Cost-benefits of incorporating levosimendan into cardiac surgery practice: German base case

Figures & data

Figure 1. Health state structure of the Markov model.

Table 1. Data input in the model. Key clinical data sources for the pharmaco-economic model.

Analysis	Population	Comparator	No. of patients	Primary outcome measure	Key secondary outcome measures
Huang et al.19	Critically ill patients requiring inotropic support	Dobutamine	2052	Mortality (longest follow-up available, up to 30 days)	Frequency of adverse events
Harrison et al.17	Patients undergoing cardiac surgery requiring perioperative levosimendan	Placebo	1155	Mortality (longest follow-up available, up to 30 days)	Hemodynamic parameters (unspecified follow-up)
Landoni et al.18	Patients with low output syndrome and decompensated heart failure (with sub-group analysis on cardiac surgery patients)	Placebo, dobutamine	5480	Mortality (longest follow-up available, up to 180 days)	Length of hospital stay, frequency of adverse events

Table 2. Data input in the model. Data inputs for hospital length of Stay; mean (SD).

Drug	Intensive care unit stay from Levin et al.25	Routine care stay (assumed)	Total
Levosimendan	2.75 (0.28) days	6.52 (n/a) days	9.27 (0.28) days
Dobutamine	6.58 (0.66) days	6.52 (n/a) days	13.10 (0.66) days

Table 3. Data input in the model. Probability of adverse events.

Adverse events	Levosimendan	Dobutamine	Standard of care	p-value for overall effect	Data source
Post-operative renal failure	1.6%	6.6%	6.6%	0.03	Harrison et al.17
Atrial fibrillation	27.8%	46.3%	46.3%	0.002	Harrison et al.17
Myocardial injury	5.1%	10.3%	10.3%	0.003	Harrison et al.17
Patients requiring treatment with an intra-aortic balloon pump	2.9%	14.7%	Not reported	<0.05	Levin et al.25
Patients requiring treatment with an intra-aortic balloon pump	6.3%	Not reported	30.4%	<0.05	Levin et al.16

Table 4. Patient outcomes in the base case analysis (cohort size = 1000; time horizon = 1 year).

	Patients alive	% of patients alive	Bed days
Levosimendan	719.29	71.93%	4635
Dobutamine	649.68	64.97%	6550
Incremental (total)	69.61	6.96%	−1915
Incremental (per patient)	—	—	−1.9

Table 5. Costs breakdown from the hospital perspective (cohort size = 1000; time horizon = 1 year; costs in €).

	Cost of inotrope	Costs for adverse events not associated with a DRG code (atrial fibrillation)	Total costs	Foregone revenue	Total net costs
Levosimendan	678,010	1287	679,297	13,168,945	—
Dobutamine	23,548	1681	25,229	18,609,836	—
Incremental cost for levosimendan (total)	654,461	−394	654,068	−5,440,891	−4,786,825
Incremental (per patient)	654	0	654	−5441	−4787

Table 6. Costs breakdown from the health insurance perspective (cohort size = 1000; time horizon = 1 year; costs in €).

	Hospitalization reimbursement costs	Cost of intra-aortic balloon pump	Cost of renal dialysis	Cost of myocardial injury	Medication costs	Outpatient costs	Total costs
Levosimendan	18,609,836	69,600	42,767	91,111	407,775	368,219	19,589,309
Dobutamine	18,609,836	352,800	176,414	184,009	367,022	331,419	20,021,501
Incremental (total)	0	−283,200	−133,647	−92,898	40,753	36,800	−432,192
Incremental (per patient)	0	−283	−134	−93	41	37	−432

Table 7. Costs breakdown from the hospital perspective, with bed occupancy assumed at 80% (costs in €).

	Cost of inotrope	Costs for adverse events not associated with a DRG code (atrial fibrillation)	Total costs	Foregone revenue	Total net costs
Levosimendan	678,010	1287	679,297	10,535,156	—
Dobutamine	23,548	1681	25,229	14,887,869	—
Incremental (total)	654,461	−394	654,068	−4,352,713	−3,698,645
Incremental (per patient)	654	0	654	−4353	−3699

DRG, diagnostic related group.

Table 8. Cost-effectiveness results (cost savings per patient) presented over a variety of time horizons.

Time horizon	Cost savings per patient
30 days	€501
6 months	€467
1 year (base case)	€432
2 years	€379
5 years	€308
Lifetime	€279

Huang X, Lei S, Zhu MF, et al. Levosimendan versus dobutamine in critically ill patients: a meta-analysis of randomized controlled trials. J Zhejiang Univ Sci B 2013;14:400-15

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Harrison RW, Hasselblad V, Mehta RH, et al. Effect of levosimendan on survival and adverse events after cardiac surgery: a meta-analysis. J Cardiothorac Vasc Anesth 2013;27:1224-32

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Landoni G, Biondi-Zoccai G, Greco M, et al. Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled studies. Crit Care Med 2012;40:634-46

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Levin R, Degrange M, Porcile R, et al. Preoperative use of calcium sensitizer levosimendan reduces mortality and low cardiac output syndrome in patients with aortic stenosis and left ventricular dysfunction. Circulation 2008;118:E217

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Levin R, Degrange M, Del Mazo C, et al Preoperative levosimendan decreases mortality and the development of low cardiac output in high-risk patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting with cardiopulmonary bypass. Exp Clin Cardiol 2012;17:125-30

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