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.

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.

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.

Angina Frequency After Acute Myocardial Infarction In Patients Without Obstructive Coronary Artery Disease.

BACKGROUND: Myocardial infarction (MI) patients without obstructive coronary artery disease (CAD) are at increased risk for recurrent ischemic events, but angina frequency post-MI has not been described. METHODS AND RESULTS: Among MI patients who underwent angiography, we assessed angina at baseline, 1, 6, and 12 months using the Seattle Angina Questionnaire (SAQ). A hierarchical repeated measures modified Poisson model assessed the association between the absence of obstructive CAD (defined as epicardial stenoses >70% or left main >50%) and angina. Among 5539 MI patients from 31 US hospitals (mean age 60, 68% male), 6.9% had no angiographic obstructive CAD. More patients without obstructive CAD (vs. obstructive CAD) were female (57% vs 30%), non-white (51% vs 24%) and had NSTEMI (87% vs 51%). In unadjusted analyses, patients without obstructive CAD had less angina prior to MI but more angina and worse health status post-discharge. After adjustment for socio-demographic and clinical factors, the risk of post-MI angina was similar in patients without vs. with obstructive CAD (IRR=0.89, 95% CI 0.77-1.02). Among patients without obstructive CAD, depression and self-reported avoidance of care due to cost were independently associated with angina (IRR=1.28 per 5 points on PHQ, 95% CI 1.17-1.41; IRR=1.34, 95% 1.02-1.1.74). CONCLUSIONS: Following MI, patients without obstructive CAD experience an angina burden at least as high as those with obstructive CAD, affecting 1 in 4 patients at 12 months. As these patients are not candidates for revascularization, other anti-anginal strategies are needed to improve their health status and quality of life.

Frequency of high-risk patients not receiving high-potency statin (from a large managed care database).

We examined trends in low-density lipoprotein cholesterol (LDL-C) goal attainment in high-risk patients and use of high-potency statins (HPS) in a large, managed-care database from 2004 to 2012. The 2013 American Heart Association/American College of Cardiology prevention guidelines recommend that subjects with atherosclerotic cardiovascular disease (ASCVD) should be prescribed HPS therapy, irrespective of LDL-C levels. Previous guidelines recommend an LDL-C target <70 mg/dl. Patients diagnosed with ASCVD based on International Classification of Diseases, Ninth Revision codes with ≥1 LDL-C test from January 2004 to December 2012 were identified in the Optum Insight database. Patients were identified as treated if they received lipid-lowering therapy (LLT) within 90 days of the LDL-C measurement and untreated if they did not receive LLT treatment. LLT treated patients were stratified into HPS users or non-HPS LLT users. There were 45,101 eligible patients in 2004 and 40,846 in 2012. The proportion of high-risk patients who were treated with LLT increased from 61.4% (2004) to 70.5% (2008) then remained relatively constant until 2012 (67.9%). Mean LDL-C values in treated patients decreased from 103.7 ± 32.1 (2004) to 90.8 ± 31.4 mg/dl (2012). The proportion of patients treated with HPS increased from 13% in 2004 to 26% in 2012. Although the proportion of treated high-risk patients who achieve LDL-C <70 mg/dl levels has increased sharply from 2004, approximately 3 of 4 patients still did not meet this target. Only 1/4 of ASCVD patients are on HPS. In conclusion, our findings highlight the need for renewed efforts to support guideline-based LDL-C treatment for high-risk patients.

Combination therapy in dyslipidemia: where are we now?

Lowering low-density lipoprotein cholesterol (LDL-C) reduces the risk of cardiovascular disease: each 1.0 mmol/L (38.7 mg/dL) reduction in LDL-C reduces the incidence of major coronary events, coronary revascularizations, and ischemic stroke by approximately 20%. Statins are a well-established treatment option for dyslipidemia, with LDL-C reduction in the range of 27-55%. Several lipid goal-driven guidelines recommend reducing LDL-C to <2.59 mmol/L (100 mg/dL) or <1.81 mmol/L (70 mg/dL) in very high-risk patients. Many patients treated with statins do not reach these goals, and remain at risk of future cardiovascular events. The 2013 American College of Cardiology/American Heart Association guidelines move away from advocating LDL-C treatment targets with focus placed on identifying patients most likely to benefit from high-intensity or moderate-intensity statin therapy. While increasing the statin dose can prove efficacious in some patients, this approach typically offers limited additional LDL-C lowering, and is associated with increased incidence of adverse side effects. Indeed, this has led to the investigation of statins in combination with other lipid-modifying agents for the treatment of dyslipidemia. This review of the evidence for statin use in combination with fibrates, niacin, bile acid sequestrants, and the cholesterol absorption inhibitor, ezetimibe, in dyslipidemic patients at increased risk of cardiovascular disease, explores the impact of such combination therapies on lipids, attainment of lipid targets, inflammatory markers, and on cardiovascular outcomes and pathology. Additionally, new and emerging dyslipidemia treatments are summarized.

