OBJECTIVES: The aim of this study was to evaluate the impact of reductions in statin and clopidogrel copayments on cardiovascular resource utilization, major coronary events, and insurer spending. BACKGROUND: Copayments are widely used to contain health spending but cause patients to reduce their use of essential cardiovascular medications. Reducing copayments for post-myocardial infarction secondary prevention has beneficial effects, but the impact of this strategy for lower risk patients and other drugs remains unclear. METHODS: An evaluation was conducted of health care spending and resource use by a large self-insured employer that reduced statin copayments for patients with diabetes or vascular disease and reduced clopidogrel copayments for all patients prescribed this drug. Eligible individuals in the intervention company (n = 3,513) were compared with a control group from other companies without such a policy (n = 49,803). Analyses were performed using segmented regression models with generalized estimating equations. RESULTS: Lowering copayments was associated with significant reductions in rates of physician visits (relative change: statin users 0.80; 95% confidence interval [CI]: 0.57 to 0.98; clopidogrel users: 0.87; 95% CI: 0.59 to 0.96) and hospitalizations and emergency department admissions (relative change: statin users 0.90; 95% CI: 0.80 to 0.92; clopidogrel users: 0.89; 95% CI: 0.74 to 0.90) although not major coronary events. Patient out-of-pocket spending for drugs and other medical services decreased (relative change: statin users 0.79; 95% CI: 0.75 to 0.83; clopidogrel users 0.74; 95% CI: 0.66 to 0.82). Providing more generous coverage did not increase overall spending (relative change: statin users 1.03; 95% CI: 0.97 to 1.09; clopidogrel users 0.94; 95% CI: 0.87 to 1.03). CONCLUSIONS: Lowering copayments for statins and clopidogrel was associated with reductions in health care resource use and patient out-of-pocket spending. The policy appeared cost neutral with respect to overall health spending.

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OBJECTIVES To determine whether adherence interventions should be administered to all medication takers or targeted to nonadherers. DATA SOURCES AND STUDY SELECTION Systematic search (Medline and Embase, 1966-2009) of randomized controlled trials of interventions to improve adherence to medications for preventing or treating cardiovascular disease or diabetes. DATA EXTRACTION Articles were classified as (1) broad interventions (targeted all medication takers), (2) focused interventions (targeted nonadherers), or (3) dynamic interventions (administered to all medication takers; real-time adherence information targets nonadherers as intervention proceeds). Cohen's d effect sizes were calculated. DATA SYNTHESIS We identified 7,190 articles; 59 met inclusion criteria. Broad interventions were less likely (18%) to show medium or large effects compared with focused (25%) or dynamic (32%) interventions. Of the 33 dynamic interventions, 6 used externally generated adherence data to target nonadherers. Those with externally generated data were less likely to have a medium or large effect (20% vs. 34.8% self-generated data). CONCLUSION Adherence interventions targeting nonadherers are heterogeneous but may have advantages over broad interventions. Dynamic interventions show promise and require further study.

Aims Previous studies have suggested that upstream medical therapy to modulate the renin-angiotensin axis may facilitate left atrial remodelling and thereby prevent new-onset atrial fibrillation (AF). The purpose of this study was to evaluate the association between angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARB) on new-onset AF in a large cohort of patients with coronary artery disease (CAD).Methods and results This was a population-based study of 28 620 patients, from community-dwelling Medicare beneficiaries who had been hospitalized for acute myocardial infarction or coronary revascularization (1995–2004). All patients, 65 years and older, had a mean follow-up period of upto 3.8 ± 3.0 years. Patients with a history of AF before and during hospitalization were excluded.  We compared the incidence of new-onset AF between patients who were (N= 10 918) and were not (N= 17 702) prescribed ACEI and/or ARB within 1 month of hospital discharge following cardiac event. New-onset AF within 5 and 10 years was 39.1 and 61.1%, respectively, in patients who received ACEI/ARB, compared  34.9 and 53.6% in patients who did not receive them [unadjusted hazard ratio (HR): 1.16; 95% confidence interval (CI): 1.11, 1.21]. Multivariable analysis adjusting for patient- and hospital-related characteristics indicated that ACEI/ARB use independently had no impact on the risk of developing new-onset AF compared with non-users (adjusted HR: 0.99; 95% CI: 0.94, 1.04). Adjustment for propensity-score and health-seeking behaviours yielded nearly identical results.Conclusion Angiotensin converting enzyme inhibitor/ARB therapy initiated within 1 month after hospital discharge is not associated with a reduction in the risk of new-onset AF after myocardial infarction or coronary revascularization.

