A Technology-Assisted Web Application for Consumer Access to a Nonprescription Statin Medication.

BACKGROUND: Although statins reduce adverse cardiovascular outcomes, less than half of eligible patients receive treatment. A nonprescription statin has the potential to improve access to statins. OBJECTIVES: To assess concordance between clinician and consumer assessment of eligibility for nonprescription statin treatment using a Technology Assisted Self-Selection (TASS) Web Application (Web App) and evaluate effect on low-density lipoprotein cholesterol (LDL-C) levels. METHODS: A prospective actual use 6-month study to evaluate use of a Web App to qualify participants without a medical background for a moderate intensity statin based on current guidelines. Participants entered demographic information, cholesterol values, blood pressure and concomitant medications into the Web App, resulting in three possible outcomes- "Do Not Use," "Ask a Doctor" or "OK to Use". RESULTS: The study included 1196 participants, median age 63 (IQR, 57-68), 39.6% women, 79.3% White, 11.7% Black, and 4.1% with limited literacy. Mean LDL-C was 139.6 mg/dL (SD, 28.3) and median calculated 10-year risk of atherosclerotic cardiovascular disease was 10.1% (IQR, 7.3-14.0). Initial Web App self-selection resulted in an outcome concordant with clinician assessment in 90.7% (95% CI, 88.9-92.3) of participants and 98.1% (95% CI, 97.1-98.8) had a concordant final use outcome during treatment. Mean percent change in LDL-C was -35.5% (95% CI, -36.6 to -34.3). Serious adverse events occurred in 27 (2.3%) participants, none related to study drug. CONCLUSIONS: In this actual use study, a technology assisted Web App allowed >90% of consumers to correctly self-select for statin use and achieve clinically important LDL-C reductions.

Single Ascending and Multiple-Dose Trial of Zerlasiran, a Short Interfering RNA Targeting Lipoprotein(a): A Randomized Clinical Trial.

Importance: Lipoprotein(a) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic stenosis, with no pharmacological treatments approved by regulatory authorities. Objectives: To assess the safety and tolerability of zerlasiran, a short interfering RNA targeting hepatic synthesis of apolipoprotein(a), and effects on serum concentrations of lipoprotein(a). Design, Setting, and Participants: Single- and multiple-dose study in healthy participants and patients with stable ASCVD, respectively, with lipoprotein(a) serum concentrations greater than 150 nmol/L, conducted at 7 research sites in the US, the Netherlands, UK, and Australia between November 18, 2020, and February 8, 2023, with last follow-up on August 23, 2023. Interventions: Participants were randomized to receive (1) a single subcutaneous dose of placebo (n = 8), zerlasiran 300 mg (n = 6) or 600 mg (n = 6); or (2) 2 doses of placebo (n = 9), zerlasiran 200 mg (n = 9) at a 4-week interval or 300 mg (n = 9) or 450 mg (n = 9) at an 8-week interval. Main Outcomes Measures: The primary outcome was safety and tolerability. Secondary outcomes included serum levels of zerlasiran and effects on lipoprotein(a) serum concentrations. Results: Among 37 patients in the multiple-dose group (mean age, 56 [SD, 10.4] years; 15 [42%] women), 36 completed the trial. Among 14 participants with extended follow-up after single doses, 13 completed the trial. There were no serious adverse events. Median baseline lipoprotein(a) concentrations in the multiple-dose group were 288 (IQR, 199-352) nmol/L. Median changes in lipoprotein(a) concentration at 365 days after single doses were 14% (IQR, 13% to 15%) for the placebo group, -30% (IQR, -51% to -18%) for the 300 mg of zerlasiran group, and -29% (IQR, -39% to -7%) for the 600-mg dose group. After 2 doses, maximal median changes in lipoprotein(a) concentration were 19 (IQR, -17 to 28) nmol/L for the placebo group, -258 (IQR, -289 to -188) nmol/L for the 200 mg of zerlasiran group, -310 (IQR, -368 to -274) nmol/L for the 300-mg dose group, and -242 (IQR, -343 to -182) nmol/L for the 450-mg dose group, with maximal median percent change of 7% (IQR, -4% to 21%), -97% (IQR, -98% to -95%), -98% (IQR, -99% to -97%), and -99% (IQR, -99% to -98%), respectively, attenuating to 0.3% (IQR, -2% to 21%), -60% (IQR, -71% to -40%), -90% (IQR, -91% to -74%), and -89% (IQR, -91% to -76%) 201 days after administration. Conclusions: Zerlasiran was well tolerated and reduced lipoprotein(a) concentrations with infrequent administration. Trial Registration: ClinicalTrials.gov Identifier: NCT04606602.

