Candesartan angiotensin-receptor blockers
Description Results

CV-11974 - CV11974 - CV 11974 - candesartan - Parapres - Amias - Kenzen - Blopress - Atacand - TCV-116 - TCV 116 - candesartan cilexetil

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pathology

Benefit (demonstrated or suggested) and harm

atrial fibrillation

All results are NS for efficacy

coronary artery disease

All results are NS for efficacy

diabetes type 2

All results are NS for efficacy

heart failure

All results are NS for efficacy

inferior to placebo in terms of Hyperkalaemia in CHARM-Added, 2003

inferior to placebo in terms of Increase in creatinine in CHARM-Added, 2003

inferior to placebo in terms of Hypotension in CHARM-Alternative, 2003

inferior to placebo in terms of Hyperkalaemia in CHARM-Alternative, 2003

inferior to placebo in terms of Increase in creatinine in CHARM-Alternative, 2003

Trial	control	p<0.05	harm	NS
ARCH-J, 2003	vs placebo
CHARM-Added, 2003	vs placebo		Hyperkalaemia 4.87 [2.39; 9.94] Increase in creatinine 1.92 [1.38; 2.66]	lung cancer 1.71 [0.67; 4.33] prostate cancer 0.77 [0.29; 2.07] Hypotension 1.45 [0.97; 2.15] Angioedema 0.66 [0.11; 3.97]
CHARM-Alternative, 2003	vs placebo	Cardiovascular death or hospital admission for CHF 0.82 [0.73; 0.93]	Hypotension 4.12 [2.00; 8.49] Hyperkalaemia 6.35 [1.88; 21.38] Increase in creatinine 2.30 [1.48; 3.58]	lung cancer 3.34 [0.92; 12.10] prostate cancer 2.67 [0.71; 10.01] breast cancer 1.26 [0.34; 4.64] Cardiovascular death 0.87 [0.74; 1.02] Angioedema ∞ [NaN; ∞]
Mitrovic et al., 2003	vs placebo	Hypotension 0.25 [0.07; 0.97]		Cardiovascular death 0.63 [0.13; 3.15]
RESOLVD (candesartan alone), 1999	vs placebo			Hypotension 1.00 [0.11; 9.51]
RESOLVD association, 1999	vs placebo			Increase in creatinine ∞ [NaN; ∞]
SPICE, 2000	vs placebo			all cause death 1.02 [0.26; 3.97] all cause death or hospital admission 0.82 [0.43; 1.56] hospital admission for heart failure 0.69 [0.33; 1.45] Cough 1.05 [0.88; 1.26] hospital admission for any reason 0.69 [0.39; 1.22]
STRETCH, 1999	vs placebo
CHARM preserved, 2003	vs placebo

