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.

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.

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.

National trends in patient safety for four common conditions, 2005-2011.

BACKGROUND: Changes in adverse-event rates among Medicare patients with common medical conditions and conditions requiring surgery remain largely unknown. METHODS: We used Medicare Patient Safety Monitoring System data abstracted from medical records on 21 adverse events in patients hospitalized in the United States between 2005 and 2011 for acute myocardial infarction, congestive heart failure, pneumonia, or conditions requiring surgery. We estimated trends in the rate of occurrence of adverse events for which patients were at risk, the proportion of patients with one or more adverse events, and the number of adverse events per 1000 hospitalizations. RESULTS: The study included 61,523 patients hospitalized for acute myocardial infarction (19%), congestive heart failure (25%), pneumonia (30%), and conditions requiring surgery (27%). From 2005 through 2011, among patients with acute myocardial infarction, the rate of occurrence of adverse events declined from 5.0% to 3.7% (difference, 1.3 percentage points; 95% confidence interval [CI], 0.7 to 1.9), the proportion of patients with one or more adverse events declined from 26.0% to 19.4% (difference, 6.6 percentage points; 95% CI, 3.3 to 10.2), and the number of adverse events per 1000 hospitalizations declined from 401.9 to 262.2 (difference, 139.7; 95% CI, 90.6 to 189.0). Among patients with congestive heart failure, the rate of occurrence of adverse events declined from 3.7% to 2.7% (difference, 1.0 percentage points; 95% CI, 0.5 to 1.4), the proportion of patients with one or more adverse events declined from 17.5% to 14.2% (difference, 3.3 percentage points; 95% CI, 1.0 to 5.5), and the number of adverse events per 1000 hospitalizations declined from 235.2 to 166.9 (difference, 68.3; 95% CI, 39.9 to 96.7). Patients with pneumonia and those with conditions requiring surgery had no significant declines in adverse-event rates. CONCLUSIONS: From 2005 through 2011, adverse-event rates declined substantially among patients hospitalized for acute myocardial infarction or congestive heart failure but not among those hospitalized for pneumonia or conditions requiring surgery. (Funded by the Agency for Healthcare Research and Quality and others.).

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.

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.

National patterns of heart failure hospitalizations and mortality by sex and age.

BACKGROUND: Earlier work has demonstrated significant sex and age disparities in ischemic heart disease. However, it remains unclear if an age or sex gap exists for heart failure (HF) patients. METHODS AND RESULTS: Using data from the 2007-2008 Healthcare Cost and Utilization Project, we constructed hierarchic regression models to examine sex differences and age-sex interactions in HF hospitalizations and in-hospital mortality. Among 430,665 HF discharges, 51% were women and 0.3%, 27%, and 73% were aged <25, 25-64, and >64 years respectively. There were significant sex differences among HF risk factors, with a higher prevalence of coronary disease among men. Men had higher hospitalization rates for HF and in-hospital mortality across virtually all ages. The relationship between age and HF mortality appeared U-shaped; mortality rates for ages <25, 25-64, and >64 years were 2.9%, 1.4%, and 3.8%, respectively. No age-sex interaction was found for in-hospital mortality for adults >25 years old. CONCLUSIONS: Using a large nationally representative administrative dataset we found age and sex disparities in HF outcomes. In general, men fared worse than women regardless of age. Furthermore, we found a U-shaped relationship between age and in-hospital mortality during an HF hospitalization, such that young adults have similar mortality rates to older adults. Additional studies are warranted to elucidate the patient-specific and treatment characteristics that result in these patterns.

Community-level cardiovascular risk factors impact geographic variation in cardiovascular disease hospitalizations for women.

