The frequency of residual angina and its impact on health status and death following anatomic complete revascularization in symptomatic patients with chronic coronary disease are unknown. Data were analyzed from ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial participants randomized to invasive management with baseline angina (Seattle Angina Questionnaire Angina Frequency score <100), no prior coronary artery bypass graft surgery, and anatomic complete revascularization within 90 days of randomization. The primary outcome was frequency of residual angina after revascularization, defined as a Seattle Angina Questionnaire Angina Frequency score <100 within 6 months of randomization. Secondary outcomes included 6-month health status and medication use and 5-year all-cause and cardiovascular death. Among 2588 participants randomized to invasive management, 1442 (56%) had baseline angina and no prior coronary artery bypass graft surgery; 1034 underwent revascularization within 90 days, and 436 achieved anatomic complete revascularization. Of these, 184 (42.2%) had residual angina within 6 months. Baseline characteristics were similar between those with and without residual angina. Percutaneous coronary intervention was more common than coronary artery bypass graft surgery in those with residual angina (88% versus 80%, P=0.03). At 6 months, residual angina participants reported lower quality of life (Seattle Angina Questionnaire Quality of Life: 70±20 versus 83±20, P<0.001), greater physical limitation (Seattle Angina Questionnaire Physical Limitation: 84±20 versus 95±11, P<0.001), more dyspnea (Rose Dyspnea Scale score: 1±1.3 versus 0.4±0.8, P<0.001), and more antianginal medication use (P=0.006). Five-year all-cause and cardiovascular death did not differ significantly between groups. Residual angina is common (>40%) following anatomic complete revascularization for chronic coronary disease and is associated with reduced quality of life and greater antianginal medication use but no increase in death. Unique Identifier: NCT01471522.
Pulmonary embolism response teams (PERTs) are multidisciplinary care teams that perform rapid assessment and recommendations for patients with pulmonary embolism (PE). Challenges in creating and maintaining a PERT include physician buy-in and availability at all hours. One potential solution is to share PE interventions across specialty services. Patients with acute PE who received a PERT consultation and subsequent mechanical thrombectomy (MT) were included in this single-center, retrospective study. Patients from January 2021 to June 2024 were divided into two cohorts: one that received MT from interventional radiology (IR) and another that received MT from vascular surgery (VS). Outcomes included 30-day mortality, bleeding, 6-minute follow-up walk distance, time to intervention, total procedure time, and complication rates. A total of 76 patients were included in this analysis. IR and VS performed 61.8% (n = 47) and 38.2% (n = 29) of MTs, respectively. Of patients treated with MT, 46.1% (n = 35) had high-risk status and 53.9% (n = 41) had intermediate-high-risk status. In patients who received MT from IR, there was a 6.4% (three of 47) 30-day mortality rate compared to 6.9% (two of 29) from VS (p = 0.938). The occurrence of complications after MTs performed by IR and VS were 4.3% (two of 47) and 6.9% (two of 29), respectively (p = 0.792). Major procedure-related adverse events were 4.3% (two of 47) for IR and 6.9% (two of 29) for VS (p = 0.792). Outcomes of PE thrombectomy did not differ by whether the proceduralist was IR or VS. Intervention-sharing among different provider groups within PERTs could alleviate provider burden and make response team implementation more feasible.
