Clin Res Cardiol. 2015 May;104(5):401-9. doi: 10.1007/s00392-014-0793-0.
Incremental cost-effectiveness of dobutamine stress cardiac magnetic resonance imaging in patients at intermediate risk for coronary artery disease.
- 1Department of Internal Medicine/Cardiology, German Heart Institute Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
AIMS: The effectiveness of stress cardiac magnetic resonance (CMR) as a gatekeeper for coronary angiography (CA) has been established. Level five HTA studies according to the hierarchical model of diagnostic test evaluation are not available.
METHODS: This cohort study included 1,158 consecutive patients (mean age 63 ± 11 years, 42 % women) presenting at our institution between January 1, 2003 and December 31, 2004 with suspected coronary artery disease (CAD) for an elective CA. The patients were assessed for eligibility and propensity score matching was applied to address selection bias regarding the patients’ allocation to CMR or direct CA. Median patient follow-up was 7.9 years (95 % CI 7.8-8.0 years). The primary effect was calculated as relative survival difference. The cost unit calculation (per patient) at our institute was the source of costs.
RESULTS: Survival was similar in CMR and CA (p = 0.139). Catheterizations ruling out CAD were significantly reduced by the CMR gate-keeper strategy. Patients with prior CMR had significantly lower costs at the initial hospital stay and at follow-up (CMR vs. CA, initial: 2,904<euro> vs. 3,421<euro>, p = 0.018; follow-up: 2,045<euro> vs. 3,318<euro>, p = 0.037). CMR was cost-effective in terms of a contribution of 12,466<euro> per life year to cover a part of the CMR costs.
CONCLUSION: Stress CMR prior to CA was saving 12,466<euro> of hospital costs per life year. Lower costs at follow-up suggest sustained cost-effectiveness of the CMR-guided strategy.
Dobutamine stress CMR (DCMR) is an accurate and safe non-invasive test for coronary artery disease (CAD) with high negative predictive value 2, 3. Direct catheterization (CA) is still an alternative approach that is incentivized by the current reimbursement policy in many countries. Since long-term outcome and cost data from randomized controlled prospective trials are rarely available when new health technologies emerge, evidence based reimbursement policy requires retrospective data mining and lags behind medical and technical evolution 4. High quality observational data models, simulations and other techniques are commonly used in health technology assessment (HTA) 5, 6.
This paper presents level five HTA data7 on DCMR based on a long term follow-up of patients with suspected stable CAD (sCAD) who underwent DCMR and controls with direct CA. We expected that a DCMR guided approach would be at least as effective as direct CA with respect to survival and more patient friendly in terms of fewer hospitalizations during follow-up by avoiding direct CA 1. Generally, we suggest data mining digital documentation of early adoption phases of new technologies as source of evidence.
This study is a single center retrospective cohort trial based on a pre-specified hypothesis that compares two different pathways for managing patients with sCAD and intermediate event risk. Groups were matched by propensity scores that were computed by binary logistic regression with diagnostic path assignment as an outcome variable and age, gender, angina pectoris, CV risk factors and cardiac medications as covariates. The anthropomorphic and clinical characteristics of the CMR and CA groups did not differ significantly after propensity score matching. Two-hundred-and-nine cases in the CMR-group were eventually compared to 293 cases in the CA-group (see figure 1). Clinical data were collected from institutional quality assurance and research databases. Median patient follow-up was 7.9 years. Primary clinical endpoints were death and cardiac re-hospitalizations. The cost data were calculated per patient and hospital stay from original cost data provided to the German federal InEK/G-DRG database. We chose cost contribution accounting as method to compare both approaches. Discounting or inflation correction was not performed 1.
Similar survival was observed in the CMR and CA groups within the first four years (see figure 2), even after adjustment for revascularization by PCI or CABG. The CMR guided approach reduced catheterizations by 72%, shortened hospital stay, was associated with ambulatory follow-up as opposed to re-hospitalization and produced lower total costs compared to direct CA. Cost reduction occurred early and was maintained at follow-up (see figure 3). Increased total costs in the CA group were mainly driven by staff costs and costs allocated for materials and infrastructure in the cardiology ward and the catheterization laboratory 1.
DCMR guided catheterization in patients at intermediate risk for CAD was at least as effective as direct catheterization in terms of survival and more cost-effective in terms of a substantial contribution margin to cover a part of the CMR costs (see figure 4). Comparative effectiveness is sustained during a median follow-up of more than six years 1.
