Návar, Ann Marie

BACKGROUND: While health systems have implemented resources to improve lipid management in people with atherosclerotic cardiovascular disease, the population-level effectiveness is unclear. METHODS: Electronic health record data from patients with atherosclerotic cardiovascular disease between January 1, 2021, and December 31, 2023, across 16 US academic health systems were analyzed. Atherosclerotic cardiovascular disease (defined by diagnosis and procedure codes) was established on or before the index date defined as the date of the most recent LDL-C (low-density lipoprotein-cholesterol) or the last day of the study period for those without an LDL-C available. Systems were surveyed to identify lipid management programs (eg, prevention/lipid clinic, electronic health record–based tools, and lipid management algorithms). Sequential multilevel multivariable logistic regression modeling was used to (1) assess the system-level association between an LDL-C <70 mg/dL and the presence of lipid management programs, adjusting for patient-level demographic and clinical characteristics, and (2) whether system-level uptake of statin or nonstatin lipid-lowering therapy was associated with an LDL-C <70 mg/dL. RESULTS: We included 1 738 042 patients with atherosclerotic cardiovascular disease (median, 88 365 per system; range, 17 086–2 48 371). About 81% of the health systems had prevention or lipid clinics. The proportion of those on statins ranged from 31.0% to 60.4% across health systems (median, 46.3%). Lower proportions were observed in the use of high-intensity statins (16.2%–33.1%), nonstatins (2.6%–8.1%), and combination lipid-lowering therapy (1.7%–6.3%). Among those with an LDL-C level available (n=890 521), 42.5% had an LDL-C <70 mg/dL, ranging 35.8% to 49.4% across systems. There was no association between the odds of achieving LDL-C <70 mg/dL and health system lipid management algorithm, prevention clinics/lipid clinics, or electronic health record–based tools. Neither system-level high-intensity statin utilization nor nonstatin use was associated with an LDL-C <70 mg/dL. CONCLUSIONS: Despite variability in lipid management resources and lipid-lowering therapy use across systems, many did not reach an LDL-C <70 mg/dL, and there was low uptake of lipid-lowering therapy. Innovative implementation strategies are needed for system-level lipid management.

Abstract Background Cardiovascular disease (CVD) is the leading cause of death globally for both men and women, yet women remain historically underrepresented in cardiovascular clinical trials (CV trials), despite facing a disproportionately high burden of morbidity and mortality in many forms of CVD. Purpose We aim to determine the representation of women across a broad range of CV trials. Methods The participation of women in CV trials registered on ClinicalTrials.gov from 2017 to 2023 was systematically determined through the extraction of publicly available information. Data was extracted to identify the country of study, disease type, trial size, clinical intervention and age of the participants. We calculated the proportion of women and the ratio of number of females to male participants (F:M ratio) for each trial. The female participation to prevalence ratio (PPR) was estimated for each trial based on the relative prevalence of the disease by sex in the specified region. Results We identified 1,079 registered CV trials, which included 1,396,104 participants, of whom 571,641 (41.0%) were women. The median F:M ratio was significantly lower for studies on arrhythmia (0.5), coronary heart disease (CHD) (0.39), acute coronary syndrome (ACS) (0.32) and heart failure (HF) (0.51), but was higher for obesity (1.44) and pulmonary hypertension (PH) (2.86) CV trials. F:M ratio was higher for trials on lifestyle intervention (1.51) than for drug trials. PPRs were low for clinical trials on CHD (0.66), ACS (0.79), and stroke (0.74). There was a trend to increasing PPR from 2017 to 2023, p=0.056. Conclusion Representation of women in CV trials varies by disease state, region, intervention, and sponsor type. Better understanding of reasons for these differences may enable more tailored interventions to improve representation of women globally and across therapeutic areas.Figure 1 Figure 2