Prospective clinical research studies are challenged by low enrollment rates and underrepresentation of individuals from racial and ethnic minority groups. To determine the effect of electronic message content on study enrollment among racial and ethnic groups. Four sequential randomized clinical trials (RCTs) were conducted between October 30, 2023, and November 13, 2024, in which University of Pennsylvania Health System patients (aged ≥18 years) were contacted electronically via email, text message, or both. The most effective arm from each RCT served as the control in the subsequent observational study. This analysis of all 4 RCTs was performed on the intention-to-treat principle from December 2024 through September 2025. Messages varied by method, source, framing, and incentive structure. The primary outcome was enrollment fraction (number enrolled divided by total contacted) among Black and Hispanic participants. Overall enrollment fraction was a secondary outcome. Overall, 26 215 patients were contacted and 26 029 were offered enrollment in the Penn Medicine BioBank; 63.2% were Black and 7.2% were Hispanic. Their mean (SD) age was 60.5 (17.9) years, and 60.1% were female. In the first recruitment RCT (RCT 1) (n = 8038), the enrollment fraction among 4581 Black and Hispanic patients was 0% with email, 0.5% with text, and 0.2% with email plus text (P = .06 for text vs email; P = .20 for email plus text vs email). Due to technical issues, more than 80% of participants who attempted to consent in RCT 1 failed; consent attempts were higher with text (4.8%) and email plus text (4.4%) than email alone (0.6%) (P < .001 for text vs email and email plus text vs email). In RCT 2 (n = 4271), the enrollment fraction among 1902 Black and Hispanic patients was 1.0% with research team outreach and 1.8% with clinical team outreach (P = .12). In RCT 3 (n = 3217 Black and Hispanic patients), the enrollment fraction was 3.2% with a control message, 3.6% with an appeal to altruism, and 4.1% with an appeal to social proof (P > .05 for all comparisons). In RCT 4 (n = 10 689), the enrollment fraction among 8629 Black and Hispanic patients was 2.5% with no incentive, 6.8% with $25, 5.5% with $15 plus a 5% chance at $200, 5.8% with a 5% chance at $500, and 6.5% with a 1% chance at $2500 (P < .001 for each incentive vs no incentive; P > .05 for each incentive compared with another). In this series of RCTs, the enrollment fraction among Black and Hispanic patients was improved with outreach by text message and with an incentive. ClinicalTrials.gov Identifier: NCT05827718.
Tirzepatide, a GLP-1 receptor agonist (GLP-1RA), is the first approved medication for the treatment of moderate to severe OSA and has previously been found to reduce cardiovascular risks in patients with type 2 diabetes mellitus (T2DM). Our study analyzed the effects of GLP-1RA in preventing cardiovascular and pulmonary complications in patients with OSA and T2DM during a 5-year follow-up period. Through the TriNetX database, patients with OSA and T2DM from 2010-2022 were included. We compared patients receiving GLP-1RA versus other diabetic medications including metformin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylurea, and thiazolidinedione. Using a propensity score model, participants were matched on a range of demographic and clinical factors. Patients were evaluated for cardiovascular and pulmonary outcomes using a Kaplan-Meier survival analysis. We additionally analyzed the incidence rate of ED visits and inpatient admissions. After matching, 5,750 to 21,065 patients were included in the GLP-1RA versus other diabetes medication groups. GLP-1RA showed a lower risk of acute respiratory failure compared to metformin (HR 0.89; 95%CI 0.80-0.98), DPP-4 inhibitors (HR 0.78; 95%CI 0.71-0.85), sulfonylureas (HR 0.70; 95%CI 0.64-0.76) and TZD (HR 0.76; 95%CI 0.65-0.89). GLP-1RA group demonstrated significantly lower risk of pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and heart failure when compared to DPP-4 inhibitors, sulfonylureas, and TZD. GLP-1RA use was associated with a lower risk of pulmonary complications including acute respiratory failure, pulmonary hypertension, and COPD as well as lower ED visits and inpatient admissions compared to other diabetes medications. Further prospective studies are needed to evaluate the benefits of GLP-1RA.
