Improved quality of life and nonspecific symptoms with fixed‐dose combination drugs

Hypertension is often referred to as the “silent killer,” as hypertensive patients remain asymptomatic until they experience a critical vascular event such as coronary heart disease, heart failure, or a cerebrovascular accident. In treating hypertension, physicians routinely search for secondary causes, symptoms related to end organ damage, and side effects of antihypertensive medications. On the other hand, clinicians may not ask about quality of life or nonspecific symptoms, despite growing evidence that patients with uncontrolled hypertension may experience underrecognized emotional distress and symptoms not related to end organ damage, secondary causes of hypertension, or medication side effects.1 In fact, national guidelines do not suggest these additional screening questions when assessing patients with hypertension.2 While the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) specifically states that a patient cannot monitor hypertension by symptoms, the Eighth Joint National Committee (JNC 8) fails to comment on symptoms related to hypertension at all.3, 4 In the article “Quality of life and emotional impact of a fixed-dose combination of antihypertensive drugs in patients with uncontrolled hypertension,” Schmieder and colleagues show how control of hypertension with a fixed-dose combination (FDC) pill of olmesartan, amlodipine, and hydrochlorothiazide is associated with reduction in patient emotional distress and nonspecific symptoms.5 These associations support the use of triple-drug combination therapy over single-drug therapy and suggest physicians should inquire about nonspecific symptoms when counseling hypertensive patients. The emotional burden related to uncontrolled hypertension is reduced with control of hypertension, yet treatment decisions must be balanced against other issues, such as increasing pill burden, reduced adherence, and adverse impact on health-related quality of life.6-9 Schmieder and colleagues and an earlier study describe improvement in the emotional burden of hypertension and quality of life associated specifically with triple-combination therapy.10 Aside from physically consuming fewer pills, combination therapy also improves adherence and leads to improved blood pressure control, which, in turn, reduces patient anxiety about hypertension.11 Many professional societies and authors recommend the use of combination therapies; however, current hypertensive guidelines do not comment on the use of combination pills to reduce pill burden.12 Schmieder and colleagues' article argues that this should be considered as guidelines are updated. Another benefit of combination therapy is the potential for reduced clinical inertia, a known barrier to effective treatment of hypertension. This phenomenon has been described as the lack of treatment intensification in patients not at evidence-based goals of care.13 One form of clinical inertia is patient clinical inertia, which is possibly due to a patient's low health literacy or skepticism that their disease poses a serious health risk.14 Patient clinical inertia may be more important in the management of hypertension than other diseases, as patients seemingly do not experience symptoms during the disease course until reaching end organ damage. However, Schmieder and colleagues describe how hypertensive patients experience nonspecific symptoms such as “fatigue,” “dizziness,” and “sleep disturbance.” These symptoms significantly improve with FDC treatment of hypertension. While hypertension therapy cannot be directed through monitoring of these nonspecific symptoms, clinicians can counsel patients about the presence of these associated symptoms and how they may improve with treatment of hypertension. This may help nonadherent patients garner insight into their “silent” disease and invest in their hypertensive therapy, overcoming patient clinical inertia.1 While there are multiple significant associations with FDC therapy and the treatment of uncontrolled hypertension, the study design has multiple limitations, primarily attributable to a lack of a comparison group. The impact of reduced pill burden cannot be directly measured as a comparison group with non-FDC triple therapy was not included. Future comparative effectiveness research could compare health-related quality of life in patients receiving combination therapy with those receiving single-drug therapies. Furthermore, this nested-observational study did not include a normotensive comparison group and thus nonspecific symptoms could not be assigned to uncontrolled hypertension. Also, these symptoms were measured only twice, at the start and end of the study, and improvement in symptoms can be affected by regression to the mean. Future studies might include a retrospectively matched normotensive comparison group to better define the proportion of hypertensive patients who experience these symptoms and reduce likelihood of regression to the mean. In conclusion, the study by Schmieder and colleagues describes the impact of uncontrolled hypertension on patient quality of life, including but not limited to the emotional burden of hypertensive therapy and patient-reported nonspecific symptoms. It highlights that hypertensive patients experience underrecognized mental and physical symptoms associated with uncontrolled hypertension. During a 24-month treatment period, FDC therapy was associated with improvement in hypertensive control, quality of life, and nonspecific symptoms. When treating hypertensive patients, clinicians should consider employing combination therapy when appropriate and exploring nonspecific symptoms during counseling of hypertension.