Quality of life after PCI with drug-eluting stents or coronary-artery bypass surgery.

BACKGROUND: Previous studies have shown that among patients undergoing multivessel revascularization, coronary-artery bypass grafting (CABG), as compared with percutaneous coronary intervention (PCI) either by means of balloon angioplasty or with the use of bare-metal stents, results in greater relief from angina and improved quality of life. The effect of PCI with the use of drug-eluting stents on these outcomes is unknown. METHODS: In a large, randomized trial, we assigned 1800 patients with three-vessel or left main coronary artery disease to undergo either CABG (897 patients) or PCI with paclitaxel-eluting stents (903 patients). Health-related quality of life was assessed at baseline and at 1, 6, and 12 months with the use of the Seattle Angina Questionnaire (SAQ) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The primary end point was the score on the angina-frequency subscale of the SAQ (on which scores range from 0 to 100, with higher scores indicating better health status). RESULTS: The scores on each of the SAQ and SF-36 subscales were significantly higher at 6 and 12 months than at baseline in both groups. The score on the angina-frequency subscale of the SAQ increased to a greater extent with CABG than with PCI at both 6 and 12 months (P=0.04 and P=0.03, respectively), but the between-group differences were small (mean treatment effect of 1.7 points at both time points). The proportion of patients who were free from angina was similar in the two groups at 1 month and 6 months and was higher in the CABG group than in the PCI group at 12 months (76.3% vs. 71.6%, P=0.05). Scores on all the other SAQ and SF-36 subscales were either higher in the PCI group (mainly at 1 month) or were similar in the two groups throughout the follow-up period. CONCLUSIONS: Among patients with three-vessel or left main coronary artery disease, there was greater relief from angina after CABG than after PCI at 6 and 12 months, although the extent of the benefit was small. (Funded by Boston Scientific; ClinicalTrials.gov number, NCT00114972.).

A pilot trial of injectable, extended-release naltrexone for the treatment of co-occurring cocaine and alcohol dependence.

BACKGROUND: There is a high co-occurrence of cocaine and alcohol use disorders, and patients with both of these problems are difficult to treat. There is a reasonable rationale and some empirical data to justify a pilot trial of an injectable, extended-release formulation of naltrexone for treating co-occurring cocaine and alcohol addiction. METHODS: Eighty cocaine (n = 80) and alcohol dependent, treatment-seeking subjects were randomly assigned to receive either two monthly extended-release injections of naltrexone or two matching placebo injections in an 8-week clinical trial, with weekly medical management plus cognitive behavioral therapy visits. RESULTS: No differences in reduction in cocaine or alcohol use were observed between the injectable naltrexone and placebo groups during the 8-week trial. CONCLUSIONS: Injectable extended-release naltrexone, while an ideal method for ensuring medication adherence in these traditionally hard-to-treat patients, did not result in any measurable reduction in cocaine or alcohol use over the course of 8 weeks of treatment.

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.

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.

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.

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.

Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis.

CONTEXT: Clinicians and trialists have difficulty with identifying which patients are highest risk for cardiovascular events. Prior ischemic events, polyvascular disease, and diabetes mellitus have all been identified as predictors of ischemic events, but their comparative contributions to future risk remain unclear. OBJECTIVE: To categorize the risk of cardiovascular events in stable outpatients with various initial manifestations of atherothrombosis using simple clinical descriptors. DESIGN, SETTING, AND PATIENTS: Outpatients with coronary artery disease, cerebrovascular disease, or peripheral arterial disease or with multiple risk factors for atherothrombosis were enrolled in the global Reduction of Atherothrombosis for Continued Health (REACH) Registry and were followed up for as long as 4 years. Patients from 3647 centers in 29 countries were enrolled between 2003 and 2004 and followed up until 2008. Final database lock was in April 2009. MAIN OUTCOME MEASURES: Rates of cardiovascular death, myocardial infarction, and stroke. RESULTS: A total of 45,227 patients with baseline data were included in this 4-year analysis. During the follow-up period, a total of 5481 patients experienced at least 1 event, including 2315 with cardiovascular death, 1228 with myocardial infarction, 1898 with stroke, and 40 with both a myocardial infarction and stroke on the same day. Among patients with atherothrombosis, those with a prior history of ischemic events at baseline (n = 21,890) had the highest rate of subsequent ischemic events (18.3%; 95% confidence interval [CI], 17.4%-19.1%); patients with stable coronary, cerebrovascular, or peripheral artery disease (n = 15,264) had a lower risk (12.2%; 95% CI, 11.4%-12.9%); and patients without established atherothrombosis but with risk factors only (n = 8073) had the lowest risk (9.1%; 95% CI, 8.3%-9.9%) (P < .001 for all comparisons). In addition, in multivariable modeling, the presence of diabetes (hazard ratio [HR], 1.44; 95% CI, 1.36-1.53; P < .001), an ischemic event in the previous year (HR, 1.71; 95% CI, 1.57-1.85; P < .001), and polyvascular disease (HR, 1.99; 95% CI, 1.78-2.24; P < .001) each were associated with a significantly higher risk of the primary end point. CONCLUSION: Clinical descriptors can assist clinicians in identifying high-risk patients within the broad range of risk for outpatients with atherothrombosis.

