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.

Efficacy of a centralized, blended electronic, and human intervention to improve direct oral anticoagulant adherence: Smartphones to improve rivaroxaban ADHEREnce in atrial fibrillation (SmartADHERE) a randomized clinical trial.

BACKGROUND: Improving adherence to direct oral anticoagulants (DOAC) is challenging, and simple text messaging reminders have not been effective. METHODS: SmartADHERE was a randomized trial that tested a personalized digital and human direct oral anticoagulant adherence intervention compared to usual care. Eligibility required age ≥ 18, newly-prescribed (≤90 days) rivaroxaban for atrial fibrillation (AF), 1 of 4 at-risk criteria for nonadherence, and a smartphone. The intervention consisted of combination of a medication management smartphone app, daily app-based reminders, adaptive text messaging, and phone-based counseling for severe nonadherence. The primary outcome was the proportion of days covered by rivaroxaban (PDC) at 6 months. There were 25 U.S. sites, all cardiology and electrophysiology outpatient practices, activated for a target sample size of 378, but the study was terminated by the sponsor prior to reaching target enrollment. RESULTS: There were 139 participants (age 65±9.6 years, 30% female, median CHA2DS2-VASc score 3 with IQR 2 to 4, mean total medication burden 7.7±4.4). DOAC adherence was high in both arms with no difference in the primary outcome (PDC 0.86±0.25 intervention vs 0.88±0.25 control, p=0.62) or in secondary outcomes including PDC ≥ 0.80 and medication persistence. Per protocol analyses had similar results. Because of the high overall PDC, the likelihood to answer the primary hypothesis was only 51% even if target enrollment were achieved. There were no study-related adverse events. CONCLUSIONS: The use of a centralized digital and human adherence intervention was feasible across multiple sites. Overall adherence was much higher than expected despite prescreening for at-risk individuals. SmartADHERE illustrates the challenges of trials of behavioral and technology interventions, where enrollment itself may lead to selection bias or treatment effects. Pragmatic study designs, such as cluster randomization or stepped-wedge implementation, should be considered to improve enrollment and generalizability.

Rivaroxaban Plus Aspirin Versus Aspirin Alone in Patients With Prior Percutaneous Coronary Intervention (COMPASS-PCI).

BACKGROUND: The COMPASS trial (Cardiovascular Outcomes for People using Anticoagulation Strategies) demonstrated that dual pathway inhibition (DPI) with rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily versus aspirin 100 mg once daily reduced the primary major adverse cardiovascular event (MACE) outcome of cardiovascular death, myocardial infarction, or stroke, as well as, mortality, in patients with chronic coronary syndromes or peripheral arterial disease. Whether this remains true in patients with a history of percutaneous coronary intervention (PCI) is unknown. METHODS: In a prespecified subgroup analysis from COMPASS, we examined the outcomes of patients with chronic coronary syndrome with or without a previous PCI treated with DPI versus aspirin alone. Among patients with a previous PCI, we studied the effects of treatment according to the timing of the previous PCI. RESULTS: Of the 27 395 patients in COMPASS, 16 560 patients with a chronic coronary syndrome were randomly assigned to DPI or aspirin, and, of these, 9862 (59.6%) had previous PCI (mean age 68.2±7.8, female 19.4%, diabetes mellitus 35.7%, previous myocardial infarction 74.8%, multivessel PCI 38.0%). Average time from PCI to randomization was 5.4 years (SD, 4.4) and follow-up was 1.98 (SD, 0.72) years. Regardless of previous PCI, DPI versus aspirin produced consistent reductions in MACE (PCI: 4.0% versus 5.5%; hazard ratio [HR], 0.74 [95% CI, 0.61-0.88]; no PCI: 4.4% versus 5.7%; HR, 0.76 [95% CI, 0.61-0.94], P-interaction=0.85) and mortality (PCI: 2.5% versus 3.5%; HR, 0.73 [95% CI, 0.58-0.92]; no PCI: 4.1% versus 5.0%; HR, 0.80 [95% CI, 0.64-1.00], P-interaction=0.59), but increased major bleeding (PCI: 3.3% versus 2.0%; HR, 1.72 [95% CI, 1.34-2.21]; no PCI: 2.9% versus 1.8%; HR, 1.58 [95% CI, 1.15-2.17], P-interaction=0.68). In those with previous PCI, DPI compared with aspirin produced consistent (robust) reductions in MACE irrespective of time since previous PCI (as early as 1 year and as far as 10 years; P-interaction=0.65), irrespective of having a previous myocardial infarction (P-interaction=0.64). CONCLUSIONS: DPI compared with aspirin produced consistent reductions in MACE and mortality but with increased major bleeding with or without previous PCI. Among those with previous PCI 1 year and beyond, the effects on MACE and mortality were consistent irrespective of time since last PCI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01776424.

