Faculty Bibliography

BACKGROUND:In patients with diabetes mellitus (DM) and high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI), the optimal duration of dual antiplatelet therapy (DAPT) remains uncertain. AIMS/OBJECTIVE:We sought to compare early DAPT discontinuation in DM and non-DM patients enrolled in the prospective XIENCE Short DAPT programme. METHODS:The effects of 1- versus 3-month DAPT on ischaemic and bleeding outcomes were compared using propensity score stratification. The primary endpoint was a composite of all-cause death or myocardial infarction (MI) at 1 year. The incidence of Bleeding Academic Research Consortium (BARC) Type 2 to 5 bleeding was the key secondary endpoint. RESULTS:Out of 3,352 included patients, 1,299 (38.8%) had DM; diabetic patients had a higher 1-year incidence of death or MI (DM vs non-DM: 10.1% vs 6.6%) and similar BARC 2-5 bleeding (DM vs non-DM: 9.5% vs 9.2%). With 1- versus 3-month DAPT, the incidence of death or MI did not statistically differ in DM patients (adjusted hazard ratio [adjHR] 0.70, 95% confidence interval [CI]: 0.47-1.05) and non-DM patients (adjHR 1.26, 95% CI: 0.87-1.81), although heterogeneity by DM status was evident (p for interaction=0.015). BARC 2-5 bleeding was numerically lower with 1-month DAPT in both groups (DM: adjHR 0.67, 95% CI: 0.45-1.01; non-DM: adjHR 0.78, 95% CI: 0.56-1.07; p for interaction=0.973). CONCLUSIONS:Among HBR patients with DM undergoing PCI, 1-month DAPT, as compared to 3-month DAPT, was not associated with an excess of fatal or non-fatal MI and even reduced the occurrence of bleeding. These findings should be interpreted in the context of a predominantly stable patient population with low procedural complexity and may not be generalisable to higher-risk cases.

BACKGROUND:In the ISCHEMIA Trial, 5179 patients with stable coronary disease were randomized to initial invasive or conservative management. METHODS:PCI was recommended with a SYNTAX score 0-22 (low) and CABG with a SYNTAX score ≥33 (high). Either could be recommended for intermediate scores. The composite primary outcome was cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. There were two cohorts in this analysis. The descriptive cohort included patients who underwent CABG or PCI within 180 days of randomization and had no primary outcome before revascularization. The comparative cohort excluded participants with prior CABG, single vessel disease, SYNTAX score ≥ 45, and without core laboratory assessment. We focused on the intermediate (23-32) SYNTAX comparative group for which either CABG or PCI could be recommended. RESULTS:For 1935 patients in the descriptive cohort (485 CABG, 1450 PCI), the SYNTAX score was 27.3 ± 11.0 in the CABG group and 15.3 ± 8.6 in the PCI group, p<0.0001. Most patients with low SYNTAX scores underwent PCI (87.1%), while most with high SYNTAX scores underwent CABG (72.6%). For the 1203 patients (385 CABG, 818 PCI) in the entire comparative cohort, the adjusted 4-year primary event rate was 14.5% for CABG and 13.2% for PCI (difference 1.3%, 95% CI, -4.9% to 7.7%). For the 346 patients (163 CABG, 183 PCI) in the intermediate SYNTAX group, the adjusted 4-year primary event rate was 10.6% for CABG and 18.3% for PCI (difference -7.6%, 95% CI, -16.1% to 0.9%). CONCLUSIONS:Selection of revascularization method resulted in more PCI in the low SYNTAX group and more CABG in the high SYNTAX group. There was no statistical evidence of a difference between PCI and CABG in the intermediate SYNTAX group but the CIs are broad, reflecting uncertainty. GOV IDENTIFIER/UNASSIGNED:NCT01471522; https://clinicaltrials.gov/ct2/show/NCT01471522.

