Clinical and economic outcomes of liberal versus selective drug-eluting stent use: insights from temporal analysis of the multicenter Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) registry.

BACKGROUND: Although the benefits of drug-eluting stents (DES) for reducing restenosis after percutaneous coronary intervention are well established, the impact of alternative rates of DES use on population-level outcomes is unknown. METHODS AND RESULTS: We used data from the Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) registry to examine the clinical impact and cost-effectiveness of varying DES use rates in routine care. Between 2004 and 2007, 10,144 patients undergoing percutaneous coronary intervention were enrolled in the EVENT registry at 55 US centers. Clinical outcomes and cardiovascular-specific costs were assessed prospectively over 1 year of follow-up. Use of DES decreased from 92 in 2004 to 2006 (liberal use era; n=7587) to 68 in 2007 (selective use era; n=2557; P<0.001). One-year rates of death or myocardial infarction were similar in both eras. Over this time period, the incidence of target lesion revascularization increased from 4.1 to 5.1, an absolute increase of 1.0 (95 confidence interval, 0.1 to 1.9; P=0.03), whereas total cardiovascular costs per patient decreased by $401 (95 confidence interval, 131 to 671; P=0.004). The risk-adjusted incremental cost-effectiveness ratio for the liberal versus selective DES era was $16,000 per target lesion revascularization event avoided, $27,000 per repeat revascularization avoided, and $433 000 per quality-adjusted life-year gained. CONCLUSIONS: In this prospective registry, a temporal reduction in DES use was associated with a small increase in target lesion revascularization and a modest reduction in total cardiovascular costs. These findings suggest that although clinical outcomes are marginally better with unrestricted DES use, this approach represents a relatively inefficient use of healthcare resources relative to several common benchmarks for cost-effective care.

Economic evaluation of clopidogrel plus aspirin for secondary prevention of cardiovascular events in Canada for patients with established cardiovascular disease: Results from the CHARISMA trial.

BACKGROUND: The Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial found a statistically significant reduction in cardiovascular events when clopidogrel was added to aspirin in a prespecified subgroup of patients with established cardiovascular disease. However, the economic implications of such a strategy for the Canadian health care system are unknown. METHODS: For each patient in the CHARISMA trial with established cardiovascular disease, costs were estimated by multiplying resource utilization by unit costs derived from populations of Canadian patients in 2008 dollars. Changes in life expectancy due to nonfatal events were estimated with parametric regression models based on the Saskatchewan Health database. RESULTS: For patients with established cardiovascular disease, a strategy of clopidogrel plus aspirin for median duration of 28 months was associated with a 12.5% relative reduction in cardiovascular death, myocardial infarction, or stroke compared with aspirin alone (6.9% vs 7.9%, P =.048). Mean cost per patient was CAD$1,488 higher for clopidogrel plus aspirin, and life expectancy increased by 0.057 years. The resulting incremental cost-effectiveness ratio for adding clopidogrel was CAD$25,969 per life-year gained or CAD$21,549 per quality-adjusted life-year. These results were sensitive to the cost of clopidogrel but relatively insensitive to plausible variations in discount rate, costs other than clopidogrel, and the prognostic impact of nonfatal events. CONCLUSION: Among the subgroup of patients with established cardiovascular disease in the CHARISMA trial, adding clopidogrel to aspirin increases life expectancy at a cost generally considered acceptable in Canada.

Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at increased surgical risk: results from the SAPPHIRE trial.

OBJECTIVES: To evaluate the cost-effectiveness of carotid stenting vs. carotid endarterectomy using data from the SAPPHIRE trial. BACKGROUND: Carotid stenting with embolic protection has been introduced as an alternative to carotid endarterectomy for prevention of cerebrovascular and cardiovascular events among patients at increased surgical risk. METHODS: Between August 2000 and July 2002, 310 patients with an accepted indication for carotid endarterectomy but at high risk of complications were randomized to and subsequently underwent either carotid stenting (n = 159) or endarterectomy (n = 151). Clinical outcomes, resource use, costs, and quality of life were assessed prospectively for all patients over a 1-year period. Life expectancy, quality-adjusted life expectancy, and health care costs beyond the follow-up period were estimated for patients alive at 1 year, based on observed clinical events during the first year of follow-up. RESULTS: Although initial procedural costs were significantly higher for stenting than for endarterectomy (mean difference: $4,081/patient; 95% CI, $3,849-$4,355), mean post-procedure length of stay was shorter for stenting (1.9 vs. 2.9 days; P < 0.001) with significant associated cost offsets. As a result, initial hospital costs were just $559/patient higher with stenting (95% CI, $3,470 less to $2,289 more). Neither follow-up costs after discharge nor total 1-year costs differed significantly. The incremental cost-effectiveness ratio for stenting compared with endarterectomy was $6,555 per quality-adjusted life year (QALY) gained, with over 98 percent of bootstrap estimates < $50,000/QALY gained. CONCLUSIONS: Although carotid stenting with embolic protection is more costly than carotid endarterectomy, by commonly accepted standards, stenting is an economically attractive alternative to endarterectomy for patients at high surgical risk.