Influence of age on the pharmacokinetics, pharmacodynamics, efficacy, and safety of rivaroxaban.

OBJECTIVE: Atrial fibrillation, peripheral and coronary artery disease, and venous thromboembolism are major risk factors for stroke, disability, and death in the rapidly growing older (≥ 65 years.) population. In the absence of clear guidelines on the appropriate use of the newer non-vitamin K antagonist oral anticoagulants in this population, this study specifically reviews the available literature for rivaroxaban and the impact of age that may affect the pharmacokinetics, pharmacodynamics, efficacy, and safety of this anticoagulant. METHODS: This review includes a summary of data obtained from the available literature concerning both older healthy subjects and older patients with various aspects of cardiovascular disease enrolled in rivaroxaban clinical trials and data from real world evidence studies. RESULTS: Evaluation of the clinical pharmacology in healthy, older adults reveal no clinically relevant effect of age on rivaroxaban pharmacokinetics and pharmacodynamics. Population pharmacokinetic studies in older patients with thromboembolic diseases suggest a moderate effect of increasing age on rivaroxaban clearance, albeit not clinically significant. Additionally, sub-group analyses from large, phase 3 clinical trials demonstrate consistent efficacy and safety in the older patient population vs the overall population. These findings are further supported by real-world evidence studies. CONCLUSION: A favorable clinical profile with rivaroxaban was observed across age sub-groups, supporting the premise that dosing in older adults does not necessitate adjustment. However, it is prudent that a cautious and individualized approach is taken for treatment with any anticoagulant in older adults.

Major Cardiovascular Events in Patients with Gout and Associated Cardiovascular Disease or Heart Failure and Chronic Kidney Disease Initiating a Xanthine Oxidase Inhibitor.

BACKGROUND: Several observational studies and meta-analyses have suggested that treating hyperuricemia in patients with gout and moderate or severe chronic kidney disease (CKD) may improve renal and cardiovascular (CV) outcomes. OBJECTIVE: To evaluate the impact of initiating allopurinol or febuxostat treatment on major CV events in patients with gout, preexisting CV disease (CVD) or heart failure (HF), and stage 3 or 4 CKD in a real-world setting. METHODS: Patients with gout (aged >18 years) who initiated allopurinol or febuxostat treatment between 2009 and 2013 after a diagnosis of stage 3 or 4 CKD and CVD-including coronary artery disease (CAD), cerebrovascular disease, and peripheral vascular disease (PVD)-or HF were selected from the MarketScan databases. The major CV events included CAD-specific, cerebrovascular disease-specific, and PVD-specific events. Cox proportional hazards modeling identified the predictors of major CV events in aggregate, and of CAD, cerebrovascular disease, and PVD events, individually. RESULTS: During follow-up, 2426 patients (370 receiving febuxostat and 2056 receiving allopurinol; 63% male; mean age, 73 years) had 162 major CV events (3.8% in those receiving febuxostat vs 7.2% in those receiving allopurinol; P = .015). The rates of major CV events per 1000 person-years were 51.8 (95% confidence interval [CI], 28-87) in patients initiating febuxostat and 99.3 (95% CI, 84-117) among those initiating allopurinol. Overall, 49.4% of patients had a CAD event, 32.5% had a PVD event, and 23.5% had a cerebrovascular disease-specific event. Febuxostat initiation was associated with a significantly lower risk for a major CV event versus patients who initiated allopurinol (hazard ratio, 0.52; P = .02), driven in large part by lower PVD-specific events (P = .026). CONCLUSION: Patients with moderate-to-severe CKD and CVD or HF who initiated febuxostat treatment had a significantly lower rate of major CV events than patients who initiated allopurinol.

Reducing the risk of stroke in elderly patients with non-valvular atrial fibrillation: a practical guide for clinicians.

