Link between effectiveness and cost data Costing was conducted prospectively on the same patient sample as that used in the effectiveness analysis.

Transcription

1 Heparin after percutaneous intervention (HAPI): a prospective multicenter randomized trial of three heparin regimens after successful coronary intervention Rabah M, Mason D, Muller D W, Hundley R, Kugelmass A D, Weiner B, Cannon L, O'Neill W W, Safian R D Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology Three different post-procedural heparin strategies in patients with stable and unstable ischaemic syndromes. The three treatment strategies were as follows: (1) a prolonged heparin infusion (13 U/kg/h, target 'activated clotting time' (ACT) 160 to 190 s for 12 to 24 hours; vascular sheaths were removed when the ACT was less than 150 s, followed by discharge within 8 to 12 h; (2) heparin was not given immediately after the procedure; vascular sheaths were removed when the ACT was less than 150 s, followed by reinstitution of heparin (13 U/kg/h, target ACT 160 to 190 s) 4 hours later for a duration of 12 to 18 hours; patients were then discharged from the hospital; (3) heparin was not given after intervention; vascular sheaths were removed when the ACT was less than 150 s, followed by discharge within 8 to 12 hours. Vascular sheaths were removed by trained nurses, technicians, or cardiology fellows, using manual or clamp compression devices at the discretion of the operator. Haemoglobin measurements were obtained in all patients 8 and 16 hours after intervention. Type of intervention Secondary prevention. Economic study type Cost-effectiveness analysis. Study population Patients with stable and unstable ischaemic syndromes, who had successful balloon angioplasty, laser or atherectomy of a native coronary artery. Success was defined as final diameter stenosis less than 35% without flow-limiting dissection, using on-line visual estimates of stenosis severity. The excluded patients were those with cardiogenic shock, myocardial infarction within five days, intracoronary stent implantation and need for chronic warfarin anticoagulation. Setting Hospital. The economic analysis was carried out in the USA. Dates to which data relate Effectiveness and resource use data corresponded to patients enrolled in the study between May 1995 and June The price year was Source of effectiveness data Effectiveness data were derived from a single study. Link between effectiveness and cost data Costing was conducted prospectively on the same patient sample as that used in the effectiveness analysis. Page: 1 / 5

2 Study sample Power calculations were used to determine the sample size which was based on the assumption of 15% incidence of bleeding and vascular complications for patients receiving prolonged heparin; a total of 1,650 patients (550 patients per arm) would be required (two-tailed t test) to demonstrate a 43% reduction to 8.5% (90% power, alpha = 0.05). The study sample consisted of 414 patients with a mean (SD) age of 62 (11) years, randomly assigned to either: group 1 = continuous post-procedural heparin infusion (n=157) with a mean (SD) age of 62 (10) years; group 2 = sheaths removed, reinstitution of post-procedural heparin (n= 120) with a mean (SD) age of 62 (11) years; or group 3 = no heparin post-procedure (n=137) with a mean (SD) age of 61 (11) years. Study design This was a multi-centre, randomised trial, carried out in 6 centres in 28 countries. The duration of the follow-up was one month after intervention to capture delayed complications. The study appears not to have had any loss to follow-up since clinical follow-up was obtained in all patients at one month following discharge. All patients received aspirin (325 mg daily) at least 24 hours before intervention. After successful intervention, the patients were randomised to one of three treatment groups. Data were analysed after entry of 100 and 400 patients to ensure safety, and interim reports were presented to the Human Investigations Committee. Because of significant differences in outcome during interim analysis, the study was prematurely terminated at the recommendation of the committee. Analysis of effectiveness The principle used in the analysis of effectiveness appears to have been intention to treat. The primary end point of the study was the combined incidence of in-hospital bleeding and vascular events. Secondary end-points included inhospital ischaemic events and one-month follow-up outcome (the incidence of delayed cardiac and vascular events). Hypertension was more prevalent in group 2 patients. The study groups were comparable in terms of the remaining baseline characteristics. Factors associated with combined bleeding and vascular events were evaluated by univariate and multivariate analysis (using the Cox proportional hazard regression model). Effectiveness results The combined incidence of bleeding and vascular events was 21% in group 1, 14% in group 2 and 8% in group 3 (p=0.01). The overall incidence of in-hospital ischaemic complications was 2.2%; there was no difference between groups. At 30 days, the incidence of delayed cardiac and vascular events was similar for all three groups. Clinical conclusions The present study confirms and extends the findings from the literature that there are no data to suggest that routine post-procedural heparin decreases the risk of ischaemic complications. Several studies suggest the safety of omitting post-procedural heparin in patients with a variety of unstable ischaemic syndromes, including unstable angina and postinfarction angina, and these were routinely excluded from earlier studies because of fear of ischaemic complications. Measure of benefits used in the economic analysis No summary benefit measure was identified in the economic analysis, and only separate clinical outcomes were reported. Direct costs Costs were not discounted due to the short time frame of the cost analysis. Some quantities were reported separately from the costs. Some cost items were reported separately. Cost analysis covered the costs of pharmacy, catheterisation laboratory, and hospital stay. The perspective adopted in the cost analysis was not explicitly specified. Medicare cost-tocharge ratios for each institution were used to estimate the hospital cost. The price year was Page: 2 / 5

