Does a fixed-dose combination of amlodipine and atorvastatin improve persistence with therapy in the Australian population?

Abstract

Aim: To compare persistence in people who initiate the combination of amlodipine and statin as a fixed-dose combination (FDC) or separate pill combination (SePC), and assess the impact of prior medicine exposure on this outcome.

Method: Prescription dispensing data from a national administrative dataset was used to identify patients initiating FDCs or SePCs of amlodipine and statin between April and September 2013. Each cohort was stratified according to dispensing of calcium channel blockers (CCBs) or statins in the prior 12 months. Time to cessation of combination therapy (persistence) was analyzed over 12 months using Kaplan Meyer survival analysis and Cox proportional hazards (PH) models. Patient factors associated with length of treatment were identified using Cox PH modeling.

Results: Of 26,000 people who initiated combination amlodipine and statin, the majority initiated SePCs (77%). The unadjusted cessation rates at 12 months were SePC 40% and FDC 44%. Following adjustment for patient factors, the risk of ceasing combination therapy was higher in those taking the SePC versus FDC, hazard ratio (95% CI): 1.15 (1.11, 1.21). Patients naïve to both therapies had double the cessation rate compared to those who had at least one prior dispensing of a statin. Factors positively associated with persistence were prior use of other antihypertensive drugs and reaching the medicine subsidy safety-net: factors that were more common in users of SePC amlodipine and statin.

Conclusion: In this study we found a lower risk (15%) of ceasing combination therapy when people initiate amlodipine and statin in the form of a FDC. While this outcome supports findings in other countries that FDCs improve persistence with combination therapy, prior experience with component or similar medicines has a larger impact on persistence regardless of formulation initiated.

Keywords:

• Adherence
• persistence
• fixed-dose combinations
• hypertension
• hyperlipidemia

Transparency

Declaration of funding

This work was supported by an Australian Government National Health and Medical Research Council (NHMRC) centre for research excellence in post-marketing surveillance of medicines and devices grant (GNT1040938).

Author contributions: L.E.B. designed the research, analyzed the data, and drafted the manuscript. E.E.R. and N.P. participated in the research design, data analysis and interpretation, critical review and revision of the final manuscript.

Declaration of financial/other relationships

L.E.B. has disclosed that she is also a part-time employee of the Commonwealth Department of Health. E.E.R. has disclosed that she is supported by an NHMRC Fellowship (GNT1110139). N.P. has disclosed that she is supported by an NHMRC Early Career Fellowship (Grant Number GNT1035889). All authors declare no financial relationships with any organization that might have an interest in the submitted work in the previous three years and no other activities or relationships that could appear to have influenced the submitted work.

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