Cost-Effectiveness of Combination of Baricitinib and Remdesivir in Hospitalized Patients with COVID-19 in the United States: A Modelling Study.

INTRODUCTION: Baricitinib-remdesivir (BARI-REM) combination is superior to remdesivir (REM) in reducing recovery time and accelerating clinical improvement among hospitalized patients with coronavirus disease 2019 (COVID-19), specifically those receiving high-flow oxygen/noninvasive ventilation. Here we assessed the cost-effectiveness of BARI-REM versus REM in hospitalized patients with COVID-19 in the USA. METHODS: A three-state model was developed addressing costs and patient utility associated with COVID-19 hospitalization, immediate post hospital care, and subsequent lifetime medical care. Analysis was performed from the perspective of a payer and a hospital. Both perspectives evaluated two subgroups: all patients and patients who required oxygen. The primary measures of benefit in the model were patient quality-adjusted life years (QALYs) accrued during and after hospitalization, cost per life years gained, cost per death avoided, and cost per use of mechanical ventilation avoided. RESULTS: In the base-case payer perspective with a lifetime horizon, treatment with BARI-REM versus REM resulted in an incremental total cost of $7962, a gain of 0.446 life years and gain of 0.3565 QALYs over REM. The incremental cost-effectiveness ratios of using BARI-REM were estimated as $22,334 per QALY and $17,858 per life year. The base-case and sensitivity analyses showed that the total incremental cost per QALY falls within the reduced willingness-to-pay threshold of $50,000/QALY applied under health emergencies. In all hospitalized patients, treatment with BARI-REM versus REM reduced total hospital expenditures per patient by $1778 and total reimbursement payments by $1526, resulting in a $252 reduction in net costs per patient; it also resulted in a net gain of 0.0018 QALYs and increased survival of COVID-19 hospitalizations by 2.7%. CONCLUSION: Our study showed that BARI-REM is cost-effective compared to using REM for hospitalized patients with COVID-19. The base-case results of this cost-effectiveness model were most sensitive to average annual medical costs for recovered patients.

One-Year Clinical Effectiveness Comparison of Prasugrel with Ticagrelor: Results from a Retrospective Observational Study using an Integrated Claims Database.

BACKGROUND: No direct comparisons of ticagrelor and prasugrel with 1-year clinical follow-up have been reported. OBJECTIVES: Our objective was to compare 1-year clinical outcomes among patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with either ticagrelor or prasugrel in a real-world setting. METHODS: This retrospective study included patients from a payer database who were aged ≥18 years and had ACS managed with PCI with no history of transient ischemic attack (TIA)/stroke. Data were propensity matched for prasugrel use with a 3:1 prasugrel:ticagrelor ratio. Post-discharge net adverse clinical event (NACE) rate at 1 year was evaluated for noninferiority using a pre-defined 20% margin. NACE was a composite of major adverse cardiovascular events (MACE) or rehospitalization for bleeding. RESULTS: In total, 15,788 ACS-PCI patients were included (prasugrel 12,797; ticagrelor 2991). Prasugrel-treated patients were younger; less likely to be female, have prior myocardial infarction (MI), diabetes, or non-ST-segment elevation MI (NSTEMI); and more likely to have unstable angina (UA) than ticagrelor-treated patients. Prior to matching, NACE and MACE (P < 0.01) were lower, with no difference in bleeding with prasugrel compared with ticagrelor. After matching, there was no significant difference in baseline characteristics. Noninferiority was demonstrated for NACE, MACE, and bleeding between prasugrel and ticagrelor. NACE and MACE were significantly lower with prasugrel use, primarily driven by heart failure, with no significant difference in all-cause death, MI, UA, revascularization, TIA/stroke, or bleeding. CONCLUSIONS: In this retrospective study, physicians preferentially used prasugrel rather than ticagrelor in younger ACS-PCI patients with lower risk of bleeding or comorbidities. After propensity matching, clinical outcomes associated with prasugrel were noninferior to those with ticagrelor.

Accuracy of Medical Claims for Identifying Cardiovascular and Bleeding Events After Myocardial Infarction : A Secondary Analysis of the TRANSLATE-ACS Study.