Importance Cardiovascular (CV) disease is the leading cause of death globally for both men and women, yet women remain historically underrepresented in CV clinical trials, despite facing a disproportionately high burden of morbidity and mortality in many forms of CV disease. Objective To determine the representation of women across a broad range of CV trials. Evidence Review The participation of women in CV trials registered on ClinicalTrials.gov from 2017 to 2023 was systematically determined through the extraction of publicly available information. Data were extracted to identify the country of study, disease type, trial size, clinical intervention, and age of the participants. The proportion of women and the ratio of number of female to male participants (F:M ratio) were calculated for each trial. The women’s participation:prevalence ratio (PPR) was estimated for each trial based on the relative prevalence of the disease by sex in the specified region. Findings A total of 1079 registered CV trials were identified, including 1 396 104 participants, of whom 571 641 (41.0%) were women. The F:M ratio was significantly lower for studies on arrhythmia (median [IQR], 0.5), coronary heart disease (median [IQR], 0.39 [0.33-0.70]), acute coronary syndrome (median [IQR], 0.32 [0.24-0.51]), and heart failure (median [IQR], 0.51 [0.32-0.87]) but higher for obesity (median [IQR], 1.44 [1.08-4.50]) and pulmonary hypertension (median [IQR], 2.86 [1.50-3.97]) trials. The F:M ratio was higher for trials on lifestyle interventions (median [IQR], 1.51 [0.77-3.24]) than for drug trials. PPRs were low for clinical trials on coronary heart disease (median [IQR], 0.66 [0.50-0.86]), acute coronary syndrome (median [IQR], 0.79 [0.51-0.87]), and stroke (median [IQR], 0.74 [0.61-0.95]). Representation of women in CV trials varied by disease state, region, intervention, and sponsor type. Conclusions and Relevance These findings highlight both progress and persistent challenges in representation of women within CV trials. These gaps not only limit the generalizability of trial outcomes but also perpetuate inequities in evidence-based care for women with CV conditions.

BACKGROUND: Mortality due to ischemic heart disease (IHD) has declined in countries with high socioeconomic development. Whether these declines extend to other settings, and whether socioeconomic development influences IHD mortality among men and women differently, is unknown. METHODS: We obtained annual data on sex-specific IHD mortality rates for countries/territories in the GBD study (Global Burden of Disease) from 1980 to 2021. The sociodemographic index (SI), a measure of socioeconomic development, was retrieved for each country/territory. Age-adjusted IHD mortality rates were modeled as a smooth function of sex, year, and SI. RESULTS: From 1980 to 2021, IHD mortality rates did not decrease in low SI settings for men or women. In contrast, mortality rates relative to 1980 declined by >25% in average SI settings (age-adjusted mortality per 100 000, 153–107 for women and 218–161 for men) and >50% in high SI settings (age-adjusted mortality per 100 000, 162–69 for women and 258–114 for men). Comparing the 20th versus 80th percentile of SI in 2021 (corresponding to lower versus higher socioeconomic development), mortality rates were 81% higher for men and 111% higher for women living in socioeconomically deprived settings ( P for difference by sex: 0.01), although absolute differences were larger in men. The association of low SI with higher IHD mortality was especially pronounced for mortality attributable to environmental/occupational risk factors (eg, particulate matter air pollution, lead exposure, and extremes of temperature), with mortality rates being 174% higher among women and 199% higher among men. CONCLUSIONS: Across the past 4 decades, low socioeconomic development was associated with no improvement in IHD mortality rates for men or women, in contrast to the large reductions observed in settings with high socioeconomic development. In contemporary settings, socioeconomic deprivation is associated with larger relative excess mortality in women and larger absolute excess mortality in men.

Background: Nationally, many ASCVD patients fail to achieve an LDL-C <70 mg/dL, and uptake of both statin and non-statin therapies is low. The degree to which this varies across health systems is less clear. Methods: A cross sectional analysis was performed where lipid levels and lipid lowering therapies (LLT) were assessed using electronic health record data in patients with a previous diagnosis of ASCVD. The data was obtained across 14 US healthcare systems between 1/1/2021-12/31/2022. Proportions of patients with an active prescription of any statin, high intensity statin, ezetimibe, PCSK9i, and combination therapy (two or more agents) within 395 days of the most recent LDL-C value (index date) was evaluated overall and by participating site. Additionally, the proportion of patients with an LDL-C <70 mg/dL at the index date was also assessed. Results: Across 14 health systems, 1,118,623 patients with ASCVD were identified (median 61,840 per health system, range 8,161-182,315). Overall, 675,776 (60.4%) had an LDL-C level in the past year (range 39.1% - 70.8%). Of those with a lipid level, achievement of LDL-C <70 mg/dL ranged from 34.6-47.2%. In total, 42.6% were on any statin, 20.1% were on a high intensity statin, 4.3% on ezetimibe, and 1.2% on a PCSK9i. Only 2.9% were on combination therapy of a statin with ezetimibe or a PCSK9i. Variability was seen across health systems in utilization of each of these therapies, however even in the highest performing health systems, LLT uptake and achievement of LDL-C < 70mg/dL remained low ( Figure). Conclusion: Variability in utilization of LLT in ASCVD patients between health systems suggests that system-level factors may impact achieving guideline-based LDL-C goals. Despite the variability, the highest proportion of patients achieving an LDL-C <70mg/dL remained under 50% indicating the need for aggressive implementation efforts.

