Faculty Bibliography

BACKGROUND:In August 2025, the American Heart Association and American College of Cardiology released updated hypertension guidelines. Under the new guidelines, therapy is advised at blood pressure ≥130/80 mm Hg in adults with diabetes, chronic kidney disease, or a Predicting Risk of Cardiovascular Disease Events-estimated 10-year cardiovascular disease risk ≥7.5%. The long-term population-level changes following these guidelines remains uncertain. METHODS:We analyzed NHANES (National Health and Nutrition Examination Survey) 2009 to 2018 data linked to mortality through 2019. Hypertensive adults without baseline cardiovascular disease were included. Treatment eligibility was defined using guideline criteria. Cox models estimated associations between antihypertensive therapy and all-cause and cardiovascular mortality. Simulation analyses projected lives saved under full and partial treatment uptake. RESULTS:The weighted cohort represented 81.0 million US adults with hypertension. Of these, 22.8 million (28%) were guideline eligible for therapy; 13.1 million (57%) were treated, and 9.7 million (43%) remained untreated. Antihypertensive therapy was associated with a 23% reduction in all-cause mortality (hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]) and 50% reduction in cardiovascular mortality (HR, 0.50 [95% CI, 0.36-0.68]). At 10 years, universal treatment of eligible but untreated adults was projected to prevent ~200 900 all-cause and ~ 162 600 cardiovascular deaths. Benefits were greatest in adults with diabetes. CONCLUSIONS:In this nationally representative cohort, nearly 1 in 3 US adults with hypertension were newly eligible for therapy under the guideline, yet >2 in 5 remained untreated. Extending treatment to all eligible adults could prevent >200 000 all-cause and 160 000 cardiovascular deaths over the next decade.

BACKGROUND:Among high-bleeding risk (HBR) patients undergoing coronary stenting, abbreviated dual antiplatelet therapy (DAPT) reduces bleeding without ischemic risk trade-off; whether these benefits persist across the entire spectrum of bleeding risk has not been investigated. OBJECTIVES/OBJECTIVE:The aim of this study is to explore the value of the novel PRECISE-HBR score as a risk stratification tool to guide DAPT duration in patients at high bleeding risk. METHODS:The XIENCE Short DAPT program combined 3 international single-arm studies of HBR patients treated with cobalt-chromium everolimus-eluting stents who discontinued DAPT at 1 month (XIENCE 28 USA/Global) or 3 months (XIENCE 90), if event free and treatment adherent. Bleeding risk was classified as nonhigh (PRECISE-HBR score ≤22), high (score 23-26), or very high (score ≥27). Clinical outcomes were assessed between 1 and 12 months using propensity score stratification. RESULTS:Among 3,364 patients, the PRECISE-HBR score was ≤22, 23-26, and ≥27 in 359 (10.7%), 744 (22.1%), and 2,261 (67.2%), respectively. Rates of BARC (Bleeding Academic Research Consortium) type 3-5 bleeding (0.3%, 2.5%, 5.6%) and death or myocardial infarction (2.9%, 4.6%, 9.8%) increased progressively across risk categories. One- versus 3-month DAPT was associated with a significant reduction in BARC type 3-5 bleeding in patients with a score ≥27 (HR: 0.59, 95% CI: 0.39-0.88) but not in those <27 (HR: 2.31, 95% CI: 0.89-5.99; P-interaction = 0.012). Ischemic risk was similar between 1- and 3-month DAPT, irrespective of the PRECISE-HBR score (P-interaction = 0.40). CONCLUSIONS:The PRECISE-HBR score identified patients at increased risk for both bleeding and ischemic events who seemed to derive greater benefit from 1-month DAPT after stent implantation.

