Clinical effectiveness of low-dose chlorthalidone (6.25 mg) + atenolol combination in stage I hypertensive patients: a multicenter, randomized, controlled study.
OBJECTIVE
To compare the efficacy and safety of low-dose chlorthalidone + atenolol combination with atenolol and atenolol + amlodipine combination in stage I hypertensive patients uncontrolled on active run-in monotherapy.


METHODS
Newly diagnosed stage I hypertensive patients were randomized to active run-in monotherapy either with atenolol 25 mg (98/300) or chlorthalidone 6.25 mg (100/300) or amlodipine 2.5 mg (102/300). A total of 282/300 patients (atenolol 92, chlorthalidone 91, amlodipine 99) completed the active run-in phase successfully. Patients uncontrolled on active run-in monotherapy (atenolol 33, chlorthalidone 45, amlodipine 47) received the study treatment, namely atenolol 50 mg alone, chlorthalidone 6.25 mg+atenolol 25 mg and atenolol 25 mg+amlodipine 2.5 mg, respectively. Efficacy of the therapy was evaluated by BP measurement at weeks 12 and 20 post-therapy.


RESULTS
Post-active run-in monotherapies, the study treatment groups showed a significant fall in mean SBP and DBP from baseline (p<0.05). The mean fall in SBP and DBP was comparable for study treatments (atenolol 50 mg, atenolol 25 mg+chlorthalidone 6.25 mg and atenolol 25 mg+amlodipine 2.5 mg) (p=0.337 for SBP and p=0.054 for DBP) at week 12 and (p=0.744 for SBP and p=0.855 for DBP) at week 20; also, the percentage of responders was comparable for the three study treatment groups (p=0.799) indicating that the low-dose chlorthalidone+atenolol combination is noninferior to the high-dose atenolol alone and atenolol+amlodipine combination. No serious laboratory/clinical adverse events were reported in this study.


CONCLUSIONS
Chlorthalidone 6.25 mg in combination with atenolol 25 mg is effective and safe in stage I (JNC 7) essential hypertensive patients. This low dose of chlorthalidone could reduce dose-related concerns over metabolic adverse effects and may lead to wider usage of this proven antihypertensive agent in combination therapy.
Pareek
A
A
Ipca Laboratories Ltd, Mumbai, India. anilpareek@ipca.co.in
Karnik
N
N
Salagre
S B
SB
Zawar
S D
SD
Joglekar
V K
VK
Chandurkar
N
N
Naik
G S
GS
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D001262:Atenolol / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D002752:Chlorthalidone / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000145:classification / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D001262:Atenolol; D002752:Chlorthalidone