Losartan angiotensin-receptor blockers
Description Results

Losartan Monopotassium Salt - Losartan Potassium - DuP753 - DuP 753 - DuP-753 - MK954 - MK 954 - MK-954 - Cozaar - Losartan

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pathology

Benefit (demonstrated or suggested) and harm

acute myocardial infarction

All results are NS for efficacy

inferior to Captopril in terms of Cardiovascular death in OPTIMAAL, 2002

atrial fibrillation

All results are NS for efficacy

diabetes type 2

All results are NS for efficacy

diabetic kidney disease

All results are NS for efficacy

heart failure

All results are NS for efficacy

Trial	control	p<0.05	harm	NS
Dickstein et al., 1995	vs captopril
ELITE, 1997	vs captopril			Cardiovascular death 0.53 [0.27; 1.03] Hypotension 1.68 [0.56; 5.09] Angioedema 0.00 [0.00; NaN] Hyperkalaemia 0.35 [0.07; 1.72] Increase in creatinine 1.00 [0.65; 1.53]
ELITE II, 2000	vs captopril
Hamroff et al., 1999	vs captopril
Lang et al., 1997	vs captopril
Losartan Phase III International, 1996	vs captopril	all cause death 0.17 [0.05; 0.62]
Losartan Phase III U.S., 1995	vs captopril			all cause death 0.48 [0.12; 1.89]
Losartan phase II S, 1996	vs captopril
losartan phase II US, 1996	vs captopril
HEAAL, 2009	vs captopril	all cause death or hospital admission 0.90 [0.82; 0.99] hospital admission for heart failure 0.87 [0.77; 0.99]		all cause death 0.94 [0.84; 1.05] Adverse effect leading to treatment discontinuation 1.11 [0.88; 1.39] Hypotension 1.18 [0.61; 2.29] Angioedema ∞ [NaN; ∞] Hyperkalaemia 2.24 [0.69; 7.26] death or CV hospitalization 0.92 [0.84; 1.00] Increase in creatinine 1.33 [0.87; 2.04]

Trial	Treatments	Patients	Method
Dickstein et al., 1995	Losartan, 25 mg, 50mg daily (n=108) vs. Enalapril, 10 mg twice daily (n=58)	patients with moderate or severe chronic heart failure in New York Heart Association functional class III or IV and an ejection fraction < or = 35%	double blind Parallel groups Sample size: 108/58 Primary endpoint: clinical status and exercise performance FU duration: 8 wk
ELITE, 1997	Losartan titrated to 50 mg once daily (n=352) vs. Captopril,titratedto 50 mg three times daily (n=370)	ACE inhibitor naive patients (aged 65 years or more) with New York HeartAssociation (NYHA) class II–IV heart failure and ejection fractions of 40% or less	Double blind Parallel groups Sample size: 352/370 Primary endpoint: tolerability measure of a persist ing FU duration: 48 wk
ELITE II, 2000	Losartan, target dose 50 mg daily (n=1578) vs. Captopril, target dose 50 mg 3 times daily (n=1574)	patients aged 60 years or older with New York Heart Association class II–IV heart failure and ejection fraction of 40% or less.	Double blind Parallel groups Sample size: 1578/1574 Primary endpoint: All-cause mortalityur=na FU duration: median 1.5y
Hamroff et al., 1999	Losartan, 50 mg daily (plus ACE inhibitor) (n=16) vs. Placebo (plus ACE inhibitor) (n=17)	patients with severe congestive heart failure (NYHA III-IV) despite treatment with maximally recommended or tolerated doses of ACE inhibitors	double blind Parallel groups Sample size: 16/17 Primary endpoint: exercise capacity FU duration: 6 mo
Lang et al., 1997	Losartan titrated to 25 mg ou 50 mg daily (n=78) vs. Enalapril, titrated to 10 mg twice daily (n=38) Three arms: losartan 25mg/d, losaratan 50mg/d and enalapril 20mg/d. The 2 losartan group has been pooled	patients with congestive heart failure (New York Heart Association functionalclasses II to IV) and left ventricular ejection fraction <= 45%previously treated with stable doses of ACE inhibitors and diureticagents, with or without concurrent digitalis and othervasodilators	Double blind Parallel groups Sample size: 78/38 Primary endpoint: maximal treadmill FU duration: 12 wk
Losartan Phase III International, 1996	Losartan, 50 mg daily (n=254) vs. Placebo (n=131)	patients with heart failure who had never received ACE inibitors or who had discontinued ACE inhibitors	double blind Parallel groups Sample size: 254/131 Primary endpoint: Exercise FU duration: 12 wk
Losartan Phase III U.S., 1995	Losartan, 50 mg daily (n=237) vs. Placebo (n=114)	patients with heart failure who had never received ACE inibitors or who had discontinued ACE inhibitors	double blind Parallel groups Sample size: 237/114 Primary endpoint: Exercise FU duration: 12 wk
Losartan phase II S, 1996	losartan 50 or 25 mg/d (n=108) vs. enalapril 10mg twice daily (n=58)	patient with heart failure	double blind Parallel groups Sample size: 108/58 Primary endpoint: exercise FU duration: 8 weeks
losartan phase II US, 1996	losartan 25 and 50 mg/d (n=78) vs. enalapril 10mg twice daily (n=38)	patients with heart failure	double blind Parallel groups Sample size: 78/38 Primary endpoint: exercise FU duration: 12 weeks
HEAAL, 2009	losartan 150mg daily (n=1921) vs. losartan 50 mg daily (n=1913)	patients with systolic heart failure who couldn't tolerate ACE inhibitors	double blind Parallel groups Sample size: 1921/1913 Primary endpoint: death, admission for heart failure FU duration: 4.7 y (median)

