Publications

INTRODUCTION: Two of the main reasons recent guidelines do not recommend routine population-wide screening programs for asymptomatic carotid artery stenosis (AsxCS) is that screening could lead to an increase of carotid revascularization procedures and that such mass screening programs may not be cost-effective. Nevertheless, selective screening for AsxCS could have several benefits. This article presents the rationale for such a program.

AREAS COVERED: The benefits of selective screening for AsxCS include early recognition of AsxCS allowing timely initiation of preventive measures to reduce future myocardial infarction (MI), stroke, cardiac death and cardiovascular (CV) event rates.

EXPERT OPINION: Mass screening programs for AsxCS are neither clinically effective nor cost-effective. Nevertheless, targeted screening of populations at high risk for AsxCS provides an opportunity to identify these individuals earlier rather than later and to initiate a number of lifestyle measures, risk factor modifications, and intensive medical therapy in order to prevent future strokes and CV events. For patients at 'higher risk of stroke' on best medical treatment, a prophylactic carotid intervention may be considered.

Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases.

BACKGROUND: Ultrasound enhancing agents (UEAs) are an invaluable adjunct to stress and transthoracic echocardiography (STE) to improve left ventricular visualization. Despite multiple single center studies evaluating UEA use, investigation into the rates, sources of variation, and outcomes of UEA use on a national level in the United States (US) has been limited by lack of validation of UEA codes for claims analyses.

METHODS: We conducted a retrospective cross-sectional study, 2019-2022, using linked multicenter electronic medical record (EMR) data from > 30 health systems linked to all-payor claims data representing > 90% of the US population. Individuals receiving STE in both EMR and claims data on the same day during the study window were included. UEA receipt as identified by presence of a Current Procedural Terminology (CPT) or National Drug Code (NDC) for UEA use within 1-day of the index STE event. We evaluated the performance of claims to identify UEA use, using EMR data as the gold standard, stratified by inpatient and outpatient status.

RESULTS: Amongst 54,525 individuals receiving STE in both EMR and claims data, 12,853 (23.6%) had a UEA claim in EMR, 10,461 (19.2%) had a UEA claim in claims, and 9140 (16.8%) had a UEA claim in both within the 1-day window. The sensitivity, specificity, accuracy, positive, and negative predictive values for UEA claims were 71.1%, 96.8%, 90.8%, 87.4%. and 91.6% respectively. However, amongst inpatients, the sensitivity of UEA claims was substantially lower (6.8%) compared to outpatients (79.7%).

CONCLUSIONS: While the overall accuracy of claims to identify UEA use was high, there was substantial under-capture of UEA use by claims amongst inpatients. These results call into question published rates of UEA use amongst inpatients in studies using administrative claims, and highlight ongoing need to improve inpatient coding for UEA use.

BACKGROUND: Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent influence of frailty progression remains uncertain.

METHODS: Medicare Fee-for-service beneficiaries ≥ 65 years at cohort inception with continuous enrollment from 2003-2015 were included. Frailty trajectory was measured by annualized change in a validated claims-based frailty index (CFI) over a 5-year period. Linear mixed effects models, adjusting for baseline frailty, were used to estimate CFI change over a 5-year period. Survival analysis was used to evaluate associations of frailty progression and future health outcomes (major adverse cardiovascular and cerebrovascular events [MACCE], all-cause death, heart failure, myocardial infarction, ischemic stroke, and days alive at home [DAH] within the following calendar year).

RESULTS: 26.4 million unique beneficiaries were included (mean age 75.4 ± 7.0 years, 57% female, 13% non-White). In total, 20% had frailty progression, 66% had no change in frailty, and 14% frailty regression over median follow-up of 2.4 years. Compared to those without a change in CFI, when adjusting for baseline frailty, those with frailty progression had significantly greater risk of incident MACCE (hazard ratio [HR] 2.30, 95% confidence interval [CI] 2.30-2.31), all-cause mortality (HR 1.59, 95% CI 1.58-1.59), acute myocardial infarction (HR 1.78, 95% CI 1.77-1.79), heart failure (HR 2.78, 95% CI 2.77-2.79), and stroke (HR 1.78, 95% CI 1.77-1.79). There was also a graded increase in risk of each outcome with more rapid progression and significantly fewer DAH with the most rapid vs. the slowest progression group (270.4 ± 112.3 vs. 308.6 ± 93.0 days, rate ratio 0.88, 95% CI 0.87-0.88, p < 0.001).

CONCLUSIONS: In this large, nationwide sample of Medicare beneficiaries, frailty progression, independent of baseline frailty, was associated with fewer DAH and a graded risk of MACCE, all-cause mortality, myocardial infarction, heart failure, and stroke compared to those without progression.

BACKGROUND: Secondary prevention lifestyle and pharmacological treatment of atherosclerotic cardiovascular disease (ASCVD) reduce a high proportion of recurrent events and mortality. However, significant gaps exist between guideline recommendations and usual clinical practice.

OBJECTIVES: Describe the state of the art, the roadblocks, and successful strategies to overcome them in ASCVD secondary prevention management.

METHODS: A writing group reviewed guidelines and research papers and received inputs from an international committee composed of cardiovascular prevention and health systems experts about the article's structure, content, and draft. Finally, an external expert group reviewed the paper.

RESULTS: Smoking cessation, physical activity, diet and weight management, antiplatelets, statins, beta-blockers, renin-angiotensin-aldosterone system inhibitors, and cardiac rehabilitation reduce events and mortality. Potential roadblocks may occur at the individual, healthcare provider, and health system levels and include lack of access to healthcare and medicines, clinical inertia, lack of primary care infrastructure or built environments that support preventive cardiovascular health behaviours. Possible solutions include improving health literacy, self-management strategies, national policies to improve lifestyle and access to secondary prevention medication (including fix-dose combination therapy), implementing rehabilitation programs, and incorporating digital health interventions. Digital tools are being examined in a range of settings from enhancing self-management, risk factor control, and cardiac rehab.