Patients with extensive ischaemic change are often excluded from endovascular thrombectomy. We aimed to synthesise the evidence from recent trials in these patients by performing a systematic review and individual patient data meta-analysis to estimate treatment benefit, including within clinical and imaging subgroups. In this systematic review and meta-analysis, we searched PubMed and Embase for randomised trials published between March 1, 2018, and March 1, 2025, that evaluated efficacy and safety of endovascular thrombectomy compared with medical management in patients with large-core ischaemic stroke (based on an Alberta Stroke Program Early CT Score [ASPECTS] of ≤5 or estimated ischaemic core ≥50 mL) presenting within 24 h of onset. Individual patient-level data from all eligible trials were obtained. A central imaging core laboratory readjudicated ASPECTS and reanalysed ischaemic core volume. A two-stage meta-analysis with random-effects model was used to evaluate the distribution of 90-day modified Rankin Scale (mRS) scores (the primary outcome) using adjusted pooled generalised odds ratios (aGenORs). Missing data were handled by multiple imputation. Safety outcomes were all-cause mortality within 90-day follow-up and neurological worsening within 24-48 h of randomisation, reported as adjusted pooled relative risk (aRR); and symptomatic intracerebral haemorrhage within 36 h of randomisation (reported as risk difference). Subgroup analyses based on clinical and imaging characteristics were done, including subgroups defined by ischaemic core volume, ASPECTS, and time window from onset to randomisation. The meta-analysis was registered with PROSPERO (CRD420251058584). We included 1886 patients (944 assigned to endovascular thrombectomy and 942 assigned to medical management) from six trials. Baseline characteristics were similar between treatment groups. At day 90, the distribution of mRS scores was improved in patients in the endovascular thrombectomy group (median score 4 [IQR 3-6]; n=940) versus those in the medical management group (5 [4-6]; n=931; aGenOR 1·63 [95% CI 1·42-1·88], p<0·0001). The endovascular thrombectomy group also had reduced mortality (292 [31·1%]) compared with the medical management group (347 [37·3%]; aRR 0·82 [95% CI 0·70-0·97], p=0·022). No significant differences were observed in symptomatic intracranial haemorrhage (ten [1·1%] of 944 vs nine [1·0%] of 942 patients; pooled unadjusted risk difference -0·17 percentage points [95% CI -1·01 to 0·67], p=0·69) or neurological worsening (197 [22·0%] of 896 patients vs 161 [17·9%] of 899; aRR 1·19 [0·87-1·62], p=0·27). Improved functional outcomes with endovascular thrombectomy were consistent across clinical and imaging subgroups, except for those with an estimated ischaemic core volume of 150 mL or greater, in whom point estimates favoured endovascular thrombectomy, particularly in the early time window (0-6 h), but wide 95% CIs limited interpretation. Endovascular thrombectomy was associated with improved functional outcomes and reduced mortality versus medical management in patients with large-core ischaemic stroke presenting within 24 h of onset. With the exception of very extensive ischaemic changes (core volume ≥150 mL) presenting beyond 6 h, where evidence remains limited, benefit was sustained across ASPECTS and ischaemic core strata for patients presenting up to 24 h after onset. None.
Recent randomized trials have questioned the incremental benefit of intravascular imaging-guided PCI, and the populations most likely to benefit remain uncertain. This study evaluates the long-term outcomes of intravascular imaging-guided PCI and associated factors with greater treatment benefit. Randomized controlled trials (RCTs) comparing PCI guided by intravascular ultrasound (IVUS), optical coherence tomography (OCT), or angiography were systematically identified. The primary outcome was major adverse cardiac events (MACE), defined as a composite of cardiovascular death, target-vessel myocardial infarction, and target-vessel or target-lesion revascularization. Pairwise and network meta-analyses were performed. Subgroup analyses were conducted according to lesion complexity, clinical presentation (acute coronary syndrome [ACS] vs. chronic coronary syndrome [CCS]), and trial region (Asian vs. non-Asian). A total of 23,338 patients from 29 RCTs were included (8,443 IVUS-guided PCI, 5,115 OCT-guided PCI, and 9,780 angiography-guided PCI). Imaging-guided PCI was associated with a significantly lower risk of MACE compared with angiography-guided PCI (HR, 0.74; 95%CI, 0.63-0.87). No significant difference in MACE risk was observed between IVUS- and OCT-guided PCI. The benefit of imaging-guided PCI was greater in trials enrolling patients with complex lesions, ACS, and Asian populations, but a significant interaction was observed only between Asian vs. non-Asian populations (P < 0.01 for interaction). Intravascular imaging-guided PCI was associated with a lower risk of MACE compared with angiography-guided PCI, and its benefit was more consistently observed in trials enrolling patients with Asian populations than non-Asian trials. Further investigation into the benefits of imaging guidance according to patient profiles is warranted. IVUS, intravascular ultrasound; MACE, major adverse cardiovascular events; OCT, optical coherence tomography; PCI, percutaneous coronary intervention; RCT, randomized controlled trial.