Introduction: Guidelines are increasingly recommending a goal LDL-C <55 mg/dL in persons with atherosclerotic cardiovascular disease (ASCVD). The proportion and characteristics of US adults with ASCVD with an LDL-C <55 mg/dL remains unclear. Aims: To evaluate lipid management in ASCVD patients and factors associated with achieving an LDL-C <55mg/dL. Methods: Using electronic health record data from 8 US health systems, we evaluated LDL-C levels and treatment patterns in persons with prevalent ASCVD seen as outpatients between 1/1/2021-12/31/2021 with an LDL-C level within the prior year. Multivariable logistic regression modeling with generalized estimating equations was used to evaluate factors associated with an LDL-C <55 mg/dL. Results: Among 178,240 eligible ASCVD patients, 43.5% (77,472) had an LDL- C <70 mg/dL and 22.0% (39,270) had an LDL-C <55 mg/dL. Older age was associated with higher odds of LDL-C <55 mg/dL (OR 1.10 per 10 years, 95% CI 1.07-1.13), while female sex (OR 0.71, 95% CI 0.68-0.64) Black race (OR 0.77, 95% CI 0.70-0.86), and non-coronary artery disease forms of ASCVD including peripheral artery disease (PAD, OR 0.61, 95% CI 0.58-0.64) and cerebrovascular disease (CeVD, OR 0.72, 95% CI 0.66-0.79) were associated with lower odds of LDL-C <55 mg/dL in multivariable modeling. Overall, while 75.0% were on a statin, only 36.9% were on a high-intensity statin, 5.7% were on ezetimibe, and 1.7% were on a PCSK9i. Combination therapy was rare: only 4.2% were on a statin+ezetimibe, 0.5% on statin+PCSK9i, and 0.3% on all three. Conclusions: Less than a quarter of US patients with ASCVD achieve an LDL <55 mg/dL. Achieving this goal is even less common among younger adults, women, Black persons, and those with PAD and CeVD. Current therapeutic regimens often fail to use high-intensity statins, and markedly underutilize combinations of statins with ezetimibe and/or PCSK9 inhibitors.

Background: The 2013 ACC/AHA Cholesterol Guidelines departed from prior ATPIII guidelines, recommending statin treatment based on patients’ predicted 10-year ASCVD risk and de-emphasizing LDL-C targets. However, the degree to which these new guidelines have been adopted by clinicians in community practice is unknown. Methods: We surveyed 522 clinicians in 133 cardiology, primary care, and endocrinology practices participating in the Patient and Provider Assessment of Lipid Management (PALM) Registry. Clinicians were asked about their likelihood of prescribing statins in 4 hypothetical patient scenarios. Results: Among responders, 79% were physicians (60% cardiologists, 38% primary care or general practice, 2% endocrinology), 18% were advanced practice providers, and 3% trainees. When queried, 73% of providers reported primarily using the 2013 ACC/AHA Guidelines to guide lipid management. However, only half reported “often” or “always” calculating 10-year ASCVD risk to aid lipid management decisions for primary prevention. When presented with a high 10-year ASCVD risk patient (>15%) with a high LDL-C (150 mg/dL), 92% of providers recommended statins. Similarly, 83% of providers would use statins in a diabetic patient with a LDL-C of 140 mg/dL. Yet, only 37% reported they would prescribe a statin to an older adult (age 70) for whom guidelines recommend statin based on high 10-year ASCVD risk alone (10.1%). And up to 40% would prescribe a statin to a younger (age 40) with a low 10-year risk, but a high LDL (165 mg/dL) who would not otherwise meet criteria for statin therapy under the new guidelines. Cardiologists and non-cardiologists were similarly likely prescribe statins in most scenarios with the exception of to the younger patient with elevated LDL-C were cardiologists used statins more commonly (32% vs. 42%. OR 1.5, 95% CI 1.1-2.2, p=0.02). Conclusion: Initial survey results show that while most clinicians claim adoption of the 2013 ACC/AHA Guidelines, reported practices are not always adherent to these guidelines. Providers do not always calculate 10-year ASCVD risk to guide lipid management and many do not prescribe statins to patients eligible based on 10-year ASCVD risk.