Trends and Outcomes Associated With Bariatric Surgery and Pharmacotherapies With Weight Loss Effects Among Patients With Heart Failure and Obesity.

BACKGROUND: Utilization patterns of bariatric surgery among older patients with heart failure (HF), and the associations with cardiovascular outcomes, are not well known. METHODS: Medicare beneficiaries with HF and at least class II obesity from 2013 to 2020 were identified with Medicare Provider Analysis and Review 100% inpatient files and Medicare 5% outpatient files. Patients who underwent bariatric surgery were matched to controls in a 1:2 ratio (matched on exact age, sex, race, body mass index, HF encounter year, and HF hospitalization rate pre-surgery/matched period). In an exploratory analysis, patients prescribed pharmacotherapies with weight loss effects (semaglutide, liraglutide, naltrexone-bupropion, or orlistat) were identified and matched to controls with a similar strategy in addition to HF medical therapy data. Cox models evaluated associations between weight loss therapies (as a time-varying covariate) and mortality risk and HF hospitalization rate (calculated as the rate of HF hospitalizations following index HF encounter per 100 person-months) during follow-up. RESULTS: Of 298 101 patients with HF and body mass index ≥35 kg/m2, 2594 (0.9%) underwent bariatric surgery (45% men; mean age, 56.2 years; mean body mass index, 51.5 kg/m2). In propensity-matched analyses over a median follow-up of 4.7 years, bariatric surgery was associated with lower risk of all-cause mortality (HR, 0.55 [95% CI, 0.49-0.63]; P<0.001), greater reduction in HF hospitalization rate (rate ratio, 0.72 [95% CI, 0.67-0.77]; P<0.001), and lower atrial fibrillation risk (HR, 0.78 [95% CI, 0.65-0.93]; P=0.006). Use of pharmacotherapies with weight loss effects was low (4.8%), with 96.3% prescribed GLP-1 (glucagon-like peptide-1) agonists (semaglutide, 23.6%; liraglutide, 72.7%). In propensity-matched analysis over a median follow-up of 2.8 years, patients receiving pharmacotherapies with weight loss effects (versus matched controls) had a lower risk of all-cause mortality (HR, 0.82 [95% CI, 0.71-0.95]; P=0.007) and HF hospitalization rate (rate ratio, 0.87 [95% CI, 0.77-0.99]; P=0.04). CONCLUSIONS: Bariatric surgery and pharmacotherapies with weight loss effects are associated with a lower risk of adverse outcomes among older patients with HF and obesity; however, overall utilization remains low.

Sex-Specific Prognosis of Left Ventricular Size and Function Following Repair of Degenerative Mitral Regurgitation.

BACKGROUND: Prior studies have demonstrated worse long-term outcomes for women after surgery for severe mitral regurgitation (MR). The current Class I indications for surgery for severe degenerative MR use cutoffs of left ventricular end-systolic dimension (LVESD) and left ventricular ejection fraction (EF) that do not account for known sex-related differences. OBJECTIVES: The primary objective of this study was to assess long-term mortality following mitral valve repair in women compared with men on the basis of preoperative left ventricular systolic dimensions and EF. METHODS: Consecutive patients who underwent isolated mitral valve repair for degenerative MR at a single institution between 1994 and 2016 were screened. Adjusted HRs for all-cause mortality were compared according to baseline LVESD, LVESD indexed to body surface area (LVESDi), and EF for men and women. RESULTS: Among 4,589 patients, 1,825 were women (40%), and after a median follow-up period of 7.2 years, 344 patients (7.5%) had died. The risk for mortality for women increased from the baseline hazard at an LVESD of 3.6 cm, whereas an inflection point for increased risk with LVESD was not evident in men. Regarding LVESDi, the risk for women increased at 1.8 cm/m2 compared with 2.1 cm/m2 in men. For EF, women and men had a similar inflection point (58%); however, mortality was higher for women as EF decreased. CONCLUSIONS: After mitral valve repair, women have a higher risk for all-cause mortality at lower LVESD and LVESDi and higher EF. These results support consideration of sex-specific thresholds for LVESDi in surgical decision making for patients with severe MR.