Importance: Pragmatic clinical trial designs have proposed the use of medical claims data to ascertain clinical events; however, the accuracy of billed diagnoses in identifying potential events is unclear. Objectives: To compare the 1-year cumulative incidences of events when events were identified by medical claims vs by physician adjudication and to assess the accuracy of bill-identified events using physician adjudication as the criterion standard. Design, Setting, and Participants: This post hoc analysis of a clinical trial assessed the medical claims forms and records for all rehospitalizations at 233 US hospitals within 1 year of the index acute myocardial infarction (MI) of 12 365 patients enrolled in the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study between April 1, 2010, and October 31, 2012. Fourteen patients (0.1%) died during the index hospitalization and were excluded from analysis. Recurrent MI, stroke, and bleeding events were identified per the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and procedural codes in medical bills. These events were independently adjudicated by study physicians through medical record reviews using the prespecified criteria of recurrent MI and stroke and the bleeding definition by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) scale. Medical claims were reported on a Uniform Bill-04 claims form; claims were collected from all hospitals visited by patients enrolled in TRANSLATE-ACS. Agreement between medical claims-identified events and physician-adjudicated events over the 12 months after discharge was assessed with the κ statistic. Data were analyzed from January 30, 2015, to March 2, 2017. Main Outcomes and Measures: Event rates within 1 year after MI. Results: Among 12 365 patients with acute MI, 8890 (71.9%) were men and mean (SD) age was 60 (11.6) years. The cumulative 1-year incidence of events identified by medical claims was 4.3% for MI, 0.9% for stroke, and 5.0% for bleeding. Incidence rates based on physician adjudication were 4.7% for MI, 0.9% for stroke, and 5.4% for bleeding. Agreement between medical claims-identified and physician-adjudicated events was modest, with a κ of 0.76 (95% CI, 0.73 to 0.79) for MI and 0.55 (95% CI, 0.41 to 0.68) for stroke events. In contrast, agreement between medical claims-identified and physician-adjudicated bleeding events was poor, with a κ of 0.24 (95% CI, 0.19 to 0.30) for any hospitalized bleeding event and 0.15 (95% CI, 0.11 to 0.20) for moderate or severe bleeding on the GUSTO scale. Conclusions and Relevance: Event rates at 1 year after MI were lower for MI, stroke, and bleeding when medical claims were used to identify events than when adjudicated by physicians. Medical claims diagnoses were only modestly accurate in identifying MI and stroke admissions but had limited accuracy for bleeding events. An alternative approach may be needed to ensure good safety surveillance in cardiovascular studies. Trial Registration: clinicaltrials.gov Identifier: NCT01088503.

Health-related quality of life outcomes with prasugrel among medically managed non-ST-segment elevation acute coronary syndrome patients: Insights from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial.

BACKGROUND: Few studies have assessed treatment effects on health-related quality of life (HRQoL) in patients with acute coronary syndrome (ACS) treated without revascularization. The TRILOGY ACS trial randomized patients with ACS to either prasugrel or clopidogrel therapy plus aspirin. Outcomes showed a complex pattern suggestive of late benefits with respect to repeat clinical events and benefits confined to patients who underwent angiography. Here, we examine the HRQoL correlates of these patterns. METHODS: HRQoL was measured at baseline and 3, 12, and 24 months or end of study (EOS) in 7243 patients aged <75 years using the EuroQol 3-level, group 5-dimension index (EQ-5D). Linear mixed effects models for repeated measures were used to examine treatment differences in HRQoL overall, stratified by angiography status, and among patients who did and did not have non-fatal events. RESULTS: No baseline differences in HRQoL were seen between patients randomized to prasugrel (n=3620) or clopidogrel (n=3623). At 24 months, remaining patients assigned to prasugrel (n=1450) vs. clopidogrel (n=1443) had higher EQ-5D index scores (86.4 vs. 84.9, P=.01). Mixed effects models found no difference in EQ-5D scores among prasugrel and clopidogrel patients overall across subgroups stratified by angiography status. However, among patients with non-fatal clinical events, patients on clopidogrel reported a larger decrement in HRQoL than patients on prasugrel (79.5±18.1 vs. 80.6±18.0; P=.02). CONCLUSIONS: Overall, there was no difference in HRQoL outcomes among patients receiving prasugrel vs. clopidogrel. However, the differential effects of the treatments among patients with non-fatal events require further investigation.

How Reliable are Patient-Reported Rehospitalizations? Implications for the Design of Future Practical Clinical Studies.