hypertension

All results are NS for efficacy

inferior to atenolol in terms of PAD inférieure à 90 in LIFE, 2002

inferior to atenolol in terms of lung cancer in LIFE, 2002

inferior to atenolol in terms of cardiovascular mortality in OPTIMAAL, 2001

Trial	control	p<0.05	harm	NS
RENAAL, 2001	vs atenolol	microvascular events 0.79 [0.66; 0.95]		All deaths 1.02 [0.80; 1.30] renal death 0.92 [0.83; 1.03]
RENAAL, 2001	vs atenolol
LIFE, 2002	vs atenolol	apparition d'un premier évènement cardiovasculaire 0.86 [0.77; 0.96] PAS inférieure à 140 1.08 [1.03; 1.12] PA inférieure à140/90 1.07 [1.02; 1.11] stroke (fatal and non fatal) 0.75 [0.63; 0.88] cardiovascular event 0.86 [0.77; 0.96] New onset diabetes 0.75 [0.64; 0.89]	PAD inférieure à 90 0.98 [0.97; 1.00] lung cancer 2.41 [1.23; 4.71]	cardiovascular death 0.87 [0.72; 1.04] cancer occurence(prespecified endpoint) 1.11 [0.96; 1.29] cancer occurence 1.11 [0.96; 1.29] all cause death 0.89 [0.78; 1.01] coronary event 1.05 [0.86; 1.28] Cardiovascular death 0.87 [0.72; 1.04] Heart failure 0.95 [0.76; 1.18] cancer 1.11 [0.96; 1.29] Myocardial infarction ( fatal and non fatal) 1.05 [0.86; 1.28] cancer death 1.03 [0.80; 1.34]
ELITE, 1997	vs atenolol	all-cause mortality 0.56 [0.32; 0.99]		cardiovascular mortality 0.53 [0.27; 1.03] stroke 1.40 [0.32; 6.22] MI 0.79 [0.18; 3.50]
ELITE-II, 2000	vs atenolol			all-cause mortality 1.12 [0.96; 1.31] cardiovascular mortality 1.15 [0.97; 1.38] stroke 1.63 [0.77; 3.44] MI 1.10 [0.67; 1.83]
OPTIMAAL, 2001	vs atenolol		cardiovascular mortality 1.15 [1.01; 1.31]	all-cause mortality 1.11 [0.99; 1.25] stroke 1.06 [0.84; 1.33] MI 1.01 [0.88; 1.15]
LIFE (diabetic subgroup), 2002	vs atenolol	All deaths 0.61 [0.45; 0.83] Cardiovascular death 0.65 [0.44; 0.96] Cardiovascular events 0.76 [0.58; 0.99]		Stroke 0.82 [0.58; 1.16] Fatal and nonfatal MI 0.85 [0.57; 1.27]