BACKGROUND/UNASSIGNED:Cardiac stress testing is a cornerstone of risk stratification and management in patients with chronic coronary disease, yet the consistency and accuracy of its interpretation remain poorly defined. This analysis evaluated variation in the interpretation of myocardial ischemia between enrollment sites and core laboratories in the ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches). METHODS/UNASSIGNED:ISCHEMIA was a global (37 countries, 2012-2018) randomized trial of an initial invasive versus conservative strategy in patients with chronic coronary disease and moderate or severe ischemia. This analysis included participants with site-interpreted qualifying stress tests-nuclear, echocardiography (echo), cardiac magnetic resonance, or exercise tolerance test-and independent core laboratory adjudication. Core laboratories, serving as the reference standard, reinterpreted tests blinded to site results. A trinary outcome variable (site underestimation, concordance, or overestimation) was defined by comparing site-determined ischemia levels to standardized core lab assessments. Adjusted mixed-effects logistic regression models with random site intercepts assessed variability. RESULTS/UNASSIGNED:Among 6971 participants (mean age, 62.8 years; 73% men), site interpretations showed 0% no/mild (by design), 43% moderate, and 57% severe ischemia. Core labs reclassified these as 8% none, 11% mild, 30% moderate, and 51% severe ischemia. For the imaging modalities, median site-core lab agreement rates were ≈55%; nearly 25% of site-classified moderate/severe cases were downgraded to no or mild ischemia by core labs. Adjusted median odds ratios for site overestimation were 2.36 (95% CI, 2.02-2.82; nuclear), 1.98 (95% CI, 1.62-2.60; echo), 1.89 (95% CI, 1.0-5.41; cardiac magnetic resonance), and 2.15 (95% CI, 1.76-2.79; exercise tolerance test). Adjusted median odds ratios for underestimation ranged from 1.25 to 1.77. CONCLUSIONS/UNASSIGNED:In ISCHEMIA, enrollment sites frequently overestimated or underestimated the severity of myocardial ischemia compared with core laboratory assessments, highlighting the need for strategies to improve the consistency and accuracy of stress testing interpretation in patients with chronic coronary disease. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

IMPORTANCE:The relative efficacy and safety of oral P2Y purinergic receptor 12 (P2Y12) inhibitors (clopidogrel, ticagrelor, or prasugrel) after percutaneous coronary intervention (PCI) are not well defined. OBJECTIVE:To assess the efficacy and safety of oral P2Y12 inhibitors in patients who underwent PCI. DATA SOURCES AND STUDY SELECTION:PubMed and Embase were searched until November 15, 2025, for randomized clinical trials comparing at least 2 of the 3 agents. DATA EXTRACTION AND SYNTHESIS:Data were abstracted by 2 independent authors according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Random-effects odds ratios (ORs) and 95% confidence intervals were calculated. Data were analyzed in December 2025. MAIN OUTCOMES AND MEASURES:The primary efficacy outcome was major adverse cardiovascular events (MACE), while the primary safety outcome was major bleeding. The primary analysis compared prasugrel and ticagrelor in reference to clopidogrel using a mixed treatment comparison meta-analysis. RESULTS:Data were analyzed from 15 randomized clinical trials that included 48 904 patients (mean [SD] age, 63.2 [4.21] years; 13 330 female patients [27.3%]). Compared with clopidogrel, there was a lower risk of MACE (OR, 0.80; 95% CI, 0.69-0.93) driven by lower myocardial infarction (OR, 0.71; 95% CI, 0.62-0.82) and stent thrombosis (OR, 0.48; 95% CI, 0.37-0.62) with prasugrel. MACE was not reduced with ticagrelor compared with clopidogrel, although there was lower stent thrombosis (OR, 0.73; 95% CI, 0.59-0.91). Furthermore, there was lower risk of MACE with prasugrel compared to ticagrelor (OR, 0.83; 95% CI, 0.70-0.98) driven by lower myocardial infarction (OR, 0.78; 95% CI, 0.65-0.94) and stent thrombosis (OR, 0.66; 95% CI, 0.49-0.88). There was a higher risk of major bleeding with ticagrelor vs clopidogrel (OR, 1.24; 95% CI, 1.01-1.52) driven by higher intracranial hemorrhage (OR, 1.89; 95% CI, 1.08-3.33). Prasugrel ranked first, followed by ticagrelor and clopidogrel, for MACE, myocardial infarction, and stent thrombosis. CONCLUSIONS AND RELEVANCE:In this systematic review and meta-analysis of 15 randomized clinical trials in patients who underwent PCI, prasugrel provided the optimal balance between efficacy and safety compared with ticagrelor and clopidogrel.