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.

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.

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.

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 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.

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.

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.

Disease-specific health status after stent-assisted percutaneous coronary intervention and coronary artery bypass surgery: one-year results from the Stent or Surgery trial.

BACKGROUND: Functional status and quality of life are important outcomes in the evaluation of revascularization approaches for symptomatic coronary artery disease. Few data are available regarding the comparative improvement in disease-specific health status after CABG versus percutaneous coronary intervention (PCI) in the era of coronary stenting. METHODS AND RESULTS: Cardiac-specific health status was evaluated at baseline and at 6 and 12 months after intervention with the Seattle Angina Questionnaire (SAQ) in patients randomized to stent-assisted PCI (n=488) versus CABG (n=500) in the Stent or Surgery trial. Scores for physical limitation, angina frequency, and quality of life improved significantly for both treatment groups at 6 months (range of improvement from 13.6 to 34.7 points) and 12 months (14.3 to 38.2 points; all P<0.001). CABG patients had greater improvement than those assigned to PCI, although the magnitude of the difference decreased over time (difference at 6 months, 4.03 to 6.48 points; 12 months, 2.05 to 2.93 points). A component of this reduction is accounted for by PCI-arm patients who required repeat intervention. Differences between treatment groups were greatest for the 6-month angina frequency scores (difference=6.48 points; 95% CI 3.96 to 8.99). Overall, treatment satisfaction was high and did not differ significantly between groups. CONCLUSIONS: Both CABG and stent-assisted PCI dramatically improved cardiac-related health status in patients with multivessel disease at 6- and 12-month follow-up. During the first postprocedure year, patients' angina burden and physical limitations were alleviated to a greater extent with CABG.

Cost-effectiveness of targeting patients undergoing cardiac surgery for therapy with intravenous amiodarone to prevent atrial fibrillation.

OBJECTIVES: This study evaluated the cost-effectiveness of administering prophylactic intravenous (IV) amiodarone therapy to patients undergoing cardiac surgery according to their predicted risk of postoperative atrial fibrillation. BACKGROUND: Atrial fibrillation (AF) is a common complication of cardiovascular surgery that is associated with a significant increase in hospitalization costs. Intravenous amiodarone has been shown to decrease the incidence of postoperative AF. METHODS: All 8,709 patients who underwent coronary artery bypass grafting (CABG), 1,217 patients who underwent valve replacement and 624 patients who underwent CABG and valve replacement procedures (CABG + valve) from January 1, 1994, to June 30, 1999, at Emory University Hospitals were studied. Models predicting the risk of AF were developed using logistic regression; linear regression was used to estimate the influence of AF on hospitalization costs. Cost-effectiveness was evaluated for patient subsets identified according to their predicted risk of AF. RESULTS: Postoperative AF rates were 17.7% for CABG, 24.6% for valve and 33.8% for CABG + valve. Using 5,000 dollars as an acceptable cost per episode of atrial fibrillation averted, prophylactic IV amiodarone in CABG patients was not found to be cost-effective. Therapy would be recommended for roughly 5% of valve patients with a predicted risk of atrial fibrillation >45%, and roughly two thirds of CABG + valve patients who have a predicted risk of >30%. CONCLUSIONS: Cost-effectiveness of prophylactic IV amiodarone varies according to type of surgery and the predicted risk of atrial fibrillation. Older patients undergoing valve replacement, particularly those with a history of chronic obstructive pulmonary disease, and those undergoing concomitant CABG are likely to be the most appropriate candidates for IV amiodarone therapy in the perioperative period.

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.

Pulmonary outcomes of off-pump vs on-pump coronary artery bypass surgery in a randomized trial.