BACKGROUND:Despite the increasing use of catheter-based therapies (CBTs) for acute pulmonary embolism (PE), evidence is limited regarding the long-term outcome. OBJECTIVES/OBJECTIVE:We aimed to investigate the efficacy of CBT for high- and intermediate-risk PE in older adults. METHODS:We included Medicare fee-for-service beneficiaries aged 65 to 99 years admitted for PE from 2017 to 2020 and compared in-hospital and long-term outcomes between patients treated with and without CBT. Propensity score matching weight and instrumental variable analyses were implemented. RESULTS:We included 6,742 and 23,750 patients with high-risk and intermediate-risk PE, of which 11.4% and 15.1% patients were treated with CBT. In high-risk PE, patients treated with CBT, compared with those without, experienced lower in-hospital death (29.0% vs 43.9%; adjusted OR [aOR]: 0.73; 95% CI: 0.61-0.87) and 3-year mortality (45.7% vs 65.5%; adjusted HR: 0.76; 95% CI: 0.67-0.85) but higher intracranial hemorrhage (2.1% vs 1.0%; aOR: 2.29; 95% CI: 1.18-4.44). In intermediate-risk PE, we found no evidence that the incidence of in-hospital death differed between the 2 groups (3.1% vs 4.1%; aOR: 0.93; 95% CI: 0.75-1.16), but patients treated with CBT experienced lower 3-year mortality (14.9% vs 30.3%; adjusted HR: 0.69; 95% CI: 0.63-0.75) and higher incidence of intracranial hemorrhage (0.5% vs 0.3%; aOR: 2.04; 95% CI: 1.17-3.55). The association between the use of CBT and lower 3-year mortality was consistent in the instrumental variable analysis. CONCLUSIONS:Among older adults with high-risk or intermediate-risk PE, patients treated with CBT experienced lower mortality over the follow-up of up to 3 years, but higher risk of in-hospital bleeding complications.

BACKGROUND:Acute pulmonary embolism (PE) is a common cause of cardiovascular morbidity and mortality. Catheter-based therapies (CBT) are emerging technologies that provide reperfusion for patients with PE. However, the optimal timing of these interventions from initial presentation is unknown. AIMS/OBJECTIVE:This study aimed to determine whether the timing of CBT affects outcomes among patients with acute PE managed with CBT. METHODS:This was a retrospective cohort study of patients with PE who underwent CBT and were included in the Nationwide Readmissions Database between January 2017 and December 2020. Patients who underwent early CBT (≤1 day from admission) were compared with those who underwent delayed CBT (>1 day). The primary outcome was death at 90 days, and secondary outcomes included 90-day readmissions. Propensity scores were estimated using logistic regression, and propensity score weighting (PSW) was utilised to compare outcomes between early and delayed CBT. Cox proportional hazards modelling was used to estimate the risk of primary and readmission outcomes. RESULTS:A total of 12,137 patients were included: 1,992 (16.4%) had high-risk PE, and 1,856 (15.3%) were treated with delayed CBT. After PSW, early CBT was associated with a lower risk of 90-day death in both intermediate-risk (hazard ratio [HR] 0.55, 95% confidence interval [CI]: 0.46-0.66) and high-risk (HR 0.89, 95% CI: 0.80-0.99) PE. Early CBT was associated with lower rates of all-cause readmission in patients with intermediate-risk PE (HR 0.86, 95% CI: 0.78-0.95) and in those with high-risk PE (HR 0.84, 95% CI: 0.69-1.05). CONCLUSIONS:Among patients with intermediate- or high-risk PE, early CBT was associated with a lower risk of 90-day death and readmission. A further prospective study on the optimal timing for reperfusion using CBT is needed.

Pulmonary embolism response teams (PERTs) are being increasingly used for the management of patients admitted with acute pulmonary embolism (PE) and are endorsed by societal guidelines. Whether PERT improves outcomes remains unknown. The objective of this meta-analysis was to compare the outcomes of patients with acute PE treated by a PERT versus no PERT.A systematic review and study level meta-analysis was conducted by searching PubMed and EMBASE databases from inception until November 10, 2024 and included studies evaluating efficacy of PERT vs no PERT in patients admitted for acute PE. Outcomes included all-cause mortality (in-hospital and 30-day mortality), major and clinically relevant bleeding, advanced therapies utilization, length of stay (LOS), and 30-day readmission. Twenty-four retrospective observational studies met the inclusion criteria, comprising 15,809 patients (mean age 61.6 years with 49% male) with acute PE of which 6228 were treated with a PERT and 9,581 without a PERT. Lower all-cause mortality (in-hospital or 30-day mortality) [odds ratio (OR)= 0.72; 95% CI: 0.56 to 0.93; 24 studies], major or clinically relevant bleeding (OR= 0.60; 95% CI: 0.42 to 0.86; 15 studies), higher utilization of advanced therapies (OR= 3.16; 95% CI: 1.81 to 5.49; 19 studies), and lower hospital LOS (MD= -1.49; 95% CI: -2.59 to -0.39; 14 studies) were seen in the patients treated by a PERT compared to those not treated by a PERT. In this large meta-analysis of observational studies comparing outcomes in patients treated by PERT versus not treated by PERT, there were significantly lower short-term mortality, lower major or clinically relevant bleeding, higher utilization of advanced therapies and lower hospital length of stay with the existence of PERT. PERT should be the standard of care for the management of patients with acute PE.