The diagnostic accuracy of nicorandil for fractional flow reserve (FFR) measurement has been validated, whereas data on outcomes of FFR-guided revascularization strategy using nicorandil remain limited. This study aimed to compare clinical outcomes following FFR-guided strategy using nicorandil versus conventional hyperemic agents, such as adenosine or papaverine. From the J-PRIDE registry, 2369 patients (3295 lesions) and 831 patients (1009 lesions) were classified into the nicorandil and non-nicorandil groups, respectively. The primary study endpoint was the cumulative 1-year incidence of target vessel failure (TVF; a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization) on a lesion basis. Patients with multivessel disease, aortic stenosis, and severe angiographic stenosis were more likely to receive nicorandil. Overall, the cumulative 1-year incidence of TVF did not differ significantly between the nicorandil and non-nicorandil groups (3.2% versus 2.4%; adjusted hazard ratio [aHR]: 1.23; 95% confidence interval [CI]: 0.78-1.94; P = 0.37). Similarly, in both the deferred and revascularized population, the 1-year TVF rate was comparable between the two groups (2.9% versus 2.5%; aHR: 1.07; 95% CI: 0.62-1.86; P = 0.80; 3.6% versus 2.1%; aHR: 1.35; 95% CI: 0.58-3.11; P = 0.48, respectively). A significant interaction was observed only between the effect of nicorandil on TVF and hemodialysis (P for interaction = 0.028). The 1-year TVF rate was comparable between the nicorandil and non-nicorandil groups, supporting the clinical applicability of nicorandil for FFR measurement in clinical practice.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors and angiotensin receptor-neprilysin inhibitors (ARNI) are heart failure (HF) therapies selected for price negotiations under the Inflation Reduction Act. This study aimed to summarize the cost-effectiveness of SGLT2 inhibitors and ARNIs for HF, examine how cost-effectiveness varies by ejection fraction (EF) and drug price, and estimate the effect of negotiated prices on cost-effectiveness. A systematic literature search identified cost-effectiveness analyses of SGLT2 inhibitors and ARNIs versus standard of care for the treatment of HF from a US perspective, published through 2025. Analyses were stratified by HF with reduced EF (<40%, HFrEF), moderately reduced EF (40% to 49%, HFmrEF), and preserved EF (≥50%, HFpEF). Incremental cost-effectiveness ratios were estimated at negotiated drug prices from base-case, threshold, and sensitivity analyses of drug pricing. Key drivers of cost-effectiveness were identified from the top 3 variables in 1-way sensitivity analyses. Of 821 studies identified, 16 were included: 11 HFrEF, 2 HFrEF/HFmrEF/HFpEF, and 3 HFmrEF/HFpEF. Across all EF categories, incremental cost-effectiveness ratios (2024 US dollars) versus standard of care ranged from $59 600 to $187 100/quality-adjusted life year (QALY) gained with SGLT2 inhibitors, $24 400 to $92 300 with ARNIs, and $69 300 to $91 500 with SGLT2 inhibitors + ARNIs. Incremental cost-effectiveness ratios in studies of HFrEF were <$120 000/QALY gained and all but 1 were ≥$120 000/QALY gained in studies of HFmrEF/HFpEF. At negotiated drug prices across all EF categories, the incremental cost-effectiveness ratio was estimated to be $47 800/QALY gained with SGLT2 inhibitors, $39 900/QALY gained with ARNIs, and $44 400/QALY gained with SGLT2 inhibitors+ARNIs. The key drivers of cost-effectiveness included drug price (17 studies), cardiovascular death risk with SGLT2 inhibitors and ARNIs (15 studies), and duration of intervention effectiveness (5 studies). At negotiated prices resulting from the Inflation Reduction Act, SGLT2 inhibitors and ARNIs seem cost-effective in HFrEF, with projected cost-effectiveness in HFmrEF/HFpEF dependent on price reductions and less certain treatment-effect estimates.
Sarcopenia is the accelerated loss of skeletal muscle mass and function associated with ageing. Sarcopenia screening consists of body composition imaging and physical function tests; however, these tests can be burdensome and inconsistent. This review aimed to synthesise the available evidence on the diagnostic accuracy of blood biomarkers for sarcopenia (and related conditions). Literature searches were conducted using medical subject headings and words relevant to sarcopenia, biomarkers, and diagnostic accuracy. There were no restrictions on the population. Studies that used correlation or regression analyses, or had no control group, were excluded. Pooled estimates of sensitivity, specificity, and area under the curve (AUC) were calculated. The searches identified 150 studies assessing 170 unique biomarkers, and 20 had sufficient studies for meta-analysis. The serum creatinine-cystatin C ratio (CCR) demonstrated pooled sensitivity of 0.69 (95% CI: 0.63-0.75), specificity of 0.74 (95% CI: 0.69-0.80) and AUC of 0.71 (95% CI: 0.68-0.74) (25 studies). Myostatin (10 studies) and irisin (six studies) had pooled sensitivities of 0.76 (95% CI: 0.61-0.87) and 0.74 (95% CI: 0.56-0.86), specificities of 0.71 (95% CI: 0.65-0.76) and 0.72 (95% CI: 0.60-0.81), and AUCs of 0.72 (95% CI: 0.66-0.79) and 0.72 (95% CI: 0.65-0.78), respectively. The diagnostic accuracy of other identified blood biomarkers varied and ranged from fail to excellent. This review provides evidence on the use of biomarkers to diagnose sarcopenia, which can inform the development of targeted screening and intervention in research and practice. The integration of biomarker-based diagnostics offers a critical opportunity to reduce the global burden of sarcopenia.