OBJECTIVES/OBJECTIVE:The SELUTION SLR 014 In-stent Restenosis (SELUTION4ISR) trial showed noninferiority of DCB for the outcome of target lesion failure (TLF) when compared with standard of care (80% DES and 20% POBA). It was notable that in the DCB vs DES subgroup analysis there was a numerically higher rate of TLF with DCB (15.3% vs 7.1%). The authors aimed to re-evaluate the outcomes of drug-eluting stent (DES), drug-coated balloon (DCB), or plain old balloon angioplasty (POBA) in patients with coronary in-stent restenosis (ISR). METHODS:The authors searched PubMed and EMBASE databases for randomized clinical trials (RCTs) that compared these 3 percutaneous revascularization strategies for ISR until March 15, 2026. Outcomes included major adverse cardiovascular events (MACE), target lesion revascularization, all-cause mortality, cardiovascular mortality, and stent thrombosis. RESULTS:From 19 RCTs that randomized 4238 patients with ISR at mean follow-up of 19.6 months, there was a significant reduction in MACE and TLR with both DCB (OR, 0.35; 95% CI, 0.24-0.52 and OR, 0.28; 95% CI, 0.16-0.49, respectively) and DES (OR, 0.35; 95% CI, 0.24-0.52 and OR, 0.22; 95% CI, 0.12-0.42, respectively) when compared with POBA. There were no significant differences in clinical outcomes between DCB and DES. CONCLUSIONS:In patients with ISR, DCB reduced MACE/TLR when compared with POBA. There were no clinical differences between DCB and DES even after inclusion of the SELUTION4ISR trial, thus suggesting that DCB are reasonable alternative to repeat stenting in patients presenting with ISR.

BACKGROUND:Patients with diabetes frequently have multivessel disease and are at increased risk of adverse outcomes. The outcomes with a new-generation ultra-thin strut sirolimus-eluting stent (SES) vs everolimus-eluting stent (EES) is unclear as stent-to-stent comparison trials have routinely excluded these patients or included a small proportion of such patients. OBJECTIVES/OBJECTIVE:The purpose of this study was to compare the clinical outcomes of ultra-thin biodegradable polymer (BP) SES vs durable polymer (DP) EES when combined with contemporary optimal medical therapy in patients with diabetes and multivessel disease. METHODS:The TUXEDO-2 is an investigator-initiated prospective, open-label, multicenter, 2 × 2 factorial, randomized (1:1) controlled trial. Patients undergoing percutaneous coronary intervention were randomized to receive either a Supraflex Cruz SES or Xience EES. The participants were also randomized to Ticagrelor or Prasugrel. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial infarction or ischemia-driven target lesion revascularization at 1-year follow up. The trial was designed to test noninferiority of BP-SES vs DP-EES, with a noninferiority margin of 4.5% (1-sided upper 97.5% confidence bound). RESULTS:= 0.005). There were no significant differences in cardiac death (3.6% vs 3.4%), target vessel myocardial infarction (6.61% vs 7.54%), and ischemia-driven target lesion revascularization (0.8% vs 1.0%) between the 2 groups. Nonfatal myocardial infarction (4.7% vs 6.4%) and stent thrombosis was similar (1.0 % vs 0.7%) between the 2 groups. CONCLUSIONS:In patients with diabetes and multivessel disease undergoing percutaneous coronary intervention, ultra-thin biodegradable polymer SES was noninferior to durable polymer EES at 1 year follow-up. (Trial Registration Number CTRI/2019/11/022088).

BACKGROUND/UNASSIGNED:Recent observational studies have suggested that early treatment (<12 hours from diagnosis) of intermediate risk pulmonary embolism (PE) with catheter-based therapies may reduce morbidity and mortality. However, the effect of early versus late mechanical thrombectomy on acute pulmonary hemodynamics and right ventricular mechanics is less well defined. METHODS/UNASSIGNED:Patients enrolled in SYMPHONY-PE were divided into one of 2 groups based on the time from baseline CT pulmonary angiography to mechanical thrombectomy: Early <12 hours versus late ≥12 hours. The primary safety end point was the rate of major adverse events within 48 hours, as adjudicated by an academic independent safety board. The primary efficacy end point was the core-lab assessed mean change in right ventricle-to-left ventricle ratio from baseline to 48 hours. RESULTS/UNASSIGNED:=0.431) between groups, and there were no mortalities. The differences in efficacy outcomes were greatest in higher-risk patients per the Composite Pulmonary Embolism Shock score. CONCLUSIONS/UNASSIGNED:Early mechanical thrombectomy was associated with larger reductions in right ventricle-to-left ventricle ratio and mean pulmonary artery pressure, with no significant differences in safety event rates compared with patients who underwent late thrombectomy. Randomized trials are needed to test these associations. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06062329.