One-year costs associated with cardiovascular disease in Canada: Insights from the REduction of Atherothrombosis for Continued Health (REACH) registry.

BACKGROUND AND OBJECTIVES: To provide a contemporary estimate of the economic burden of atherothrombosis in Canada, annual cardiovascular-related hospitalizations, medication use and associated costs across the entire spectrum of atherothrombotic disease were examined. METHODS: The REduction of Atherothrombosis for Continued Health (REACH) registry enrolled 1964 Canadian outpatients with coronary artery disease, cerebrovascular disease or peripheral arterial disease (PAD), or three or more cardiovascular risk factors. Baseline data on cardiovascular risk factors and associated medication use, and one-year follow-up data on cardiovascular events, hospitalizations, procedures and medication use were collected. Annual hospitalization and medication costs (Canadian dollars) were derived and compared among patients according to the presence of established atherothrombotic disease at baseline, specific arterial beds affected and the number of affected arterial beds. RESULTS: Average annualized medication costs were $1,683, $1,523 and $1,776 for patients with zero, one, and two or three symptomatic arterial beds, respectively. Average annual hospitalization costs increased significantly with the number of beds affected ($380, $1,403 and $3,465, respectively; P<0.0001 for overall linear trend). Mean hospitalization costs for patients with any coronary artery disease, any cerebrovascular disease and any PAD were $1,743, $1,823 and $4,677, respectively. After adjusting for other clinical factors, PAD at baseline was independently associated with a significant increase in hospitalization costs. CONCLUSION: Costs associated with vascular-related hospitalizations and interventions for Canadian patients increased with the number of affected arterial beds, and were particularly high for patients with PAD and/or polyvascular disease. These contemporary data provide insight into the economic burden associated with atherothrombotic disease in Canada, and highlight the need for increased preventive strategies to lessen the burden for patients and society.

Vascular hospitalization rates and costs in patients with peripheral artery disease in the United States.

BACKGROUND: Peripheral artery disease (PAD) is common and imposes a high risk of major systemic and limb ischemic events. The REduction of Atherothrombosis for Continued Health (REACH) Registry is an international prospective registry of patients at risk of atherothrombosis caused by established arterial disease or the presence of ≥3 atherothrombotic risk factors. METHODS AND RESULTS: We compared the 2-year rates of vascular-related hospitalizations and associated costs in US patients with established PAD across patient subgroups. Symptomatic PAD at enrollment was identified on the basis of current intermittent claudication with an ankle-brachial index (ABI) <0.90 or a history of lower-limb revascularization or amputation. Asymptomatic PAD was diagnosed on the basis of an enrollment ABI <0.90 in the absence of symptoms. Overall, 25 763 of the total 68 236-patient REACH cohort were enrolled from US sites; 2396 (9.3%) had symptomatic and 213 (0.8%) had asymptomatic PAD at baseline. One- and cumulative 2-year follow-up data were available for 2137 (82%) and 1677 (64%) of US REACH patients with either symptomatic or asymptomatic PAD, respectively. At 2 years, mean cumulative hospitalization costs, per patient, were $7445, $7000, $10 430, and $11 693 for patients with asymptomatic PAD, a history of claudication, lower-limb amputation, and revascularization, respectively (P=0.007). A history of peripheral intervention (lower-limb revascularization or amputation) was associated with higher rates of subsequent procedures at both 1 and 2 years. CONCLUSIONS: The economic burden of PAD is high. Recurring hospitalizations and repeat revascularization procedures suggest that neither patients, physicians, nor healthcare systems should assume that a first admission for a lower-extremity PAD procedure serves as a permanent resolution of this costly and debilitating condition.

Cost-effectiveness of targeting patients undergoing percutaneous coronary intervention for therapy with bivalirudin versus heparin monotherapy according to predicted risk of bleeding.

