Cost-Effectiveness of Icosapent Ethyl in REDUCE-IT USA: Results From Patients Randomized in the United States.

BACKGROUND: In 3146 REDUCE-IT USA (Reduction of Cardiovascular Events With Icosapent Ethyl Intervention Trial USA) participants, icosapent ethyl (IPE) reduced first and total cardiovascular events by 31% and 36%, respectively, over 4.9 years of follow-up. METHODS AND RESULTS: We used participant-level data from REDUCE-IT USA, 2021 US costs, and IPE costs ranging from $4.59 to $11.48 per day, allowing us to examine a range of possible medication costs. The in-trial analysis was participant-level, whereas the lifetime analysis used a Markov model. Both analyses considered value from a US health sector perspective. The incremental cost-effectiveness ratio (incremental costs divided by incremental quality-adjusted life-years) of IPE compared with standard care (SC) was the primary outcome measure. There was incremental gain in quality-adjusted life-years with IPE compared with SC using in-trial (3.28 versus 3.13) and lifetime (10.36 versus 9.83) horizons. Using an IPE cost of $4.59 per day, health care costs were lower with IPE compared with SC for both in-trial ($29 420 versus $30 947) and lifetime ($216 243 versus $219 212) analyses. IPE versus SC was a dominant strategy in trial and over the lifetime, with 99.7% lifetime probability of an incremental cost-effectiveness ratio <$50 000 per quality-adjusted life-year gained. At a medication cost of $11.48 per day, the cost per quality-adjusted life-year gained was $36 208 in trial and $9582 over the lifetime. CONCLUSIONS: In this analysis, at $4.59 per day, IPE offers better outcomes than SC at lower costs in trial and over a lifetime and is cost-effective at $11.48 per day for conventional willingness-to-pay thresholds. Treatment with IPE should be strongly considered in US patients like those enrolled in REDUCE-IT USA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.

Assessment and management of statin-associated muscle symptoms (SAMS): A clinical perspective from the National Lipid Association.

Statin-associated muscle symptoms (SAMS) are the most common form of statin intolerance and are associated with increased risk of cardiovascular events that manifest from statin underutilization and discontinuation. The reported frequencies of SAMS are divergent in the literature. The writing group estimates the prevalence of SAMS, namely all muscle symptoms temporally related to statin use but without regard to causality, to be about 10% (range 5% to 25%), and the prevalence of pharmacological SAMS, specifically muscle symptoms resulting from pharmacological properties of the statin, to be about 1-2% (range 0.5% to 4%). In clinical practice, SAMS are likely to result from a combination of pharmacological and nonpharmacological effects, however this does not make the symptoms any less clinically relevant. Regardless of the etiology, SAMS need to be addressed in accordance with patients' preferences and experiences. This clinical perspective reviews the epidemiology and underlying pathophysiology of SAMS, and the cardiovascular consequences resulting from statin discontinuation. We present patient-centered clinical and communication strategies to mitigate SAMS and improve medication adherence and outcomes among statin users. Treatment strategies include 1) optimizing lifestyle interventions, 2) modulating risk factors that may contribute to muscle symptoms, 3) optimizing statin tolerability by dose reduction, decreased dosing frequency, or use of an alternate statin with more favorable pharmacokinetic properties, and 4) use of non-statins, emphasizing those with evidence for atherosclerotic risk reduction, either in combination with or in place of statin therapy depending on the patient's circumstances. The focus of this clinical perspective is sustainable lipoprotein goal achievement, which is important for cardiovascular risk reduction.

Cost-effectiveness of Icosapent Ethyl for High-risk Patients With Hypertriglyceridemia Despite Statin Treatment.

