Faculty Bibliography

BACKGROUND/UNASSIGNED:Patient-centered prognostic assessment in chronic coronary disease is vital for treatment optimization. Although the Seattle Angina Questionnaire Summary Score (SAQ-SS) correlates with clinical outcomes, clinicians lack guidance on how to weigh prior, current, or changes in scores, and whether prognostic significance varies by revascularization strategy. METHODS/UNASSIGNED:The ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches; 2012-2019) was a global, multicenter, randomized controlled trial. This secondary analysis evaluated the prognostic value of serial SAQ-SS assessments. The SAQ-SS ranges from 0 to 100, with higher scores indicating better health status. To simulate routine clinical care, the follow-up in ISCHEMIA was equated to outpatient clinic visits-we defined the 3-month SAQ-SS as the prior score and the 6-month assessment as the current score in the clinic. Analyses were stratified by treatment strategy: conservative management and invasive management with revascularization. Cox proportional hazards models assessed the association of the prior score, the current score, and the change in scores with ISCHEMIA's primary composite end point (cardiovascular death, myocardial infarction, hospitalization for unstable angina, heart failure, and resuscitated cardiac arrest), adjusting for 17 clinical covariates. RESULTS/UNASSIGNED:This analysis included 3405 participants (1965 in conservative management: 77.4% male, mean age 64.3 years±9.5; 1440 in invasive management: 77.6% male, mean age 64.0 years±9.4). Over a median follow-up of 3.2 years, 215 (11.0%) and 96 (6.7%) participants in the conservative and invasive cohorts, respectively, experienced the primary composite end point. Higher prior, current, and change SAQ-SS were each independently associated with a lower risk of cardiovascular events. In the conservative cohort, each 5-point increase in the current SAQ-SS was associated with a 7% lower risk of the primary end point (hazard ratio, 0.93 [95% CI, 0.90-0.96]); in the invasive cohort, the association was 9% (hazard ratio, 0.91 [95% CI, 0.86-0.96]). CONCLUSIONS/UNASSIGNED:In patients with chronic coronary disease, the most recent SAQ-SS is the strongest health status predictor of future cardiovascular events. Serial SAQ-SS assessments provide a practical, dynamic, and patient-centered approach for updating prognosis in chronic coronary disease management. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

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: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).

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.

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.

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.