BACKGROUND: Although bivalirudin compared with unfractionated heparin with glycoprotein IIb/IIIa inhibitors reduces bleeding and hospitalization costs in patients undergoing percutaneous coronary intervention (PCI), little is known about the economic impact of bivalirudin versus heparin alone and at what threshold of procedural bleeding risk bivalirudin would be considered cost-effective. METHODS AND RESULTS: A validated model was used to predict risk of major bleeding for 81,628 National Cardiovascular Data Registry (NCDR) CathPCI Registry patients from 2004 to 2006 who received unfractionated heparin only. Costs were derived from multiple sources including wholesale acquisition costs (for drugs) and single-center data (for PCI-related complications). Based on ISAR-REACT 3, we assumed that bivalirudin would reduce the risk of major bleeding by 33% compared with unfractionated heparin alone. A Markov model was used to estimate lost life expectancy associated with a major bleed. Major bleeding was predicted to occur in 2.2% of patients. Bivalirudin for all patients was estimated to increase costs by $571 per patient, yielding cost-effectiveness ratios of $287,473 per bleeding event averted and $1,173,360 per quality-adjusted life-year gained. Bivalirudin was cost saving for patients with a predicted bleeding risk >20% (0.16% of CathPCI population). At willingness-to-pay thresholds of $50K and $100K per quality-adjusted life-year gained, bivalirudin was cost-effective for patients with a bleeding risk > or = 8% (2.5% patients) and > or = 5% (7.9% patients), respectively. CONCLUSIONS: This decision-analytic modeling study demonstrates that for patients undergoing PCI, substitution of bivalirudin for unfractionated heparin monotherapy is projected to increase costs for virtually all patients and would be considered cost-effective for only a minority of patients with a high bleeding risk. From a policy standpoint, studies such as this, aimed at identifying the appropriate risk threshold for initiating treatment, may help in the development of informed guidelines for the use of expensive therapies.

Cost effectiveness of eplerenone in patients with heart failure after acute myocardial infarction who were taking both ACE inhibitors and beta-blockers: subanalysis of the EPHESUS.

BACKGROUND: The EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure and Survival Study) showed that the use of aldosterone blockade with eplerenone decreased mortality in patients with heart failure after acute myocardial infarction, and a subsequent analysis showed eplerenone to be highly cost effective in this population. OBJECTIVE: To assess the cost effectiveness of eplerenone in an EPHESUS subgroup population who were taking both ACE inhibitors and beta-blockers (beta-adrenoceptor antagonists) at baseline. In the EPHESUS, a total of 6632 patients were randomized to receive eplerenone 25-50 mg/day (n = 3319) or placebo (n = 3313) concurrently with standard therapy and were followed for up to 2.5 years. Of these, 4265 (64.3%) patients (eplerenone: n = 2113; placebo: n = 2152) were taking both ACE inhibitors and beta-blockers at baseline. METHODS AND MAIN OUTCOME MEASURES: Resource use after the initial hospitalization included additional hospitalizations, outpatient services, emergency room visits, and medications. Eplerenone was priced at an average wholesale price of $US3.60 per day (year 2004 value). Bootstrap methods were used to estimate the fraction of the joint distribution of the cost and effectiveness. A net-benefit regression model was used to derive the propensity score-adjusted cost-effectiveness curve. The incremental cost effectiveness of eplerenone in cost per life-year gained (LYG) and cost per quality-adjusted life-year (QALY) gained beyond the trial period was estimated using data from the Framingham Heart Study, the Saskatchewan Health database, and the Worcester Heart Attack Registry. Both costs and effectiveness were discounted at 3%. Although not all resource use could be accounted for, the overall perspective was societal. RESULTS: As in the overall EPHESUS population, the total direct treatment costs were higher in the eplerenone arm than the placebo arm for patients who were taking both ACE inhibitors and beta-blockers ($US14,563 vs $US12,850, difference = $US1713; 95% CI 721, 2684). The number of LYGs with eplerenone compared with placebo was 0.1665 based on the Framingham data, 0.0979 using the Saskatchewan data, and 0.2172 using the Worcester data. The incremental cost-effectiveness ratio (ICER) was $US10,288/LYG with the Framingham data, $US17,506/LYG with the Saskatchewan data, and $US7888/LYG with the Worcester data (99% <$US50,000/LYG for all three sources). The ICERs were systematically higher when calculated as the cost per QALY gained ($US14,926, $US25,447, and $US11,393, respectively) as the utilities were below 1 with no difference between the treatment arms. CONCLUSION: As for the overall EPHESUS population, aldosterone blockade with eplerenone is effective in reducing mortality and is cost effective in increasing years of life for the EPHESUS subgroup of patients who were taking both ACE inhibitors and beta-blockers.

Cost-effectiveness of prasugrel versus clopidogrel in patients with acute coronary syndromes and planned percutaneous coronary intervention: results from the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with Prasugrel-Thrombolysis in Myocardial Infarction TRITON-TIMI 38.