Importance: The Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial (REDUCE-IT) demonstrated the efficacy of icosapent ethyl (IPE) for high-risk patients with hypertriglyceridemia and known cardiovascular disease or diabetes and at least 1 other risk factor who were treated with statins. Objective: To estimate the cost-effectiveness of IPE compared with standard care for high-risk patients with hypertriglyceridemia despite statin treatment. Design, Setting, and Participants: An in-trial cost-effectiveness analysis was performed using patient-level study data from REDUCE-IT, and a lifetime analysis was performed using a microsimulation model and data from published literature. The study included 8179 patients with hypertriglyceridemia despite stable statin therapy recruited between November 21, 2011, and May 31, 2018. Analyses were performed from a US health care sector perspective. Statistical analysis was performed from March 1, 2018, to October 31, 2021. Interventions: Patients were randomly assigned to IPE, 4 g/d, or placebo and were followed up for a median of 4.9 years (IQR, 3.5-5.3 years). The cost of IPE was $4.16 per day after rebates using SSR Health net cost (SSR cost) and $9.28 per day with wholesale acquisition cost (WAC). Main Outcomes and Measures: Main outcomes were incremental quality-adjusted life-years (QALYs), total direct health care costs (2019 US dollars), and cost-effectiveness. Results: A total of 4089 patients (2927 men [71.6%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive IPE, and 4090 patients (2895 men [70.8%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive standard care. Treatment with IPE yielded more QALYs than standard care both in trial (3.34 vs 3.27; mean difference, 0.07 [95% CI, 0.01-0.12]) and over a lifetime projection (10.59 vs 10.35; mean difference, 0.24 [95% CI, 0.15-0.33]). In-trial, total health care costs were higher with IPE using either SSR cost ($18 786) or WAC ($24 544) than with standard care ($17 273; mean difference from SSR cost, $1513 [95% CI, $155-$2870]; mean difference from WAC, $7271 [95% CI, $5911-$8630]). Icosapent ethyl cost $22 311 per QALY gained using SSR cost and $107 218 per QALY gained using WAC. Over a lifetime, IPE was projected to be cost saving when using SSR cost ($195 276) compared with standard care ($197 064; mean difference, -$1788 [95% CI, -$9735 to $6159]) but to have higher costs when using WAC ($202 830) compared with standard care (mean difference, $5766 [95% CI, $1094-$10 438]). Compared with standard care, IPE had a 58.4% lifetime probability of costing less and being more effective when using SSR cost and an 89.4% probability of costing less than $50 000 per QALY gained when using SSR cost and a 72.5% probability of costing less than $50 000 per QALY gained when using WAC. Conclusions and Relevance: This study suggests that, both in-trial and over the lifetime, IPE offers better cardiovascular outcomes than standard care in REDUCE-IT participants at common willingness-to-pay thresholds.

Barriers to PCSK9 inhibitor prescriptions for patients with high cardiovascular risk: Results of a healthcare provider survey conducted by the National Lipid Association.

BACKGROUND: Statin therapy is recommended for reducing atherosclerotic cardiovascular disease (ASCVD) risk. Significant risk can remain because of insufficient clinical response or statin intolerance. Proprotein convertase subtilisin/kexin type-9 (PCSK9) therapy lowers low-density lipoprotein cholesterol and has recently been shown to lower ASCVD events. OBJECTIVE: The aim of the study was to assess the barriers and challenges experienced with the access and approval reimbursement process for PCSK9 inhibitor prescriptions. METHODS: In 2016, the National Lipid Association conducted an online survey on PCSK9 inhibitor use and barriers to prescription among experienced healthcare workers who provide care to high-risk patients with ASCVD or familial hypercholesterolemia (FH). RESULTS: There were 434 respondent healthcare workers with extensive experience in treating lipid disorders. PCSK9 inhibitors are considered by 71.3% of respondent providers with statin-intolerant patients. There were high rates (>85%) of initial denial. The major barriers to approvals were insurer processes, provider documentation (inadequate documentation of maximally tolerated statin dose, diagnostic criteria for FH, number of statins failed if statin intolerant and most recent low-density lipoprotein cholesterol), and administrative burden (time, staff, paperwork, and appeals). Provider approval rates for getting ≥75% patients approved were higher for FH (43%) than for ASCVD patients (36%). Among providers with good approval rates, documentation was the most critical factor. Barriers more difficult to overcome include perceived higher threshold requirements by payers, drugs not on formulary, and drug costs. CONCLUSIONS: Healthcare providers encounter significant barriers to PCSK9 inhibitor prescriptions; many of these are related to documentation issues and can be overcome with checklists, staff support, and experience.

Development and Content Validity of the Statin Experience Assessment Questionnaire (SEAQ)©.

