. 2014 Jan 15;15:15. doi: 10.1186/1471-2369-15-15

Table 3.

Study design of economic evaluations on ACEIs and ARBs

Study, country/region	Source of effectiveness data	Intervention group	Control group	Decision model type	Time horizon (years)	Evaluation type
ACEIs
Golan et al. 1999 US [33]	UERNN, LEAPP and EADN trial	‘Treat all’ strategy^a	(1) Screen for MiA^b;	Markov model with 5 states	10	CEA & CUA (Life-years & QALYs)
Golan et al. 1999 US [33]	UERNN, LEAPP and EADN trial	‘Treat all’ strategy^a	(2) Screen for gross proteinuria^c.	Markov model with 5 states	10	CEA & CUA (Life-years & QALYs)
Sakthong et al. 2001 Thailand [34]	LEAN trial and the opinion of nephrologists	Enalapril at the dose of 10 mg/day	Placebo	Markov model with 4 stages	25	CEA (Life years)
Rosen et al. 2005 US [35]	UERNN, EADN, LEAN, H-MH studies and HOPE trial	Medicare first-dollar coverage of ACEIs	Year 2005’s Medicare practice	Markov model adding a cardiovascular events component.	lifetime	CEA & CUA (Life-years & QALYs)
Campbell et al. 2007 US [36]	UERNN, EADN, H-MH studies and IRMA-2 trial	ACEI therapy in normoalbuminimuric, microalbuminuric, and macroalbuminuric patients	No ACEI initiation in patients	Markov model	8	CEA (CVD event avoided, life saved, dialysis prevented, composite endpoint avoided)
Adarkwah et al. 2010 Germany [37]	EADN and two meta-analyses	‘Treat all’ strategy^a	(1) Screen for MiA^b;	Markov model with 5 states	50	CUA (QALY)
			(2) Screen for MaA^c;
			(3) no-screening and no-treatment alternative.
Adarkwah et al. 2011 Netherlands [38]	EADN and two meta-analyses	‘Treat all’ strategy^a	(1) Screen for MiA^b;	Markov model with 5 states	50	CUA (QALY)
Adarkwah et al. 2011 Netherlands [38]	EADN and two meta-analyses	‘Treat all’ strategy^a	(2) Screen for MaA^c.	Markov model with 5 states	50	CUA (QALY)
ARBs
Losartan
Herman et al. 2003 US [39]	RENAAL trial	Losartan	Placebo^d	A regression-based method	3.5 / 4	CEA (Number of ESRD days)
Souchet et al. 2003 France [40]	RENAAL trial	Losartan (initial daily dosing of losartan was 50 mg, with the possibility of titration to 100 mg/day)	Placebo^d	A regression-based method	3.5 / 4	CEA (Number of ESRD days)
Burgess et al. 2004 Canada [41]	RENAAL trial	Losartan	Placebo^d	A regression-based method	3.5 / 4	CEA (Number of ESRD days)
Szucs et al. 2004 Switzerland [42]	RENAAL trial	Losartan (initial daily dosing of losartan was 50 mg, with the possibility of titration to 100 mg/day)	Placebo^d	A regression-based method	3.5 / 4	CEA (Number of ESRD days)
Seng et al. 2005 Hong Kong [32] (only data of Hong Kong were included)	RENAAL trial	Losartan	Placebo^d	A regression-based method	3.5	CEA (Number of ESRD days)
Arredondo et al. 2005 Mexico [43]]	RENAAL trial	Losartan	Placebo^d	A variation of the cumulative incidence competing risk method / Weibull model	25 (life time)	CEA (Cumulative incidence of ESRD, life expectancy)
Vora et al. 2005 UK [44]	RENAAL trial	Losartan (50–100 mg QD)	Conventional antihypertensive treatment^d (excluding ACEIs or angiotensin II antagonists)	Weibull model	life time	CEA (Cumulative incidence of ESRD, life expectancy)
Carides et al. 2006 US [45]	RENAAL trial	Losartan	Placebo^d	A cumulative incidence competing risk method / Weibull model	25 (life time)	CEA (Cumulative incidence of ESRD, life expectancy)
Stafylas et al. 2007 Greece [46]	RENAAL trial	Losartan (50–100 mg QD)	Placebo^d	Markov model with 6 states	3.5/4	CEA (Number of ESRD days)
de Portu et al. 2011 Italy, France, Germany, Switzerland, US [47]	RENAAL trial	Losartan	Standard care^d	Standard methods by comparing the economic outcomes deriving from additional losartan to standard care vs standard care alone	3.4	CEA (Number of ESRD days)
Irbesartan
Rodby RA et al. 2003 US [48]	IDNT trial	Irbesartan titrated from 75 to 300 mg/day	(1) ‘Control’^d;	Markov model with 5 stages	25	CEA (Life expectancy)
Rodby RA et al. 2003 US [48]	IDNT trial	Irbesartan titrated from 75 to 300 mg/day	(2) Amlodipine titrated from 2.5 to 10 mg/day.	Markov model with 5 stages	25	CEA (Life expectancy)
Palmer AJ et al. 2003 Belgium, France [49]	IDNT trial	Irbesartan titrated from 75 to 300 mg/day	(1) ‘Control’^d;	Markov model with 5 stages	25	CEA (Life expectancy)
Palmer AJ et al. 2003 Belgium, France [49]	IDNT trial	Irbesartan titrated from 75 to 300 mg/day	(2) Amlodipine titrated from 2.5 to 10 mg/day.	Markov model with 5 stages	25	CEA (Life expectancy)
Coyle D et al. 2004 Canada [50]	IDNT trial	Irbessartan	(1) Amlodipine;	Markov model with 5 stages	25	CEA (Life expectancy)
Coyle D et al. 2004 Canada [50]	IDNT trial	Irbessartan	(2) Standard care^d	Markov model with 5 stages	25	CEA (Life expectancy)
Palmer AJ et al. 2004 UK [51]	IDNT trial	Irbesartan 300 mg per day	(1) ‘Control’^d;	Markov model with 5 stages	25	CEA (Life expectancy)
Palmer AJ et al. 2004 UK [51]	IDNT trial	Irbesartan 300 mg per day	(2) Amlodipine 10 mg per day.	Markov model with 5 stages	25	CEA (Life expectancy)
Palmer AJ et al. 2004 US [52]	IRMA-2 study and IDNT	‘Early irbesartan’^e	(1) ‘Control’^d;	Markov model with 7 stages	25	CEA (Years free of ESRD, cumulative incidence ESRD, life expectancy)
Palmer AJ et al. 2004 US [52]	IRMA-2 study and IDNT	‘Early irbesartan’^e	(2) ‘Late irbesartan’^f	Markov model with 7 stages	25
Palmer AJ et al. 2005 Spain [53]	IRMA-2 study and IDNT	‘Early irbesartan’^e	Standard antihypertensive medications^d	Markov model with 7 stages	25	CEA (Years free of ESRD, cumulative incidence ESRD, life expectancy)
Palmer AJ et al. 2006 Switzerland [54]	IRMA-2 study and IDNT	‘Early irbesartan’^e	Conventional antihypertensive treatment^d initiated when patients had developed MiA.	Markov model with 7 stages	25	CEA (Years free of ESRD, cumulative incidence of ESRD, life expectancy)
Palmer AJ et al. 2006 France [55]	IRMA-2 study and IDNT	‘Early irbesartan’^e	(1) ‘Control’^d;	Markov model with 7 stages	25	CEA & CUA (Years free of ESRD, life expectancy, QALY)
Palmer AJ et al. 2006 France [55]	IRMA-2 study and IDNT	‘Early irbesartan’^e	(2) ‘Late irbesartan’^f	Markov model with 7 stages	25	CEA & CUA (Years free of ESRD, life expectancy, QALY)
Palmer AJ et al. 2007 Hungary [56]	IRMA-2 study and IDNT	‘Early irbesartan’^e	‘Placebo’^d: standard antihypertensive medications initiated when patients developed MiA.	Markov model with 7 stages	25	CEA (Years free of ESRD, cumulative incidence ESRD, life expectancy)
Palmer AJ et al. 2007 UK [57]	IRMA-2 study and IDNT trial	‘Early irbesartan’^e	(1) ‘Control’^d;	Markov model with 7 stages	25	CEA (Years free of ESRD, cumulative Incidence of ESRD, life expectancy)
Palmer AJ et al. 2007 UK [57]	IRMA-2 study and IDNT trial	‘Early irbesartan’^e	(2) ‘Late irbesartan’^f	Markov model with 7 stages	25
Coyle D et al. 2007 Canada [58]	IRMA-2 study and IDNT	‘Early irbesartan’^e	(1) ‘Late irbesartan’^f;	Markov model with 7 stages	25	CEA (Life expectancy)
Coyle D et al. 2007 Canada [58]	IRMA-2 study and IDNT	‘Early irbesartan’^e	(2) ‘Conventional’^d	Markov model with 7 stages	25	CEA (Life expectancy)
Yang W.C. et al. 2007 Taiwan [59]	IRMA-2 study and IDNT	‘Early irbesartan’^e	(1) ‘Standard’^d;	Markov model with 7 stages	25	CEA (Life expectancy, number of years free of ESRD, cumulative incidence of ESRD)
			(2) ‘Late irbesartan’^f;
			(3) ‘Late amlodipine’^g
Annemans et al. 2008 China, Taiwan, Malaysia, Thailand, South Korea [60]	IRMA-2 study and IDNT trial	‘Early irbesartan’^e	(1) ‘Standard’^d;	Markov model with 7 stages	25	CEA (Cumulative incidence of ESRD, number of days in dialysis, number of years free of ESRD, life expectancy)
			(2) ‘Late irbesartan’^f;
			(3) ‘Late amlodipine’^g
Valsartan
Smith DG et al. 2004 US [61]	MARVAL study	Valsartan	Amlodipine	Markov model with 7 stages	8	CUA (Quality-adjusted survival)

