Optimizing the Management of Uncontrolled Hypertension: What do Triple Fixed-Dose Drug Combinations Add?

Fixed-dose triple drug combinations represent one of the latest innovations of pharmacotherapy for hypertension (HT). They combine a traditional renin-angiotensin system blocker, a diuretic and a calcium channel blocker. The main benefit is the simplification of treatment regimen because 3 different agents are combined at different doses in a single pill. Improving adherence to treatment partly explains why this kind of combination may effectively reduce blood pressure (BP). BP lowering by a single- pill triple-drug combination can be approximately predicted, by using appropriate formulas described in previous meta-analysis of randomized trials. Thus, clinicians may select the appropriate dose for each of the combined drugs. Selection of different types of fixed-dose triple-drug combinations relies upon clinical experience, commercial availability and evidence from clinical trials and metaanalyses for each agent alone. However, triple fixed-dose drug combinations should be reserved only for patients with uncontrolled BP with 2 agents, poor adherence in complex therapeutic regimens or on inappropriate free-drug combinations. Also, triple therapy may help overcome clinical inertia by prescribing more potent antihypertensive formulations in one pill. In contrast, this type of multiple-drug fixed-dose combination might be less safe in very old and frail patients, as well as in those with chronic kidney disease. Although new combinations may help overcome the clinical inertia of achieving individualized BP targets, doctors should also pay attention reinforcement of lifestyle changes.