INTRODUCTION: The National Lipid Association Statin Intolerance (SI) Panel recognized the need for better understanding of the patient SI experience. OBJECTIVE: The objective of this research was to develop a patient-reported outcome (PRO) questionnaire to assess a patient's experience with SI. METHODS: Questionnaire development was informed via a series of research activities: literature review, concept elicitation, item generation, and content evaluation. Following the literature review and concept elicitation, a draft questionnaire was constructed and subsequently modified based on feedback from therapeutic area experts and patients via cognitive debriefing interviews. RESULTS: Muscle-related symptoms were the most commonly reported symptoms associated with SI in the literature review (35 of 41 articles reviewed [85%]) and in semi-structured interviews with experts (n = 5 [100%]) and patients (n = 17 of 20 [85.0%]). Physical and other impacts of SI symptoms on daily activities were also frequently reported. A 17-item draft questionnaire was created, and cognitive debriefing with experts (n = 5) and patients (n = 15) was conducted. Overall, the items, response options, and instructions were comprehensible and positively reviewed; minor changes resulted in the 15-item Statin Experience Assessment Questionnaire (SEAQ)©. Using a 30-day recall period, the SEAQ© assesses the severity and impact of six SI symptoms (muscle ache, muscle pain, muscle cramps, muscle weakness, tiredness, and joint pain) on an 11-point numeric scale. Statin discontinuation and likelihood of discontinuation due to symptoms are assessed and scored on a yes/no and five-point verbal response scale, respectively. CONCLUSION: The SEAQ

Effect of Pharmacist Counseling Intervention on Health Care Utilization Following Hospital Discharge: A Randomized Control Trial.

BACKGROUND: Reduction in 30-day readmission rates following hospitalization for acute coronary syndrome (ACS) and acute decompensated heart failure (ADHF) is a national goal. OBJECTIVE: The aim of this study was to determine the effect of a tailored, pharmacist-delivered, health literacy intervention on unplanned health care utilization, including hospital readmission or emergency room (ER) visit, following discharge. DESIGN: Randomized, controlled trial with concealed allocation and blinded outcome assessors SETTING: Two tertiary care academic medical centers PARTICIPANTS: Adults hospitalized with a diagnosis of ACS and/or ADHF. INTERVENTION: Pharmacist-assisted medication reconciliation, inpatient pharmacist counseling, low-literacy adherence aids, and individualized telephone follow-up after discharge MAIN MEASURES: The primary outcome was time to first unplanned health care event, defined as hospital readmission or an ER visit within 30 days of discharge. Pre-specified analyses were conducted to evaluate the effects of the intervention by academic site, health literacy status (inadequate versus adequate), and cognition (impaired versus not impaired). Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) are reported. KEY RESULTS: A total of 851 participants enrolled in the study at Vanderbilt University Hospital (VUH) and Brigham and Women's Hospital (BWH). The primary analysis showed no statistically significant effect on time to first unplanned hospital readmission or ER visit among patients who received interventions compared to controls (aHR = 1.04, 95% CI 0.78-1.39). There was an interaction of treatment effect by site (p = 0.04 for interaction); VUH aHR = 0.77, 95% CI 0.51-1.15; BWH aHR = 1.44 (95% CI 0.95-2.12). The intervention reduced early unplanned health care utilization among patients with inadequate health literacy (aHR 0.41, 95% CI 0.17-1.00). There was no difference in treatment effect by patient cognition. CONCLUSION: A tailored, pharmacist-delivered health literacy-sensitive intervention did not reduce post-discharge unplanned health care utilization overall. The intervention was effective among patients with inadequate health literacy, suggesting that targeted practice of pharmacist intervention in this population may be advantageous.

The CardioMetabolic Health Alliance: Working Toward a New Care Model for the Metabolic Syndrome.

The Cardiometabolic Think Tank was convened on June 20, 2014, in Washington, DC, as a "call to action" activity focused on defining new patient care models and approaches to address contemporary issues of cardiometabolic risk and disease. Individual experts representing >20 professional organizations participated in this roundtable discussion. The Think Tank consensus was that the metabolic syndrome (MetS) is a complex pathophysiological state comprised of a cluster of clinically measured and typically unmeasured risk factors, is progressive in its course, and is associated with serious and extensive comorbidity, but tends to be clinically under-recognized. The ideal patient care model for MetS must accurately identify those at risk before MetS develops and must recognize subtypes and stages of MetS to more effectively direct prevention and therapies. This new MetS care model introduces both affirmed and emerging concepts that will require consensus development, validation, and optimization in the future.

Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management.

Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of statin-associated myopathy, and provides guidance for diagnosis and management of SAMS. Statin-associated myopathy, with significant elevation of serum creatine kinase (CK), is a rare but serious side effect of statins, affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. Statin-associated muscle symptoms cover a broader range of clinical presentations, usually with normal or minimally elevated CK levels, with a prevalence of 7-29% in registries and observational studies. Preclinical studies show that statins decrease mitochondrial function, attenuate energy production, and alter muscle protein degradation, thereby providing a potential link between statins and muscle symptoms; controlled mechanistic and genetic studies in humans are necessary to further understanding. The Panel proposes to identify SAMS by symptoms typical of statin myalgia (i.e. muscle pain or aching) and their temporal association with discontinuation and response to repetitive statin re-challenge. In people with SAMS, the Panel recommends the use of a maximally tolerated statin dose combined with non-statin lipid-lowering therapies to attain recommended low-density lipoprotein cholesterol targets. The Panel recommends a structured work-up to identify individuals with clinically relevant SAMS generally to at least three different statins, so that they can be offered therapeutic regimens to satisfactorily address their cardiovascular risk. Further research into the underlying pathophysiological mechanisms may offer future therapeutic potential.

Low literacy is associated with uncontrolled blood pressure in primary care patients with hypertension and heart disease.

OBJECTIVES: To evaluate the association between low literacy and uncontrolled blood pressure (BP) and their associations with medication adherence. METHODS: Cross-sectional study of 423 urban, primary care patients with hypertension and coronary disease. The relationship between low literacy (Rapid Estimate of Adult Literacy in Medicine ≤ 44) and uncontrolled BP (≥140/90 mmHg, ≥130/80 mmHg for patients with diabetes) was evaluated by crude and adjusted logistic regression. Relationships with self-reported adherence and refill adherence were explored using adjusted linear and logistic regression. RESULTS: Overall, 192 (45%) subjects had low literacy and 227 (52.9%) had uncontrolled BP. Adjusting for age, gender, race, employment, education, mental status, and self-reported adherence, low literacy was associated with uncontrolled BP (OR 1.75, 95% CI 1.06-2.87). Lower self-reported adherence was associated with uncontrolled BP; the relationship between refill adherence and uncontrolled BP was not statistically significant. CONCLUSION: Low literacy is independently associated with uncontrolled BP. PRACTICE IMPLICATIONS: Awareness of the relationships among patient literacy, BP control, and medication adherence may guide healthcare providers as they communicate with patients.

An assessment by the Statin Muscle Safety Task Force: 2014 update.

The National Lipid Association's Muscle Safety Expert Panel was charged with the duty of examining the definitions for statin-associated muscle adverse events, development of a clinical index to assess myalgia, and the use of diagnostic neuromuscular studies to investigate muscle adverse events. We provide guidance as to when a patient should be considered for referral to neuromuscular specialists and indications for the performance of a skeletal muscle biopsy. Based on this review of evidence, we developed an algorithm for the evaluation and treatment of patients who may be intolerant to statins as the result of adverse muscle events. The panel was composed of clinical cardiologists, clinical lipidologists, an exercise physiologist, and a neuromuscular specialist.

An assessment by the Statin Intolerance Panel: 2014 update.

This article from the National Lipid Association Statin Intolerance Panel provides a framework for understanding statin intolerance and makes general recommendations for health professionals. For specific guidance on adverse events related to muscle, liver, cognition, and glucose metabolism, one should refer to the other reports of the Statin Safety Task Force for those topics. Although statin adverse effects rarely lead to permanent sequelae, symptomatic intolerance frequently hinders cardiovascular risk reduction by statins. We emphasize here the advisory role of the clinician helping each patient to make personal decisions on statin tolerability. We identify a pressing need for further research on statin intolerance and make suggestions for research design.