BACKGROUND: In patients with acute coronary syndromes and planned percutaneous coronary intervention, the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) demonstrated that treatment with prasugrel versus clopidogrel was associated with reduced rates of cardiovascular death, MI, or stroke and an increased risk of major bleeding. We evaluated the cost-effectiveness of prasugrel versus clopidogrel from the perspective of the US healthcare system by using data from TRITON-TIMI 38. METHODS AND RESULTS: Detailed resource use data were prospectively collected for all patients recruited from 8 countries (United States, Australia, Canada, Germany, Italy, Spain, United Kingdom, and France; n=3373 prasugrel, n=3332 clopidogrel). Hospitalization costs were estimated on the basis of diagnosis-related group and in-hospital complications. Cardiovascular medication costs were estimated by using net wholesale prices (clopidogrel=$4.62/d; prasugrel=$5.45/d). Life expectancy was estimated from in-trial cardiovascular and bleeding events with the use of statistical models of long-term survival from a similar population from the Saskatchewan Health Database. Over a median follow-up of 14.7 months, average total costs (including study drug) were $221 per patient lower with prasugrel (95% confidence interval, -759 to 299), largely because of a lower rate of rehospitalization involving percutaneous coronary intervention. Prasugrel was associated with life expectancy gains of 0.102 years (95% confidence interval, 0.030 to 0.180), primarily because of the decreased rate of nonfatal MI. Thus, compared with clopidogrel, prasugrel was an economically dominant treatment strategy. If a hypothetical generic cost for clopidogrel of $1/d is used, the incremental net cost with prasugrel was $996 per patient, yielding an incremental cost-effectiveness ratio of $9727 per life-year gained. CONCLUSIONS: Among acute coronary syndrome patients with planned percutaneous coronary intervention, treatment with prasugrel versus clopidogrel for up to 15 months is an economically attractive treatment strategy. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov. Unique identifier: NCT00097591.

Economic impact of angina after an acute coronary syndrome: insights from the MERLIN-TIMI 36 trial.

BACKGROUND: Angina in patients with coronary artery disease is associated with worse quality of life; however, the relationship between angina frequency and resource utilization is unknown. METHODS AND RESULTS: Using data from the MERLIN-TIMI 36 trial, we assessed the association between the extent of angina after an acute coronary syndrome (ACS) and subsequent cardiovascular resource utilization among 5460 stable outpatients who completed the Seattle Angina Questionnaire at 4 months after an ACS and who were then followed for an additional 8 months. Angina frequency was categorized as none (score, 100; 2739 patients), monthly (score, 61 to 99; 1608 patients), weekly (score, 31 to 60; 854 patients), and daily (score, 0 to 30; 259 patients). Multivariable regression models evaluated the association between angina frequency and overall costs attributable to cardiovascular hospitalizations, outpatient visits and procedures, and medications. As compared with no angina, overall costs increased in a graded fashion with higher angina frequency-no angina, $2928 (reference); monthly angina, $3909 (adjusted relative cost ratio, 1.29; 95% CI, 1.21 to 1.39); weekly angina, $4558 (adjusted relative cost ratio, 1.52; 95% CI, 1.48 to 1.67); and daily angina, $6949 (adjusted relative cost ratio, 2.32; 95% CI, 2.01 to 2.69; P for trend <0.001). Differences in costs were attributable primarily to higher rates of ACS hospitalization and coronary revascularization among patients with more severe angina. CONCLUSIONS: Among stable outpatients after ACS, a direct graded relationship was found between higher angina frequency and healthcare costs. As compared with patients without angina, patients with daily angina had a >2-fold increase in resource utilization and incremental costs of $4000 after 8 months of follow-up.

Cost-effectiveness of clopidogrel plus aspirin versus aspirin alone for secondary prevention of cardiovascular events: results from the CHARISMA trial.

