Long-term persistence with single-pill, fixed-dose combination therapy versus two pills of amlodipine and perindopril for hypertension: Australian experience

Abstract

Objective: To study treatment persistence and mortality using a single-pill, fixed-dose combination tablet compared with a two-pill combination for hypertension.

Research design and methods: We analyzed Australian Pharmaceutical Benefit Scheme records 2011–2014 in a 10% random sample of concessional patients prescribed concomitant amlodipine and perindopril – either as a single-pill, fixed-dose combination tablet (n = 9340) or as two-pill combination therapy (n = 3093). Main outcome measures were: (a) proportions failing to continue amlodipine + perindopril over time, (b) proportions failing to continue any subsequent calcium channel and angiotensin inhibition therapy over time and (c) proportions dying.

Results: After 12 months, 34% of single-pill and 57% of two-pill users discontinued amlodipine + perindopril, median persistence time 42 months versus 7 months; 28% and 47% respectively discontinued any calcium channel–angiotensin inhibition therapy. After 48 months, 8% of single-pill and 18% of two-pill users had died. In a multivariate model adjusted for age, gender, duration and intensity of prior hypertension therapy, initial dose of amlodipine and perindopril, diabetes, hyperlipidemia, and complexity of care, the hazard ratio for risk of discontinuation over 42 months in the two-pill versus single-pill amlodipine + perindopril group was 1.94 (95% CI 1.83–2.06). The hazard ratio for discontinuation in two-pill versus single-pill users of any calcium channel–angiotensin inhibition therapy was 1.86 (1.74–1.99). The adjusted hazard ratio for risk of death over 48 months was 1.83 (1.55–2.16), but the mortality outcome may be an overestimate due to residual confounding.

Conclusions: Use of a single-pill, fixed-dose combination in hypertension is associated with superior persistence and reduced mortality compared with use of two pills, suggesting a higher priority for the use of fixed-dose combinations.

Keywords:

• Hypertension therapy
• persistence
• fixed-dose combinations
• mortality

Transparency

Declaration of funding

This study was supported by a research grant from Servier Laboratories (Australia) Pty Ltd, a company that markets perindopril and related products.

Author contributions: All authors contributed equally to study design, interpretation and manuscript preparation. E.C. conducted data extraction and analysis.

Declaration of financial/other relationships

L.A.S. has disclosed that he is a consultant to Servier Laboratories (Australia) and other pharmaceutical companies. E.C. and M.O. have disclosed that they are paid consultants to the study.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

Raw data for the study was supplied by the Australian Department of Human Services.