The risk of atherosclerosis rises markedly in perimenopausal women. The observed discrepancy between the traditional "estrogen cardioprotection hypothesis" and the complex effects of hormone replacement therapy in clinical practice suggests the existence of intermediary mechanisms that are not yet fully understood. Recent research indicates that the gut microbiota may play a pivotal role in this "estrogen paradox". By integrating current evidence, this review systematically elucidates the core driving function of the "estrogen-gut-vascular axis" in disease progression: declining estrogen levels lead to intestinal barrier dysfunction and associated imbalances in microbial metabolites (e.g. reduced short-chain fatty acids and increased pro-inflammatory metabolites), collectively accelerating atherogenesis. Targeting this axis through dietary modification, microbial therapeutics, and precision hormone interventions may break this pathological cycle. Notably, effective nutritional strategies must consider food matrix, individual microbial metabolic capacity, and timing of intervention. Furthermore, building on extensive research into age-related shifts in gut microbiota, this review proposes the novel concept of 'gut microbial age' based on functional metabolic profiles, to quantify the functional state of host-microbiome interactions. This concept aims to provide new perspectives and tools for personalized cardiovascular risk assessment and precise intervention in perimenopausal women.
Precise navigation of a guidewire tip to a target within the three-dimensional (3D) structure of a coronary artery—controlled from 140 cm away—requires “3D wiring,” a technique involving wire manipulation based on 3D imaging. Hypothesizing that 3D wiring enables the standardization of wiring techniques for chronic total occlusion (CTO) intervention, we have established a 3D wiring method utilizing fluoroscopy and intravascular ultrasound (IVUS). As a first step to visualize guidewire movement within CTO lesions, we collaborated with Terumo Corporation to develop the Navifocus WR in 2012, a CTO-specific IVUS featuring a small diameter and a short tip. Observing guidewire movement during CTO PCI using this IVUS provided the insights necessary to understand how the shaft and tip must be visualized to facilitate effective 3D wiring. We first established angiography-guided 3D wiring using “3D imaging rules” in 2014. Subsequently, to achieve real-time IVUS-guided 3D wiring, we devised the tip detection (TD) method in 2017 and developed the AnteOwl WR IVUS (Terumo Corporation)—a short-tip, pullback-compatible catheter—in 2019, establishing a strategic approach for TD-intra-plaque tracking. Contrary to the traditional view that IVUS guidance is limited to intra-plaque tracking, our 2021 findings show that re-entry is routinely feasible through TD-guided perpendicular puncture (TD-ADR: Antegrade Dissection and Re-entry). This evolution elevated the TD method into a more robust technique for wire crossing. This review aims to systematically organize the theory of 3D wiring and disseminate this knowledge to the global community.
BackgroundThe ABCD-GENE (Age, Body Mass Index, Chronic Kidney Disease, Diabetes Mellitus, and Genotyping) score is a tool used to identify increased thrombotic risk in clopidogrel-treated patients. We evaluated the association between a low ABCD-GENE score (<10) and Bleeding Academic Research Consortium (BARC)-defined bleeding among prasugrel or ticagrelor and clopidogrel-treated patients.MethodsThis was an IRB-approved retrospective cohort study of patients who underwent percutaneous coronary intervention (PCI) and CYP2C19 genotyping. The primary outcome was time to first bleed of any severity within 1 year. Time to first major bleed, defined by BARC 3a, 3b, 3c, or 5 criteria, and major adverse cardiovascular events (MACE) were secondary outcomes. BARC bleeding events were compared between prasugrel or ticagrelor and clopidogrel-treated patients and stratified by the ABCD-GENE score threshold of ≥10. Kaplan-Meier and multivariable Cox proportional hazards model were used for time-to-event analyses.ResultsOf 2547 patients, 1760 were in the low score group, and 787 were in the high score group. Kaplan-Meier analysis showed that any bleeding (P = .008) and major bleeding (P = .015) were less for those with a low score compared to a high score. Among those in the low score group, any bleeding (P < .001) and major bleeding (P = .022) were lower with clopidogrel versus prasugrel or ticagrelor. However, the ABCD-GENE score was not independently associated with bleeding in the Cox model. No difference in MACE was observed by treatment in the low score group.ConclusionsThe ABCD-GENE score was associated with BARC bleeding, yet other variables had a greater impact such as history of GI bleed, anticoagulation, P2Y12 inhibitor, and age. Patients with a low score who received prasugrel or ticagrelor had more bleeding versus clopidogrel. Our findings support further evaluation of the ABCD-GENE score as a tool for guided P2Y12 inhibitor de-escalation post-PCI.