OBJECTIVE: To determine the incremental cost-effectiveness of clopidogrel plus aspirin (C + A) compared with aspirin (A) alone during the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial from a US payer perspective. BACKGROUND: Although the CHARISMA trial did not find a benefit of adding clopidogrel to aspirin in its overall study cohort, a benefit was suggested in a prespecified subgroup of patients with established cardiovascular (CV) disease. The cost-effectiveness of dual antiplatelet therapy in this population is unknown. METHODS: Medical resource utilization was assessed prospectively, and costs for hospitalizations, physician services, outpatient care, and medications were assigned using 2007 US dollars. Life expectancy was estimated contingent on fatal and nonfatal CV events using statistical models of long-term survival from the Saskatchewan Health database. RESULTS: C + A was associated with a 12.5% relative reduction in CV death, myocardial infarction, or stroke compared with A alone (6.9% vs. 7.9%, P = 0.048) over a median 28 months of follow-up. Severe or moderate bleeding events were higher in patients receiving C + A versus A alone (3.6% vs. 2.5%, P < 0.001). Mean cost/patient was $2607 higher for C + A, while projected life expectancy increased by an average of 0.072 years due to fewer in-trial events. The resulting incremental cost-effectiveness ratio (ICER) for C + A was $36,343/year of life gained. Findings were insensitive to discount rate, life expectancy projections, post-event costs, and indirect costs from lost productivity; the ICER was most sensitive to the cost of clopidogrel. Bootstrap analysis demonstrated that the ICER for C + A remained <$50,000/life-year gained in 70.6% of bootstrap replicates and <$100,000/life-year gained in 87.4%. CONCLUSIONS: Among patients with established CV disease, adding clopidogrel to aspirin appears to increase life expectancy modestly at a cost generally considered acceptable within the US health-care system.

One-year costs in patients with a history of or at risk for atherothrombosis in the United States.

BACKGROUND: Atherothrombosis is the underlying cause of cardiovascular, cerebrovascular, and peripheral arterial disease and is the leading cause of death in the industrialized world. The objectives of the present study are (1) to examine the annual costs associated with vascular events and interventions that require hospitalization, as well as long-term medication use for the management of associated risk factors, in a US population of outpatients with multiple atherothrombotic risk factors or a history of symptomatic disease and (2) to compare costs across patient subgroups defined according to specific arterial bed(s) affected and the number of affected arterial beds. METHODS AND RESULTS: The international REduction of Atherothrombosis for Continued Health (REACH) Registry enrolled outpatients > or =45 years of age who had established coronary artery, cerebrovascular, or peripheral artery disease or > or =3 atherothrombotic risk factors. Data on risk factors, associated medications, and vascular hospitalizations and interventions were collected. Of the total 68 236-patient REACH cohort, 25 763 were enrolled from US sites. Complete 1-year data were available for 23 974 (93%) of the US patients. Annualized medication costs ranged from $2401 to $3481. Mean annual hospitalization costs per patient were $1344, $2864, $4824, and $8155 for patients with 0 (n=6145), 1 (n=14 353), 2 (n=3106), and 3 (n=370) affected arterial beds at baseline (P<0.0001 for trend). Among patients with 1 affected arterial bed, mean hospitalization costs were $2999, $2010, and $3911 for patients with coronary artery disease (n=11 063), cerebrovascular disease (n=2613), and peripheral arterial disease (n=677), respectively. Annualized medication costs ranged from $2401 to $3481. CONCLUSIONS: These results reveal the high economic burden of atherothrombosis-related clinical events and procedures and the especially high economic burden associated with polyvascular disease.

The impact of age on outcomes after coronary artery bypass surgery versus stent-assisted percutaneous coronary intervention: one-year results from the Stent or Surgery (SoS) trial.

BACKGROUND: Relative outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) may differ between younger and older patients. There are no data comparing the age-related CABG versus PCI outcomes in the stent era. METHODS: The SoS trial compared CABG (n = 500) and stent-assisted PCI (n = 488). The impact of treatment assignment on 1-year outcomes was evaluated by age < or = 65 years (n = 295, CABG; n = 298, PCI) and > 65 years (n = 205, CABG; n = 190, PCI). RESULTS: One-year procedural outcomes were similar between treatment groups regardless of age, with the exception of more repeat revascularizations after PCI (age < or = 65, 16.1% vs 4.8%; age > 65, 19.5% vs 3.4%; both P < .001). Six and 12-month Seattle Angina Questionnaire scores improved from baseline in both age and treatment groups. However, CABG was associated with greater improvement in physical limitation, angina frequency, and quality of life in younger patients at 6 and 12 months (12-month difference in improvement between CABG and PCI: 5.6, 4.8, and 3.9 points for 3 domains), whereas in the elderly a significant benefit of CABG observed at 6 months did not persist at 12 months (12-month difference: 0.9, 1.9, and 1.4). One-year costs were significantly higher after CABG regardless of age. CONCLUSIONS: Although PCI and CABG result in similar rates in clinical outcomes irrespective of age, younger patients reported more health status benefits from CABG as compared with PCI, whereas in older patients the 2 approaches resulted in similar 1-year health status benefits.

Economics methods in the Clinical Outcomes Utilizing percutaneous coronary Revascularization and Aggressive Guideline-driven drug Evaluation (COURAGE) trial.