Racial disparities in hospitalizations, procedural treatments and mortality of patients hospitalized with atrial fibrillation.

OBJECTIVES: To explore racial differences in characteristics, procedural treatments, and mortality of hospitalized atrial fibrillation (AF) patients. BACKGROUND: Despite a higher burden of AF risk factors, Black individuals have a lower prevalence of AF than their White counterparts. There is suggestion that AF may go undetected in minority groups, and there may be disparities in both diagnosis and treatment of AF. METHODS: The study sample was drawn from the Healthcare Cost and Utilization Project database created by the Agency for Healthcare Research and Quality. Outcomes included AF hospitalization rate, in-hospital procedures performed, and in-hospital mortality within 6 defined sex-race subgroups: Black males, Black females, White males, White females, other males, and other females. RESULTS: 165,319 hospitalizations (41% White male, 41% White female, 4% Black male, 4% Black female, 5% other male, 5% other female) with a primary discharge diagnosis of AF were identified. Black males and females were significantly younger than White patients and had more traditional and non-traditional risk factors. Black males and females were significantly less likely to have an ablation procedure or cardioversion than White males. Black race was an independent predictor of in-hospital mortality (Odds Ratio [95% CI] of 1.90 [1.5, 2.5] for Black males and 1.38 [1.1, 1.8] for Black females). CONCLUSION: Using a large, contemporary sample of inpatients, we found significant racial differences in baseline characteristics, treatments, and outcomes of patients hospitalized with AF. There appear to be important racial disparities in the care of minorities who are hospitalized with AF that require further investigation.

Therapeutic practice patterns related to statin potency and ezetimibe/simvastatin combination therapies in lowering LDL-C in patients with high-risk cardiovascular disease.

BACKGROUND: Statin combination therapy and statin uptitration have been shown to be efficacious in low-density lipoprotein cholesterol (LDL-C) lowering and are recommended for patients with high-risk coronary heart disease (CHD) who do not reach guideline-endorsed LDL-C goals on statin monotherapy. OBJECTIVE: This analysis evaluated treatment practice patterns and LDL-C lowering for patients with CHD/CHD risk equivalent on statin monotherapy in a real-world practice setting in the United States. METHODS: In this retrospective, observational study, patients with CHD/CHD risk equivalent on statin therapy were identified during 2004 to 2008 in a US managed care database. Prescribing patterns and effect of switching from statin monotherapy to combination ezetimibe/simvastatin therapy vs uptitration to higher statin dose/potency level and no change from initial statin potency on LDL-C lowering were assessed. Percentage of change from baseline in LDL-C levels and odds ratios for LDL-C goal attainment were estimated with analyses of covariance and logistic regression. RESULTS: Of 27,919 eligible patients on statin therapy, 2671 (9.6%) switched to ezetimibe/simvastatin therapy, 11,035 (39.5%) uptitrated statins, and 14,213 (50.9%) remained on the same statin monotherapy. LDL-C reduction from baseline and attainment of LDL-C <100 and <70 mg/dL were substantially greater for patients who switched to ezetimibe/simvastatin therapy (-24.0%, 81.2%, and 35.2%, respectively) than for patients who titrated (-9.6%, 68.0%, and 18.4%, respectively) or remained on initial statin therapy (4.9%, 72.2%, and 23.7%, respectively). The odds ratios for attainment of LDL-C <100 and <70 mg/dL were also higher for patients who switched than for patients who uptitrated and had no therapy change than for patients who titrated vs no therapy change. Similarly, among a subgroup of patients not at LDL-C <100 mg/dL on baseline therapy, attainment of LDL-C <100 and <70 mg/dL was greater for patients who switched than for statin uptitration vs no change, as well as for patients who uptritrated statins vs no therapy change. CONCLUSION: In this study, LDL-C lowering and goal attainment rates improved substantially for patients with high-risk CHD on statin monotherapy who switched to combination ezetimibe/statin or uptitrated their statin therapies; however, approximately one-third of these patients still did not attain the optional recommended LDL-C goal of <70 mg/dL. Moreover, these higher efficacy lipid-lowering therapies were infrequently prescribed, indicating the need for further assessment of barriers to LDL-C goal attainment in actual practice settings.