Non-valvular atrial fibrillation (NVAF) significantly contributes to the burden of stroke, particularly in elderly patients. The challenge of optimizing anticoagulation therapy is balancing efficacy and bleeding risk, especially as the same patients at high risk of stroke also tend to be at high risk of bleeding. Treating the elderly patient with NVAF presents special challenges because of their heightened risk for both stroke and bleeding. Despite clinical trial data and evidence-based guidelines, surveys indicate that physicians underuse anticoagulation in older patients for reasons that include overemphasis of bleeding risk, particularly with the increased risk of falling, at the cost of thromboembolic risk. Clinical trial data are now available, and real-world data are emerging, to illustrate the relative merits of the non-vitamin K antagonist oral anticoagulants compared with conventional anticoagulation in the treatment of elderly patients with this condition, and to suggest some subgroups of older patients who may be more suitable candidates for particular agents. Care of elderly patients with NVAF is often complicated by factors including risk of falling, adherence, health literacy, cognitive function, adverse effects, and involvement of caregivers, as well as other factors including the patient-provider relationship and logistical barriers to obtaining medication. Thus, conversations between clinicians and patients, as well as shared decision making, are important. In addition, elderly patients often suffer from comorbidities including hypertension, coronary heart disease, diabetes mellitus, COPD, and/or heart failure, which necessitate the use of multiple concomitant medications, increasing the risk of drug/drug interactions. This review provides an overview of clinical trial data on the use of non-vitamin K anticoagulant agents in elderly populations, and serves as a practical resource for the management of NVAF in the elderly patient.

Patterns and predictors of lipid-lowering therapy in patients with atherosclerotic cardiovascular disease and/or diabetes mellitus in 2014: Insights from a large US managed-care population.

BACKGROUND: Lowering low-density lipoprotein cholesterol with statins reduces risk of cardiovascular events. We examined patterns and predictors of filled prescriptions for lipid-lowering therapy (LLT) in subgroups of patients with atherosclerotic cardiovascular disease (ASCVD) and/or diabetes mellitus (DM). HYPOTHESIS: Statin treatment remains underutilized across subgroups of high CV risk patients. METHODS: Patients in the Optum Research Database with these criteria were included: age ≥20 years, 2 years continuous enrollment, and ASCVD and/or DM. Patients were hierarchically classified by the presence of recent acute coronary syndrome, other coronary heart disease, ischemic stroke, peripheral arterial disease (PAD), or only DM. Predictors of filled LLT regimens were examined using multinomial logistic regression. RESULTS: A total of 1 055 932 individuals met all inclusion criteria. Evidence by point-in-time analysis of filled (not only written) statin prescriptions was 45% for the overall cohort. By subgroups, this was 62%, 52%, 43%, 36%, and 40% for recent acute coronary syndrome, other coronary heart disease, ischemic stroke, PAD, and only DM, respectively. Predictors of higher rates of any statin regimen included age 50 to 69 years, male sex, absence of comorbidities, and filled prescriptions of other standard-of-care therapies. CONCLUSIONS: In 2014, only 49% of patients with ASCVD and 40% with only DM had evidence for a filled statin prescription. Those with indications of ischemic stroke, PAD, and DM were less likely to receive statins than those with coronary conditions. Other characteristics such as advanced age, female sex, and noncardiac conditions predicted less statin utilization, thereby representing good targets for quality improvement.

Development and Validation of Algorithms to Identify Statin Intolerance in a US Administrative Database.

OBJECTIVES: To develop and validate algorithms to define statin intolerance (SI) in an administrative database using electronic medical records (EMRs) as the reference comparison. METHODS: One thousand adults with one or more qualifying changes in statin therapy and one or more previous diagnoses of hyperlipidemia, hypercholesterolemia, or mixed dyslipidemia were identified from the Henry Ford Health System administrative database. Data regarding statin utilization, comorbidities, and adverse effects were extracted from the administrative database and corresponding EMR. Patients were stratified by cardiovascular (CV) risk. SI was classified as absolute intolerance or titration intolerance on the basis of changes in statin utilization and/or the occurrence of adverse effects and laboratory testing for creatine kinase. Measures of concordance (Cohen's kappa [κ]) and accuracy (sensitivity, specificity, positive predictive value [PPV], and negative predictive value) were calculated for the administrative database algorithms. RESULTS: Half of the sample population was white, 52.9% were women, mean age was 60.6 years, and 35.7% were at high CV risk. SI was identified in 11.5% and 14.0%, absolute intolerance in 2.2% and 3.1%, and titration intolerance in 9.7% and 11.8% of the patients in the EMR and the administrative database, respectively. The algorithm identifying any SI had substantial concordance (κ = 0.66) and good sensitivity (78.1%), but modest PPV (64.0%). The titration intolerance algorithm performed better (κ = 0.74; sensitivity 85.4%; PPV 70.1%) than the absolute intolerance algorithm (κ = 0.40; sensitivity 50%; PPV 35.5%) and performed best in the high CV-risk group (n = 353), with robust concordance (κ = 0.73) and good sensitivity (80.9%) and PPV (75.3%). CONCLUSIONS: Conservative but comprehensive algorithms are available to identify SI in administrative databases for application in real-world research. These are the first validated algorithms for use in administrative databases available to decision makers.