Treatment pattern changes in high-risk patients newly initiated on statin monotherapy in a managed care setting.

BACKGROUND: For high-risk patients who do not achieve guideline-recommended LDL-C levels, more intensive treatment including statin-uptitration to higher doses or potency, as well as combination therapy may be considered. A better understanding of statin treatment patterns in real-world clinical practice may contribute to improved lipid-lowering management in these patients. OBJECTIVE: We determined treatment pattern changes among patients with high risk of cardiovascular disease who were not at low-density lipoprotein cholesterol (LDL-C) goal on statin monotherapy. METHODS: Treatment pattern changes were evaluated among patients newly initiated on statins between January 1, 2006, and August 31, 2009, in the HealthCore Integrated Research Database. Rates and mean time to first and second treatment changes were examined in patients with claims for coronary heart disease (CHD), atherosclerotic vascular disease (AVD), and diabetes mellitus during 12 months before index, who were not at LDL-C <70 mg/dL at their first-eligible LDL-C test (≥ 4 weeks after index). Therapy change was assessed for 12 months after the LDL-C result. RESULTS: Of 11,473 eligible subjects, 61.3% had diabetes, 26.6% had CHD and AVD, and 12.1% had CHD and AVD and diabetes. At index, patients were prescribed medium-potency levels of statins, including simvastatin (44.7%), atorvastatin (31.5%), and other statins (23.8%). Mean ± SD LDL-C before statin initiation was 138 ± 34 mg/dL, and at the first-eligible LDL-C result after index, it was 101 ± 25 mg/dL. During follow-up, 7444 subjects (64.9%) experienced a first treatment change, with mean time to change of 93.8 ± 92 days, whereas 4029 (36.1%) had no treatment change. Discontinuation of index therapy occurred in 46.9% of subjects and medication switches or titration in 18.0% (index statin titration, switch to other statins, other lipid-lowering therapies [LLT], including ezetimibe). Of the discontinuers, 27.4% restarted LLT. Of subjects with a first treatment change who did not discontinue, 48.9% experienced a second therapy change. Results were similar between the 3 high-risk groups. CONCLUSIONS: In this managed-care setting, among patients with high risk of cardiovascular disease who were not at LDL-C goal, statins were usually started at medium-potency doses without being titrated up, whereas nearly one-half had a discontinuation of LLT within 12 months. These treatment patterns indicate the need for better patient and provider education as well as other system-wide modifications to improve medication adherence.

Hospital use and medical care costs up to 5 years after triglyceride lowering among patients with severe hypertriglyceridemia.

BACKGROUND: Severe hypertriglyceridemia is associated with resource-intensive conditions such as cardiovascular disease, diabetes, and pancreatitis. Whether triglyceride (TG) reduction reduces annual medical costs has not been studied. OBJECTIVE: The objective was to compare medical care costs after changes in triglyceride levels for up to 5 years of follow-up. METHODS: Using an observational cohort, we identified 808 individuals who had a baseline TG level ≥500 mg/dL in calendar year 2004 and had a second measure 6 to 24 weeks later. We collected all subsequent inpatient, outpatient, and pharmacy use and medical cost data through 2009. Percentage change from baseline TG level was used to create six categories: decreased ≥60%, 45%-59%, 30%-44%, 15%-29%, 0%-14%, and TG increase. We estimated and compared annualized medical care costs by adjusting for baseline costs, baseline TG, high-density lipoprotein, and low-density lipoprotein cholesterol levels, age, sex, smoking status, body mass index, blood pressure, and presence of comorbidities such as diabetes and cardiovascular disease. RESULTS: Mean age of the cohort was 55.9 ± 11.7 years and 66% were men. Patients who reduced their TG levels by ≥60% experienced a mean annualized reduction from baseline medical costs of $471, whereas costs increased in all other TG change categories. Between-group differences were most pronounced in the first three years, but none were statistically significant. CONCLUSION: This observational study was unable to establish that TG lowering among patients with severe hypertriglyceridemia produced statistically significantly lower hospital use or medical care costs. However, the nonsignificant trends observed suggest that a larger study conducted with controlled TG lowering may be warranted.

