Update on the role of candesartan in the optimal management of hypertension and cardiovascular risk reduction

Figures & data

Table 1 Randomized controlled studies assessing the antihypertensive efficacy, safety, and tolerability of candesartan (monotherapy or in combination with other antihypertensive agents) versus placebo or versus other antihypertensive agents

Trial/author^Ref	Drug	No. of randomized subjects	Study population	Age (years)	Dose of candesartan	Duration	Main outcomes	Results
Reif et al^Citation18	Cand/placebo	365	Essential hypertension	55 (mean)	2–32 mg	8 weeks	BP control	Cand effective and well tolerated for BP control
TROPHY^Citation20	Cand/placebo	809	Pre-hypertension	30–65	16 mg OD	4 years	Development of clinical Hypertension	Decreased incidence of hypertension in cand group
DHyPP^Citation21	Cand/placebo	110	Normotensive offspring of hypertensive parents	18–36	16 mg OD	12 months (24 months follow-up)	Mean ABPM at 12 and 24 months	At 12 and 24 months no difference between cand and placebo
NICE COMBI^Citation22	Cand/cand + nifedipine	258	Essential hypertension	20–80	8–12 mg	16 weeks	BP, PP, UACR	combination therapy has superior BP effects than cand alone
Bonner et al^Citation23	Cand/cand + HCTZ 12.5 mg/cand + HCTZ 25 mg	3,521	Essential hypertension	>18	32 mg	16 weeks	BP control	cand + HCTZ more effective than cand monotherapy at controlling BP
Sasaki et al^Citation24	Cand + benidipine hydrochloride	25	Hypertension + diabetes	Elderly >65	N/A	4 months	BP change from baseline	Combination effective in reducing systolic hypertension in elderly
Karlson et al^Citation25	Cand + HCTZ/placebo	4,632	Mild-to-moderate hypertension	>18	2–32 mg	12 weeks	BP control	BP-lowering effect of cand + HCTZ is dose-related
Andersson et al^Citation26	Cand/losartan/placebo	334	Essential hypertension	20–80	8–16 mg	4 weeks	Reduction in trough sitting DBP	Cand 16 mg significantly more effective than losartan/placebo
CASTLE^Citation27	Cand/amlodipine	251	Stage 1 hypertension	53.5 (mean)	16–32 mg	8 weeks	BP change from baseline	No difference
CALM^Citation28	Cand/lisinopril/cand + lisinopril	199	T2DM + hypertension + MCALB	30–75	16 mg OD	24 weeks	BP and UACR	Similar efficacy to lisinopril, but combination therapy better
CALM II^Citation29	Cand + lisinopril/lisinopril	75	Diabetes + hypertension	35–74	16 mg OD	12 months	Seated BP and 24 hour AMBP	No difference between combination and Lisinopril 40 mg OD
CHANCE^Citation48	Cand	3,013	Essential hypertension	Elderly >65	8–16 mg	8 weeks	BP control	Cand effective and tolerated for BP control in the elderly

Abbreviations: cand, candesartan; T2DM, type 2 diabetes mellitus; MCALB, microalbuminuria; BP, blood pressure; PP, pulse pressure; DBP, diastolic blood pressure; UACR, urine albumin-to-creatinine ratio; ABPM, ambulatory blood pressure monitoring; OD, once daily; N/A, not available; HCTZ, hydrochlorothiazide.

Table 2 Randomized controlled studies of candesartan with cardiovascular, cerebrovascular, retinal, or metabolic outcomes