Effect on Fasting Serum Glucose Levels of Adding Ezetimibe to Statins in Patients With Nondiabetic Hypercholesterolemia.

Statin therapy is associated with a slightly increased risk of developing diabetes mellitus and insulin resistance in patients without diabetes. Ezetimibe combined with statins may be considered for high-risk patients who do not achieve optimal low-density lipoprotein cholesterol lowering on statin monotherapy or who are statin intolerant. Changes in fasting serum glucose (FSG) levels during ezetimibe, ezetimibe/statin, and statin treatments were assessed using data pooled from clinical trials in hypercholesterolemic and heterozygous familial hypercholesterolemic patients, who were or were not receiving statin therapy. Study types included first-line trials in statin-naive/wash-out patients and second-line add-on and uptitration studies in patients on stable statin therapy. Similar analyses of FSG changes were performed separately for each study type in patients who were nondiabetic at baseline. Across all study types and treatments, mean FSG increases from baseline were small (0.5 to 3.7 mg/dl with ezetimibe/statin; 0.2 to 4.6 mg/dl with statins) and decreased over time; between-treatment differences (0.3 to 1.4 mg/dl) were nonsignificant for all comparisons. Proportions of patients with elevated FSG ≥126 mg/dl during therapy were low and similar for all treatments in the overall cohort (1.2% to 4.3%). Elevations were highest (3.3% to 25.7%) among patients with baseline factors characteristic of metabolic syndrome and prediabetes, including higher FSG, body mass index, and triglyceride levels, and numerically lower baseline high-density lipoprotein cholesterol; however, these factors were not related to FSG increases. Changes in low-density lipoprotein cholesterol, body mass index, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B were not significantly correlated with FSG increases. In conclusion, statin therapy was associated with small FSG increases, and the addition of ezetimibe did not further increase FSG levels beyond those of statins when given to patients who are statin naive or those on statin therapy.

Familial hypercholesterolemia/autosomal dominant hypercholesterolemia: Molecular defects, the LDL-C continuum, and gradients of phenotypic severity.

BACKGROUND: Familial hypercholesterolemia (FH) is a common inherited disorder in which the severity of atherosclerosis is generally proportional to the extent and duration of elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. Homozygous FH (HoFH) is generally considered the most severe condition and results in very high LDL-C levels that respond only partially to statin therapy. The diagnosis of HoFH is complicated by its presentation as a phenotypic spectrum involving multiple genes. OBJECTIVE: The objective here is to review the genetics, continuum of LDL-C concentrations, and phenotypic severity of FH. METHODS: Multiple PubMed searches were conducted as described in the main text of this article. RESULTS: Traditionally, FH has been considered an autosomal co-dominant disorder whereby both heterozygotes (HeFH) and homozygotes are affected. Recently, additional genes and loci for monogenic FH have been characterized that allow for the identification of double mutations in the known genes and loci and the description of novel forms of double heterozygous FH. Phenotypic expression and clinical severity of untreated HeFH, double HeFH, compound HeFH, and HoFH vary with some overlap both between and within the genotypes. In addition, there is overlap in LDL-C levels of treated HeFH and treated HoFH. CONCLUSIONS: These discoveries raise the possibility that new combinations of molecular defects could modulate the severity of hypercholesterolemia. These defects are unlikely to represent true homozygosity. However, they are likely to result in a phenotype consistent with HoFH or severe HeFH, which will be important as new therapies become available with indications specifically for HoFH.

A review of low-density lipoprotein cholesterol, treatment strategies, and its impact on cardiovascular disease morbidity and mortality.