BACKGROUND: Longitudinal clinical investigations often rely on patient reports to screen for postdischarge adverse outcomes events, yet few studies have examined the accuracy of such patient reports. METHODS AND RESULTS: Patients with acute myocardial infarction (MI) in the TRANSLATE-ACS study were asked during structured interviews at 6 weeks, 6 months, and 12 months postdischarge to report any rehospitalizations. The accuracy of patient-reported rehospitalizations within 1 year of postdischarge was determined using claims-based medical bill validation as the reference standard. The cumulative incidence of rehospitalizations was compared when identified by patient report versus medical bills. Patients were categorized by the accuracy in reporting events (accurate, under-, or over- reporters) and characteristics were compared between groups. Among 10 643 MI patients, 4565 (43%) reported 7734 rehospitalizations. The sensitivity and positive predictive value of patient-reported rehospitalizations were low at 67% and 59%, respectively. A higher cumulative incidence of rehospitalization was observed when identified by patient report versus medical bills (43% vs 37%; P<0.001). Overall, 18% of patients over-reported and 10% under-reported the number of hospitalizations. Compared with accurate reporters, under-reporters were more likely to be older, female, African American, unemployed, or a non-high-school graduate, and had greater prevalence of clinical comorbidities such as diabetes and past cardiovascular disease. CONCLUSIONS: The accuracy of patient-reported rehospitalizations was low with patients both under- and over-reporting events. Longitudinal clinical research studies need additional mechanisms beyond patient report to accurately identify rehospitalization events. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01088503.

One-year post-discharge resource utilization and treatment patterns of patients with acute coronary syndrome managed with percutaneous coronary intervention and treated with ticagrelor or prasugrel.

OBJECTIVE: Our objective was to compare 1-year real-world healthcare resource utilization (HRU), associated charges, and antiplatelet treatment patterns among patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with ticagrelor or prasugrel. METHODS: Using the ProMetis-Lx database, adult ACS-PCI patients treated with ticagrelor or prasugrel post-discharge were identified between 1 August 2011 and 31 May 2013 and propensity matched to adjust for baseline differences. RESULTS: Before matching, ticagrelor-treated patients (n = 2991) were older with increased baseline ischemic and bleeding risks compared with prasugrel-treated patients (n = 12,797). After matching, ticagrelor patients had higher all-cause HRU (2.5 vs. 2.4 per patient per month; P = 0.012) and cardiovascular (CV) HRU (0.4 vs. 0.3 per patient per month; P = 0.026), with the difference in CV rehospitalizations (17.7 vs. 15.7 %; P = 0.011) primarily driven by congestive heart failure (CHF) (4.9 vs. 3.8 %; P = 0.02). All-cause charges within 1 year did not significantly differ between groups ($US5456 vs. 4844 per patient per month; P = 0.37), but dyspnea-related total charges were significantly higher with ticagrelor ($US139 vs. 95 per patient per month; P = 0.005). Although infrequent, switching was slightly higher with ticagrelor (8.3 vs. 6.0 %; P < 0.001) at 1 year, and mean persistence was slightly longer with prasugrel (150 vs. 159 days; P = 0.002), with no significant difference in mean adherence (61 vs. 63 %; P = 0.17). CONCLUSION: Overall monthly HRU was slightly lower with prasugrel than with ticagrelor, with no significant difference in bleeding HRU. Prasugrel was associated with slightly higher pharmacy charges, but lower dyspnea charges, resulting in no significant difference in total charges. Patients receiving prasugrel tended to use it for longer than those receiving ticagrelor as less switching occurred. These findings may aid decision making, but must be tempered due to inherent study limitations.

High-Risk Atherosclerotic Cardiovascular Disease in a Real-World Employed Japanese Population: Prevalence, Cardiovascular Event Rates, and Costs.

AIM: To assess the prevalence of high-risk atherosclerotic cardiovascular disease (ASCVD, defined as history of acute coronary syndrome [hACS], cerebrovascular atherosclerotic disease [CeVAD], peripheral artery disease [PAD], or coronary artery disease w/diabetes [CADD]) and associated costs and cardiovascular (CV) events in Japan. METHODS: A retrospective analysis was conducted using the Japan Medical Data Center (JMDC) database (2006-2011). ASCVD prevalence was estimated on the basis of diagnoses for CeVAD, PAD, CADD, and hACS (ACS claim ＞ 30-≤ 365 days after ACS-related hospitalization) during 1/1/ 2008-12/31/2009. Population denominators used in the prevalence estimations were provided by JMDC. A subcohort with an insurance coverage for ≥ 12 months before and ≥ 24 months after first/index ASCVD claim during 1/1/2008-12/31/2009 were analyzed on the basis of costs (in 2012 US dollars) and events. RESULTS: ASCVD prevalence was 1,869/100,000 population. In total, 8,112 patients met inclusion criteria for the cost and CV event analyses. Among these patients, 4.0% experienced any event (myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina) in the year after ASCVD diagnosis, which decreased to 2.2% in year 2. First-year event rates were highest (22%) in patients with hACS. Mean [SD] all-cause costs per patient in year 1 were $7,031 [$14,359] for all patients with ASCVD combined. Extrapolated to the entire employed population, total first-year costs were estimated at $8.2 billion. CONCLUSIONS: ASCVD is not rare in Japan, even within a relatively young population of employed persons. Further, the total direct first-year cost burden of ASCVD in the employed Japanese population is high. These data may inform future economic assessments of new ASCVD treatments.

