Date of Award
Master of Physician Assistant Studies
Physician Assistant Education
Currently, 1 in 5 U.S. adults are not aware that they have HTN; thus, a minimum of 20% of patients have BPs that are not at goal.7 With such a large number of patients untreated and uncontrolled, efforts have been made to improve patient attainment of these BP goals. Single-pill fixed-dose combination drugs were made available for this purpose. This option reduces medical costs for patients, increases medication compliance, and provides greater therapeutic results. Looking at trends for fixed-dose combination antihypertensive therapy, a commonly used formulation is a thiazide diuretic combined with an ARB.
Per the European Society of Hypertension-European Society of Cardiology guidelines, agents used in combination therapy are more effective when they have complementary mechanisms of action, such as those that occur between a thiazide and an ARB.9 While a thiazide works in the kidney to inhibit sodium reabsorption and increase sodium and water excretion, an ARB blocks angiotensin II receptor effects on cells. ARBs block the vasoconstriction and aldosterone-secretion effects of angiotensin II, consequently inhibiting reabsorption of sodium and water at the distal tubules of the kidneys.10,11 These two drug classes work in conjunction to ultimately lower BP. While the current guidelines suggest that most patients with uncontrolled BP will require two antihypertensive drugs, the next questions to answer are how much of each drug is needed and what numerical drop in BP is required for an effective combination. The dose-dependent side effects of these drugs should also be considered. In particular, some providers find no benefit in treating patients with the lowest dose of hydrochlorothiazide (HCTZ), a common antihypertensive thiazide currently used in practice, and instead start treatment with a moderate dose of HCTZ. On the contrary, some providers find there is no difference in BP lowering effects when comparing low versus moderate HCTZ dosing. This anecdotal information poses the question of whether BP is lowered more effectively with 25 mg of HCTZ compared to 12.5 mg of HCTZ, when used in dual therapy with an ARB, over a minimum course of 8 weeks.
Diep, Amanda Amy, "Is more always better? Efficacy of HCTZ, low versus high dose therapy in dual combination treatment for hypertension" (2019). Physician's Assistant Program Capstones. 14.