This study evaluated the serial anatomical and morphological changes in de novo coronary lesions treated with a drug-coated balloon (DCB) using integrated-backscatter intravascular ultrasound (IB-IVUS). The aim of this study was to investigate coronary vessel behaviors following balloon angioplasty using DCB. A total of 46 de novo coronary artery lesions treated with IVUS-guided DCB were studied. Each patient underwent coronary angiography and IVUS imaging before/after the intervention, and this was repeated at 8-month follow-up. Quantitative IVUS measurements included the external elastic membrane (EEM), lumen, and plaque plus media (P + M) cross-sectional area (CSA). Plaque composition was classified as lipid pool, fibrosis, dense fibrosis, and calcification using IB-IVUS. The average length and diameter of DCB were 18.7 ± 5.0 and 2.6 ± 0.4 mm, respectively. Acute lumen gain correlated better with vessel dilatation than plaque reduction. Overall mean EEM, P + M, and lumen CSA did not change significantly during follow-up. The Δlumen CSA was negatively correlated with the ΔP + M CSA (r=-0.66, p < 0.001) and positively correlated with ΔEEM CSA (r = 0.52, p < 0.001). By IB-IVUS, ΔP + M CSA correlated positively with both Δfibrosis area and Δlipid pool area. Late lumen gain (Δ lumen CSA > 0) was documented in 30 lesions (65%). Lesions with late lumen gain showed a greater increase in EEM CSA (P = 0.006) and a greater decrease in P + M CSA (P = 0.007), respectively. In conclusion, de novo coronary lesions treated with DCB demonstrated lumen patency with preserved P + M and EEM CSA. A combination of arterial remodeling and plaque changes affected lumen changes during follow-up.
CYP2C19 and CYP3A4 contribute to clopidogrel bioactivation. CYP2C19 no-function alleles diminish clopidogrel's antiplatelet effects and clinical effectiveness. Coadministration of either a CYP2C19 or a CYP3A4 inhibitor may also reduce clopidogrel's antiplatelet effects and lead to phenoconversion in patients without a CYP2C19 no-function allele (normal/rapid/ultrarapid metabolizers: NM/RM/UMs). However, the impact of CYP2C19 or CYP3A4 inhibitor use on clopidogrel clinical effectiveness remains unclear. Rates of major atherothrombotic events (MAE) over 12 months after percutaneous coronary intervention (PCI) were evaluated in 3,242 patients across three sites who underwent CYP2C19 genotype testing and received P2Y12 inhibitor therapy. Overall, 6.8% of patients were co-prescribed a moderate or strong inhibitor of either CYP2C19 or CYP3A4, as defined by the U.S. Food and Drug Administration. In CYP2C19 genotype-predicted NM/RM/UMs treated with clopidogrel (n = 1,624), the MAE rates were numerically higher, but not significantly different in patients receiving either a CYP2C19 or a CYP3A4 inhibitor vs. no inhibitor (18.4 vs. 12.8 events/100 patient-years, adjusted hazard ratio (HR) 1.51, 95% confidence interval (CI), 0.85-2.68, P = 0.155). When evaluating CYP2C19 inhibitor and CYP3A4 inhibitor use separately, MAE rates were higher in clopidogrel-treated NM/RM/UMs receiving a CYP2C19 inhibitor compared to no inhibitor (adjusted HR 2.22, 95% CI 1.01-4.91, P = 0.048), but no significant difference was observed in those receiving a CYP3A4 inhibitor compared to no inhibitor (adjusted HR 1.26, 95% CI 0.57-2.75, P = 0.569). These results suggest that concomitant use of a CYP2C19 inhibitor, but not a CYP3A4 inhibitor, may contribute to phenoconversion and decreased clopidogrel clinical effectiveness after PCI in CYP2C19 genotype-predicted NM/RM/UMs.