Coronary spasm and vasomotor dysfunction as a cause of MINOCA.

Increasing evidence has shown that coronary spasm and vasomotor dysfunction may be the underlying cause in more than half of myocardial infarctions with non-obstructive coronary arteries (MINOCA) as well as an important cause of chronic chest pain in the outpatient setting. We review the contemporary understanding of coronary spasm and related vasomotor dysfunction of the coronary arteries, the pathophysiology and prognosis, and current and emerging approaches to diagnosis and evidence-based treatment.

Nonstatin therapy to reduce low-density lipoprotein cholesterol and improve cardiovascular outcomes.

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality, with low-density lipoprotein (LDL) cholesterol being a causative risk factor. Though statins have a decades-long track record of efficacy and safety, nonstatin agents may be used to reduce LDL cholesterol as an adjunct or alternative to statin therapy. Several new nonstatin medications have been approved in recent years, with robust data from clinical trials supporting their use in atherosclerotic disease. This review addresses the indications, evidence, and important prescribing considerations for using nonstatin lipid-lowering therapy and proposes a practical approach for determining when to initiate nonstatin therapy.

Impact of Bempedoic Acid on Total Cardiovascular Events: A Prespecified Analysis of the CLEAR Outcomes Randomized Clinical Trial.

Importance: The ATP citrate lyase (ACL) inhibitor, bempedoic acid, reduces low-density lipoprotein cholesterol (LDL-C) level and major adverse cardiovascular events (MACE) by 13% in patients at high cardiovascular risk with intolerance of statin and high-intensity statin medications. The effects of bempedoic acid on total cardiovascular events remain unknown. Objective: To determine the impact of bempedoic acid on the total incidence of MACE. Design, Setting, and Participants: Included in this prespecified analysis of the Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes trial were patients with, or at high risk for, cardiovascular disease, with hypercholesterolemia and inability to take guideline-recommended statins. Study data were analyzed from December 2016 to November 2022. Interventions: Patients were randomly assigned to treatment with bempedoic acid or placebo daily. Main Outcomes and Measures: The primary end point was the time to first event for a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization (MACE-4). The key secondary end point was time to first event for cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (MACE-3). This prespecified analysis compared the total number of cardiovascular events in the treatment groups. Results: A total of 13 970 patients (mean [SD] age, 65 [9] years; 7230 male [51.8%]) were included in the study. A total of 9764 participants (69.9%) had prior atherosclerotic cardiovascular disease and a baseline LDL-C level of 139 mg/dL; treatment with bempedoic acid resulted in a 21% reduction in LDL-C level and a 22% reduction in high-sensitivity C-reactive protein (hsCRP) level at 6 months. Median (IQR) follow-up was 3.4 (3.1-3.9) years. A total of 1746 positively adjudicated first MACE-4 events and 915 additional MACE events in 612 patients were recorded, with coronary revascularization representing 32.8% (573 of 1746) of first events and 69.4% (635 of 915) of additional events. For the total incidence of cardiovascular events, treatment with bempedoic acid was associated with a reduction in risk of MACE-4 (hazard ratio [HR], 0.80; 95% CI, 0.72-0.89; P <.001), MACE-3 (HR, 0.83; 95% CI, 0.73-0.93; P = .002), myocardial infarction (HR, 0.69; 95% CI, 0.58-0.83; P < .001), and coronary revascularization (HR, 0.78; 95% CI, 0.68-0.89; P <.001), although no statistically significant difference was observed for stroke (HR, 0.80; 95% CI, 0.63-1.03). A lower HR for protection with bempedoic acid was observed with increasing number of MACE events experienced by patients. Conclusion and Relevance: Lowering LDL-C level with bempedoic acid reduced the total number of cardiovascular events in patients with high cardiovascular risk, statin therapy intolerance, and elevated LDL-C levels.

Use of Coronary Artery Calcium Quantification and Distribution for Coronary Vascular Disease Risk Reclassification in a Primary Prevention Setting.