Comparison of healthcare resource utilization and costs in patients hospitalized for acute coronary syndrome managed with percutaneous coronary intervention and receiving prasugrel or ticagrelor.

OBJECTIVE: To compare healthcare resource utilization (HCRU) and healthcare costs in patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with prasugrel or ticagrelor. METHODS: Hospital charge master data were used to identify ACS-PCI patients aged ≥ 18 years with ≥ 1 in-hospital claim for prasugrel or ticagrelor between August 1, 2011-April 30, 2013. Treatment groups were propensity matched for baseline and index hospitalization characteristics. HCRU and costs were assessed through 90-days post-discharge. Costs were determined based on hospital-specific cost-to-charge ratios and adjusted to 2013 US dollars. RESULTS: Before matching, ticagrelor patients were older, more-often female, and had increased cardiovascular (CV) and bleeding risks compared with prasugrel patients. Propensity-matched length of index hospital stay (4.7 vs 4.9 days, p = 0.23) and risk for all-cause [30-day: relative risk (RR) = 0.86; 95% CI = 0.73-1.0; 90-day: RR = 0.90; 95% CI = 0.80-1.0, and CV-related (30-day: RR = 0.77; 95% CI = 0.59-1.0; 90-day: RR = 0.89; 95% CI = 0.73-1.1) re-hospitalizations did not significantly differ between prasugrel and ticagrelor, respectively. Compared to ticagrelor, the propensity-matched risk of re-hospitalization for myocardial infarction (MI) (30-day: RR = 0.39; 95% CI = 0.21-0.75; 90-day: RR = 0.53; 95% CI = 0.34-0.81) and an outpatient medical encounter for dyspnea (30-day: RR = 0.49; 95% CI = 0.33-0.74; 90-day: RR = 0.60; 95% CI = 0.46-0.80) were significantly lower for prasugrel patients, with no significant differences in bleeding encounters between groups (30-day: RR = 0.87; 95% CI = 0.54-1.40; 90-day: RR = 1.0; 95% CI = 0.71-1.50). Matched total healthcare costs were not significantly different between groups during the index hospitalization ($36,011 vs $37,247, p = 0.21), 30-days post-discharge ($2007 vs $2522, p = 0.48), 90-days post-discharge ($4564 vs $5242, p = 0.49), and aggregate of the index hospitalization through 90-day follow-up ($40,576 vs $42,494, p = 0.09) timeframes. CONCLUSIONS: Re-hospitalization for MI and outpatient encounters for dyspnea were lower in prasugrel treated than in ticagrelor treated ACS-PCI patients up to 90-days post-index hospitalization discharge, with no difference in bleeding encounters or healthcare costs between the two populations. This data supports the utility of prasugrel in routine clinical practice. These findings should be considered within limitations of observational research.

Changes in low-density lipoprotein cholesterol levels after discharge for acute myocardial infarction in a real-world patient population.

Aggressively managing low-density lipoprotein cholesterol (LDL-C) after myocardial infarction (MI) is a cornerstone of secondary prevention. The changes in LDL-C after MI and the factors associated with LDL-C levels are unknown. Therefore, we directly measured fasting LDL-C levels in 797 MI patients from 24 US hospitals from 2005 to 2008. Mean LDL-C levels at discharge, 1 month, and 6 months were 95.1, 81.9, and 87.1 mg/dL, respectively. In a hierarchical, multivariable, repeated measures model, older age, male sex, and hypertension were associated with lower LDL-C levels, whereas self-reported avoidance of health care because of cost was associated with higher LDL-C. Both the presence and intensity of statin therapy at discharge were strongly associated with LDL-C levels, with adjusted mean 6-month changes of -3.4 mg/dL (95% confidence interval (CI): -12.1, 5.3) for no statins; 1.7 mg/dL (95% CI: -4.7, 8.1) for low statins; -10.2 mg/dL (95% CI: -14.5, -6.0) for moderate statins; and -13.9 mg/dL (95% CI: -19.7, -8.0) for intensive statins (P < 0.001). In conclusion, we found that greater reductions in LDL-C levels after MI were strongly associated with the presence and intensity of statin therapy, older age, male sex, hypertension, and better socioeconomic status. These findings support the use of intensive statin therapy in post-MI patients and provide estimates of the expected LDL-C changes after MI in a real-world population.