Percutaneous coronary intervention (PCI) remains a major therapeutic option for the treatment of chronic coronary artery disease. In the COURAGE trial, 2287 patients with chronic coronary disease were randomized between PCI with medical management and medical management alone. Embedded within the COURAGE trial is a detailed economic analysis being conducted in three health care systems: the US Veterans Administration (VA), Canada, and the US non-VA. Resource use and costs are being collected for each system and overall. Survival is assessed internally in the trial with mean follow-up of 4.5 years. Long-term mean survival will be estimated by projecting survival beyond the trial period by extrapolating the in-trial hazard rates. Utility is being assessed at baseline and at 1, 3, and 6 months and annually thereafter, using a computer-administered standard gamble. Quality-adjusted life years are calculated by multiplying survival by utility. The incremental cost-effectiveness ratio of PCI will be defined as the additional cost of PCI divided by the gain in life years and quality-adjusted life years. The 95% confidence regions of efficacy and costs will be determined by bootstrap over a range of acceptability thresholds, which will then be displayed in the cost-effectiveness plane and as a cost-effectiveness acceptability curve. A multilevel regression model will assess cost-effectiveness from a net benefit perspective. These approaches should provide the most detailed assessment available of the cost-effectiveness of PCI for coronary artery disease.

Long-term cost-effectiveness of early and sustained clopidogrel therapy for up to 1 year in patients undergoing percutaneous coronary intervention after presenting with acute coronary syndromes without ST-segment elevation.

BACKGROUND: The superiority of clopidogrel and aspirin versus aspirin alone for up to 1 year in patients who undergo percutaneous coronary intervention (PCI) after presenting with acute coronary syndromes without ST-segment elevation was demonstrated in the PCI-CURE study. We evaluated the long-term cost-effectiveness of clopidogrel use for up to 1 year using patient-level outcomes and resource use from PCI-CURE, and estimates of life expectancy gains based on external sources. METHODS: PCI-CURE involved 2658 patients who underwent PCI between 1998 and 2000 after being randomized in the CURE trial to clopidogrel (n = 1313) or placebo (n = 1345). Roughly two thirds (clopidogrel n = 821, placebo n = 909) underwent PCI during the initial hospitalization (early PCI). Costs were applied to hospitalizations according to diagnosis-related group. Clopidogrel was assigned the average wholesale price of 3.22 dollars per day. Life expectancy gains resulting from the prevention of major clinical events were estimated using external sources. RESULTS: Average total costs were higher with clopidogrel (difference [based on costing method] 253 dollars-423 dollars). For patients who underwent PCI during the initial hospitalization, the difference ranged from 155 dollars lower to 90 dollars higher with clopidogrel. The estimated life expectancy gain with clopidogrel was 0.0885 years, whereas it was 0.0962 years for the early PCI subgroup. Incremental cost per year of life gained with clopidogrel ranges from 2856 dollars to 4775 dollars overall and from dominant (life expectancy benefit with cost savings) to 935 dollars for the early PCI subgroup. CONCLUSIONS: Clopidogrel given for up to 1 year in patients undergoing PCI after presentation with acute coronary syndromes is a highly cost-effective treatment strategy.

Long-term cost effectiveness of early and sustained dual oral antiplatelet therapy with clopidogrel given for up to one year after percutaneous coronary intervention results: from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial.

OBJECTIVES: This study sought to evaluate the long-term cost effectiveness of a clopidogrel loading strategy before percutaneous coronary intervention (PCI) followed by continued treatment for one year. BACKGROUND: The Clopidogrel for the Reduction of Events During Observation (CREDO) trial, a randomized trial of 2,116 patients, showed the effectiveness of antiplatelet therapy with clopidogrel 300 mg before PCI and 75 mg daily for one year afterward compared with placebo load and placebo days 29 to 365 in reducing the combined risk of death, myocardial infarction, and stroke. All patients received clopidogrel on days 1 to 28 and aspirin on days 1 to 365. METHODS: All hospitalizations were assigned a diagnosis-related group. Associated costs were estimated three ways (including professional costs): 1) Medicare costs, 2) MEDSTAT costs, and 3) blend with Medicare for those age > or = 65 years and MEDSTAT for those age <65 years. Clopidogrel 75 mg cost 3.22 dollars. Life expectancy in trial survivors was estimated using external data. Confidence intervals were assessed by bootstrap. RESULTS: The primary composite end point occurred in 89 (8.45%) clopidogrel patients and in 122 (11.48%) placebo patients (relative risk reduction [RRR] 26.9%; 95% confidence interval [CI] 3.9% to 44.4%). The number of life-years gained (LYG) with clopidogrel was 0.1526 (95% CI 0.0263 to 0.2838) using Framingham data and 0.1920 (95% CI 0.054 to 0.337) using Saskatchewan data. Average total costs were 664 dollars higher for the clopidogrel arm (95% CI -461 dollars to 1,784 dollars). The incremental cost-effectiveness ratios (ICERs) based on Framingham data ranged from 3,685 dollars/LYG to 4,353 dollars/LYG, with over 97% of bootstrap-derived ICER estimates below 50,000 dollars/LYG. The ICERs based on Saskatchewan data were 2,929 dollars/LYG to 3,460 dollars/LYG, with over 98% of estimates below 50,000 dollars/LYG. CONCLUSIONS: Platelet inhibition with clopidogrel loading before PCI followed by therapy for one year is highly cost effective.