BACKGROUND:Randomized trials of chronic total occlusion (CTO) revascularization vs medical therapy have yielded inconsistent results. OBJECTIVES/OBJECTIVE:The aim of this study was to evaluate outcomes with an initial invasive strategy (INV) vs an initial conservative strategy (CON) in patients with coronary computed tomographic angiography (CCTA)-determined CTO in the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial. METHODS:Participants in ISCHEMIA who underwent CCTA evaluated for CTO by the core laboratory (3,113 of 5,179 randomized patients [60%]) were categorized into subgroups with (100% stenosis) and without (<100% stenosis) CTO. Primary analysis compared outcomes in those randomized to INV vs CON using an intention-to-treat approach. Secondary analyses compared outcomes using inverse probability weighting to model successful CTO revascularization (REV) in all INV participants vs CON participants. RESULTS:Of the 3,113 CCTA-evaluable participants, 1,470 had at least 1 CTO (752 INV and 718 CON). INV did not reduce cardiovascular (CV) death or myocardial infarction (MI) (5-year difference -3.5%; 95% CI: -7.8% to 0.8%) and resulted in more procedural MIs (2.5%; 95% CI: 1.0%-4.0%) but fewer spontaneous MIs (-6.3%; 95% CI: -9.7% to -3.2%) than CON. CTO REV modeled across INV had a high probability (>90%) of any lower CV death or MI, MI, spontaneous MI, unstable angina, and heart failure counterbalanced by a higher rate of procedural MI. CTO REV significantly improved angina-related quality of life (mean difference 4.6 points), Rose Dyspnea Scale score (rescaled) (mean difference 5.3 points), and EQ-5D visual analog scale score (4.6 points). CONCLUSIONS:In the ISCHEMIA trial, the risks and benefits of INV compared with CON were similar among patients with and without CCTA-determined CTO (more frequent procedural MI, less frequent spontaneous MI, and significantly improved angina and dyspnea-related quality of life). In an observational comparison, successful CTO REV was associated with a high probability of lower CV death or MI (driven by lower MI) compared with CON. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

BACKGROUND:Guideline-directed medical therapy (GDMT) with multiple risk factor goals is recommended for patients with chronic coronary disease (CCD), yet achieving all GDMT goals is uncommon. The relative importance of these goals and timing of their attainment on cardiovascular events is uncertain. OBJECTIVES/OBJECTIVE:This study aims to describe the relationship between achieving specific GDMT goals, when they are achieved, and clinical outcomes. METHODS:This was an observational study of participants with CCD in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. The primary outcome was cardiovascular (CV) death or myocardial infarction (MI). GDMT goals were systolic blood pressure (SBP) <130 mm Hg, low-density lipoprotein cholesterol <70 mg/dL, not smoking, and antiplatelet therapy. Frequency of GDMT goals met at baseline and during follow-up is described. Bayesian joint modeling for longitudinal goal status and time-to-event analyses characterized the relative importance of specific GDMT goal attainment and timing with CV death/MI. RESULTS:All 5,179 ISCHEMIA participants were included. Among 4,914 participants with complete data on all 4 GDMT goals at baseline, 386 (9%), 2,073 (42%), 1,843 (38%), and 612 (12%) met 0-1, 2, 3, and 4 GDMT goals, respectively. The 4-year cumulative event rate for CV death/MI was highest for participants who attained no GDMT goals (24.5%; 95% credible interval [CrI]: 13.5%-42.2%) and lowest for those who attained all goals at baseline and remained at goal during follow-up (8.7%; 95% CrI: 6.7%-10.9%). SBP goal attainment was associated with a significant absolute event reduction in CV death/MI (-5.1%; 95% CrI: -11.3% to -1.0%), followed by antiplatelet therapy (-11.2%; 95% CrI: -29.1% to 0.8%), achieving low-density lipoprotein cholesterol <70 mg/dL (-2.0%; 95% CrI: -6.0% to 2.4%), and not smoking (-1.7%; 95% CrI: -9.3% to 4.2%). Ten millimeters of mercury lower SBP during follow-up was associated with 10% relative risk reduction of CV death/MI (RR [relative risk] = 0.90; 95% CrI: 0.82-0.98), after adjusting for other GDMT goals and baseline characteristics. CONCLUSIONS:Among participants with CCD, early attainment and maintenance of GDMT goals, especially SBP, were associated with fewer cardiovascular events. Compared with no GDMT goals at target, having all 4 GDMT goals at target at baseline was associated with an absolute 16% fewer CV deaths and MIs. (ISCHEMIA [International Study of Comparative Health Effectiveness With Medical and Invasive Approaches]; NCT01471522).