Patterns of statin initiation, intensification, and maximization among patients hospitalized with an acute myocardial infarction.

BACKGROUND: Intensive statins are superior to moderate statins in reducing morbidity and mortality after an acute myocardial infarction. Although studies have documented rates of statin prescription as a quality performance measure, variations in hospitals' rates of initiating, intensifying, and maximizing statin therapy after acute myocardial infarction are unknown. METHODS AND RESULTS: We assessed statin use at admission and discharge among 4340 acute myocardial infarction patients from 24 US hospitals (2005-2008). Hierarchical models estimated site variation in statin initiation in naïve patients, intensification in those undergoing submaximal therapy, and discharge on maximal therapy (defined as a statin with expected low-density lipoprotein cholesterol lowering ≥ 50%) after adjustment for patient factors, including low-density lipoprotein cholesterol level. Site variation was explored with a median rate ratio, which estimates the relative difference in risk ratios of 2 hypothetically identical patients at 2 different hospitals. Among statin-naïve patients, 87% without a contraindication were prescribed a statin, with no variability across sites (median rate ratio, 1.02). Among patients who arrived on submaximal statins, 26% had their statin therapy intensified, with modest site variability (median rate ratio, 1.47). Among all patients without a contraindication, 23% were discharged on maximal statin therapy, with substantial hospital variability (median rate ratio, 2.79). CONCLUSIONS: In a large, multicenter acute myocardial infarction cohort, statin therapy was begun in nearly 90% of patients during hospitalization, with no variability across sites; however, rates of statin intensification and maximization were low and varied substantially across hospitals. Given that more intense statin therapy is associated with better outcomes, changing the existing performance measures to include the intensity of statin therapy may improve care.

Adherence and persistence with prasugrel following acute coronary syndrome with percutaneous coronary intervention.

PURPOSE: To measure the adherence and persistence of patients with acute coronary syndrome (ACS) initiating prasugrel after percutaneous coronary intervention (PCI). METHODS: Using the Thomson Reuters MarketScan Commercial and Medicare Supplemental database, a retrospective cohort study identified patients initiating prasugrel following ACS-PCI hospitalization in 2009-2011. Prasugrel adherence over 12 months was measured using the medication possession ratio (MPR); predictors of adherence were identified using a logistic regression model. Persistence was defined as time on continuous therapy; a Cox model identified predictors of prasugrel discontinuation. RESULTS: Among 1,340 patients, the mean age was 57 years; 79.5 % were male. Median prasugrel MPR was 93.2 %; 69.0 % of patients had an MPR ≥80 %. Predictors of adherence <80 % included prior PCI [odds ratio (OR) 0.60; 95 % confidence interval (CI) 0.40-0.90], prior depression (OR 0.37; 95 % CI 0.16-0.84), prior bleeding (OR 0.41; 95 % CI 0.19-0.86), and baseline anticoagulant use (OR 0.13; 95 % CI 0.03-0.55). Baseline statin use predicted higher adherence (OR 1.56; 95 % CI 1.21-2.02). The median duration of prasugrel therapy was 259 days. Predictors of discontinuation included prior anemia [hazard ratio (HR) 1.63; 95 % CI 1.21-2.21], prior cardiomyopathy (HR 2.72; 95 % CI 1.44-5.13), and prior ischemic heart disease (HR 1.15; 95 % CI 1.00-1.32); baseline statin use predicted reduced risk of discontinuation (HR 0.85; 95 % CI 0.75-0.97). CONCLUSIONS: Although adherence to prasugrel was generally high, the duration of therapy was frequently below recommendations. An awareness of risk factors for low adherence or early discontinuation can point to appropriate targets for intervention.

Adherence and dosing frequency of common medications for cardiovascular patients.

