Christopher P. Cannon

Objective: Remote interventions leveraging team‐based care may ameliorate persistent gaps in obesity medication implementation, but prospective studies are lacking. In this paper, the design, enrollment, and implementation of a remote intervention for obesity medications are described. Methods: The Supplementary Anti‐Obesity Medication Integration into a Longitudinal Obesity (SAIL) study is a fully remote program with pharmacist‐ and navigator‐led obesity medication implementation. Individuals with body mass index (BMI)‐defined overweight or obesity receiving a digital lifestyle intervention were recruited for participation in SAIL via a survey. Effectiveness outcomes included obesity medication prescription and body weight change at 6 months. Focus groups were conducted with study staff after program completion to identify implementation barriers and solutions. Results: Between June 2023 and September 2024, 200 patients responded to the survey, of which 99 were eligible. Of these, 75 enrolled in SAIL (mean age, 50 ± 12 years; 83% women; mean BMI 36 ± 6 kg/m ² ). Focus groups identified multiple implementation challenges and opportunities, including medication access, insurance coverage, and patient education. Addressing misinformation, frequent patient engagement, and program flexibility emerged as unique strengths of SAIL. Conclusions: The final results of SAIL will inform the effectiveness of remote, algorithm‐driven, navigator‐ and pharmacist‐led programs for obesity medication prescription and management.

BACKGROUND: The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America heart failure (HF) classification incorporates cardiac biomarkers to identify early risk of HF. The HF stages may also guide the prognosis and management of cardiovascular and kidney-related events. METHODS: SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) was a randomized trial in diabetes with kidney disease comparing sotagliflozin versus placebo on cardiovascular death, HF hospitalizations, and urgent HF visits. SCORED participants were grouped by HF stage post hoc. Stage A: no HF, normal biomarkers (NT-proBNP [N-terminal pro-B-type natriuretic peptide] <125 pg/mL; high sensitivity cardiac troponin T [hs-cTnT] 2- and 5-fold, respectively. The benefits of sotagliflozin are consistent, irrespective of HF stage.

Background: Despite overwhelming evidence of clinical benefit for patients with heart failure (HF), the uptake of guideline‐directed medical therapies (GDMT) has been slow. Collaborative approaches are critically needed to improve alignment between evidence and clinical practice. Many strategies proposed to improve GDMT implementation have been either ineffective or too resource‐intensive to implement at scale across different practice contexts. Furthermore, most existing approaches focus primarily on patients with HF and reduced EF, despite growing evidence for effective pharmacologic therapy in those with HF and mildly reduced or preserved ejection fraction (HFpEF). Hypothesis: Based on this experience, we designed the Cooperative Program for ImpLementation of Optimal Therapy in Heart Failure (COPILOT‐HF) study (NCT05734690). Methods: This is a pragmatic, randomized, open‐label intervention trial to compare a comprehensive, remote, navigator‐led, algorithm‐driven strategy for optimization of GDMT prescribing in patients with HF across the full spectrum of ejection fraction with a control intervention focused on patient and provider education regarding the importance of GDMT optimization. Results: The primary efficacy endpoint of the study is the proportion of patients receiving optimal HF treatment at 3 months. Additional outcomes of interest include the proportion of patients with optimal HF therapy at 6 months and 12 months as well as health resource utilization, including hospitalizations and deaths. Conclusions: COPILOT‐HF will evaluate the effectiveness of an early implementation of a remote pharmacist‐led medication titration strategy across the HF spectrum.

Background and Aims: Large-scale genome-wide association studies have identified common genetic variants that predict the risk of peripheral artery disease (PAD). This study assessed whether a polygenic risk score (PRS) is associated with PAD and the incidence of major adverse limb events (MALE) independent of clinical risk factors in patients with established cardiometabolic disease. Methods: A genetic analysis was performed, pooling individual patient-level data from six TIMI trials. The association of a recently validated PAD PRS with prevalent PAD and the incidence of MALE (acute limb ischaemia, chronic limb-threatening ischaemia, major amputation, or peripheral revascularization) was assessed. Results: A total of 68 816 patients were included in this analysis, with a median follow-up of 2.6 years. Of these, 5986 (8.7%) had known PAD at baseline. After adjusting for clinical risk factors, a higher PAD PRS was independently associated with a 15% greater odds of prevalent PAD (adjusted odds ratio per 1-SD: 1.15 [95% confidence interval 1.12–1.18], P < .0001), a magnitude of risk as strong as established clinical risk factors. A total of 577 patients experienced MALE during follow-up. A higher PAD PRS was associated with a 30% increased risk of MALE (adjusted hazard ratio per 1-SD: 1.30 [1.19–1.42], P < .0001). Adding the PAD PRS to clinical risk factors resulted in a statistically significant but modest improvement in discrimination (area under the curve went from 0.651 to 0.662 P < .0001). Conclusions: In a broad spectrum of patients with cardiometabolic disease, the PAD PRS is associated with an increased risk of PAD and the incidence of MALE beyond clinical risk factors; however, the improvement in discrimination was statistically significant but clinically modest.