Trial	Treatments	Patients	Method
ARCH-J, 2003	Candesartan, 8 mg daily (n=148) vs. Placebo (n=144)	patients with chronic heart failure who were not receiving ACE inhibitor therapy	double blind Parallel groups Sample size: 148/144 Primary endpoint: progression of CHF or addition or dose escalation of CHF medications FU duration: 155 d
CHARM-Added, 2003	Candesartantarget dose 32 mg once daily (n=1276) vs. Placebo (n=1272)	patients with New York Heart Association functional class II–IV CHF and left-ventricular ejection fraction40% or lower, and who were being treated with ACE inhibitors.	double blind Parallel groups Sample size: 1276/1272 Primary endpoint: cardiovascular death or FU duration: Median, 41 mo
CHARM-Alternative, 2003	candesartan (target dose32 mg once daily) (n=1013) vs. Placebo (n=1015)	patients with symptomatic heart failure and left-ventricular ejection fraction 40% or less who were notreceiving ACE inhibitors because of previous intolerance	double blind Parallel groups Sample size: 1013/1015 Primary endpoint: Cardiovascular death or hospital admission for CHF FU duration: Median, 33.7 mo
Mitrovic et al., 2003	Candesartan, 2 mg, 4mg, 8mg, 16mg daily (n=174) vs. Placebo (n=44)	patients with CHF (New York Heart Association class II or III) with impaired left ventricular function (ejection fraction <=40%) and pulmonary capillary wedge pressure >=13 mm Hg	double blind Parallel groups Sample size: 174/44 Primary endpoint: hemdodynamic FU duration: 12 wk
RESOLVD (candesartan alone), 1999	Candesartan, 4 mg, 8mg, 16mg daily (n=327) vs. Enalapril, 10 mg twice daily (n=109)	Patients with New York Heart Association functional class NYHA II, III, or IV CHF, 6-minute walk distance (6MWD) >500 m, and ejection fraction (EF) <0.40	Double blind Parallel groups Sample size: 327/109 Primary endpoint: hemodynamic FU duration: 43 wk
RESOLVD association, 1999	Candesartan, 4 mg, 8mg daily, plus enalapril, 10 mg twice daily (n=332) vs. Enalapril, 10 mg twice daily (n=109)	Patients with New York Heart Association functional class NYHA II, III, or IV CHF, 6-minute walk distance (6MWD) >500 m, and ejection fraction (EF) <0.40	Parallel groups Sample size: 332/109 Primary endpoint: hemodynamic FU duration: 43 wk
SPICE, 2000	Candesartan, 16 mg daily (n=179) vs. Placebo (n=91)	patients with chronic heart failure and left ventricular ejection fraction less than 35%, and history of discontinuing an ACE inhibitor because of intolerance	double blind Parallel groups Sample size: 179/91 Primary endpoint: tolerability FU duration: 12 wk
STRETCH, 1999	Candesartan, 4 mg, 8mg, 16mg daily (n=633) vs. Placebo (n=211)	Male and female patients 21 to 80 years of age with mild to moderate symptomatic CHF (NYHA class II or III)	Double blind Parallel groups Sample size: 633/211 Primary endpoint: total exercise time FU duration: 12 wk
CHARM preserved, 2003	candesartan target dose 32 mg once daily (n=1514) vs. placebo (n=1509)	patients with NYHA II-IV heart failure and LVEF higher than 40%	double blind Parallel groups Sample size: 1514/1509 Primary endpoint: cardiovascular death or admission to FU duration: 36.6 months

