Associate Professor of Medicine,
Université de Montréal
Head of Cardiology
Manager of the CV Program,
Centre Hospitalier de l’Université de Montréal (CHUM)
In a patient with hypertension not at BP target with an ARB, when should I use add-on therapy (e.g., a fixed-dose ARB/diuretic combination), and when should I titrate the ARB dose?
Many patients can be adequately managed with antihypertensive monotherapy, reaching their target blood pressure (BP) with standard dosing. When using antihypertensive monotherapy as initial treatment, one should ensure that one is using an agent at a dose that has proven to be effective for BP lowering. For example, the ARB olmesartan at a dose of 20 mg has been shown to have an efficacy in BP lowering similar to that of amlodipine 5 mg daily.1
While monotherapy may be effective for many individuals, research consistently indicates that combination therapy is required for most patients to achieve BP targets. Additional BP lowering can be achieved by titrating the dose of the monotherapy,2 but even greater BP lowering can be achieved by adding another agent from another class at a low dose. The 2015 CHEP guidelines recommend this latter approach, stating that “Additional antihypertensive drugs should be used if target blood pressure levels are not achieved with standard-dose monotherapy.”3 Furthermore, the guidelines advise that “Low doses of multiple drugs may be more effective and better tolerated than higher doses of fewer drugs.”3
Where possible, combination therapies should be administered in fixed-dose combinations, with one of the components being the same agent as was used in monotherapy (e.g., switching from a once-daily ARB to a once-daily ARB/diuretic combination). One of the advantages of combination therapy is that there may be an additive or synergistic antihypertensive effect using lower doses of individual components, while each agent in the combination may counteract the side effects of the other.4 All of this can help patients—including those in difficult-to-treat populations—achieve their target BP in a timely manner and help motivate them to adhere to therapy over the long term.4
Finally, it should be noted that, while there may be differences in terms of antihypertensive efficacy between agents in the ARB class,5 moving to an ARB/diuretic combination is the preferred option when faced with inadequate efficacy with ARB monotherapy.
1. Chrysant SG, Marbury TC, Robinson TD. Antihypertensive efficacy and safety of olmesartan medoxomil compared with amlodipine for mild-to-moderate hypertension. J Hum Hypertens 2003; 17(6):425-32.
2. Smith DH. Dose-response characteristics of olmesartan medoxomil and other angiotensin receptor antagonists. Am J Cardiovasc Drugs 2007; 7(5):347-56.
3. Canadian Hypertension Education Program (CHEP). The 2015 Canadian Hypertension Education Program Recommendations. Available at: www.hypertension.ca. Accessed July 2015.
4. Kalra S, Kalra B, Agrawal N. Combination therapy in hypertension: An update. Diabetol Metab Syndr 2010; 2(1):44.
5. Oparil S, Williams D, Chrysant SG, et al. Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension. J Clin Hypertens (Greenwich) 2001; 3(5):283-91, 318.
Development of this article was sponsored by Merck Canada Inc. The author had complete editorial independence in the development of this article and is responsible for its accuracy. The sponsor exerted no influence in the selection of the content or material published.