Background Adherence to medications that are prescribed after myocardial infarction is poor. Eliminating out-of-pocket costs may increase adherence and improve outcomes. Methods We enrolled patients discharged after myocardial infarction and randomly assigned their insurance-plan sponsors to full prescription coverage (1494 plan sponsors with 2845 patients) or usual prescription coverage (1486 plan sponsors with 3010 patients) for all statins, beta-blockers, angiotensin-converting-enzyme inhibitors, or angiotensin-receptor blockers. The primary outcome was the first major vascular event or revascularization. Secondary outcomes were rates of medication adherence, total major vascular events or revascularization, the first major vascular event, and health expenditures. Results Rates of adherence ranged from 35.9 to 49.0% in the usual-coverage group and were 4 to 6 percentage points higher in the full-coverage group (P<0.001 for all comparisons). There was no significant between-group difference in the primary outcome (17.6 per 100 person-years in the full-coverage group vs. 18.8 in the usual-coverage group; hazard ratio, 0.93; 95% confidence interval [CI], 0.82 to 1.04; P=0.21). The rates of total major vascular events or revascularization were significantly reduced in the full-coverage group (21.5 vs. 23.3; hazard ratio, 0.89; 95% CI, 0.90 to 0.99; P=0.03), as was the rate of the first major vascular event (11.0 vs. 12.8; hazard ratio, 0.86; 95% CI, 0.74 to 0.99; P=0.03). The elimination of copayments did not increase total spending ($66,008 for the full-coverage group and $71,778 for the usual-coverage group; relative spending, 0.89; 95% CI, 0.50 to 1.56; P=0.68). Patient costs were reduced for drugs and other services (relative spending, 0.74; 95% CI, 0.68 to 0.80; P<0.001). Conclusions The elimination of copayments for drugs prescribed after myocardial infarction did not significantly reduce rates of the trial's primary outcome. Enhanced prescription coverage improved medication adherence and rates of first major vascular events and decreased patient spending without increasing overall health costs. (Funded by Aetna and the Commonwealth Fund; MI FREEE ClinicalTrials.gov number, NCT00566774 .).

BACKGROUND: Medications are a cornerstone of the prevention and management of cardiovascular disease. Long-term medication adherence has been the subject of increasing attention in the developed world but has received little attention in resource-limited settings, where the burden of disease is particularly high and growing rapidly. To evaluate prevalence and predictors of non-adherence to cardiovascular medications in this context, we systematically reviewed the peer-reviewed literature. METHODS: We performed an electronic search of Ovid Medline, Embase and International Pharmaceutical Abstracts from 1966 to August 2010 for studies that measured adherence to cardiovascular medications in the developing world. A DerSimonian-Laird random effects method was used to pool the adherence estimates across studies. Between-study heterogeneity was estimated with an I(2) statistic and studies were stratified by disease group and the method by which adherence was assessed. Predictors of non-adherence were also examined. FINDINGS: Our search identified 2,353 abstracts, of which 76 studies met our inclusion criteria. Overall adherence was 57.5% (95% confidence interval [CI] 52.3% to 62.7%; I(2) 0.98) and was consistent across study subgroups. Studies that assessed adherence with pill counts reported higher levels of adherence (62.1%, 95% CI 49.7% to 73.8%; I(2) 0.83) than those using self-report (54.6%, 95% CI 47.7% to 61.5%; I(2) 0.93). Adherence did not vary by geographic region, urban vs. rural settings, or the complexity of a patient's medication regimen. The most common predictors of poor adherence included poor knowledge, negative perceptions about medication, side effects and high medication costs. INTERPRETATION: Our study indicates that adherence to cardiovascular medication in resource-limited countries is sub-optimal and appears very similar to that observed in resource-rich countries. Efforts to improve adherence in resource-limited settings should be a priority given the burden of heart disease in this context, the central role of medications in their management, and the clinical and economic consequences of non-adherence.