Prior work has shown significant geographic variation in cardiovascular (CV) risk factors including metabolic syndrome, obesity, and hypercholesterolemia. However, little is known about how variations in CV risk impact cardiovascular disease (CVD)-related hospitalizations. Community-level CV risk factors (hypertension, dyslipidemia, hyperglycemia, and elevated waist circumference) were assessed from community-wide health screenings sponsored by Sister to Sister (STS) from 2008 to 2009 in 17 major US cities. Using data from the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (HCUP-NIS), CVD hospitalizations were identified based on ICD-9 codes for acute myocardial infarction (AMI), congestive heart failure (CHF), and stroke. We linked STS data with HCUP-NIS hospitalizations based on common cities and restricted the analysis to women discharged from hospitals inside the STS cities. Using hierarchical models with city as the random intercept, we assessed the impact of city-specific CV risk factors on between-city variance of AMI, CHF, and stroke. Analyses were also adjusted for patient age and clinical comorbidities. Our analysis yielded a total of 742,445 all-cause discharges across 70 hospitals inside of 13 linked cities. The overall city-specific range proportion of AMI, CHF, and stroke hospitalizations were 1.13 % (0.75-1.59 %), 2.57 % (1.44-3.92 %), and 1.24 % (0.66-1.84 %), respectively. After adjusting for city-specific CV risk factors, between-city variation was no longer statistically significant for all CVD conditions explored. In conclusion, we found that geographic variations in AMI, CHF, and stroke hospitalizations for women may be partially explained by community-level CV risk factors. This finding suggests that interventions to reduce CVD should be tailored to the unique risk profile and needs of high-risk communities.

Characteristics of women lost to follow-up in cardiovascular community health interventions: findings from the Sister to Sister campaign.

Community-based interventions (CBI) have been targeted as a potential means of tackling cardiovascular disease in women. However, there have been mixed results in terms of their impact on health, with at least some of this being attributed to high attrition rates. This study explores factors that may be contributing to the low retention of women in cardiovascular CBIs. In 2009, Sister to Sister, a national organization that sponsors community health fairs, provided free cardiovascular health screenings for a total of 9,443 women nationwide. All participants were invited to enroll in a 1 year, survey-based observational study to assess the effectiveness of these community health screenings. Of these 9,443 women, 5.9 % actively participated in the follow-up study. Participants were more likely to have health insurance (75.5 vs. 65.3 %, p < 0.001), have an annual income above 75,000 dollars (26.7 vs. 19.7 %, p < 0.001), and identify themselves as white (50.0 vs. 31.5 %, p < 0.001). They were also more likely to have hypertension (32.1 vs. 27.4 %, p = 0.018) and metabolic syndrome (35.7 vs. 20.4 %, p < 0.001). Our results suggest that white, affluent women with health insurance and cardiovascular risk factors are more likely to engage in CBIs that require longitudinal assessment. This study gives insight into the demographics, socioeconomic status, and cardiovascular comorbidities of women who participate in cardiovascular CBIs. The results may prove to be useful in understanding the biopsychosocial barriers to participation in CBIs in order to develop more effective interventions in the future.

Love your heart: a pilot community-based intervention to improve the cardiovascular health of African American women.

Cardiovascular disease remains the leading cause of death for women, and racial and ethnic minority groups disproportionately suffer from cardiovascular risk factors. We developed an intensive, culturally-tailored 12-week nutrition and physical activity program, Love Your Heart, to reduce cardiovascular risk factors for African American women in the Boston area from January to April 2011. The pilot study partnered an academic institution with two community-based organizations, the Boston Black Women's Health Institute (BBWHI) and Body by Brandy Wellness Center (BBBWC). The study sample consisted of 34 women with a mean age of 48 years (SD +/- 3), with high rates of hypertension (79%), obesity (79%), and elevated waist circumference (94%). Over 12 weeks of follow-up, there were substantial reductions in hypertension and elevated waist circumference. We found that a culturally tailored weight management program reduced weight and cardiovascular risk factors for African American women in an urban community. While small, our study suggests that targeted community-based interventions focusing on personal and group wellness have the power to reduce health disparities and improve cardiovascular health for African American women.

A large observational study of cardiovascular outcomes associated with atorvastatin or simvastatin therapy in hypertensive patients without prior cardiovascular disease.

The objective of this study was to examine whether differences in effectiveness exist between statins in hypertensive patients seen in clinical practice. We assessed cardiovascular (CV) outcomes in hypertensive patients without cardiovascular disease who began therapy with atorvastatin (10 or 20 mg/d) or simvastatin (20 or 40 mg/d) between January 1, 2003, and September 30, 2005, using claims data from 92 US managed care plans in the PharMetrics database. A total of 98,471 hypertensive patients were identified, comprising 74,685 atorvastatin users (mean dose 13.6 mg/d) and 23,786 simvastatin users (mean dose 28.6 mg/d), and followed a median 1.5 years for the occurrence of a first CV event. The crude CV event rates were 2.81 and 3.92 per 100 person-years for atorvastatin and simvastatin, respectively [unadjusted hazard ratio (HR): 0.73; 95% confidence interval (CI): 0.68-0.78, P < 0.001]. After adjusting for clinical and demographic confounders, use of atorvastatin was associated with fewer CV events compared with simvastatin (HR: 0.91; 95% CI: 0.84-0.98, P = 0.009). However, the lipid-lowering efficacy of the 2 statins could not be assessed as patient lipid data were unavailable. In conclusion, hypertensive patients without cardiovascular disease who initiated atorvastatin (10 or 20 mg/d) had a significantly lower risk of subsequent CV events compared with those who initiated simvastatin at doses of similar potency (20 or 40 mg/d). As with all observational studies, the study is subject to certain limitations, and the findings should be regarded as hypothesis generating.