The main cost-driver in the CA group was a high rate of catheterizations ruling out significant stenosis. The increased costs located at the catheterization laboratory may be related to an increased rate of PCIs. The FAME trial 8 supports the hypothesis that the lack of information on the functional impact of a lesion may increase the propensity to perform an unnecessary potentially harmful PCI. Invasive interventions and the associated risk of complications might be significantly reduced using an image guided approach. A reduced rate of hospital stays reflects a patient friendly ambulatory management profile of the DCMR guided strategy 1.
As DCMR is not reimbursed in Germany there was no cost calculation for DCMR. Moreover, the costs generated in ambulatory patients with a negative test in the DCMR pathway are not transferable as they depend on the prevalence of the disease. Thus, we calculated the contribution of costs that would be available to cover partial costs of CMR. Downstream and secondary costs may be assumed to be lower in patients with a more ambulatory profile in spite of additional imaging costs. Our data suggest that in-hospital cost savings provide a substantial contribution margin to cover imaging costs with no overall cost increase 1.
Diagnostic performance of CMR in terms of reclassification of probability of CAD was not an issue in this study 7. Anyhow, a recent editorial 9 comments on the pitfalls of substituting true diagnosis of functionally significant CAD by gold-standards. The low prevalence of CAD in the cohort reduces the sensitivity of both diagnostic tests (CMR and angiography) and compares well with findings in routine patients 10. The discrepancy found between functional and morphologic diagnosis of CAD is partially explained by lack of functional impact of many borderline coronary lesions 1.
Recently published HTA studies on DCMR gated catheterization 11-17 vary widely with respect to study design, adopt the stakeholder perspective of the payer and do not provide level five HTA data 7 1. Evaluation of emerging technologies faces multiple challenges. There are conflicting needs and expectations of the variety of stakeholders. Historical incentives set by service valuation and payment may distort adoption. A standardized and validated concept of value is often lacking 18. Comprehensive HTA analysis should account for stakeholder interests and cost impact 19. The International Society for Pharmacoeconomics and Outcomes Research recognizes the necessity and challenge of using secondary data sources, particularly retrospective data, in HTA and specifies principles for good research practice in this field 5. We propose to exploit early phases of the life-cycle as natural experiment. Every new technology that enters the market is characterized by parallel use of the new technology and standard operating procedures in a quasi-random setting and thus provides controlled data from the same source population. Secondary data mining and outcome research in these source populations based on a pre-specified hypothesis and statistical matching techniques addressing randomization are valuable sources of evidence. An increasing number of digital records comprising outcome and cost data, big-data analyses and advanced statistical approaches 20 will facilitate this endeavor in future1.
The German Heart Institute is a high volume supra-regional center and was engaged in the early validation of DCMR effectiveness 21. Outcome differences are comparable to a multicenter analysis 22, 23. Controlled study design, careful matching, lower rates of hospitalizations and invasive procedures as well as costs directly calculated from process times and low-level expenses are expected to assure the transferability of a contribution margin of in-hospital cost saving by DCMR 1. In agreement with our findings a reduction of hospitalizations, invasive procedures, and recurrent tests for ischemia in patients with suspected acute coronary syndrome was found recently13.
- Petrov G, Kelle S, Fleck E, Wellnhofer E. Incremental cost-effectiveness of dobutamine stress cardiac magnetic resonance imaging in patients at intermediate risk for coronary artery disease. Clin Res Cardiol. 2015; 104(5): 401-9.
- Charoenpanichkit C, Hundley WG. The 20 year evolution of dobutamine stress cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2010; 12: 59.
- Nandalur KR, Dwamena BA, Choudhri AF, Nandalur MR, Carlos RC. Diagnostic performance of stress cardiac magnetic resonance imaging in the detection of coronary artery disease: a meta-analysis. J Am Coll Cardiol. 2007; 50(14): 1343-53.
- Wallner PE, Konski A. A changing paradigm in the study and adoption of emerging health care technologies: coverage with evidence development. J Am Coll Radiol. 2008; 5(11): 1125-9.
- Berger ML, Mamdani M, Atkins D, Johnson ML. Good research practices for comparative effectiveness research: defining, reporting and interpreting nonrandomized studies of treatment effects using secondary data sources: the ISPOR Good Research Practices for Retrospective Database Analysis Task Force Report–Part I. Value Health. 2009; 12(8): 1044-52.
- Goeree R, Levin L, Chandra K, Bowen JM, Blackhouse G, Tarride JE, et al. Health technology assessment and primary data collection for reducing uncertainty in decision making. J Am Coll Radiol. 2009; 6(5): 332-42.
- Mark DB, Anderson JL, Brinker JA, Brophy JA, Casey DE, Jr., Cross RR, et al. ACC/AHA/ASE/ASNC/HRS/IAC/Mended Hearts/NASCI/RSNA/SAIP/SCAI/SCCT/SCMR/SNMMI 2014 Health Policy Statement on Use of Noninvasive Cardiovascular Imaging: A Report of the American College of Cardiology Clinical Quality Committee. J Am Coll Cardiol. 2014; 63(7): 698-721.
