Clinical effectiveness of low-dose chlorthalidone (6.25 mg) + atenolol combination in stage I hypertensive patients: a multicenter, randomized, controlled study

ABSTRACT

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 non-inferior to the high-dose atenolol alone and atenolol + amlodipine combination. No serious laboratory/clinical adverse events were reported in this study.

Conclusion: 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.

Key words: :

• Amlodipine
• Atenolol
• Chlorthalidone
• Stage I essential hypertension

Acknowledgements

Declaration of interest: This study was sponsored by Ipca Laboratories Ltd., Mumbai, India. A. Pareek and N.B. Chandurkar, who are employees of Ipca Labs Ltd, were involved in the conceptualization, coordination and execution of the study, at all the centers. N.D. Karnik, S.B. Salagre, S.D. Zawar and V.K. Joglekar, who were study investigators, did not receive any financial benefit and declare that they have no conflicts of interest of a declarable nature.

The authors thank S.R Kulkarni and G.S. Naik (of Ipca Labs Ltd) for technical assistance and S.P. Dixit (of Ipca Labs Ltd) for statistical analysis and data management for this study. The authors would also like to thank C.Y. Nimkar, who served as an external consultant for statistical analysis.