Lipid treatment assessment project 2: a multinational survey to evaluate the proportion of patients achieving low-density lipoprotein cholesterol goals.

BACKGROUND: Information about physicians' adherence to cholesterol management guidelines remains scant. The present survey updates our knowledge of lipid management worldwide. METHODS AND RESULTS: Lipid levels were determined at enrollment in dyslipidemic adult patients on stable lipid-lowering therapy in 9 countries. The primary end point was the success rate, defined as the proportion of patients achieving appropriate low-density lipoprotein cholesterol (LDL-C) goals for their given risk. The mean age of the 9955 evaluable patients was 62+/-12 years; 54% were male. Coronary disease and diabetes mellitus had been diagnosed in 30% and 31%, respectively, and 14% were current smokers. Current treatment consisted of a statin in 75%. The proportion of patients achieving LDL-C goals according to relevant national guidelines ranged from 47% to 84% across countries. In low-, moderate-, and high-risk groups, mean LDL-C was 119, 109, and 91 mg/dL and mean high-density lipoprotein cholesterol was 62, 49, and 50 mg/dL, respectively. The success rate for LDL-C goal achievement was 86% in low-, 74% in moderate-, and 67% in high-risk patients (73% overall). However, among coronary heart disease patients with > or =2 risk factors, only 30% attained the optional LDL-C goal of <70 mg/dL. In the entire cohort, high-density lipoprotein cholesterol was <40 mg/dL in 19%, 40 to 60 mg/dL in 55%, and >60 mg/dL in 26% of patients. CONCLUSIONS: Although there is room for improvement, particularly in very-high-risk patients, these results indicate that lipid-lowering therapy is being applied much more successfully than it was a decade ago.

Troponin-positive, MB-negative patients with non-ST-elevation myocardial infarction: An undertreated but high-risk patient group: Results from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network-Get With The Guidelines (NCDR ACTION-GWTG) Registry.

BACKGROUND: Despite the 2000 and 2007 redefinition of myocardial infarction (MI), patients who are troponin (Tn) positive ([+]) but MB negative ([-]) may not be considered to have MI, particularly in the absence of known coronary disease (prior MI or revascularization; coronary artery disease [CAD]). How this affects treatment and outcomes has not been well described. METHODS: Direct arrival patients with non-ST elevation MI (NSTEMI) enrolled in the American College of Cardiology NCDR ACTION-GWTG Registry were included. Patients missing marker data who were Tn (-) and had CAD were excluded. Troponin (+) patients were categorized as MB (+) (n = 11,563) or MB (-) (n = 4,501). Treatments and in-hospital outcomes were compared between the 2 groups using logistic regression. RESULTS: Of the 16,064 NSTEMI patients, 28% were MB (-). The MB (-) patients were older (median age 68 vs 65 years) and had more comorbidities (hypertension 71% vs 66%, diabetes 31% vs 27%, heart failure 22% vs 19%; all Ps < .01). After adjusting for baseline characteristics, MB (-) patients were significantly less likely to receive clopidogrel, antithrombins, glycoprotein IIb/IIIa antagonists, or angiography (all Ps < .001). In-hospital mortality was lower in MB (-) patients (3.8% vs 4.9%, P < .01), which remained significant after adjusting for baseline variables (odds ratio 0, 69, 95% CI 0.6-0.9, P = .002). CONCLUSIONS: Patients without known CAD who have NSTEMI and are MB (-) have a higher risk profile but are less likely to receive guideline-recommended acute pharmacologic treatment than those who are MB (+). Given the relatively high mortality in this group, increased emphasis on improving quality of care in Tn (+)/MB (-) patients is warranted.

