation (AF), but large-scale studies with electrocardiogram (ECG) documentation are not available. METHODS:The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation study included all patients with AF and AFL in Finland from 2007 to 2018. Based on the digitally recorded ECGs, patients were categorized into AF-only, AFL-only, or combined AF and AFL groups. IS rates and adjusted incidence rate ratios (IRRs) were calculated. RESULTS:A total of 40 986 patients with new-onset AF/AFL and 532 041 digitally documented ECGs were identified. The AF-only group included 30 261 patients (48.2% women, mean age 71.8 years), the AFL-only group 2409 patients (38.8% women, mean age 70.8 years), and the AF & AFL group 8316 patients (53.9% women, mean age 72.4 years). Of these, 31 795 (77.6%) initiated anticoagulation during a mean follow-up of 1.2 years. Overall, IS was observed in 3165 (7.7%) patients. The crude rate of IS was highest in the AF & AFL group [2.1 per 100 patient-years, 95% confidence interval (CI) 1.9-2.2] compared to the AF-only group (1.9 per 100 patient-years, 95% CI 1.8-1.9) and AFL-only group (1.1 per 100 patient-years, 95% CI 0.9-1.3). Adjusted IRR of IS was lower in the AFL-only group (0.60, 95% CI 0.49-0.74) and slightly higher in the AF & AFL group (1.11, 95% CI 1.02-1.20) compared with patients with AF-only. These findings were consistent in analyses restricted to follow-up time without anticoagulation and before catheter ablation, as well as across CHA2DS2-VA score categories. CONCLUSIONS:In this large cohort of patients, those with AFL-only had a substantially lower risk of IS than patients with AF-only, suggesting clinically meaningful differences in thromboembolic risk between these arrhythmias.
BACKGROUND AND AIMS:Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) has improved outcomes in randomized trials, yet some recent European trials reported neutral results despite positive findings from East Asian studies. This study assessed whether benefit was consistent across settings. METHODS:Randomized trials comparing IVUS-guided with angiography-guided drug-eluting stent PCI were systematically reviewed and meta-analysed. Pooled risk ratios (RRs) used restricted maximum likelihood random-effects models with Hartung-Knapp-Sidik-Jonkman adjustment. Geographic effect modification was pre-specified as the primary hypothesis, and the interaction test for cardiac death was the primary analysis. RESULTS:Seventeen trials (14 033 patients; 10 East Asian [10 155], 7 non-Asian [3878]) were included. The pooled RR for cardiac death was.71 (95% confidence interval [CI] .53-.94, P = .022), with a significant geographic interaction: East Asian RR.56 (.46-.69) vs non-Asian RR 1.23 (.85-1.76; interaction P < .001). Treatment effects diverged for target-vessel myocardial infarction (TV-MI; interaction P = .011), target-vessel revascularization (TVR; interaction P = .004), and major adverse cardiovascular events (MACE; interaction P = .040). IVUS guidance reduced definite stent thrombosis (RR .39, 95% CI .19-.79; interaction P = .433). All-cause death was similar (RR .89, 95% CI .76-1.04). CONCLUSIONS:Considering all studies, IVUS-guided PCI reduced cardiac death, TV-MI, TVR, MACE, and stent thrombosis. However, significant interactions were present such that the relative reductions in cardiac death, TV-MI, TVR, and MACE were greater in the Asian compared with non-Asian trials (although stent thrombosis was reduced consistently across geographies). Differences in how the information derived from IVUS was used to optimize stent implantation may contribute to this geographic heterogeneity.
BACKGROUND AND AIMS:Hypertensive patients exhibit heightened susceptibility to pro-thrombotic state, elevating their cardiovascular event risk. G protein-coupled receptors (GPCRs) serve as central mediators of platelet function; however, the mechanisms through which GPCRs contribute to platelet hyperreactivity remain unclear. This study explores protease-activated receptor 4 (PAR4) on platelet hyperactivation in hypertension. METHODS:Platelet GPCR expression from 150 hypertensive patients, spontaneously hypertensive rats (SHRs), and L-NAME-induced hypertensive mice were analysed using RNA-seq and flow cytometry. In vivo and ex vivo thrombosis model, and in vitro platelet functional studies assessed PAR4 overexpression on platelet activation and confirmed by using PAR4-deficient mice. Megakaryocytes and transforming growth factor beta 1 (TGF-β1)-deficient mice were employed to investigate transcriptional regulation of PAR4. RESULTS:PAR4 expression was elevated in platelets from hypertensive patients and positively correlated with integrin αⅡbβ3 activation and P-selectin exposure, a finding validated in SHRs and hypertensive mice. PAR4 overexpression potentiated thrombin- and AYPGKF-induced platelet activation via Gq and G12/13 signalling of PAR4 but not SFLLRN-induced platelet activation of PAR1, driving arterial thrombus formation. Mechanistic studies using TGF-β1-deficient mice identified TGF-β1 activated transcription factor Smad2, enabling its binding to the PAR4 promoter and PAR4 transcription upregulation. Angiotensin Ⅱ initiated TGF-β1/Smad2 signalling, and valsartan, an angiotensin Ⅱ receptor blocker (ARB), reduced PAR4 expression to attenuate thrombus formation in hypertension. CONCLUSIONS:Angiotensin Ⅱ-driven TGF-β1 upregulates platelet PAR4 transcription to enhance platelet activation in hypertension. Valsartan reverses platelet PAR4 overexpression to inhibit thrombus formation, revealing a new pleiotropic antithrombotic pharmacological mechanism of ARBs in hypertension.
Despite significant advances in stent technology, long-term complications-such as restenosis and stent thrombosis-remain relatively common and clinically impactful due to their association with recurrent myocardial infarction and adverse outcomes. Among the causes of stent failure, neoatherosclerosis has gained recognition as a key pathological mechanism, driven by impaired vascular healing, chronic inflammation, platelet activation, and immune responses following coronary stenting. Advances in diagnostic accuracy, particularly intracoronary imaging, have provided new insights into its development. In response, emerging strategies-including refined pharmacotherapy, targeted intraprocedural interventions, novel stent designs, and alternative drug-delivery systems-are being explored. This review presents recent preclinical, diagnostic, and clinical advances in understanding and addressing neoatherosclerosis and discusses current and emerging therapeutic approaches (Graphical Abstract).