PURPOSE: Myocardial infarction (MI) survivors benefit from receiving secondary prevention, including beta-blockers, angiotensin-blocking agents, and statins, as recommended by guidelines. Compliance with these guidelines is suboptimal. We sought to describe the initiation of secondary prevention in MI survivors, and to describe the variation in initiation by discharging the hospital, the physician, and the physician "responsible" for secondary prevention prescribing decisions in British Columbia in 1997-2004. METHODS: We assembled a cohort of 28 613 patients discharged alive from the hospital after their first MI and were not readmitted within 30 days. Physicians responsible for prescribing post-MI secondary prevention medications were identified as the physicians prescribing the greatest number of cardiac medications (post-discharge cardiac prescribers). We used multilevel logistic regression to assess the variation in drug initiation at discharging hospital, discharging physician, and post-discharge cardiac prescriber levels, which were adjusted for patient and provider characteristics during the study period. RESULTS: Beta-blockers initiation increased from 56 to 71% over the 8-year study period; angiotensin-converting enzyme/angiotensin II receptor blocker initiation increased from 37 to 70%, and statin initiation increased from 22 to 66% (0-28% for high-potency statins). The probability for initiating an average patient with the study drugs varied widely in age-sex-adjusted models at the hospital and physician levels. Further adjustment did not meaningfully change findings. The variation was largest for statins. The maximum between-provider variance was found for high-potency statins in 2003-2004 at the post-discharge cardiac prescriber level. CONCLUSIONS: Study-drug initiation is increasing among MI survivors, but the variation in initiation is wide between discharging hospitals and physicians. Copyright (c) 2011 John Wiley & Sons, Ltd.

Background While the role of hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) in secondary prevention of cardiovascular (CV) events and mortality is established, their value for primary prevention is less clear. To clarify the role of statins for patients without CV disease, we performed a meta-analysis of randomized controlled trials (RCTs). Methods MEDLINE, EMBASE, Cochrane Collaboration, and American College of Physicians Journal Club databases were searched for RCTs published between 1966 and June 2005. We included RCTs with follow-up of 1 year or longer, more than 100 major CV events, and 80% or more of the population without CV disease. From each trial, demographic data, lipid profile, CV outcomes, mortality, and adverse outcomes were recorded. Summary relative risk (RR) ratios with 95% confidence intervals (CIs) were calculated using a random effects model. Results Seven trials with 42 848 patients were included. Ninety percent had no history of CV disease. Mean follow-up was 4.3 years. Statin therapy reduced the RR of major coronary events, major cerebrovascular events, and revascularizations by 29.2% (95% CI, 16.7%-39.8%) (P<.001), 14.4% (95% CI, 2.8%-24.6%) (P = .02), and 33.8% (95% CI, 19.6%-45.5%) (P<.001), respectively. Statins produced a nonsignificant 22.6% RR reduction in coronary heart disease mortality (95% CI, 0.56-1.08) (P = .13). No significant reduction in overall mortality (RR, 0.92 [95% CI, 0.84-1.01]) (P = .09) or increases in cancer or levels of liver enzymes or creatine kinase were observed. Conclusion In patients without CV disease, statin therapy decreases the incidence of major coronary and cerebrovascular events and revascularizations but not coronary heart disease or overall mortality.

OBJECTIVE: To compare the effectiveness of statins of different treatment intensity used to treat elderly patients with acute coronary syndrome (ACS) in typical care settings. DESIGN: Retrospective cohort study using linked hospital and pharmacy claims data. SETTING: Statewide pharmacy benefits programmes in Pennsylvania and New Jersey. PARTICIPANTS: 18,311 Medicare patients discharged alive after ACS who received a prescription for a statin within 90 days of hospital discharge. MAIN OUTCOME MEASURES: Using multivariable and propensity-matched Cox proportional hazards regression models, patients who were prescribed high-intensity and moderate-intensity statins were compared based on the drug-dose combination that they initially received. Individual drug-dose combinations were also compared. Our primary outcome was the composite of all-cause death or recurrent ACS. RESULTS: Patients who received moderate-intensity statins were as likely to experience a primary outcome as patients treated with high-intensity statins (adjusted HR 1.02, 95% CI 0.96 to 1.08). Propensity matching did not change the results. Individually, all moderate-intensity statins were as effective as high-intensity atorvastatin with the exception of lovastatin (adjusted HR 1.22, 95% CI 1.09 to 1.36). Similarly, all high-intensity statins seem as effective as high-intensity atorvastatin but the CIs surrounding these estimates were wide. CONCLUSIONS: This analysis of elderly patients with ACS treated in typical care settings does not demonstrate the superiority of high-intensity over moderate-intensity statin treatment or significant differences among individual statins.