heart failure with preserved LVEF

All results are NS for efficacy

hypertension

All results are NS for efficacy

Trial	control	p<0.05	harm	NS
HSCS, 1974	vs placebo			cardiovascular death 0.74 [0.39; 1.42] All-cause death 1.02 [0.60; 1.72] Coronary event 0.94 [0.31; 2.87] Cardiovascular death 0.74 [0.39; 1.42] Heart failure 0.00 [0.00; NaN] Stroke 0.83 [0.55; 1.24] cardiovascular event 0.73 [0.51; 1.03]
SCOPE, 2003	vs placebo			cardiovascular death 0.95 [0.76; 1.18] all cause death 0.97 [0.82; 1.14] coronary event 1.10 [0.79; 1.54] Cardiovascular death 0.95 [0.76; 1.18] cancer 1.08 [0.89; 1.31] stroke (fatal and non fatal) 0.77 [0.59; 1.01] Myocardial infarction ( fatal and non fatal) 1.10 [0.79; 1.54] cardiac death 0.99 [0.52; 1.90] cardiovascular event 0.90 [0.76; 1.06] New onset diabetes 0.80 [0.63; 1.03]
HIJ-CREATE, 2009	vs placebo
Takahashi et al, 2006	vs placebo	cardiovascular event 0.35 [0.17; 0.76]		all cause mortality 0.00 [0.00; NaN]
Suzuki et al, 2008	vs placebo	cardiovascular event 0.58 [0.40; 0.83]		all cause mortality 0.66 [0.41; 1.04] Cardiovascular mortality 0.60 [0.30; 1.19]
TROPHY, 2006	vs placebo	hypertension 0.84 [0.75; 0.95]		cancer 1.32 [0.30; 5.84] death cancer ∞ [NaN; ∞] lung cancer 1.00 [0.14; 7.08] Serious adverse events 0.60 [0.31; 1.15] cardiovascular events 0.16 [0.02; 1.36]
CASE-J, 2008	vs placebo	New onset diabetes 0.64 [0.42; 0.96]		all cause death 0.85 [0.62; 1.15] Heart failure 1.25 [0.65; 2.40] stroke (fatal and non fatal) 1.27 [0.87; 1.86] Myocardial infarction ( fatal and non fatal) 0.94 [0.49; 1.82]
ALPINE, 2003	vs placebo	New onset diabetes 0.12 [0.02; 0.99]		cardiovascular death NaN [NaN; NaN] all cause death NaN [NaN; NaN] coronary event 0.99 [0.06; 15.80] Cardiovascular death NaN [NaN; NaN] stroke (fatal and non fatal) NaN [NaN; NaN] Myocardial infarction ( fatal and non fatal) 0.99 [0.06; 15.80] cardiovascular event 0.99 [0.06; 15.80]
E-COST, 2005	vs placebo	stroke (fatal and non fatal) 0.58 [0.41; 0.82] Myocardial infarction ( fatal and non fatal) 0.41 [0.20; 0.86]		all cause death 0.94 [0.24; 3.77] Cardiovascular death ∞ [NaN; ∞] Heart failure 0.81 [0.52; 1.26]
E-COST-R, 2005	vs placebo			all cause death 1.04 [0.27; 4.01] Cardiovascular death 1.04 [0.27; 4.01] Heart failure 0.68 [0.34; 1.34] stroke (fatal and non fatal) 0.89 [0.51; 1.55] Myocardial infarction ( fatal and non fatal) 2.09 [0.39; 11.03]
HIJ-CREATE, 2009	vs placebo	New onset diabetes 0.39 [0.16; 0.93]		all cause death 1.17 [0.84; 1.64] Cardiovascular death 1.12 [0.66; 1.91] Heart failure 0.91 [0.60; 1.38] stroke (fatal and non fatal) 0.92 [0.62; 1.36] Myocardial infarction ( fatal and non fatal) 1.12 [0.66; 1.88]
Takahashi, 2006	vs placebo			all cause death 0.00 [0.00; NaN] Heart failure 0.39 [0.15; 1.02]