Clinical and economic benefits observed when follow-up triglyceride levels are less than 500 mg/dL in patients with severe hypertriglyceridemia.

BACKGROUND: Increased levels of triglycerides are associated with an increased risk of cardiovascular disease and pancreatitis. In this study we investigated the association between patients with severely increased triglycerides whose follow-up triglyceride levels were <500 mg/dL and reduction of important clinical events and associated health care costs. METHODS: By using two large U.S. health care claims databases, we identified an initial cohort of 41,210 patients with severe hypertriglyceridemia between June 2001 and September 2010 who had a follow-up laboratory test result 6 to <24 weeks after the initial severe hypertriglyceridemia laboratory value. Of these, 8493 patients' follow-up triglyceride levels remained elevated (≥500 mg/dL) whereas 32,717 were <500 mg/dL. After their qualifying follow-up triglyceride level, patients' cardiovascular events, diabetes-related events, pancreatitis episodes, kidney disease, and related costs were identified. Adjusted incidence rate ratios with the use of Cox proportional hazards models were developed for each outcome. RESULTS: Patients whose triglycerides remained ≥500 mg/dL had a greater rate of pancreatitis episodes (hazard ratio [HR]1.79; 95% confidence interval [CI] 1.47-2.18), cardiovascular events (HR1.19; 95% CI 1.10-1.28), diabetes-related events (HR1.42; 95% CI 1.27-1.59), and kidney disease (HR1.13; 95% CI 1.04-1.22) compared with patients whose follow-up triglycerides were <500 mg/dL, after we adjusted for important confounders. Adjusted all-cause total and cardiovascular-related costs were significantly lower in the first 3 years in patients whose follow-up triglyceride levels were <500 mg/dL compared with those whose triglyceride levels remained increased. CONCLUSION: When follow-up triglyceride levels were <500 mg/dL, we observed an associated reduction in the risk of clinical events and decrease in health care resource use and costs.

Effect of a pharmacist intervention on clinically important medication errors after hospital discharge: a randomized trial.

BACKGROUND: Clinically important medication errors are common after hospital discharge. They include preventable or ameliorable adverse drug events (ADEs), as well as medication discrepancies or nonadherence with high potential for future harm (potential ADEs). OBJECTIVE: To determine the effect of a tailored intervention on the occurrence of clinically important medication errors after hospital discharge. DESIGN: Randomized, controlled trial with concealed allocation and blinded outcome assessors. (ClinicalTrials.gov registration number: NCT00632021) SETTING: Two tertiary care academic hospitals. PATIENTS: Adults hospitalized with acute coronary syndromes or acute decompensated heart failure. INTERVENTION: Pharmacist-assisted medication reconciliation, inpatient pharmacist counseling, low-literacy adherence aids, and individualized telephone follow-up after discharge. MEASUREMENTS: The primary outcome was the number of clinically important medication errors per patient during the first 30 days after hospital discharge. Secondary outcomes included preventable or ameliorable ADEs, as well as potential ADEs. RESULTS: Among 851 participants, 432 (50.8%) had 1 or more clinically important medication errors; 22.9% of such errors were judged to be serious and 1.8% life-threatening. Adverse drug events occurred in 258 patients (30.3%) and potential ADEs in 253 patients (29.7%). The intervention did not significantly alter the per-patient number of clinically important medication errors (unadjusted incidence rate ratio, 0.92 [95% CI, 0.77 to 1.10]) or ADEs (unadjusted incidence rate ratio, 1.09 [CI, 0.86 to 1.39]). Patients in the intervention group tended to have fewer potential ADEs (unadjusted incidence rate ratio, 0.80 [CI, 0.61 to 1.04]). LIMITATION: The characteristics of the study hospitals and participants may limit generalizability. CONCLUSION: Clinically important medication errors were present among one half of patients after hospital discharge and were not significantly reduced by a health-literacy-sensitive, pharmacist-delivered intervention. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Improving Medication Adherence through Graphically Enhanced Interventions in Coronary Heart Disease (IMAGE-CHD): a randomized controlled trial.