Hormone replacement therapy among postmenopausal women presenting with acute myocardial infarction: insights from the GUSTO-III trial.

BACKGROUND: The role of hormone replacement therapy (HRT) in the prevention of cardiovascular disease has been controversial. In large observational studies, HRT appears to lower cardiovascular disease risk. However, prospective randomized trials do not substantiate this. METHODS: We sought to characterize the use of HRT in women presenting with acute myocardial infarction and to investigate an association between HRT and inhospital or 30-day outcomes among women enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries III (GUSTO-III) trial. Of the 15,059 patients in GUSTO-III, 4124 were women. Menopausal status, HRT use, and clinical outcomes data were prospectively collected. RESULTS: Postmenopausal women taking HRT were significantly younger than those not taking HRT, and US women were more likely to be prescribed HRT than non-US women. While unadjusted 30-day mortality was substantially lower in HRT patients (6.1% vs 12.7%, P < .001), HRT use was not independently predictive of mortality after correcting for baseline differences (χ(2) = 0.15, P = .70). CONCLUSION: Hormone replacement therapy appears to have no early mortality benefit in women sustaining acute myocardial infarction. These findings further challenge the role of HRT in cardiovascular medicine.

Does a single-pill antihypertensive/lipid-lowering regimen improve adherence in US managed care enrolees? A non-randomized, observational, retrospective study.

BACKGROUND: A previous study in 4703 patients suggested that a single-pill combination of amlodipine and atorvastatin is associated with greater adherence to therapy than a two-pill calcium channel antagonist (calcium channel blocker [CCB]) and HMG-CoA reductase inhibitor (statin) regimen. However, the impact of prior medication use on the potential adherence benefits of single-pill amlodipine/atorvastatin has not been studied. OBJECTIVE: To compare adherence to single-pill amlodipine/atorvastatin versus two-pill CCB + statin regimens in a large managed care population, stratified according to prior CCB and statin use. METHODS: This retrospective study was conducted among managed care enrolees in the US. Patients included in the analysis had to have a pharmacy claim for single-pill amlodipine/atorvastatin or claims for both a CCB and a statin within any 30-day window between April 2004 and April 2005. Adherence was measured over 6 months following the index date (the date of the first single-pill amlodipine/atorvastatin claim or of the claim for the second medication class for any two-pill CCB + statin regimen) as the proportion of days covered (PDC) by both CCB and statin therapy; patients were considered 'adherent' if PDC was > or =80%. Patients were divided into four cohorts based on pre-index CCB and statin use: (i) naive (CCB)/naive (statin); (ii) experienced (CCB)/naive (statin); (iii) naive (CCB)/experienced (statin); and (iv) experienced (CCB)/experienced (statin). Within each cohort, adherence was compared for patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin or other two-pill CCB + statin regimens (including amlodipine or atorvastatin but not both) at index. Multivariable logistic regression with propensity score weighting was used to adjust for covariates, including age, sex and co-morbidities. RESULTS: In total, 35,430 patients were included in the analysis. At month 6 (after adjusting for covariates), patients in the experienced (CCB)/naive (statin) cohort receiving single-pill amlodipine/atorvastatin were more than twice as likely to be adherent as those receiving two-pill amlodipine + atorvastatin (odds ratio [OR] 2.20; p < 0.0001) or other two-pill CCB + statin regimens (OR 2.75; p < 0.0001). Similarly, patients in the naive (CCB)/experienced (statin) cohort receiving single-pill amlodipine/atorvastatin were more likely to be adherent than those receiving two-pill amlodipine + atorvastatin (OR 1.72; p < 0.0001) or other two-pill CCB + statin regimens (OR 2.81; p < 0.0001). In contrast, in the naive (CCB)/naive (statin) cohort there was no significant difference in adherence between patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin (OR 1.00), although patients receiving single-pill amlodipine/atorvastatin were slightly more likely to be adherent than those receiving other two-pill CCB + statin regimens (OR 1.29; p < 0.01). In the experienced (CCB)/experienced (statin) cohort there was also no significant difference between patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin (OR 1.08), and only a slightly greater likelihood of achieving adherence to single-pill amlodipine/atorvastatin versus other two-pill CCB + statin regimens (OR 1.19; p < 0.01). CONCLUSIONS: This large retrospective study confirms previous observations that single-pill amlodipine/atorvastatin can help improve adherence versus two-pill CCB + statin regimens. However, greater improvements in adherence are likely to be observed in patients with prior experience of either CCB or statin therapy than in those either naive to, or experienced with, both therapies.