Cardiac Damage Staging (CDS) is associated with prognosis and may evolve after transcatheter aortic valve replacement (TAVR). However, the prognostic value of CDS at 1-year and the trajectory of CDS, and its underlying factors, remains unclear. From a single-center registry, patients who underwent TAVR between 2016 and 2023 and had echocardiographic assessment at baseline, immediately post-TAVR, and 1-year, were included. We evaluated (1) temporal changes in CDS, (2) factors associated with CDS evolution, and (3) the association between 1-year CDS and long-term survival. CDS was assessed using the original schema and dichotomized as early stage (stage 0-2) versus advanced stage (stage 3-4). Among 762 patients, 676 were classified as early stage and 86 as advanced stage at baseline. In the baseline early stage group, 25 (3.7%) worsened to advanced stage immediately post-TAVR, and 48 (7.1%) had worsened by 1-year. Among baseline advanced stage group, 39 (45.3%) improved to early stage immediately post-TAVR, increasing to 50 (58.1%) at 1-year. Absence of baseline atrial fibrillation (AF) was associated with CDS improvement, whereas baseline AF and mild tricuspid regurgitation (TR) were associated with CDS worsening. Advanced stage CDS at 1-year was associated with higher all-cause mortality (adjusted HR 1.90; 95% CI 1.10-3.29; p = 0.02). Among the baseline early stage group, worsening to advanced stage was associated with a two-fold higher mortality risk. CDS evolves during the first year post-TAVR and is influenced by AF and TR. CDS at 1-year after TAVR was associated with long-term survival.
Redo transcatheter aortic valve replacement (TAVR) when implanting a second transcatheter valve within a tall-frame self-expanding valve can be challenging because of unfavorable coronary-related anatomy. However, computed tomography (CT)-based data in Asian patients with smaller aortic root dimensions remain limited.This study aimed to evaluate the CT-based geometric coronary constraints by simulating implantation of a balloon-expandable SAPIEN 3 (S3) within a previously implanted self-expanding Evolut valve in Asian patients. Consecutive patients who underwent TAVR using Evolut at a single center between May 2021 and May 2023 and had post-procedural CT were analyzed. Virtual S3-in-Evolut implantation was simulated at three depths (node 4: low; node 5: intermediate; node 6: high). Geometric coronary constraint was assessed based on the relationship between the neo-skirt plane and coronary ostia and the valve-to-aorta distance. Among 113 patients, the distribution of geometric coronary constraint differed by simulated S3 implantation depth. With high S3 implantation (node 6), severe, intermediate, and low constraint were observed in 63.7%, 23.9%, and 12.4% of patients, respectively; with intermediate implantation (node 5), in 31.0%, 29.2%, and 39.8%; and with low implantation (node 4), in 3.5%, 16.8%, and 79.6%. In multivariable analysis, smaller sino-tubular junction diameter was independently associated with severe geometric coronary constraint.Geometric coronary constraints that may affect coronary access after redo TAVR with S3-in-Evolut configurations depend on the implantation depth of both the index Evolut and the simulated S3. However, the hemodynamic significance and clinical impact of these geometric findings require validation through flow studies.
Understanding the concomitant evolution of bleeding vs ischemic risk after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) treated with 1-month dual antiplatelet therapy (DAPT) would help optimize dynamic treatment strategies. The aim of this study was to describe the timing of bleeding and ischemic events during 1 year after PCI in this population. Timings of major bleeding events and of major adverse cardiovascular events (MACE) were analyzed in patient-level data from 7 prospective studies including HBR patients treated with PCI and 1-month DAPT. Among 7,266 patients (mean age 76 ± 9.0 years, 31.5% women), Bleeding Academic Research Consortium (BARC) types 3 to 5 bleeding occurred in 284 (4.0%), with 73 (1.0%) occurring ≤30 days after and 211 (2.9%) >30 days after index PCI. MACE occurred in 433 patients (6.0%), among which 64 (0.9%) occurred ≤30 days after index PCI and 369 (5.1%) after 30 days. During the first 30 days, there was no significant difference between rates of MACE and BARC types 3 to 5 bleeding events (22.3% vs 25.7%; P = 0.407). However, MACE rates were significantly higher than rates of BARC types 3 to 5 bleeding between 31 and 90 days (7.2% vs 4.9%; P = 0.024) and between 91 and 365 days (5.3% vs 3.1%; P < 0.001) CONCLUSIONS: Among HBR patients undergoing PCI treated with 1-month DAPT, the risk for major bleeding and MACE is highest in the first 30 days. MACE remain consistently more frequent than bleeding after the first month, when event rates stabilize over time while on single antiplatelet therapy.