Trial	Treatments	Patients	Method
RENAAL, 2001	losartan 50 to 100 mg once daily (n=751) vs. placebo (n=762)	patients with type 2 diabetes and nephropathy	double-blind Parallel groups Sample size: 751/762 Primary endpoint: doubling of the creatinine, end-stage renal disease, death FU duration: 3.4 y
RENAAL, 2001	lLosartan 50 to 100 mg once daily (n=751) vs. placebo (n=762)	patients with type 2 diabetes and nephropathy	double-blind Parallel groups Sample size: 751/762 Primary endpoint: doubling of the base-line serum creatinine concentration, end-stage renal disease, or death FU duration: 3.4 years
LIFE, 2002	losartan (n=4605) vs. atenolol (n=4588)	patients aged 55–80 years, with previously treated or untreated hypertension (sitting blood pressure 160–200/95–115 mm Hg) and ECG signs of LVH.	Double blind Parallel groups Sample size: 4605/4588 Primary endpoint: Cardiovascular mortality, stroke, and myocardial infarction FU duration: 4.8 y (mean)
ELITE, 1997	Losartan titrated to 50 mg once daily for 48 weeks (n=352) vs. Captopril titrated to 50 mg three times daily for 48 weeks (n=370)	naive patients (aged 65 years or more) with NYHA class II-IV heart failure and ejection fractions of 40% or less	double-blind Parallel groups Sample size: 352/370 Primary endpoint: persisting increase in serum creatinine of 26.5 mumol/L or more FU duration: 1 y
ELITE-II, 2000	Losartan titrated to 50 mg once daily (n=1578) vs. Captopril titrated to 50 mg three times daily (n=1574)	patients aged 60 years or older with New York Heart Association class II-IV heart failure and ejection fraction of 40% or less. Patients	double-blind Parallel groups Sample size: 1578/1574 Primary endpoint: all cause death FU duration: 1.5 y
OPTIMAAL, 2001	losartan (titrated to 50 mg once daily) (n=2744) vs. Captopril (titrated to 50 mg three times daily) (n=2733)	patients 50 years of age or older, with confirmed acute myocardial infarction and heart failure during the acute phase or a new Q-wave anterior infarction or reinfarction	NA Parallel groups Sample size: 2744/2733 Primary endpoint: all cause death FU duration: 2.7 y
LIFE (diabetic subgroup), 2002	losartan 50mg daily at step 1 (n=586) vs. atenolol 50mg daily at step 1 (n=609)	patients with diabetes (subgroup) , hypertension, and signs of left-ventricular hypertrophy on electrocardiograms of all 9193 patients included in the trial, 1195 had diabetes	double-blind Parallel groups Sample size: 586/609 Primary endpoint: CV events FU duration: 4.7 years

miscellaneous

All results are NS for efficacy

inferior to atenolol in terms of PAD inférieure à 90 in LIFE, 2002

inferior to atenolol in terms of lung cancer in LIFE, 2002

patients at high risk for cardiovascular events

All results are NS for efficacy

inferior to atenolol in terms of PAD inférieure à 90 in LIFE, 2002

inferior to atenolol in terms of lung cancer in LIFE, 2002