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Candesartan Versus Losartan Efficacy Comparison Study Group - CANDLE
Description:
CANDLE was a multicenter, double-blind, randomized trial that compared antihypertensive effects of two angiotensin receptor blockers (ARB), candesartan and losartan, among 332 patients with systemic hypertension.
Hypothesis:
Following eight weeks of therapy, candesartan will be associated with greater blood pressure reduction, as compared to losartan.
Study Design
Study Design:
Patients Enrolled: 332
Mean Follow Up: Eight weeks
Mean Patient Age: Mean age 55 years
Female: 42
Patient Populations:
Age 18-80, and DBP 90-114 mm Hg on two sequential outpatient visits
Exclusions:
Hypersensitivity to ARBs, secondary hypertension, orthostatic hypotension, SBP ≥200 mm Hg, or use of other antihypertensive medications
Primary Endpoints:
Change from baseline to week 8 of trough sitting DBP
Secondary Endpoints:
Changes from baseline to week 8 of trough sitting SBP, trough standing DBP and SBP, and peak sitting and standing DBP and SBP
Drug/Procedures Used:
Patients were recruited for the study if they had sitting diastolic blood pressure (DBP) between 95-114 mm Hg on two sequential outpatient visits.
Following a 4-5-week single-blinded placebo run-in period, patients were randomly assigned to receive candesartan 16 mg once daily (n=160), or losartan 50 mg once daily (n=169). If following four weeks of double-blind therapy, patients still had DBP >90 mm Hg, the dose of study medication was doubled (to candesartan 32 mg once daily, or losartan 100 mg once daily). Patients were followed for eight weeks, with an additional visit two weeks after study completion.
Blood pressure and heart rate were measured during each visit. Safety assessment included monitoring for adverse effects, as well as measurement of serum chemistry parameters at the beginning and end of the study.
Blood pressure was defined as "controlled" when DBP was below 90 mm Hg. "Trough" for this study was defined as 24 ± 3 hours after drug administration.
Principal Findings:
Mean trough sitting blood pressure at baseline was 154/100.
Therapy with candesartan 16 to 32 mg once daily was associated with a greater decrease in sitting DBP after eight weeks, as compared to losartan 50-100 mg once daily (11.0 mm Hg vs. 8.9 mm Hg DBP reduction, respectively, p=0.016).
Following the first four weeks of treatment, the starting doses of candesartan and losartan were associated with controlled blood pressure in 45% and 39% of patients, respectively.
Overall, 61% of the patients reported adverse effects (58% of those receiving candesartan and 64% of those receiving losartan). There was no difference between the two groups in frequency of specific adverse effects. No patient deaths occurred during the study. Changes in laboratory parameters in both treatment groups over the course of the study were negligible.
Interpretation:
In a diverse hypertensive population, therapy with candesartan 16-32 mg/day was associated with significantly greater DBP reduction, compared to losartan 50-100 mg/day. This study was the first to directly compare a newer, more potent ARB (candesartan cilexetil) with a prototype ARB (losartan) in a "real-life" cohort of patients with hypertension. The blood pressure changes were clinically significant. Notably, patients with severe hypertension (systolic blood pressure [SBP] >200 mm Hg) were excluded from this trial.
References:
Gradman AH, Lewin A, Bowling BT, et al. Comparative effects of candesartan cilexetil and losartan in patients with systemic hypertension. Candesartan Versus Losartan Efficacy Comparison (CANDLE) Study Group.Heart Dis 1999;1:52-7.
Keywords: Angiotensin Receptor Antagonists, Biphenyl Compounds, Losartan, Benzimidazoles, Outpatients, Blood Pressure, Tetrazoles, Heart Rate, Hypertension
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