Background: Prior ATPIII lipid guidelines recommended statin therapy for patients with clinical ASCVD to achieve low density lipoprotein cholesterol (LDL-C) targets, while the 2013 ACC/AHA lipid guidelines recommend high-intensity statin therapy for all ASCVD patients. How closely these recommendations are followed in routine clinical practice is unknown. Methods: We evaluated statin use, intensity, and LDL-C values in 1,483 patients with ASCVD (coronary heart disease, cerebrovascular disease, and peripheral arterial disease) enrolled and seen serially at 62 geographically dispersed US cardiology and primary care clinics in the Patient and Provider Assessment of Lipid Management (PALM) Registry between May - September 2015. Factors associated with high intensity statin use (atorvastatin ≥40 mg or rosuvastatin ≥20 mg daily) and LDL-C <70 mg/dL were evaluated in multivariable logistic regression. Results: Of 1,483 ASCVD patients, 86.2% were on a statin, but only 31.4% were on a high-intensity statin. Overall, 64.0% had an LDL-C <100 mg/dL, but only 29.0% had an LDL-C <70 mg/dL. Factors associated with high-intensity statin use in multivariable regression were younger age (OR 0.74 per 10 year increase, p<0.001, 95% CI 0.66-0.83), male sex (OR 1.69, p<0.001, 95% CI, 1.32-2.16), cerebrovascular disease (OR 1.55, p=0.008, 95% CI 1.12-2.13), coronary heart disease (OR 2.42, p<0.001, 95% CI 1.67-3.50), and being seen by a cardiologist (OR 1.35, p =0.04, 95% CI 1.01-1.81). Factors associated with an increased likelihood of LDL-C<70 were male sex (OR 1.55, p=0.001, 95% CI 1.20-2.01), white (OR 1.62, p=0.03, 95% CI 1.04-2.5-, diabetes (OR 1.64, p<0.001, 95% CI 1.29-2.09) and being seen by a cardiologist (OR 1.94, p<0.001, 95% CI 1.41-2.67). Discussion: Substantial gaps in care remain for secondary prevention of ASCVD despite simplified recommendations. While the majority of patients with ASCVD in community practice are on a statin, only one-third are on high intensity statins and over two-thirds have LDL ≥70 mg/dL.

AbstractBackgroundNon‐statin lipid lowering therapies (LLTs) provide additional treatment options for patients. Use patterns and patient perceptions of non‐statin LLT remain incompletely described.HypothesisThe guideline‐recommended statin intensity remains underutilized in patients treated with and without non‐statin LLT.MethodsThe PALM Registry collected LLT information on patients with or at risk of ASCVD treated at 125 US clinics in 2015. We compared patient perceptions, lipid levels and statin use among patients treated with and without non‐statin LLT.ResultsAmong 7720 patients, 1930 (25.0%) were treated with a non‐statin LLT (1249 fish oil, 417 fibrates, 329 ezetimibe, 196 niacin). Concurrent statin treatment occurred in 73.7%, of which 45.4% were dosed under the guideline‐recommended intensity. Compared with patients on statin alone, patients receiving both a statin and non‐statin LLT (n = 1423) were more likely to be male, white race and to perceive themselves as higher risk of ASCVD compared with their peers (38.5% vs. 34.9%, p = .047). Only 27.4% of patients treated with non‐statin LLT alone perceived themselves at higher risk. Most (75.7%) patients treated with a non‐statin LLT alone reported never being treated with a statin, despite ASCVD in 30.8% of these patients. Among those previously treated with a statin, 59.3% reported being willing to try a statin again.ConclusionsNon‐statin LLT is used in one in four patients with or at risk for ASCVD; its use is frequently in place of statin therapy or in the absence of guideline‐recommended statin intensity. More work is needed to establish statins as first line therapy.

Background Current treatment guidelines strongly recommend statin therapy for secondary prevention. However, it remains unclear whether patients’ perceptions of cardiovascular risk, beliefs on cholesterol, or the intensity of prescribed statin therapy differs for patients with coronary artery disease ( CAD ) versus cerebrovascular disease (Ce VD ) versus both CAD and Ce VD ( CAD &Ce VD ). Methods and Results The PALM (Patient and Provider Assessment of Lipid Management) registry collected data on statin use, intensity, and core laboratory low‐density lipoprotein cholesterol levels for 3232 secondary prevention patients treated at 133 US clinics. Among individuals with Ce VD only (n=403), CAD only (n=2202), and Ce VD & CAD (n=627), no significant differences were observed in patient‐perceived cardiovascular disease risk, beliefs on cholesterol lowering, or perceived effectiveness and safety of statin therapy. However, patients with Ce VD only were less likely to receive any statin therapy (76.2% versus 86.2%; adjusted odds ratio 0.64, 95% CI 0.45–0.91), or guideline‐recommended statin intensity (34.6% versus 50.4%; adjusted odds ratio 0.60, 95% CI 0.45–0.81) than those with CAD only. Individuals with Ce VD only were also less likely to achieve low‐density lipoprotein cholesterol <100 mg/ dL (59.2% versus 69.7%; adjusted odds ratio 0.79, 95% CI 0.64–0.99) than individuals with CAD alone. There were no significant differences in the use of any statin therapy or guideline‐recommended statin intensity between individuals with CAD &Ce VD and those with CAD only. Conclusions Despite lack of significant differences in patient‐perceived cardiovascular risk or statin beliefs, patients with Ce VD were significantly less likely to receive higher intensity statin or achieve low‐density lipoprotein cholesterol <100 mg/ dL than those with CAD only.