OBJECTIVES: To compare adherence between once-daily (QD) and twice-daily (BID) dosing with chronic-use prescription medications used by patients with cardiovascular disease. STUDY DESIGN: Retrospective cohort database analysis. METHODS: Analysis consisted of 1,077,474 patients aged >18 years with a prescription index date from January 1 to December 31, 2007, for an antidiabetic, antihyperlipidemic, antiplatelet, or cardiac agent with QD or BID dosing. Adherence (medication possession ratio [MPR]) was the number of days of medication supplied between the first prescription fill date and the subsequent 365 days divided by 365 days. Overall mean MPR and comparisons between dosing frequency groups were assessed with a generalized estimating equation. Covariates included age at index date, gender, Charlson comorbidity index, therapeutic class, dosing frequency, and the interaction between therapeutic class and dosing frequency group. RESULTS: Overall, the adjusted mean MPR ± standard error (SE) value for QD agents was 13.6% greater than BID agents (0.66 ± 0.0006 vs 0.57 ± 0.0016; P <.01). The adjusted mean MPR value for QD agents was 2.9%, 17.5%, and 29.4% greater than BID agents in the antidiabetic, antihyperlipidemic, and antiplatelet therapeutic classes, respectively. For cardiac agents, the adjusted mean MPR value was similar between QD and BID agents. Carvedilol represented approximately 80% of the cardiac agents in the BID group. The adjusted mean MPR ± SE for carvedilol phosphate QD was 0.73 ± 0.0024 and 0.65 ± 0.0027 for carvedilol BID (11% difference; P <.01). CONCLUSIONS: In this large analysis, the QD dosing regimen was related to greater adherence versus a BID regimen.

Opportunities for pharmacotherapy at the intersection of metabolic syndrome and hemostasis.

Hemostatic balance is regulated by many factors that may become perturbed by cardio-metabolic abnormalities. Indeed, patients with multiple components of the metabolic syndrome have increased risk of atherosclerosis, hemostatic disorders and thrombotic events. This review focuses on the interrelationship between the metabolic syndrome components and thrombotic and thromboembolic events, the potential underlying mechanisms that lead to metabolic and hemostatic disorders in metabolic syndrome patients, the existing therapeutics aimed at reducing major cardiovascular events, and new therapeutic approaches to address pro-coagulant states.

Factors associated with clopidogrel use, adherence, and persistence in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

OBJECTIVE: Recent guidelines recommend use of aspirin and either clopidogrel or prasugrel for at least 12 months following use of drug-eluting or bare metal stents in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). This study evaluated factors associated with clopidogrel use and adherence in ACS patients following PCI. RESEARCH DESIGN AND METHODS: The US employer-based MarketScan commercial claims database was used to examine factors associated with clopidogrel use and adherence. Adherence was defined as a medication possession ratio of 80% or higher. Multivariate logistic regression analyses were conducted to identify factors associated with clopidogrel use and adherence and included patient demographics, comorbidities, and prior beta-blocker, statin, and angiotensin converting enzyme inhibitor (BSI) use as factors. RESULTS: A total of 10,465 patients aged 18-65 years who met inclusion criteria were hospitalized for ACS and underwent PCI between 01/01/2005 and 12/31/2006. Overall, the rate of clopidogrel use was 92.8% for ACS-PCI patients and 66.8% of the clopidogrel users were adherent. Receiving PCI without stenting (Odds Ratio [OR] = 3.28), comorbid hypertension (OR = 1.50), diabetes (OR = 1.49), and atrial fibrillation (OR = 1.91) were associated with decreased filled prescriptions for clopidogrel. Younger age (OR = 0.83) and prior use of clopidogrel (OR = 0.54) or other BSI medications (OR = 0.44) were associated with increased use of clopidogrel (all p values < 0.05). Factors significantly associated with non-adherence of clopidogrel were prior use of clopidogrel (OR = 1.40), prior hospitalization (OR = 1.34), chronic pulmonary disease (OR = 1.31), PCI without stenting (OR = 1.32), diabetes (OR = 1.17), and younger age (OR = 1.29). Prior use of BSI medications (OR = 0.82) increased adherence to clopidogrel. CONCLUSIONS: Prior use of clopidogrel, comorbid conditions such as diabetes and chronic pulmonary disease, prior hospitalization, PCI without stenting, and younger age had a negative impact on clopidogrel adherence. These findings may assist programs to improve thienopyridine compliance through a better understanding of patients' disease profiles and concomitant medication use.

Potential unrecognised costs of clopidogrel pretreatment in acute coronary syndrome.