Trial/author^Ref	Drug	No. of randomized subjects	Study population	Age (years)	Dose of candesartan	Duration	Main outcomes	Results
DIRECT-Prevent 1^Citation31	Cand/placebo	1,421	Normotensive, TIDM without diabetic retinopathy	18–50	8–32 mg OD	4.7 years (median follow up)	Incidence of retinopathy	Nonsignificant reduction in the incidence of retinopathy
DIRECT-Protect 1^Citation31	Cand/placebo	1,905	Normotensive T1DM with diabetic retinopathy	18–55	8–32 mg OD	4.8 years (median follow up)	Progression of retinopathy	No significant effect on retinopathy progression
DIRECT-Protect 2^Citation32	Cand/placebo	1,905	Normotensive, normoalbuminuric, or treated hypertensive T2DM with diabetic retinopathy	37–75	16–32 mg OD	4.7 years (median follow up)	Progression and regression of retinopathy	Nonsignificant reduction in progression k of retinopathy
MITEC^Citation34	Cand/amlodipine	209	Essential hypertension, T2DM	40–74	8 mg OD	36 months	Effect on CIMT	Similar reduction in natural progression of CIMT
CHARM-Overall^Citation35	Cand/placebo	7,601	CHF and reduced LVEF < 40%	66 (mean)	32 mg OD	37.7 months (median follow-up)	Reduction in all cause mortality	Reduced CV deaths and hospital admissions for HF
CHARM-Added^Citation36	Cand/placebo	2,548	CHF and reduced LVEF ≤ 40%	64 (mean)	32 mg OD	41 months (median follow up)	Composite of CV death or hospital admission for HF	Reduction in relevant CV events
CHARM-Preserved^Citation37	Cand/placebo	3,025	CHF and reduced LVEF < 40%	67.2 (mean)	32 mg OD	36.6 months (median follow up)	CV death or admission for HF	Moderate impact in preventing admission for HF
CHARM-Alternative^Citation38	Cand/placebo	2,028	CHF and reduced LVEF ≤ 40%	66.3 (mean)	32 mg OD	33.7 months (median follow up)	Composite of CV death or hospital admission for HF	Reduced CV mortality and morbidity
RESOLVD^Citation39	Cand/cand + enalapril/enalapril	768	CHF and reduced LVEF < 40%	63 (mean)	4–16 mg OD	43 weeks	Change in 6MWD, LVEF, neurohormone levels, QOL	Combination of cand and enalapril more beneficial in reducing LV remodeling
SCOPE^Citation40	Cand/placebo	4,964	Elderly hypertensives with preserved cognitive function	70–89	8–16 mg OD	3–5 years	Assessment of CV and cognitive outcomes in elderly	Reduction in CV events and preserved cognitive function
ACCESS^Citation41	Cand/placebo	342	Hypertension, cerebral ischemia	68.3 (mean)	8–16 mg OD	12 months	Case fatality and disability	Reduced 12-month mortality and vascular events rate
CASE-J^Citation42	Cand/amlodipine	4,728	Hypertension, T2DM	63.8 (mean)	4–12 mg OD	3.2 years	Reduction in the incidences of CV mortality and morbidity	No significant difference from amlodipine in CV end point
HIJ-CREATE^Citation43	Cand/non-ARB-based therapy	2,049	CAD	20–80	4–12 mg OD	60 months	Time to first major cardiac event	No difference in time to first major cardiac event
ISHIN^Citation44	Cand/cand + probucol/placebo	132	CAD	65.3 (mean)	8 mg OD	6 months	Prevention of neointimal hyperplasia after stent implantation	Cand alone failed to reduce neointimal hyperplasia
ALPINE^Citation45	HCTZ/HCTZ + atenolol/cand/cand + felodipine	392	Essential hypertension	55 (mean)	16 mg OD	12 months	Metabolic profile (glucose, lipids) and BP control	Aggravated metabolic profile with HCTZ alone or + atenolol
MEDICA^Citation46	Cand/HCTZ/placebo	26	Hypertension	18–70	16–32 mg OD	12 weeks each of 3 consecutive arms	Effect on insulin sensitivity	Worse metabolic outcomes with HCTZ
Koh et al^Citation47	Ramipril/cand/ramipril + cand	38	Essential hypertension	32–62	16 mg OD	8 weeks	Endothelial function, adipocytokine profile, BP control	Combination improved BP, endothelial function and adipocytokine profile

Abbreviations: Cand, candesartan; HCTZ, hydrochlorothiazide; ARB, angiotensin receptor blocker; Bp, blood pressure; CHF, chronic heart failure; LVEF, left ventricular ejection fraction; T2DM, type 2 diabetes mellitus; T1DM, type 1 diabetes mellitus; CAD, coronary artery disease; OD, once daily; BP, blood pressure; CV, cardiovascular; HF, heart failure; CIMT, carotid intima media thickness; 6MWD, 6-minute walking distance; QOL, quality of life; LV, left ventricular.

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