Cardiovascular (CV) disease is a leading cause of death worldwide, accounting for approximately 31.4% of deaths globally in 2012. It is estimated that, from 1980 to 2000, reduction in total cholesterol accounted for a 33% decrease in coronary heart disease (CHD) deaths in the United States. In other developed countries, similar decreases in CHD deaths (ranging from 19%-46%) have been attributed to reduction in total cholesterol. Low-density lipoprotein cholesterol (LDL-C) has now largely replaced total cholesterol as a risk marker and the primary treatment target for hyperlipidemia. Reduction in LDL-C levels by statin-based therapies has been demonstrated to result in a reduction in the risk of nonfatal CV events and mortality in a continuous and graded manner over a wide range of baseline risk and LDL-C levels. This article provides a review of (1) the relationship between LDL-C and CV risk from a biologic, epidemiologic, and genetic standpoint; (2) evidence-based strategies for LDL-C lowering; (3) lipid-management guidelines; (4) new strategies to further reduce CV risk through LDL-C lowering; and (5) population-level and health-system initiatives aimed at identifying, treating, and lowering lifetime LDL-C exposure.

Statin combination therapy and cardiovascular risk reduction.

In numerous clinical trials, lowering LDL-C with statin therapy has been demonstrated to reduce the risk of cardiovascular disease (CVD) in primary and secondary prevention settings. Guidelines recommend statins for first-line therapy in cholesterol-lowering management of patients with CVD risk. Despite increased statin monotherapy use over the last decade, a number of patients with high CVD risk do not achieve optimal LDL-C lowering. Guidelines recommend consideration of statin combination therapy with nonstatin agents for these patients. However, combination therapy approaches have been hampered by neutral findings. Recently, ezetimibe added to simvastatin therapy reduced cardiovascular events in acute coronary syndrome patients, more than simvastatin alone. This article provides an overview of various agents in combination with statin therapy on cardiovascular outcomes. Other lipid-lowering agents in development, including PCSK9 and CETP inhibitors in development, are also described.

Inverse relationship between high-density lipoprotein cholesterol raising and high-sensitivity C-reactive protein reduction in older patients treated with lipid-lowering therapy.

BACKGROUND: Little is known regarding relationships between high-sensitivity C-reactive protein (hsCRP) and lipoproteins other than low-density lipoprotein cholesterol (LDL-C). High-density lipoprotein (HDL), with both anti-inflammatory and cholesterol-mediating effects, is of particular interest. This exploratory analysis assessed associations between hsCRP and lipids in older (>65 years) patients with moderate and/or high cardiovascular disease risk, before and after treatment with ezetimibe/simvastatin (E/S) or atorvastatin (ATV). METHODS: An analysis of a multicenter, randomized, double-blind, 12-week study. Correlations were assessed in 1054 patients with both baseline and 12-week hsCRP ≤ 10 mg/L, pooled across doses of E/S (10/20 and 10/40 mg) and ATV (10, 20, and 40 mg), and combined E/S + ATV treatments. Because of multiple comparisons, observed relationships were considered significant only if P values were < .01. RESULTS: Correlations between baseline levels of hsCRP and either LDL-C, non-HDL-C, or apolipoprotein B were weak and nonsignificant in the E/S, ATV, and E/S + ATV groups. After 12 weeks of treatment, these correlations increased slightly and significantly in all groups, except for LDL-C in the ATV group. HDL-C was significantly but inversely correlated with hsCRP in the ATV and E/S + ATV groups at baseline, and in all groups at 12 weeks. Only with HDL-C did change correlate with change in hsCRP in both the E/S and combined groups. CONCLUSIONS: Relationships between hsCRP and lipid factors in older patients were weak at baseline and somewhat stronger after treatment. HDL-C was inversely and consistently correlated with baseline and 12-week on-treatment hsCRP and with therapy-induced changes in HDL-C and hsCRP.

Vivir Con Un Corazón Saludable: a Community-Based Educational Program Aimed at Increasing Cardiovascular Health Knowledge in High-Risk Hispanic Women.