OBJECTIVE: To examine adherence in clinical practice to the American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations of observing a 5-day waiting period after clopidogrel administration before undergoing coronary artery bypass graft (CABG) surgery and to examine the costs of waiting. METHODS: This retrospective study used a nationwide inpatient database (Solucient ACTracker) to identify patients who were admitted for acute coronary syndrome (ACS), and who had same-stay CABG. Cost of additional days of stay was estimated using regression analysis. RESULTS: The recommended 5-day waiting was adhered to in 16.9% (n=3,809) of patients. The percentage of patients with ACS undergoing CABG surgery on day 0 was 14.6%. Adherence to the waiting was higher for teaching and rural hospitals; and in female and elderly patients and urgent admissions. CONCLUSIONS: The recommended 5-day waiting for CABG surgery after clopidogrel treatment is poorly adhered to in clinical practice. This study was unable to determine specific reasons for the low adherence; however, there may be a compromise between the clinically urgent need for revascularisation and increased risk of bleeding, as well as economic costs associated with waiting. The cost of an additional hospital day in this group of patients was approximately £1,400 per day or £7,000 for 5 days. Thus, a full 5-day wait would have a significant economic impact on hospital costs.

Adherence to guidelines for sensitivity analysis: cost-effectiveness analyses of dual oral antiplatelet therapy.

OBJECTIVE: Cost-effectiveness analyses of new treatments for cardiovascular disease frequently require input parameters whose values are known with uncertainty due to limited data. The objective of this paper is to examine the extent to which published sensitivity analyses addressing this uncertainty adhere to Health Technology Assessment (HTA) guidelines. RESEARCH DESIGN AND METHODS: A systematic review of published cost-effectiveness analyses was performed for an example drug treatment scenario, dual oral antiplatelet therapy compared with aspirin alone following acute coronary syndromes and/or percutaneous coronary intervention. The following medical literature databases were searched for articles published from January 1997 to June 2007: PubMed, Cochrane Collaboration, EMBASE and the Health Economic Evaluation Database (HEED). Evidence tables were created to show the sensitivity of the cost-effectiveness estimates to changes in the input parameter values, as well as the data sources used for the reference-case and sensitivity analysis input parameter values. The extent to which the sensitivity analyses adhered to HTA guidelines were also examined. RESULTS: Cost-effectiveness ratios were most sensitive to changes in the efficacy of dual antiplatelet therapy and reference-case model assumptions about costs beyond the trial period. Although alternative values tested in the sensitivity analysis for some input parameters were based on observed ranges or distributions, alternative values tested for many other input parameters were assumed without justification. CONCLUSIONS: Sensitivity analyses in the cost-effectiveness studies of dual oral antiplatelet therapy were not fully adherent with HTA guidelines. In particular, long-term costs and benefits were not always included in the sensitivity estimates, the impact of differential effects on death and myocardial infarction was not explored, and justification for the alternative parameter values tested was not always provided.

Cost of care for new versus recurrent acute coronary syndrome patients.

INTRODUCTION: The economic burden of acute coronary syndrome (ACS) continues long after the acute event has resolved. This study compared ACS-related costs between new and recurrent ACS patients using retrospective claims data from a large US health plan. METHODS: Patients with ACS were identified using ICD-9 codes between the 1st January 2001 and the 30th June 2003. The first diagnosis was defined as the index event. Patient claims were examined 1 year before, and up to 1 year after, the index event. Hospitalisations, revascularisations and costs for new and recurrent cohorts were compared. Multivariate regression was used to examine cost predictors. RESULTS: In total, 15,508 patients were identified, 82% had new ACS. The new ACS cohort was more likely to have myocardial infarction and be hospitalised for the index event, leading to higher index event costs. However, the recurrent ACS cohort had more re-hospitalisations, longer lengths of inpatient stay and a higher probability of revascularisation during follow-up. The index event cost per patient and per patient-month was higher for new ACS patients. After adjusting for confounding factors, multivariate cost models revealed annualised follow-up medical costs were 9.9% higher (p=0.017) and annualised follow-up pharmacy costs were 8.3% higher (p< or =0.0001) for the new ACS cohort. CONCLUSION: Newly diagnosed ACS patients had significantly higher adjusted costs in the year following the index event, but recurrent ACS patients still experienced high medical costs. More emphasis by providers and patients on adherence to treatment guidelines may be one step to improving patient outcomes. *This paper was presented in part at the Academy of Managed Care Pharmacy Annual Meeting, 7th April 2006.

Clopidogrel loading doses and outcomes of patients undergoing percutaneous coronary intervention for acute coronary syndromes.