In a large screening program of asymptomatic middle-aged individuals, we sought to assess the degree of risk reclassification provided by comparing multiethnic study on subclinical atherosclerosis coronary artery calcium scoring (CACS) versus atherosclerotic cardiovascular disease (ASCVD) and Reynolds risk score (RRS) score. All 5,324 consecutive patients (aged 57 ± 8 years, 76% male) who underwent CACS screening at the Cleveland Clinic as part of a primary prevention executive health between March 16 and October 21 were included. The 10-year ASCVD, RRS, and multiethnic study on subclinical atherosclerosis CACS (MESA-CACS) risk scores were calculated and categorized as <1, 1 to 4.99, 5 to 9.99, and ≥10%. Compared with ASCVD, using MESA-CACS resulted in a downgraded risk in 1,667 subjects (31%), whereas 738 (14%) had an upgrade in risk (total of 45% reclassification). Similarly, compared with RRS, using MESA-CACS resulted in an upgraded risk in 797 (15%) and a downgrade in 1,380 (26%) subjects (total of 41% reclassification). However, by further dividing by the distribution of the coronary calcification, ASCVD overestimates the risk only for patients with coronary artery calcium (CAC) in 0 or 1 coronary artery only, whereas MESA-CACS overestimates if the CAC was noted in ≥2 arteries. Similarly, RRS only overestimates the risk for patients with 0 CAC, whereas it underestimates the risk for patients with any CAC. In conclusion, the use of MESA-CACS, along with CAC distribution in primary prevention clinics, results in differential and significant reclassification of traditional scores when calculating the 10-years coronary vascular disease risk. Overall, RRS underestimates and ASCVD overestimates the cardiovascular disease risk compared with MESA-CACS.

Sex Differences in Thoracic Aortic Disease and Dissection: JACC Review Topic of the Week.

Despite its higher prevalence among men, women with thoracic aortic aneurysm and dissection (TAAD) have lower rates of treatment and surgical intervention and often have worse outcomes. A growing number of women with TAAD also desire pregnancy, which can be associated with an increased risk of aortic complications. Understanding sex-specific differences in TAAD has the potential to improve care delivery, reduce disparities in treatment, and optimize outcomes for women with TAAD.

Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients.

Importance: The effects of bempedoic acid on cardiovascular outcomes in statin-intolerant patients without a prior cardiovascular event (primary prevention) have not been fully described. Objective: To determine the effects of bempedoic acid on cardiovascular outcomes in primary prevention patients. Design, Setting, and Participants: This masked, randomized clinical trial enrolled 13 970 statin-intolerant patients (enrollment December 2016 to August 2019 at 1250 centers in 32 countries), including 4206 primary prevention patients. Interventions: Participants were randomized to oral bempedoic acid, 180 mg daily (n = 2100), or matching placebo (n = 2106). Main Outcome Measures: The primary efficacy measure was the time from randomization to the first occurrence of any component of a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization. Results: Mean participant age was 68 years, 59% were female, and 66% had diabetes. From a mean baseline of 142.2 mg/dL, compared with placebo, bempedoic acid reduced low-density lipoprotein cholesterol levels by 30.2 mg/dL (21.3%) and high-sensitivity C-reactive protein levels by 0.56 mg/L (21.5%), from a median baseline of 2.4 mg/L. Follow-up for a median of 39.9 months was associated with a significant risk reduction for the primary end point (111 events [5.3%] vs 161 events [7.6%]; adjusted hazard ratio [HR], 0.70 [95% CI, 0.55-0.89]; P = .002) and key secondary end points, including the composite of cardiovascular death, MI, or stroke (83 events [4.0%] vs 134 events [6.4%]; HR, 0.64 [95% CI, 0.48-0.84]; P < .001); MI (29 events [1.4%] vs 47 events [2.2%]; HR, 0.61 [95% CI, 0.39-0.98]); cardiovascular death (37 events [1.8%] vs 65 events [3.1%]; HR, 0.61 [95% CI, 0.41-0.92]); and all-cause mortality (75 events [3.6%] vs 109 events [5.2%]; HR, 0.73 [95% CI, 0.54-0.98]). There was no significant effect on stroke or coronary revascularization. Adverse effects with bempedoic acid included a higher incidence of gout (2.6% vs 2.0%), cholelithiasis (2.5% vs 1.1%), and increases in serum creatinine, uric acid, and hepatic enzyme levels. Conclusions: In a subgroup of high-risk primary prevention patients, bempedoic acid treatment was associated with reduced major cardiovascular events. Trial Registration: ClinicalTrials.gov Identifier: NCT02993406.

Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients.