BACKGROUND: Up to 50 % of patients do not take medications as prescribed. Interventions to improve adherence are needed, with an understanding of which patients benefit most. OBJECTIVE: To test the effect of two low-literacy interventions on medication adherence. DESIGN: Randomized controlled trial, 2 × 2 factorial design. PARTICIPANTS: Adults with coronary heart disease in an inner-city primary care clinic. INTERVENTIONS: For 1 year, patients received usual care, refill reminder postcards, illustrated daily medication schedules, or both interventions. MAIN MEASURES: The primary outcome was cardiovascular medication refill adherence, assessed by the cumulative medication gap (CMG). Patients with CMG<0.20 were considered adherent. We assessed the effect of the interventions overall and, post-hoc, in subgroups of interest. KEY RESULTS: Most of the 435 participants were elderly (mean age=63.7 years), African-American (91 %), and read below the 9th-grade level (78 %). Among the 420 subjects (97 %) for whom CMG could be calculated, 138 (32.9 %) had CMG<0.20 during follow-up and were considered adherent. Overall, adherence did not differ significantly across treatments: 31.2 % in usual care, 28.3 % with mailed refill reminders, 34.2 % with illustrated medication schedules, and 36.9 % with both interventions. In post-hoc analyses, illustrated medication schedules led to significantly greater odds of adherence among patients who at baseline had more than eight medications (OR=2.2; 95 % CI, 1.21 to 4.04) or low self-efficacy for managing medications (OR=2.15; 95 % CI, 1.11 to 4.16); a trend was present among patients who reported non-adherence at baseline (OR=1.89; 95 % CI, 0.99 to 3.60). CONCLUSIONS: The interventions did not improve adherence overall. Illustrated medication schedules may improve adherence among patients with low self-efficacy, polypharmacy, or baseline non-adherence, though this requires confirmation.

Estimating health and economic benefits from using prescription omega-3 fatty acids in patients with severe hypertriglyceridemia.

Patients with increased triglyceride levels compared to those with normal levels are at higher risk for coronary heart disease. In patients with severe (≥500 mg/dl) hypertriglyceridemia (SHTG), clinical trials have demonstrated that prescription ω-3 fatty acids (P-OM3s) 4 g/day can decrease triglyceride levels by 45%. However, the precise health and economic benefits of decreasing SHTG with P-OM3 are unknown. We used the previously validated Archimedes model to simulate a 20-year trial involving subjects 45 to 75 years old with SHTG. The trial consisted of an intervention arm (P-OM3 4 g/day) and a control arm. Simulation results for the control arm indicated that subjects with SHTG are at about 2 times higher risk for myocardial infarction than those with normal triglyceride levels. Using estimates from previous epidemiologic studies and meta-analyses with OM3s, the model predicted 29% to 36% decreases in various measurements of adverse cardiac events for the intervention arm. The model also predicted a decrease in ischemic stroke of 24% (95% confidence interval 15 to 33). For the 20-year simulated trial, the cost per quality-adjusted life-year gained for the currently available P-OM3 approved by the Food and Drug Administration was $47,000. Results remained robust under different clinical assumptions. In our model P-OM3 was effective in decreasing triglyceride levels and cardiovascular disease risk in patients with SHTG. In conclusion, P-OM3 medication is cost effective in our simulated trial and comparable to other cost-effective cardiovascular interventions.

A "hot" topic in dyslipidemia management--"how to beat a flush": optimizing niacin tolerability to promote long-term treatment adherence and coronary disease prevention.

Niacin is the most effective lipid-modifying agent for raising high-density lipoprotein cholesterol levels, but it also causes cutaneous vasodilation with flushing. To determine the frequency of flushing in clinical trials, as well as to delineate counseling and treatment approaches to prevent or manage flushing, a MEDLINE search was conducted of English-language literature from January 1, 1985, through April 7, 2009. This search used the title keywords niacin or nicotinic acid crossed with the Medical Subject Headings adverse effects and human. Niacin flushing is a receptor-mediated, mainly prostaglandin D(2)-driven phenomenon, the frequency, onset, and duration of which are largely determined by the distinct pharmacological and metabolic profiles of different niacin formulations. Subjective assessments include ratings of redness, warmth, itching, and tingling. In clinical trials, most (>60%) niacin users experienced mild or moderate flushing, which tended to decrease in frequency and severity with continued niacin treatment, even with advancing doses. Approximately 5% to 20% of patients discontinued treatment because of flushing. Flushing may be minimized by taking niacin with meals (or at bedtime with a low-fat snack), avoiding exacerbating factors (alcohol or hot beverages), and taking 325 mg of aspirin 30 minutes before niacin dosing. The current review advocates an initially slow niacin dose escalation from 0.5 to 1.0 g/d during 8 weeks and then from 1.0 to 2.0 g in a single titration step (if tolerated). Through effective counseling, treatment prophylaxis with aspirin, and careful dose escalation, adherence to niacin treatment can be improved significantly. Wider implementation of these measures should enable higher proportions of patients to reach sufficient niacin doses over time to prevent cardiovascular events.