CONCLUSIONS: Effective strategies for secondary prevention management exist, but there are barriers to their implementation. WHF roadmaps can facilitate the development of a strategic plan to identify and implement local and national level approaches for improving secondary prevention.

IMPORTANCE: Familial hypercholesterolemia (FH) is a genetic disorder that often results in severely high low-density lipoprotein cholesterol (LDL-C) and high risk of premature coronary heart disease (CHD). However, the impact of FH variants on CHD risk among individuals with moderately elevated LDL-C is not well quantified.

OBJECTIVE: To assess CHD risk associated with FH variants among individuals with moderately (130-189 mg/dL) and severely (≥190 mg/dL) elevated LDL-C and to quantify excess CHD deaths attributable to FH variants in US adults.

DESIGN, SETTING, AND PARTICIPANTS: A total of 21 426 individuals without preexisting CHD from 6 US cohort studies (Atherosclerosis Risk in Communities study, Coronary Artery Risk Development in Young Adults study, Cardiovascular Health Study, Framingham Heart Study Offspring cohort, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis) were included, 63 of whom had an FH variant. Data were collected from 1971 to 2018, and the median (IQR) follow-up was 18 (13-28) years. Data were analyzed from March to May 2023.

EXPOSURES: LDL-C, cumulative past LDL-C, FH variant status.

MAIN OUTCOMES AND MEASURES: Cox proportional hazards models estimated associations between FH variants and incident CHD. The Cardiovascular Disease Policy Model projected excess CHD deaths associated with FH variants in US adults.

RESULTS: Of the 21 426 individuals without preexisting CHD (mean [SD] age 52.1 [15.5] years; 12 041 [56.2%] female), an FH variant was found in 22 individuals with moderately elevated LDL-C (0.3%) and in 33 individuals with severely elevated LDL-C (2.5%). The adjusted hazard ratios for incident CHD comparing those with and without FH variants were 2.9 (95% CI, 1.4-6.0) and 2.6 (95% CI, 1.4-4.9) among individuals with moderately and severely elevated LDL-C, respectively. The association between FH variants and CHD was slightly attenuated when further adjusting for baseline LDL-C level, whereas the association was no longer statistically significant after adjusting for cumulative past LDL-C exposure. Among US adults 20 years and older with no history of CHD and LDL-C 130 mg/dL or higher, more than 417 000 carry an FH variant and were projected to experience more than 12 000 excess CHD deaths in those with moderately elevated LDL-C and 15 000 in those with severely elevated LDL-C compared with individuals without an FH variant.

CONCLUSIONS AND RELEVANCE: In this pooled cohort study, the presence of FH variants was associated with a 2-fold higher CHD risk, even when LDL-C was only moderately elevated. The increased CHD risk appeared to be largely explained by the higher cumulative LDL-C exposure in individuals with an FH variant compared to those without. Further research is needed to assess the value of adding genetic testing to traditional phenotypic FH screening.

IMPORTANCE: Drug-coated balloons offer a potentially beneficial treatment strategy for the management of coronary in-stent restenosis. However, none have been previously evaluated or approved for use in coronary circulation in the United States.

OBJECTIVE: To evaluate whether a paclitaxel-coated balloon is superior to an uncoated balloon in patients with in-stent restenosis undergoing percutaneous coronary intervention.

DESIGN, SETTING, AND PARTICIPANTS: AGENT IDE, a multicenter randomized clinical trial, enrolled 600 patients with in-stent restenosis (lesion length <26 mm and reference vessel diameter >2.0 mm to ≤4.0 mm) at 40 centers across the United States between May 2021 and August 2022. One-year clinical follow-up was completed on October 2, 2023.

INTERVENTIONS: Participants were randomized in a 2:1 allocation to undergo treatment with a paclitaxel-coated (n = 406) or an uncoated (n = 194) balloon.

MAIN OUTCOMES AND MEASURES: The primary end point of 1-year target lesion failure-defined as the composite of ischemia-driven target lesion revascularization, target vessel-related myocardial infarction, or cardiac death-was tested for superiority.

RESULTS: Among 600 randomized patients (mean age, 68 years; 157 females [26.2%]; 42 Black [7%], 35 Hispanic [6%] individuals), 574 (95.7%) completed 1-year follow-up. The primary end point at 1 year occurred in 17.9% in the paclitaxel-coated balloon group vs 28.6% in the uncoated balloon group, meeting the criteria for superiority (hazard ratio [HR], 0.59 [95% CI, 0.42-0.84]; 2-sided P = .003). Target lesion revascularization (13.0% vs 24.7%; HR, 0.50 [95% CI, 0.34-0.74]; P = .001) and target vessel-related myocardial infarction (5.8% vs 11.1%; HR, 0.51 [95% CI, 0.28-0.92]; P = .02) occurred less frequently among patients treated with paclitaxel-coated balloon. The rate of cardiac death was 2.9% vs 1.6% (HR, 1.75 [95% CI, 0.49-6.28]; P = .38) in the coated vs uncoated balloon groups, respectively.

CONCLUSIONS AND RELEVANCE: Among patients undergoing coronary angioplasty for in-stent restenosis, a paclitaxel-coated balloon was superior to an uncoated balloon with respect to the composite end point of target lesion failure. Paclitaxel-coated balloons are an effective treatment option for patients with coronary in-stent restenosis.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04647253.