BACKGROUND: Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects ("statin-intolerant" patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo. The primary end point was a four-component composite of major adverse cardiovascular events, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. RESULTS: A total of 13,970 patients underwent randomization; 6992 were assigned to the bempedoic acid group and 6978 to the placebo group. The median duration of follow-up was 40.6 months. The mean LDL cholesterol level at baseline was 139.0 mg per deciliter in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter; the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid. The incidence of a primary end-point event was significantly lower with bempedoic acid than with placebo (819 patients [11.7%] vs. 927 [13.3%]; hazard ratio, 0.87; 95% confidence interval [CI], 0.79 to 0.96; P = 0.004), as were the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (575 [8.2%] vs. 663 [9.5%]; hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P = 0.006); fatal or nonfatal myocardial infarction (261 [3.7%] vs. 334 [4.8%]; hazard ratio, 0.77; 95% CI, 0.66 to 0.91; P = 0.002); and coronary revascularization (435 [6.2%] vs. 529 [7.6%]; hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = 0.001). Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause. The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels. CONCLUSIONS: Among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization). (Funded by Esperion Therapeutics; CLEAR Outcomes ClinicalTrials.gov number, NCT02993406.).

Appropriateness of Cardiovascular Disease Prevention Recommendations Obtained From a Popular Online Chat-Based Artificial Intelligence Model.

This study examines the appropriateness of artificial intelligence model responses to fundamental cardiovascular disease prevention questions.

Rethinking Menopausal Hormone Therapy: For Whom, What, When, and How Long?

Menopausal hormone therapy (HT) was widely used in the past, but with the publication of seminal primary and secondary prevention trials that reported an excess cardiovascular risk with combined estrogen-progestin, HT use declined significantly. However, over the past 20 years, much has been learned about the relationship between the timing of HT use with respect to age and time since menopause, HT route of administration, and cardiovascular disease risk. Four leading medical societies recommend HT for the treatment of menopausal women with bothersome menopausal symptoms. In this context, this review, led by the American College of Cardiology Cardiolovascular Disease in Women Committee, along with leading gynecologists, women's health internists, and endocrinologists, aims to provide guidance on HT use, including the selection of patients and HT formulation with a focus on caring for symptomatic women with cardiovascular disease risk.

National, regional, and urban-rural patterns in fixed-terrestrial broadband internet access and cardiac rehabilitation utilization in the United States.

Objective: Sparse patterns in fixed-terrestrial broadband internet access are predominantly observed among older adults and low income areas, which are interrelated factors also associated with low center-based cardiac rehabilitation (CR) utilization in the United States (US). Telehealth CR is proposed to increase CR utilization under an assumption that fixed-terrestrial broadband internet access is readily available nationwide and parallels CR utilization demand. We aimed to characterize national, geographical, and urban-rural patterns in fixed-terrestrial broadband internet access, CR eligibility rates, and center-based utilization throughout the US. Methods: Centers for Disease Control data were used to estimate CR eligibility rates and center-based utilization for 2017-2018 among Medicare fee-for-service beneficiaries aged ≥65 years. Census Bureau data for 2018 were used to estimate fixed-terrestrial broadband internet access among households of adults aged ≥65 years. Results: Southern states exhibited the highest percentage of households without broadband internet [median (IQR): 32% (24-39)] coupled with the highest CR eligibility rates [per 1,000 beneficiaries, median (IQR): 18 (15-21)] and lowest participation rates [percentage completing ≥1 session, median (IQR): 25% (17-33)]. Compared with urban areas, rural areas demonstrated significantly higher eligibility rates [15.5 (13.2-18.4) vs. 17.4 (14.5-21.0)], participation rates [30.6% (22.0-39.4) vs. 34.6% (22.6-48.3)], and percentage of households without broadband internet [23.8% (18.1-29.2) vs. 31.6% (26.5-37.6)], respectively. Conclusion: Overlapping patterns in fixed-terrestrial broadband internet access and CR eligibility rates and center-based utilization suggest telehealth CR policies need to account for the possibility that lack of broadband-quality internet access could be a barrier to accessing telehealth CR delivery models.

Geographical and Urban-Rural Disparities in Cardiac Rehabilitation Eligibility and Center-Based Use in the US.

This cross-sectional study analyzes county-level eligibility, participation, adherence, and completion rates for cardiac rehabilitation services among Medicare beneficiaries.