Trial	Treatments	Patients	Method
HSCS, 1974	deserpidine 1mg/d + methylclothiazide 10mg/d (n=233) vs. placebo (n=219)	stroke	Double blind Parallel groups Sample size: 233/219 Primary endpoint: FU duration: 2.3y
SCOPE, 2003	candesartan, 8–16 mg once daily (target 160/90) (n=2477) vs. placebo (n=2460)	patients aged 70–89 years, with systolic blood pressure 160– 179 mmHg, and/or diastolic blood pressure 90–99 mmHg, and a Mini Mental State Examination (MMSE) test score > 24	double-blind Parallel groups Sample size: 2477/2460 Primary endpoint: major cardiovascular events FU duration: 3.7 y (mean)
HIJ-CREATE, 2009	cardesartan adjusted dose for target arterial pressure of <130/85 mmHg (n=1025) vs. usual care (non-ARB-based pharmacotherapy including angiotensin-converting enzyme-inhibitors) (n=1024)	hypertension with angiographically documented coronary artery disease (acute or stable)	open Parallel groups Sample size: 1025/1024 Primary endpoint: MACE FU duration: up to 60 months
Takahashi et al, 2006	Candesartan 4-8mg/day (n=43) vs. Conventional treatment (n=37)	chronic haemodialysis patients	open Sample size: 43/37 Primary endpoint: FU duration:
Suzuki et al, 2008	Candesartan 12 mg/day, losartan 100 mg/day, or valsartan 160 mg/day (n=180) vs. Conventional treatment (n=180)	patients undergoing hemodialysis	open Sample size: 180/180 Primary endpoint: FU duration: 1-5 years
TROPHY, 2006	candesartan during 2y followed by 2y of placebo (n=409) vs. placebo (n=400)	subjects with repeated measurements of systolic pressure of 130 to 139 mm Hg and diastolic pressure of 89 mm Hg or lower, or systolic pressure of 139 mm Hg or lower and diastolic pressure of 85 to 89 mm Hg	double-blind Parallel groups Sample size: 409/400 Primary endpoint: new-onset hypertension FU duration: 4y
CASE-J, 2008	candesartan-based regimen (n=2354) vs. amlodipine-based regimen (n=2349)	high-risk Japanese hypertensive patients	open (blinded assessment) Parallel groups Sample size: 2354/2349 Primary endpoint: FU duration: 3.2 years
ALPINE, 2003	candesartan (n=197) vs. hydrochlorothiazide (n=196)	newly detected hypertensives	double-blind Parallel groups Sample size: 197/196 Primary endpoint: diabetes FU duration: 1 year
E-COST, 2005	candesartan, 2 to 12 mg daily (n=1053) vs. conventional antihypertensive drugs other than angiotensin converting enzyme inhibitors or ARBs (n=995)	Japanese essential hypertensive subjects (sitting blood pressure 140-180/90-110 mmHg) aged 35-79 years	single-blind Parallel groups Sample size: 1053/995 Primary endpoint: CV hospitalization FU duration:
E-COST-R, 2005	candesartan (n=69) vs. conventional treatment (n=72)	hypertensive subjects 60 to 75 years old with non-diabetic chronic renal insufficiency	open Parallel groups Sample size: 69/72 Primary endpoint: cardiovascular event FU duration:
HIJ-CREATE, 2009	angiotensin II receptor blocker-based therapy (n=1024) vs. non-angiotensin II receptor blocker-based therapy (n=1025)	patients with angiographically documented coronary artery disease and hypertension	open Parallel groups Sample size: 1024/1025 Primary endpoint: CV events FU duration: 4.2 y (median)
Takahashi, 2006	candesartan (n=43) vs. control (n=37)	patients on chronic haemodialysis in stable condition and with no clinical evidence of cardiac disorders	open Parallel groups Sample size: 43/37 Primary endpoint: cardiovascular events FU duration: 19.4 months

miscellaneous

All results are NS for efficacy

Trial	control	p<0.05	harm	NS
SCOPE, 2003	vs placebo			cardiovascular death 0.95 [0.76; 1.18] all cause death 0.97 [0.82; 1.14] coronary event 1.10 [0.79; 1.54] Cardiovascular death 0.95 [0.76; 1.18] cancer 1.08 [0.89; 1.31] stroke (fatal and non fatal) 0.77 [0.59; 1.01] Myocardial infarction ( fatal and non fatal) 1.10 [0.79; 1.54] cardiac death 0.99 [0.52; 1.90] cardiovascular event 0.90 [0.76; 1.06] New onset diabetes 0.80 [0.63; 1.03]
TROPHY, 2006	vs placebo	hypertension 0.84 [0.75; 0.95]		cancer 1.32 [0.30; 5.84] death cancer ∞ [NaN; ∞] lung cancer 1.00 [0.14; 7.08] Serious adverse events 0.60 [0.31; 1.15] cardiovascular events 0.16 [0.02; 1.36]
CASE-J, 2008	vs placebo	New onset diabetes 0.64 [0.42; 0.96]		all cause death 0.85 [0.62; 1.15] Heart failure 1.25 [0.65; 2.40] stroke (fatal and non fatal) 1.27 [0.87; 1.86] Myocardial infarction ( fatal and non fatal) 0.94 [0.49; 1.82]
ALPINE, 2003	vs placebo	New onset diabetes 0.12 [0.02; 0.99]		cardiovascular death NaN [NaN; NaN] all cause death NaN [NaN; NaN] coronary event 0.99 [0.06; 15.80] Cardiovascular death NaN [NaN; NaN] stroke (fatal and non fatal) NaN [NaN; NaN] Myocardial infarction ( fatal and non fatal) 0.99 [0.06; 15.80] cardiovascular event 0.99 [0.06; 15.80]
E-COST, 2005	vs placebo	stroke (fatal and non fatal) 0.58 [0.41; 0.82] Myocardial infarction ( fatal and non fatal) 0.41 [0.20; 0.86]		all cause death 0.94 [0.24; 3.77] Cardiovascular death ∞ [NaN; ∞] Heart failure 0.81 [0.52; 1.26]
E-COST-R, 2005	vs placebo			all cause death 1.04 [0.27; 4.01] Cardiovascular death 1.04 [0.27; 4.01] Heart failure 0.68 [0.34; 1.34] stroke (fatal and non fatal) 0.89 [0.51; 1.55] Myocardial infarction ( fatal and non fatal) 2.09 [0.39; 11.03]
HIJ-CREATE, 2009	vs placebo	New onset diabetes 0.39 [0.16; 0.93]		all cause death 1.17 [0.84; 1.64] Cardiovascular death 1.12 [0.66; 1.91] Heart failure 0.91 [0.60; 1.38] stroke (fatal and non fatal) 0.92 [0.62; 1.36] Myocardial infarction ( fatal and non fatal) 1.12 [0.66; 1.88]
Takahashi, 2006	vs placebo			all cause death 0.00 [0.00; NaN] Heart failure 0.39 [0.15; 1.02]