a: no screening was performed at all and patients started on ACEI therapy at the time of diagnosing type 2 diabetes.

b: patients were screened for MiA once a year and ACEI treatment was started if the test result is positive.

c: patients were screened for MaA once a year and ACEI treatment was started if the test result is positive.

d: standard antihypertensive therapy alone, excluding the use of ACEIs, ARBs.

e: standard antihypertensive therapy plus administration of irbesartan 300 mg/d at the onset of MiA.

f: standard antihypertensive therapy plus administration of irbesartan 300 mg/d once the patients reach the advanced diabetic nephropathy stage.

g: standard antihypertensive therapy plus administration of amlodipine titrated from 5 to 10 mg/d once the patients reach the advanced diabetic nephropathy stage.

UERNN = Use of enalapril to attenuate decline in renal function in normotensive, normoalbuminuric patients with type 2 diabetes mellitus; LEAPP = Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients; EADN = The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy; LEAN = Long-term renoprotective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus; H-MH = Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy; HOPE = The Heart Outcomes Prevention Evaluation; RENAAL = The reduction of endpoints in non-insulin dependent diabetes mellitus with the angiotensin II antagonist losartan; IDNT = The irbesartan in diabetic nephropathy trial; IMRA-2 = The irbesartan in reduction of microalbuminuria-2; MARVAL = The microalbuminuria reduction with valsartan.

CEA = cost-effectiveness analysis; CUA = cost-utility analysis.