3 Statistical analysis of costs Student's t test appears to have been used to compare the groups in terms of costs. Indirect Costs Not included. Currency US dollars ($). Sensitivity analysis Not conducted. Estimated benefits used in the economic analysis Not applicable. Cost results The total adjusted Medicare cost after successful percutaneous coronary catheterisation in group 1 was $5,800 versus $4,500 in group 2 and $1,800 in group 3, (p<0.001). Synthesis of costs and benefits Costs and benefits were not combined since the strategy of not administering heparin after a successful coronary intervention was the dominant strategy. Authors' conclusions Heparin infusion after successful coronary intervention is associated with more minor bleeding and vascular injury, prolonged length of stay and increased cost. In-hospital and one-month ischaemic events rarely occur after successful intervention, irrespective of heparin use. CRD COMMENTARY - Selection of comparators No specific post-procedural heparin strategy was regarded as the comparator since the ideal dose and duration of heparin infusion after successful coronary intervention was deemed to be unknown. Validity of estimate of measure of effectiveness The effectiveness results are likely to be internally valid given the randomised nature of the study design, power calculations performed, and the intention-to-treat analysis conducted. The study sample appears to have been representative of the study population; patients in this study represented a high-risk population, characterised by multivessel disease in nearly half of the patients, and by the need for pre-procedural IV heparin infusion in more than onethird of patients. Validity of estimate of measure of benefit The authors did not derive a measure of health benefit. The study may therefore be regarded as a cost-consequences analysis. Validity of estimate of costs Page: 3 / 5

4 Some quantities were reported separately from the costs. Adequate details of methods of cost estimation were not given. As a result, it is difficult to assess whether all important direct cost elements were included in the cost analysis. The price year was specified. The application of cost-to-charge ratios may have enhanced the internal and external validity of the cost results. The perspective adopted in the cost analysis was not explicitly specified. The effects of alternative procedures on indirect costs were not addressed. Statistical analyses were performed on resource use (hospital stay) and cost data. Other issues The authors' conclusions appear to be justified. However, the uncertainties in the data could have been explored using sensitivity analyses. The issue of generalisability to other settings or countries was not addressed, although appropriate comparisons were made with other studies. The study sample was meant to be representative of patients with a variety of unstable ischaemic syndromes, including unstable angina and post-infarction angina, who were routinely excluded from earlier studies because of fear of ischaemic complications. The authors acknowledged the following limitations for their study: the study was underpowered to detect differences in low-frequency outcomes such as death, myocardial infarction and coronary artery bypass graft surgery (CABG); the study was not designed to address the issue of the use of heparin after "suboptimal" intervention; end points of this study were clinical, not angiographic, outcomes; one month follow-up may not have been enough to uncover all additional complications, but the authors tried to avoid the dilemma of determining whether later ischaemic complications were due to the index procedure or to restenosis. Implications of the study The role of vascular sealing devices is under investigation, and there is potential for further reduction in complications with these devices. Although post-procedural heparin infusions are often used after "suboptimal" PTCA, there are no data to indicate that any level of systematic heparinisation is useful in preventing ischaemic complications; further study is needed. Routine post-procedure heparin is not recommended, even in patients who present with unstable syndromes. Source of funding None stated. Bibliographic details Rabah M, Mason D, Muller D W, Hundley R, Kugelmass A D, Weiner B, Cannon L, O'Neill W W, Safian R D. Heparin after percutaneous intervention (HAPI): a prospective multicenter randomized trial of three heparin regimens after successful coronary intervention. Journal of the American College of Cardiology 1999; 34(2): PubMedID Indexing Status Subject indexing assigned by NLM MeSH Angioplasty, Balloon, Coronary /adverse effects; Anticoagulants /administration & dosage /adverse effects; Atherectomy, Coronary /adverse effects; Blood Vessels /injuries; Drug Administration Schedule; Female; Hemorrhage /chemically induced; Heparin /administration & dosage /adverse effects; Humans; Infusions, Intravenous; Length of Stay; Male; Middle Aged; Myocardial Ischemia /etiology; Prospective Studies; Whole Blood Coagulation Time AccessionNumber Date bibliographic record published 31/12/2000 Page: 4 / 5

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