BACKGROUND: In clinical practice, the use of clopidogrel loading doses higher than the standard 300 mg dose is becoming more common in percutaneous coronary intervention (PCI) despite a paucity of clinical evidence to support such a strategy. OBJECTIVE: This study sought to assess whether patients with acute coronary syndromes (ACS) undergoing PCI would receive additional benefit from higher-than-standard (300 mg) loading doses of clopidogrel. METHODS: We performed a retrospective analysis of outcomes in 2,484 patients with ACS undergoing PCI who received either standard dose (300 mg, n = 1,199) or high-dose (> 300 mg, n = 1,285) clopidogrel loading at 1 of 14 study hospitals between January 2003 and September 2004. RESULTS: At 60 days after discharge, the rate of the combined endpoint of myocardial infarction (MI), stroke, coronary revascularization or death was higher in the high-dose group (37.1< vs. 20.5%; p < 0.0001), primarily because of a higher rate of MI in the high-dose group (34.7% vs. 17.3%; p < 0.0001). Bleeding event rates did not differ between the high-dose and standard-dose groups. Propensity scoring was used to compare event frequencies between patients with similar clinical risk, and this analysis also showed no additional clinical benefit associated with higher clopidogrel loading doses. CONCLUSION: Based on this retrospective study, the use of higher (> 300 mg) clopidogrel loading doses is not associated with additional clinical benefit in patients with ACS undergoing PCI in clinical practice.

Acute coronary syndromes in Europe: 1-year costs and outcomes.

OBJECTIVE: This study aims to estimate costs (including medications prescribed, intervention rates and hospital utilization) and health outcomes of acute coronary syndromes (ACS) during the first year following diagnosis. RESEARCH DESIGN AND METHODS: Treatment pathways for ACS patients were developed and country-specific resource use was multiplied by unit costs. Countries examined were the United Kingdom (UK), France, Germany, Italy and Spain. Patients with unstable angina and acute myocardial infarction (ST-segment elevation and non-ST-segment elevation with/without Q-wave) were considered. The study models the incidence of ACS, 1-year mortality, investigations, revascularisation, pharmaceutical use and medical management. Economic outcomes were direct healthcare costs (in 2004 Euros), including total cost, cost per patient with ACS and cost per capita. RESULTS: The estimated number of deaths in the first year following ACS diagnosis ranged from around 22 500 in Spain to over 90 000 in Germany. The largest contributors to total costs are hospital stay and revascularisation procedures. Pharmaceuticals were estimated at 14-25% of ACS total cost. The total cost of ACS in the UK is estimated around 1.9 billion Euros, compared with 1.3 billion Euros in France, 3.3 billion Euros in Germany, 3.1 billion Euros in Italy and 1.0 billion Euros in Spain. The cost per ACS patient ranges from 7009 Euros (in the UK) to 12,086 Euros (Italy). CONCLUSIONS: Countries with higher expenditure on ACS patients tended to have lower case-fatality rates, and countries with the lowest incidence of ACS also had the lowest cost per capita. The costs of ACS constitute a large proportion of total healthcare expenditure of Western European economies.

Predictors of high-cost managed care patients with acute coronary syndrome.

OBJECTIVE: To develop predictive models of high-cost acute coronary syndrome (ACS) patients using demographic, disease, and treatment characteristics. STUDY DESIGN: This was a retrospective, administrative claims analysis utilizing pharmacy, medical, and eligibility data from a large US managed care organization. METHODS: ACS was defined by ICD-9 codes for unstable angina (UA) or acute myocardial infarction (AMI). New onset patients (without ACS claims) in the prior six months were identified for the time period 07/01/99-06/30/01, and followed up to 12 months, health plan disenrollment, or death. Cost was measured as that incurred during the initial episode plus subsequent follow-up or during the subsequent follow-up only. Patients were dichotomized as high-cost (top 20%) or low-cost (bottom 80%), based on total costs. Logistic regression was used to examine the association for being classified as high-cost. RESULTS: A total of 13 731 patients were included: 51.7% with UA, 39.6% with AMI and 8.7% with both UA and AMI. The mean age was 54.2 years and 68.2% were male. A number of co-morbidities (hypertension, diabetes, heart failure, etc.) predicted high-cost patients. Among medications, prior ACE inhibitor use predicted high-cost patients. While revascularization procedures, in general, were strong predictors of high-cost, revascularization during the index ACS episode (opposed to revascularization during the follow-up) decreased the odds of being high-cost (odds ratio [95% CI] 0.615 [0.506-0.748]). CONCLUSION: High-cost patients with new onset ACS can be predicted by some characteristics, but many of these characteristics are non-modifiable co-morbidities. Payers and providers may find opportunities for clinical and cost-saving interventions for these patients.