- Pijls NH, Fearon WF, Tonino PA, Siebert U, Ikeno F, Bornschein B, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-year follow-up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study. J Am Coll Cardiol. 2010; 56(3): 177-84.
- Plein S, Motwani M. Fractional flow reserve as the reference standard for myocardial perfusion studies: fool’s gold? Eur Heart J Cardiovasc Imaging. 2013; 14(12): 1211-3.
- Patel MR, Peterson ED, Dai D, Brennan JM, Redberg RF, Anderson HV, et al. Low diagnostic yield of elective coronary angiography. N Engl J Med. 2010; 362(10): 886-95.
- Boldt J, Leber AW, Bonaventura K, Sohns C, Stula M, Huppertz A, et al. Cost-effectiveness of cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary artery disease in Germany. J Cardiovasc Magn Reson. 2013; 15: 30.
- Francis SA, Daly C, Heydari B, Abbasi S, Shah RV, Kwong RY. Cost-effectiveness analysis for imaging techniques with a focus on cardiovascular magnetic resonance. Journal for cardiovascular magnetic resonance : on Journal for techniques Focus for Cardiovascular Magnetic Resonance. 2013; 15: 52.
- Miller CD, Case LD, Little WC, Mahler SA, Burke GL, Harper EN, et al. Stress CMR Reduces Revascularization, Hospital Readmission, and Recurrent Cardiac Testing in Intermediate-Risk Patients With Acute Chest Pain. JACC Cardiovasc Imaging. 2013; 6(7): 785-94.
- Moschetti K, Muzzarelli S, Pinget C, Wagner A, Pilz G, Wasserfallen JB, et al. Cost evaluation of cardiovascular magnetic resonance versus coronary angiography for the diagnostic work-up of coronary artery disease: application of the European Cardiovascular Magnetic Resonance registry data to the German, United Kingdom, Swiss, and United States health care systems. J Cardiovasc Magn Reson. 2012; 14: 35.
- Pilz G, Patel PA, Fell U, Ladapo JA, Rizzo JA, Fang H, et al. Adenosine-stress cardiac magnetic resonance imaging in suspected coronary artery disease: a net cost analysis and reimbursement implications. Int J Cardiovasc Imaging. 2011; 27(1): 113-21.
- Sharples L, Hughes V, Crean A, Dyer M, Buxton M, Goldsmith K, et al. Cost-effectiveness of functional cardiac testing in the diagnosis and management of coronary artery disease: a randomised controlled trial. The CECaT trial. Health Technol Assess. 2007; 11(49): iii-iv, ix-115.
- Walker S, Girardin F, McKenna C, Ball SG, Nixon J, Plein S, et al. Cost-effectiveness of cardiovascular magnetic resonance in the diagnosis of coronary heart disease: an economic evaluation using data from the CE-MARC study. Heart. 2013; 99(12): 873-81.
- Wallner PE, Steinberg ML, Konski AA. Controversies in the adoption of new healthcare technologies. Front Radiat Ther Oncol. 2011; 43: 60-78.
- Mauskopf JA, Sullivan SD, Annemans L, Caro J, Mullins CD, Nuijten M, et al. Principles of good practice for budget impact analysis: report of the ISPOR Task Force on good research practices–budget impact analysis. Value Health. 2007; 10(5): 336-47.
- Roberts K, Rink B, Harabagiu SM. A flexible framework for recognizing events, temporal expressions, and temporal relations in clinical text. J Am Med Inform Assoc. 2013; 20(5): 867-75.
- Nagel E, Lehmkuhl HB, Bocksch W, Klein C, Vogel U, Frantz E, et al. Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography. Circulation. 1999; 99(6): 763-70.
- Kelle S, Nagel E, Voss A, Hofmann N, Gitsioudis G, Buss SJ, et al. A bi-center cardiovascular magnetic resonance prognosis study focusing on dobutamine wall motion and late gadolinium enhancement in 3,138 consecutive patients. J Am Coll Cardiol. 2013; 61(22): 2310-2.
- Lipinski MJ, McVey CM, Berger JS, Kramer CM, Salerno M. Prognostic value of stress cardiac magnetic resonance imaging in patients with known or suspected coronary artery disease: a systematic review and meta-analysis. J Am Coll Cardiol. 2013; 62(9): 826-38.
Wellnhofer, Ernst, MD, Ph D
German Heart Center Berlin
Augustenburger Pl 1
Email: firstname.lastname@example.org; email@example.com