Recognizing and improving health care disparities in the prevention of cardiovascular disease in women.

Innate differences in gender physiology result in unique exposures, risk, and protection that are specific to women. Recognition and appreciation of these differences results in better treatment adaptations for women and better outcomes. Disparities between genders in the treatment of major cardiovascular risk factors still exist and are mostly secondary to underestimating or misunderstanding a woman's risk. Preventive therapies are less often recommended to women. Women are more likely to be diagnosed and treated for hypertension, but are less likely to reach treatment goals. High-risk women-including diabetic women-are less likely to be on lipid-lowering agents and reach a low-density lipoprotein level less than 100 mg/dL. Diabetic women are less likely to achieve a hemoglobin A(1c) level less than 7%. Through understanding these disparities, health care providers will be better able to screen female patients and institute evidence-based therapies for the prevention of cardiovascular disease.

Peripheral arterial disease: current perspectives and new trends in management.

Peripheral arterial disease (PAD) is defined as an arterial brachial index (ABI) of < or =0.90 in the lower extremities and results from a narrowing of the arteries as a result of progressive atherosclerosis. PAD affects 12-20% of Americans aged 65 years or older; however, most are asymptomatic and many do not seek treatment. Improved awareness and education in both the general population and among health care providers about these modifiable risk factors has the potential to improve general health and decrease morbidity and mortality secondary to atherosclerotic vascular disease.

Patterns and prognostic implications of low high-density lipoprotein levels in patients with non-ST-segment elevation acute coronary syndromes.

AIMS: The patterns and prognostic significance of low high-density lipoprotein (HDL) cholesterol levels have not been well characterized. We sought to determine the prevalence and prognostic significance of low HDL cholesterol levels in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). METHODS AND RESULTS: We evaluated HDL levels among NSTE ACS patients [ischaemic ECG (electrocardiogram) changes and/or positive cardiac markers] from the CRUSADE [Can Rapid Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC(American College of Cardiology)/AHA(American Heart Association) Guidelines] initiative treated at 555 US hospitals from January 2001 through June 2006. Clinical and angiographic characteristics, treatments, and in-hospital outcomes were analysed by categories of HDL levels measured during hospitalization. Among 93 263 NSTE ACS patients with HDL measurements, 16 854 (18.1%) had very low HDL levels (10-29 mg/dL), 32 185 (34.5%) had low HDL levels (30-39 mg/dL), 35 875 (38.5%) had normal HDL levels (40-59 mg/dL), and 8349 (9.0%) had high HDL levels (60-100 mg/dL). Patients with very low HDL levels were younger, more often male, and more commonly obese and diabetic. Patients with very low HDL levels had the greatest risk of multi-vessel coronary disease on angiography and in-hospital mortality compared with patients with normal and high HDL levels. CONCLUSION: Almost one-fifth of patients with NSTE ACS have very low HDL levels--a finding that adds incrementally to a greater burden of atherosclerosis and a higher risk of mortality. Consequently, strategies for mitigating the adverse prognosis associated with very low HDL levels warrant further exploration in patients with ACS.

Evidence-based guidelines for cardiovascular risk reduction: the safety and efficacy of high-dose statin therapy.

Current clinical guidelines for management of low-density lipoprotein cholesterol (LDL-C) have evolved to reflect the findings of numerous randomized clinical trials and represent an important opportunity to effectively improve the cardiovascular (CV) risk profile of a wide range of patients. Implementation of guideline-recommended LDL-C management strategies facilitates the appropriate use of all available treatments, including lifestyle and dietary changes and pharmacotherapy. Where intensive lowering of LDL-C is required, suboptimal use of statins is a major contributor to the significant number of patients who remain at an unnecessarily increased risk of CV disease as a consequence of failing to reach their guideline-recommended LDL-C goals. This underuse may be explained by concerns over the safety and efficacy of high-dose statin regimens in certain populations. These issues are explored in the context of current, evidence-based clinical guidelines for LDL-C management and, through 3 hypothetical case studies, selection of appropriate starting doses of statins, and titration to a higher dose or switching to a more potent statin, to ensure that patients reach their individual LDL-C goals and reduce their overall CV risk, is also examined.