Fixed‐dose combinations: A valuable tool to improve adherence to antihypertensive treatment

Abstract

Hypertension is a major modifiable cardiovascular risk factor. [1][2][3] Several studies have shown that management of hypertension with all five main classes of blood pressure (BP)-lowering drugs (diuretics, β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers) substantially reduces cardiovascular morbidity and mortality. 4 However, only a minority of patients with hypertension achieve BP targets. 5-7 An important contributor to these low rates of BP control is poor adherence to treatment. 8 Indeed, a substantial proportion of patients do not adhere to antihypertensive treatment. 8,9 In turn, poor adherence increases the risk for cardiovascular and all-cause mortality. 10,11 Several predictors of nonadherence to antihypertensive treatment have been identified, including older age, belonging to a racial/ethnic minority, male sex, and depression. 8,12 Moreover, several studies have shown that an increase in the number of antihypertensive agents is associated with reduced adherence to treatment. 8,12 This observation is particularly pertinent for the management of hypertension, since most patients with hypertension require more than one agent to achieve BP targets. 13,14 In this context, a meta-analysis by Du and colleagues 15 offers valuable information in the effort to improve adherence to antihypertensive treatment. The authors analyzed nine studies in 62 481 patients with hypertension and report that the mean difference of medication adherence for fixed-dose combination (FDC) vs freeequivalent combination therapies was 14.92% (95% confidence interval, 7.38%-22.46%). 15 Moreover, patients in the FDC group were nearly two times more likely to adhere to their antihypertensive treatment (risk ratio, 1.84, 95% confidence interval, 1.00-3.39). 15 Despite the important findings reported in this meta-analysis, there are still unanswered questions regarding the role of FDCs in the management of hypertension. First, eight of nine studies included in the meta-analysis by Du and coworkers 15 were retrospective. More prospective studies are needed to clearly define the benefits of FDCs. Moreover, this meta-analysis did not evaluate whether different types of FDCs (eg, renin-angiotensin system inhibitors combined with diuretics vs renin-angiotensin system inhibitors combined with calcium channel blockers) have the same impact on adherence. 15 It appears that adherence to diuretics is lower than with other antihypertensive agents. 12 On the other hand, calcium channel blocker use was reported to be independently associated with lower risk for decline in adherence. 16 This question has particular importance, since in the ACCOMPLISH (Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension) trial, combining an angiotensin-converting enzyme inhibitor with a calcium channel blocker reduced cardiovascular events more than the combination with a diuretic, despite a similar reduction in BP. 17 Third, only fixed combinations o...

Fixed-dose Combination of Metoprolol, Telmisartan, and Chlorthalidone for Essential Hypertension in Adults with Stable Coronary Artery Disease: Phase III Study

“…A significant advantage of using FDCs is to reduce therapeutic inertia to manage hypertension allowing for simultaneous uptitration of dose as applicable [51]. Other benefits include improved medication compliance and adherence, decreased pill burden, increased efficacy, and fewer AEs owing to the complementary effect of the combinations used versus single doses [52,53]. The safety findings in our study are complementary to and aligned with the known safety profile of FDCs studied previously.…”

Fixed‐dose combination pharmacologic therapy to improve hypertension control worldwide: Clinical perspective and policy implications

“…One significant advantage is the potential for FDCs to reduce clinical or therapeutic inertia in the control of hypertension, since two drugs would be introduced or up‐titrated simultaneously . Additional key advantages and benefits include increased efficacy, decreased pill burden, improved medication adherence, and reduction (mitigation) in side effects and adverse events of a given single agent when it is used as monotherapy . In practical terms, clinical data have shown that the use of FDCs in the form of a single pill or capsule, when compared to combination therapy involving separate single agents, in the long term can be cost‐effective .…”

Fixed‐dose combinations of lipid‐lowering and antihypertensive agents: The way forward?

“…16 The suboptimal control of these risk factors is due to many causes, including physician inertia, side effects, and cost of treatment. 17 However, a major contributor to the low rates of achievement of BP and LDL-C targets appears to be suboptimal adherence to antihypertensive and lipid-lowering treatment. 18,19 On the other hand, previous studies suggested that fixed-dose combination of statins and antihypertensive agents results in better adherence to treatment than separate pill combination.…”

“…Accordingly, among patients with hypercholesterolemia who are receiving lipid‐lowering treatment, LDL‐C targets are achieved in approximately two thirds of patients . The suboptimal control of these risk factors is due to many causes, including physician inertia, side effects, and cost of treatment . However, a major contributor to the low rates of achievement of BP and LDL‐C targets appears to be suboptimal adherence to antihypertensive and lipid‐lowering treatment .…”