Are fixed-dose combination antihypertensives suitable as first-line therapy?

OBJECTIVE: To contemplate how initial antihypertensive therapy with fixed-dose combinations (FDC) might be incorporated into clinical practice, based on a compilation of evidence comparing FDCs with monotherapy and loose-dose combinations in varying patient populations. METHODS: A non-systematic search of PubMed (from 2007 to 2012) was performed for randomized, controlled trials in order to capture the evidence on FDC versus monotherapy and loose-dose combinations as first-line therapy. The literature search focused on calcium channel blocker (CCB)-renin angiotensin system (RAS) blocker combinations. Additionally, any relevant papers known to the authors were included. International recommendations from published hypertension treatment guidelines were also consulted. RESULTS: The results of this literature review identified two emergent issues. Firstly, there is a discord between antihypertensive use and actual blood pressure (BP) control achieved - despite an increase in the use of antihypertensives over the last 10 years, BP control rates remain low. Secondly, a greater association between BP and cardiovascular risk in Asians may magnify this discrepancy. A number of international guidelines are recommending early combination therapy, such as CCB-RAS blocker combinations in the majority of patients based on the available evidence, with such combinations showing benefits in terms of compliance, BP lowering and control, and safety. Additionally, recent studies have indicated that improved BP control may be achieved with simplified guidelines and the use of FDCs. Overall, these findings indicate that FDC could be used as first-line. CONCLUSIONS: The findings from this literature review suggest that physicians may need to readdress their approach to antihypertensive treatment. Earlier use of antihypertensive FDC (including first-line) may help to shrink the current gap between antihypertensive use and BP target control achieved. Most guidelines acknowledge that combination therapy is required in the majority of patients, and FDC are regarded as a suitable alternative, having demonstrated better compliance compared with loose-dose combinations.