The impact of acute coronary syndrome on clinical, economic, and cardiac-specific health status after coronary artery bypass surgery versus stent-assisted percutaneous coronary intervention: 1-year results from the stent or surgery (SoS) trial.

BACKGROUND: Data are limited regarding the impact of acute coronary syndromes (ACSs) on the relative benefits of coronary artery bypass grafting (CABG) versus stent-assisted percutaneous coronary intervention (PCI). METHODS: The SoS trial compared patients with multivessel disease who were randomly assigned to CABG (n = 500) or stent-assisted PCI (n = 488). The impact of treatment on 1-year outcomes was compared in ACS (n = 126, CABG; n = 116, PCI) and non-ACS (n = 374, CABG; n = 372, PCI) subgroups. RESULTS: Baseline characteristics were similar between treatment groups within ACS and non-ACS groups, as was the 1-year composite incidence of mortality and myocardial infarction (ACS, 5.2% for PCI vs 5.6% for CABG, P = .89; non-ACS, 7.0% vs 8.3%, P = .50). The need for repeat revascularizations was higher after PCI versus CABG within each subgroup (ACS, 15.5% vs 7.1%, P = .04; non-ACS, 18.0% vs 3.2%, P < .001). At 6 and 12 months, scores on the Seattle Angina Questionnaire improved significantly in patients with and without ACS. In patients without ACS, CABG was associated with greater improvement in physical limitation, angina frequency, and quality of life at 6 and 12 months. In patients with ACS, there was only a nonsignificant slight trend toward greater improvement with CABG at 1 year. The total 1-year costs for PCI and CABG in patients without ACS were 5760 pound sterling and 8509 pound sterling (Delta = 2749 pound sterling, 95% CI 1890 pound sterling - 3409 pound sterling), and in patients with ACS, 8014 pound sterling and 10080 pound sterling (Delta = 2066 pound sterling, 95% CI -690 pound sterling to 3487 pound sterling). CONCLUSIONS: In patients with and without ACS, CABG had similar clinical outcomes, less need for repeat revascularization and higher costs compared to PCI. The benefit of CABG relative to PCI in improving patients' health status tended to be greater in patients without ACS than in patients with ACS.

Long-term cost-effectiveness of clopidogrel given for up to one year in patients with acute coronary syndromes without ST-segment elevation.

OBJECTIVES: We sought to evaluate the long-term cost-effectiveness of clopidogrel for up to one year after an acute coronary syndrome (ACS) without ST-segment elevation. BACKGROUND: The efficacy of platelet inhibition with clopidogrel for up to one year after ACS was demonstrated in the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial, a randomized trial of 12,562 patients in 28 countries that was conducted between 1998 and 2000. Patients were given clopidogrel (300-mg load followed by 75 mg/day) versus placebo, both in addition to aspirin, for a mean of nine months. METHODS: We used patient-level clinical outcomes and resource use from the CURE trial and estimates of life expectancy gains as a result of the prevention of the clinical events of death, stroke, and myocardial infarction on the basis of data from external sources. RESULTS: Excluding clopidogrel costs, average costs of hospitalizations alone were 325 dollars less for the clopidogrel arm (95% confidence interval -722 dollars to 45 dollars) using diagnosis-related group-based Medicare reimbursement rates. When including clopidogrel costs (766 dollars greater for the clopidogrel arm), average total costs were 442 dollars higher for the clopidogrel arm (95% confidence interval 62 dollars to 820 dollars). The incremental cost-effectiveness ratio (ICER) on the basis of the Framingham Heart Study was 6,318 dollars per life-year gained (LYG) with clopidogrel, with 94% of bootstrap-derived ICER estimates <50,000 dollars/LYG; based on Saskatchewan, the ICER was 6,475 dollars/LYG with 98% of estimates <50,000 dollars. CONCLUSIONS: Platelet inhibition with clopidogrel in patients for up to one year after presentation with an acute coronary syndrome is both effective and cost-effective.