Aims: Coronary artery disease (CAD) polygenic risk scores (PRS) enhance risk stratification, but it is unknown whether the degree varies across the spectrum of atherosclerotic cardiovascular disease (ASCVD). We compared the association of a CAD PRS and coronary events in patients with ASCVD and a prior ischaemic event, ASCVD without event, and without overt ASCVD. Methods and results: Genotyped patients from 6 multinational cardiovascular trials were categorized into low (bottom 20%), intermediate (middle 60%), and high (top 20%) genetic risk using a genome-wide CAD PRS, then grouped by ASCVD status. The primary endpoint was any major coronary event, a composite of death from coronary disease, myocardial infarction, or coronary revascularization. 59 905 participants (mean age, 66 years; 71% male) were included; 47 456 (79%) had established ASCVD. Compared with low genetic risk, major coronary events were more frequent in high (HR, 2.06; 95% CI, 1.88–2.24; P < 0.001) and intermediate (HR, 1.57; 95% CI, 1.45–1.70; P < 0.001) genetic risk. Genetic risk was more strongly associated with major coronary events in patients without overt ASCVD (HR between high vs. low genetic risk, 4.63) than patients with ASCVD without (HR, 1.73) or with an ischaemic event (HR, 1.63) (Pinteraction < 0.001). Absolute risk difference between high and low genetic risk was comparable across ASCVD categories (5.0–7.0% difference at 3 years). Conclusion: A CAD PRS was associated with incident major coronary events in all ASCVD categories. Although genetics provided the strongest relative association in patients without established ASCVD, the absolute risk gradient was comparable for patients with and without ASCVD. Registration: ClinicalTrials.gov Identifiers: NCT01730534, NCT00781391, NCT01764633, NCT01225562, NCT01107886, NCT01000727.

BACKGROUND: Hypertension is a major cardiovascular risk factor, yet traditional care often results in suboptimal blood pressure (BP) control at the population level. We implemented a remote hypertension management program that monitored home BP and titrated medications per algorithm. This study assessed the program’s long-term effects by examining participants’ office BP up to 42 months post-enrollment. METHODS: Participants of the remote hypertension program were categorized into 4 groups: (1) enrolled-maintenance (achieved goal home BP of ≤130/80 mm Hg), (2) enrolled–early exit (left before achieving goal BP), (3) education-only (lifestyle modifications and medications compliance), and (4) white coat hypertension group (high office BP but normal home BP). Office BP readings of participants were collected up to 42 months post-enrollment. A linear mixed-effects regression model estimated mean BP levels and studied factors associated with above-goal systolic BP in the maintenance group. RESULTS: Office BP readings from 3601 participants (mean age, 61±11 years; 57% female; 60% white; 52% atherosclerotic cardiovascular disease) were extracted from electronic health records and analyzed. All groups sustained office BP below their qualifying values ( P 50 years was associated with above-goal systolic BP in the maintenance group. CONCLUSIONS: Participants who achieved BP control through the remote hypertension program maintained goal systolic BP in 90% of cases up to 42 months post-enrollment. These findings highlight the long-term benefits of remote, intensive management programs for effective hypertension control.

Introduction: VERTIS CV was a placebo-controlled cardiovascular (CV) outcome trial evaluating the sodium-glucose cotransporter 2 inhibitor ertugliflozin in patients with type 2 diabetes and established atherosclerotic CV disease. The aim of the current analyses was to evaluate VERTIS CV cardiorenal outcomes according to baseline use of renin-angiotensin-aldosterone system (RAAS) inhibitors or diuretics, including mineralocorticoid receptor antagonists (MRAs). Methods: Participants received ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo once daily and were followed for a mean of 3.5 years. Prespecified CV and kidney outcomes were analyzed by Cox proportional hazard modeling in participant subgroups defined by baseline use of RAAS inhibitors (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers) or diuretics (loop diuretics, non-loop diuretics, MRAs), with interaction testing to assess for treatment effect modification. Results: A total of 8,246 patients were randomized in VERTIS CV. At baseline, 6,686 (81%) participants were being treated with RAAS inhibitors, 3,542 (43%) with diuretics, 1,252 (15%) with loop diuretics, and 674 (8%) with MRAs. No significant interactions were observed for cardiorenal outcomes by baseline use of RAAS inhibitors or MRAs (pinteraction > 0.05 for all). Statistically significant interactions for a first event of hospitalization for heart failure (HHF) or CV death, and of HHF (alone), were observed with baseline use of diuretics, including loop diuretics, with an increased benefit of ertugliflozin treatment versus placebo. Conclusion: In VERTIS CV, baseline use of diuretics, particularly loop diuretics, identified a subgroup that demonstrated greater benefit with ertugliflozin on first HHF/CV death and HHF outcomes, with no modification of treatment effect observed with baseline use of RAAS inhibitors or MRAs. There was no evidence of treatment effect on the kidney composite outcomes by baseline use of RAAS inhibitors, diuretics, loop diuretics, or MRAs.