Abstract
We aim to investigate sex differences in blood concentrations of spironolactone and the active metabolite canrenone in resistant hypertension patients. Furthermore, sex differences in adherence for spironolactone and other antihypertensive drugs (AHDs) were studied. The patients in this post hoc study had all participated in a single-blind randomized controlled trial called RHYME-RCT (Dutch Trial Register, NL6736). Concentrations in blood of several AHDs were assessed in RHYME-RCT to investigate adherence to treatment. This allowed for a comparison of drug exposure to spironolactone and canrenone between males and females. In linear regression models, no statistically significant sex differences (N = 35) in spironolactone (B =−10.23, SE = 7.92, p = 0.206) or canrenone (B = 1.24, SE = 10.96, p = 0.911) concentrations after adjustment for dose and time between sampling and intake were found. Furthermore, no statistically significant differences in non-adherence to spironolactone were found between sexes (N = 54, male 15% vs. female 38%, p = 0.100), but non-adherence to spironolactone was associated with non-adherence to other AHDs (p ≤ 0.001). Spironolactone and canrenone concentrations were not different between males and females with resistant hypertension. Although not statistically significant, females were twice as likely to be non-adherent to spironolactone compared to males, and thereby also more likely to be non-adherent to other AHDs.
Highlights
Optimal pharmacological treatment is an important contributor in the management of hypertension to decrease the risk of cardiovascular diseases and death [1]
Around 12–15% of all patients diagnosed with hypertension do not reach their blood pressure goals and, depending on the drug class, 3–7% of the patients discontinue antihypertensive drug therapy due to adverse events [2,3] other factors that have an influence on the variation in response to antihypertensive drug use should be taken into account
We showed that females had higher blood concentrations of canrenone, the active metabolite of spironolactone, after correction of the dose, time between intake and sampling, age, and body mass index (BMI)
Summary
Optimal pharmacological treatment is an important contributor in the management of hypertension to decrease the risk of cardiovascular diseases and death [1]. Recent research has indicated that males and females react differently to antihypertensive drug use due to differences in pharmacokinetics (PK) and pharmacodynamics (PD). This could potentially explain part of the variation in response to antihypertension drugs, which makes sex an interesting target to investigate and improve pharmacological treatment in patient with hypertension [4,5,6,7]
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