BACKGROUND: Hispanic women suffer from high rates of cardiometabolic risk factors and an increasingly disproportionate burden of cardiovascular disease (CVD). Particularly, Hispanic women with limited English proficiency suffer from low levels of CVD knowledge associated with adverse CVD health outcomes. METHODS: Thirty-two predominantly Spanish-speaking Hispanic women completed, Vivir Con un Corazón Saludable (VCUCS), a culturally tailored Spanish language-based 6-week intensive community program targeting CVD health knowledge through weekly interactive health sessions. A 30-question CVD knowledge questionnaire was used to assess mean changes in CVD knowledge at baseline and postintervention across five major knowledge domains including CVD epidemiology, dietary knowledge, medical information, risk factors, and heart attack symptoms. RESULTS: Completion of the program was associated with a statistically significant (p < 0.001) increase in total mean CVD knowledge scores from 39 % (mean 11.7/30.0) to 66 % (mean 19.8/30.0) postintervention consistent with a 68 % increase in overall mean CVD scores. There was a statistically significant (p < 0.001) increase in mean knowledge scores across all five CVD domains. CONCLUSION: A culturally tailored Spanish language-based health program is effective in increasing CVD awareness among high CVD risk Hispanic women with low English proficiency and low baseline CVD knowledge.

Gender Disparities in Lipid-Lowering Therapy in Cardiovascular Disease: Insights from a Managed Care Population.

BACKGROUND: Numerous studies have documented the strong inverse relationship between low-density lipoprotein cholesterol (LDL-C) levels and atherosclerotic cardiovascular disease (ASCVD). However, women are less likely to be screened for hypercholesterolemia, receive lipid-lowering therapy (LLT), and achieve optimal LDL-C levels. MATERIALS AND METHODS: Data were extracted from a U.S. administrative claims database between January 2008 and December 2012 for patients with established ASCVD. The earliest date of valid LDL-C value was defined as the index date. Patients were followed for ±12 months from the index date and were stratified by gender, by baseline LDL-C level, and whether they were initially treated with a LLT then propensity score matched by gender using demographic and clinical characteristics. Both descriptive statistics and logistic regression models were used to explore the association of gender with the frequency of LDL-C monitoring, LLT treatment initiation in initially untreated patients, and prescribing patterns in initially treated patients. RESULTS: A total of 76,414 subjects with established ASCVD were identified; 42% of the sample was women. In the unmatched cohort, 50.3% of men and 32.0% of women were prescribed a preindex statin (p < 0.0001). Among matched patients (n = 51,764), women initially treated with LLT were significantly less likely to receive a prescription for a higher potency LLT. Even among those with LDL-C levels above 160 mg/dL, women were more likely to discontinue LLT, odds ratio (95% confidence interval) 1.8 (1.2-2.3). Female gender and older age were significant predictors of discontinuation, and the potency of the index medication was the strongest predictor of dose titration. Initially untreated women were less likely to initiate LLT treatment than men, irrespective of index LDL-C levels (p < 0.0001). CONCLUSIONS: The observed disparities further reinforce the need for targeted efforts to reduce the gender gap for secondary prevention in women at high risk of cardiovascular disease.

Young Hispanic Women Experience Higher In-Hospital Mortality Following an Acute Myocardial Infarction.

BACKGROUND: Although mortality rates for acute myocardial infarction (AMI) have declined for men and women, prior studies have reported a sex gap in mortality such that younger women were most likely to die after an AMI. METHODS AND RESULTS: We sought to explore the impact of race and ethnicity on the sex gap in AMI patterns of care and mortality for younger women in a contemporary patient cohort. We constructed multivariable hierarchical logistic regression models to examine trends in AMI hospitalizations, procedures, and in-hospital mortality by sex, age (<65 and ≥65 years), and race/ethnicity (white, black, and Hispanic). Analyses were derived from 194 071 patients who were hospitalized for an AMI with available race and ethnicity data from the 2009-2010 National Inpatient Sample. Hospitalization rates, procedures (coronary angiography, percutaneous coronary interventions, and cardiac bypass surgery), and inpatient mortality were analyzed across age, sex, and race/ethnic groups. There was significant variation in hospitalization rates by age and race/ethnicity. All racial/ethnic groups were less likely to undergo invasive procedures compared with white men (P<0.001). After adjustment for comorbidities, younger Hispanic women experienced higher in-hospital mortality compared with younger white men, with an odds ratio of 1.5 (95% CI 1.2 to 1.9), adjusted for age and comorbidities. CONCLUSION: We found significant racial and sex disparities in AMI hospitalizations, care patterns, and mortality, with higher in-hospital mortality experienced by younger Hispanic women. Future studies are necessary to explore determinants of these significant racial and sex disparities in outcomes for AMI.