Rationale and design of the Pharmacist Intervention for Low Literacy in Cardiovascular Disease (PILL-CVD) study.

BACKGROUND: Medication errors and adverse drug events are common after hospital discharge due to changes in medication regimens, suboptimal discharge instructions, and prolonged time to follow-up. Pharmacist-based interventions may be effective in promoting the safe and effective use of medications, especially among high-risk patients such as those with low health literacy. METHODS AND RESULTS: The Pharmacist Intervention for Low Literacy in Cardiovascular Disease (PILL-CVD) study is a randomized controlled trial conducted at 2 academic centers-Vanderbilt University Hospital and Brigham and Women's Hospital. Patients admitted with acute coronary syndrome or acute decompensated heart failure were randomly assigned to usual care or intervention. The intervention consisted of pharmacist-assisted medication reconciliation, inpatient pharmacist counseling, low-literacy adherence aids, and tailored telephone follow-up after discharge. The primary outcome is the occurrence of serious medication errors in the first 30 days after hospital discharge. Secondary outcomes are health care utilization, disease-specific quality of life, and cost-effectiveness. Enrollment was completed September 2009. A total of 862 patients were enrolled, and 430 patients were randomly assigned to receive the intervention. Analyses will determine whether the intervention was effective in reducing serious medication errors, particularly in patients with low health literacy. CONCLUSIONS: The PILL-CVD study was designed to reduce serious medication errors after hospitalization through a pharmacist-based intervention. The intervention, if effective, will inform health care facilities on the use of pharmacist-assisted medication reconciliation, inpatient counseling, low-literacy adherence aids, and patient follow-up after discharge. Clinical Trial Registration- clinicaltrials.gov. Identifier: NCT00632021.

Medication use among inner-city patients after hospital discharge: patient-reported barriers and solutions.

OBJECTIVES: To better characterize medication-related problems among inner-city patients after hospital discharge and to suggest potential interventions. PATIENTS AND METHODS: Between August 9, 2005, and April 3, 2006, we interviewed 84 patients hospitalized with acute coronary syndromes at Grady Memorial Hospital in downtown Atlanta, GA, and contacted them by telephone about 2 weeks later. English-speaking patients who managed their own medications were studied. Patients reported their adherence with filling prescriptions and taking medications after discharge, as well as barriers to and potential enablers of proper medication use. RESULTS: Most of the 84 respondents were African American (74 [88%]), male (49 [58%]), and middle-aged (mean age, 54.5 years). Only 40% of patients filled their prescriptions on the day of discharge, 20% filled them 1 or 2 days later, and 18% waited 3 to 9 days; 22% had not filled their prescriptions by the time of the follow-up telephone call (median, 12 days; interquartile range, 8-18 days). Transportation, cost, and wait times at the pharmacy were cited as the main barriers. Many patients reported it was somewhat or very difficult to understand why they were prescribed medications (21%), how to take them (11%), or how to reconcile them with the medications they had been taking before hospitalization (16%). About half the patients (40 [48%]) reported some degree of nonadherence after discharge. Patients noted that several forms of assistance could improve medication use after discharge, including lower medication costs (75%), a follow-up telephone call (68%), transportation to the pharmacy (65%), pharmacist counseling before discharge (64%), and a pillbox (56%). CONCLUSION: Patients often delay filling prescriptions and have difficulty understanding medication regimens after hospital discharge. Interventions that reduce medication costs, facilitate transportation, improve medication counseling, and supply such organizing aids as pillboxes might be beneficial.