Trial	Treatments	Patients	Method
SCOPE, 2003	candesartan, 8–16 mg once daily (target 160/90) (n=2477) vs. placebo (n=2460)	patients aged 70–89 years, with systolic blood pressure 160– 179 mmHg, and/or diastolic blood pressure 90–99 mmHg, and a Mini Mental State Examination (MMSE) test score > 24	double-blind Parallel groups Sample size: 2477/2460 Primary endpoint: major cardiovascular events FU duration: 3.7 y (mean)
TROPHY, 2006	candesartan during 2y followed by 2y of placebo (n=409) vs. placebo (n=400)	subjects with repeated measurements of systolic pressure of 130 to 139 mm Hg and diastolic pressure of 89 mm Hg or lower, or systolic pressure of 139 mm Hg or lower and diastolic pressure of 85 to 89 mm Hg	double-blind Parallel groups Sample size: 409/400 Primary endpoint: new-onset hypertension FU duration: 4y
CASE-J, 2008	candesartan-based regimen (n=2354) vs. amlodipine-based regimen (n=2349)	high-risk Japanese hypertensive patients	open (blinded assessment) Parallel groups Sample size: 2354/2349 Primary endpoint: FU duration: 3.2 years
ALPINE, 2003	candesartan (n=197) vs. hydrochlorothiazide (n=196)	newly detected hypertensives	double-blind Parallel groups Sample size: 197/196 Primary endpoint: diabetes FU duration: 1 year
E-COST, 2005	candesartan, 2 to 12 mg daily (n=1053) vs. conventional antihypertensive drugs other than angiotensin converting enzyme inhibitors or ARBs (n=995)	Japanese essential hypertensive subjects (sitting blood pressure 140-180/90-110 mmHg) aged 35-79 years	single-blind Parallel groups Sample size: 1053/995 Primary endpoint: CV hospitalization FU duration:
E-COST-R, 2005	candesartan (n=69) vs. conventional treatment (n=72)	hypertensive subjects 60 to 75 years old with non-diabetic chronic renal insufficiency	open Parallel groups Sample size: 69/72 Primary endpoint: cardiovascular event FU duration:
HIJ-CREATE, 2009	angiotensin II receptor blocker-based therapy (n=1024) vs. non-angiotensin II receptor blocker-based therapy (n=1025)	patients with angiographically documented coronary artery disease and hypertension	open Parallel groups Sample size: 1024/1025 Primary endpoint: CV events FU duration: 4.2 y (median)
Takahashi, 2006	candesartan (n=43) vs. control (n=37)	patients on chronic haemodialysis in stable condition and with no clinical evidence of cardiac disorders	open Parallel groups Sample size: 43/37 Primary endpoint: cardiovascular events FU duration: 19.4 months

patients at high risk for cardiovascular events

All results are NS for efficacy

pulmonary embolism

All results are NS for efficacy

superficial thrombophlebitis

All results are NS for efficacy

thrombosis prevention

All results are NS for efficacy