Cost-effectiveness of eplerenone compared with placebo in patients with myocardial infarction complicated by left ventricular dysfunction and heart failure.

BACKGROUND: In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), aldosterone blockade with eplerenone decreased mortality in patients with left ventricular systolic dysfunction and heart failure after acute myocardial infarction. The present study was performed to evaluate the cost-effectiveness of eplerenone compared with placebo in these patients. METHODS AND RESULTS: A total of 6632 patients with left ventricular systolic dysfunction and heart failure after acute myocardial infarction were randomized to eplerenone or placebo and followed up for a mean of 16 months. The coprimary end points were all-cause mortality and the composite of cardiovascular mortality/cardiovascular hospitalization. The evaluation of resource use included hospitalizations, outpatient services, and medications. Eplerenone was priced at the average wholesale price, 3.60 dollars per day. Survival beyond the trial period was estimated from data from the Framingham Heart Study, the Saskatchewan Health database, and the Worcester Heart Attack Registry. The incremental cost-effectiveness of eplerenone in cost per life-year and quality-adjusted life-year gained compared with placebo was estimated. The number of life-years gained with eplerenone was 0.1014 based on Framingham (95% CI, 0.0306 to 0.1740), 0.0636 with Saskatchewan (95% CI, 0.0229 to 0.1038), and 0.1337 with Worcester (95% CI, 0.0438 to 0.2252) data. Cost was 1391 dollars higher over the trial period in the eplerenone arm (95% CI, 656 to 2165) because of drug cost. The incremental cost-effectiveness ratio was 13,718 dollars per life-year gained with Framingham (96.7% under 50,000 dollars per life-year gained), 21,876 dollars with Saskatchewan, and 10,402 dollars with Worcester. CONCLUSIONS: Eplerenone compared with placebo in the treatment of heart failure after acute myocardial infarction is effective in reducing mortality and is cost-effective in increasing years of life by commonly used criteria.

Off-pump vs conventional coronary artery bypass grafting: early and 1-year graft patency, cost, and quality-of-life outcomes: a randomized trial.

CONTEXT: Previous trials of off-pump coronary artery bypass (OPCAB) have enrolled selected patients and have not rigorously evaluated long-term graft patency. A preliminary report showed OPCAB achieved improved inhospital outcomes, similar completeness of revascularization, and shorter lengths of stay compared with conventional coronary artery bypass grafting (CABG). OBJECTIVE: To assess graft patency, clinical and quality-of-life outcomes, and cost among patients while in the hospital and at 1-year follow-up. DESIGN, SETTING, AND PATIENTS: Randomized controlled trial of patients unselected for coronary anatomy, ventricular function, or comorbidities between March 10, 2000, and August 20, 2001, at a US academic center. A total of 200 patients were enrolled; 3 patients were withdrawn after randomization for mitral valve repair or replacement. Follow-up was complete for 197 patients at 30 days; 185 at 1 year. INTERVENTIONS: One surgical session consisting of elective OPCAB or CABG with cardiopulmonary bypass. The surgeon had extensive experience performing off-pump surgery; patients were subsequently managed by blinded protocols. MAIN OUTCOME MEASURES: Coronary angiography documented graft patency prior to hospital discharge and at 1 year; health-related quality of life; and cost of the index and subsequent hospitalization(s). RESULTS: Graft patency was similar for OPCAB and conventional CABG with cardiopulmonary bypass at 30 days (absolute difference, 1.3%; 95% confidence interval [CI], -0.66% to 3.31%; P =.19) and at 1 year (absolute difference, -2.2%; 95% CI, -6.1% to 1.7%; P =.27). Rates of death, stroke, myocardial infarction, angina, and reintervention were similar at 30 days and 1 year. There were no significant differences in health-related quality of life. Mean total hospitalization cost per patient at hospital discharge was 2272 dollars (95% CI, 755 dollars-3732 dollars) less for OPCAB (P =.002) and 1955 dollars (95% CI, -766 dollars to 4727 dollars) less at 1 year (P =.08). CONCLUSIONS: In this randomized single-surgeon trial among unselected patients with angiographic follow-up, OPCAB achieved similar graft patency in the hospital and at 1 year. Cardiac outcomes and health-related quality of life at 30 days and 1 year were similar and patients incurred a lower cost. OPCAB may provide complete revascularization that is durable and cost-effective.