Drug-coated balloon (DCB)-based non-stent percutaneous coronary intervention (PCI) may allow shorter dual antiplatelet therapy (DAPT), but whether a ≤ 30-day regimen is associated with worse outcomes remains unclear, particularly in patients not receiving oral anticoagulants. We conducted a single-center retrospective cohort study of patients undergoing DCB-based non-stent PCI between April 2021 and December 2024. Patients receiving oral anticoagulants were excluded. Patients were classified into short DAPT (≤ 30 days; n = 153) or standard DAPT (> 30 days; n = 184). All procedures were performed after optimal lesion preparation, frequently including debulking devices. The primary endpoint was 1-year major adverse cardiac events (MACE). Propensity score-based analyses and Kaplan-Meier methods were applied to evaluate time-to-event outcomes. A total of 337 patients were included. MACE occurred in 9/153 (5.9%) patients in the short-DAPT group and 12/184 (6.5%) in the standard-DAPT group. In unadjusted analyses, there was no significant difference between groups (OR 0.90, 95% CI 0.37-2.21). After adjustment, short DAPT was not associated with 1-year MACE (IPTW OR 0.97, 95% CI 0.40-2.32; SMRW OR 0.88, 95% CI 0.35-2.23). In the matched cohort (112 pairs), findings were consistent (OR 1.54, 95% CI 0.53-4.49). Kaplan-Meier analysis showed no significant difference between groups (log-rank p = 0.78), with no apparent early divergence between the curves. Short DAPT after DCB-based non-stent PCI in patients not receiving oral anticoagulants was not statistically associated with increased 1-year MACE. These findings should be interpreted cautiously given the observational design and potential residual confounding.
Glucocorticoid (GC) bridging therapy is recommended in patients with rheumatoid arthritis commencing a disease-modifying anti-rheumatic drug (DMARD). It is not clear whether GC therapy is better administered intramuscularly or orally and at what dose level. The aim of the LEADER trial is to identify the most effective and safest way of using steroids in patients with uncontrolled RA who are starting a DMARD. A multicentre, randomised, open-label, four-arm, parallel-group clinical trial with an internal pilot phase, economic evaluation and qualitative study of acceptability. Participants will be randomised to one of four arms: arm A, 30 mg oral prednisolone tapering over 6 weeks; arm B, 15 mg oral prednisolone tapering over 4 weeks; arm C, Intramuscularly 120 mg methylprednisolone; and arm D, Intramuscularly 80 mg methylprednisolone. Participants will be assessed at baseline (pre-GC intervention), 4, 12 and 24 weeks. The primary outcome measure is the mean DAS(CRP)-28 over 12 weeks. The primary comparison will be according to route of administration (oral vs intramuscular GC treatment) with secondary comparisons within route of administration to provide evidence of dose effectiveness. Toxicity will be measured using the Glucocorticoid Toxicity Index, a clinical outcome assessment and early morning cortisol level. LEADER will be conducted in ~30 sites delivering NHS care, recruiting a sample size of 448. Economic evaluation will compare cost-effectiveness within a trial and over a lifetime horizon from the English National Health Service perspective. The LEADER trial received MHRA and Leicester Central Research Ethics Committee ethics approval (REC reference: 24/EM/0277, IRAS 1010280), opened to recruitment on Protocol Version 4.0 and is currently recruiting on Protocol Version 5.0. Participants will provide written informed consent in accordance with the Declaration of Helsinki and applicable regulatory requirements. Trial results will be disseminated via presentations at national and international meetings, published in open-access journals and to patients. ISRCTN32090559.
Despite advances in percutaneous coronary intervention (PCI) and contemporary secondary prevention, recurrent cardiovascular events remain a major clinical challenge. Increasing evidence suggests that persistent vascular inflammation contributes to residual cardiovascular risk after PCI, even in patients receiving optimal lipid-lowering therapy. Recent studies have highlighted the clinical relevance of inflammatory biomarkers, plaque vulnerability, and intracoronary imaging findings in predicting adverse cardiovascular outcomes. In addition, anti-inflammatory therapeutic strategies have emerged as promising approaches for residual risk reduction. This review summarizes current insights into the mechanisms, assessment, and potential therapeutic implications of residual inflammatory risk after PCI.