STUDY OBJECTIVES: Comparison of pulmonary outcomes after off-pump coronary artery bypass (OPCAB) vs on-pump coronary artery grafting with cardiopulmonary bypass (CABG/CPB). STUDY DESIGN: We examined preoperative and postoperative respiratory compliance, fluid balance, hemodynamics, arterial blood gases, chest radiographs, spirometry, pulmonary complications, and time to extubation in a prospective trial of 200 patients randomized to OPCAB vs CABG/CPB performed by one surgeon. RESULTS: One CABG/CPB patient and two OPCAB patients required mitral valve repair or replacement and were withdrawn. After three crossovers from CABG/CBP to OPCAB and one crossover from OPCAB to CABG, 97 CABG/CPB patients and 100 OPCAB patients remained. There were no significant preoperative demographic differences between groups. Postoperative compliance was reduced more after OPCAB than after CABG/CPB (- 15.4 +/- 10.7 mL/cm H(2)O vs - 11.2 +/- 10.1 mL/cm H(2)O [mean +/- SD]; p = 0.007), associated with rotation of the heart into the right chest to perform posterolateral bypasses (p < 0.001) and the concomitant increased fluid requirements necessary to maintain hemodynamic stability during rotation of the heart. In addition to higher intraoperative fluid intake (4,541 +/- 1,311 mL vs 3,585 +/- 1,033 mL, p < 0.0001), OPCAB patients had higher intraoperative fluid balance (3,903 +/- 1,315 mL vs 1,772 +/- 1,373 mL, p < 0.0001), and higher postoperative pulmonary arterial diastolic pressure (15.0 +/- 5.5 mm Hg vs 11.8 +/- 5.2 mm Hg, p < 0.0001) and central venous pressure (10.4 +/- 4.5 mm Hg vs 8.4 +/- 4.7 mm Hg, p < 0.0001). Despite lower compliance, immediate postoperative Pao(2) on fraction of inspired oxygen of 1.0 (275 +/- 97 torr vs 221 +/- 92 torr, p = 0.001) was higher after OPCAB and extubation was earlier (p = 0.001). Postoperative chest radiographs, spirometry, mortality, reintubation, or readmission for pulmonary complications were not different between groups. CONCLUSIONS: Compared to CABG/CPB, OPCAB was associated with a greater reduction in postoperative respiratory compliance associated with increased fluid administration and rotation of the heart into the right chest to perform posterolateral grafts. OPCAB yielded better gas exchange and earlier extubation but no difference in chest radiographs, spirometry, or rates of death, pneumonia, pleural effusion, or pulmonary edema.

The effect of routine, early invasive management on outcome for elderly patients with non-ST-segment elevation acute coronary syndromes.

BACKGROUND: Although increasing age is an important risk factor for adverse outcome among patients with acute coronary syndromes, elderly patients are more often managed conservatively. OBJECTIVE: To examine outcome according to age and management strategy for patients with unstable angina and non-ST-segment elevation myocardial infarction (MI). DESIGN: Randomized, controlled trial conducted from December 1997 to June 2000. SETTING: 169 community and tertiary care hospitals in 9 countries. PATIENTS: 2220 patients hospitalized with unstable angina and non-ST-segment elevation MI who were randomly assigned to an early invasive or conservative management strategy. INTERVENTIONS: Medical therapy and coronary angiography at 4 to 48 hours versus medical therapy and predischarge exercise testing. MEASUREMENTS: Rates of 30-day and 6-month mortality, nonfatal MI, rehospitalization, stroke, and hemorrhagic complications. RESULTS: Among patients 65 years of age and older, the early invasive strategy compared with the conservative strategy yielded an absolute reduction of 4.8 percentage points (8.8% vs. 13.6%; P = 0.018) and a relative reduction of 39% in death or MI at 6 months. Outcomes of the 2 strategies were similar, however, among patients younger than 65 years of age (6.1% vs. 6.5%; P > 0.2). Among patients older than 75 years of age, the early invasive strategy conferred an absolute reduction of 10.8 percentage points (10.8% vs. 21.6%; P = 0.016) and a relative reduction of 56% in death or MI at 6 months. The additional cost per death or MI prevented with the early invasive strategy was lower for elderly patients, but major bleeding rates were higher with this strategy in patients older than 75 years of age (16.6% vs. 6.5%; P = 0.009). LIMITATIONS: Because this study involved patients in the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction (TACTICS-TIMI) 18 trial, its generalizability to elderly patients with excluded comorbid conditions is unknown. CONCLUSION: Despite an increased risk for major bleeding in patients older than 75 years of age, a routine early invasive strategy can significantly improve ischemic outcomes in elderly patients with unstable angina and non-ST-segment elevation MI.