Taken in combination, aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins (combination pharmacotherapy) greatly reduce cardiac events. These therapies are underused, even among patients with drug insurance. Out-of-pocket spending is a key barrier to adherence. We estimated the impact of providing combination pharmacotherapy without cost sharing ("full coverage") to insured patients after a myocardial infarction (MI). Under base-case assumptions, compared to standard coverage, three years of full coverage will reduce mortality and reinfarction rates and will save 5,974 per patient. Our analysis suggests that covering combination therapy for such patients will save both lives and money.

OBJECTIVES: The benefits of statin therapy for patients with coronary artery disease have been well documented, including those occurring after coronary artery bypass graft surgery. The purposes of this study were to assess statin prescription rates in patients who have undergone coronary artery bypass graft surgery and to identify the determinants of postoperative statin administration. METHODS: A retrospective cohort of 9284 Medicare patients aged 65 years or older who underwent coronary artery bypass graft surgery (1995-2004) was assembled by using linked hospital and pharmacy claims data. Rates of statin use after hospital discharge were calculated, and predictors of postoperative statin use were identified by using generalized estimating equations. RESULTS: Overall, 35.9% of patients received statins within 90 days of coronary artery bypass graft surgery discharge. Use of statins within 90 days after coronary artery bypass graft surgery steadily improved during the study period, from 13.1% in 1995 to 60.9% in 2004. Patient factors independently associated with an increase in postoperative statin therapy included preoperative statin use (odds ratio, 7.69), later year of operation (odds ratio, 1.22 per additional year), and additional postoperative medications (odds ratio, 1.16 per additional medication). Factors independently associated with a decrease in postoperative statin therapy included peripheral vascular disease (odds ratio, 0.60), diabetes mellitus (odds ratio, 0.67), stroke (odds ratio, 0.77), and older age (odds ratio, 0.96 per additional year). Surgeon and hospital characteristics were not independently associated with postoperative statin use. CONCLUSIONS: Statins are considerably underused after coronary artery bypass graft surgery, although recent prescription rates are increasing. Patterns of use do not appear to correlate with coronary artery disease risk. These findings highlight the need for targeted quality improvement initiatives to increase the rate of statin administration to this at-risk population.

Antiplatelet agents are central to the treatment and prevention of cardiovascular disease. Although aspirin is the most widely used agent, randomized trials have assessed whether adding clopidogrel to aspirin ("dual-antiplatelet therapy") offers additional benefit with acceptable safety. Unfortunately, these trials have reached conflicting results, in part because of the heterogenous populations they studied. To clarify the role of dual-antiplatelet therapy for patients with vascular disease, a systematic review and meta-analysis of randomized controlled trials was performed. Medline and the Cochrane Collaboration and American College of Physicians Journal Club databases were searched for trials published from 1966 to August 2006 that compared aspirin and clopidogrel with antiplatelet monotherapy. Only trials that presented clinically relevant efficacy and safety outcomes were included. From each trial, demographic data and outcomes were recorded. Summary odds ratios and 95% confidence intervals (CIs) were calculated using a random-effects model. Eight trials comprising 91,744 patients were included. Mean follow-up ranged from 28 days to 18 months. Compared with aspirin alone, dual therapy with aspirin and clopidogrel reduced the odds ratio of the composite outcome of death, reinfarction, and stroke by 15% (95% CI 23% to 6%) in patients with acute coronary syndromes and by 34% (95% CI 44% to 22%) in patients who underwent percutaneous coronary intervention. Dual therapy also significantly reduced the odds of fatal and nonfatal reinfarction in these patient groups but did not significantly reduce the odds of all-cause mortality. Dual therapy was associated with significantly increased risk for major bleeding in studies >1 month in duration (odds ratio 1.80, 95% CI 1.40 to 2.30). In conclusion, combining aspirin and clopidogrel significantly reduces the odds of major cardiovascular events in patients with acute coronary syndromes or those who undergo percutaneous coronary intervention but at the expense of significant increases in the risk for bleeding.