Abstract
The aim of this study was to comparatively evaluate clinical, laboratory and hemodynamic effects on the long term of different triple combination antihypertensive medications in a well-characterized Italian cohort. We considered the data of a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. For the current analysis, we excluded normotensive subjects, patients treated with <3 or ≥3 antihypertensive drugs without taking angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium-channel blockers (CCB) and/or thiazide/thiazide-like diuretics. The remaining participants were divided into three groups depending on whether they were treated with Perindopril/Amlodipine/Indapamide, ACE-inhibitors (other than perindopril)/CCBs/Thiazide or ARBs/CCBs/Thiazide, either with separate drugs or fixed pill combinations. A further group of age- and sex-matched volunteers was selected as control and included patients receiving other antihypertensive treatments. The long-term (12 years) effects of the different antihypertensive treatments were compared among the pre-defined groups. During the observation period, there was a trend towards increase in both systolic and diastolic blood pressure (BP) in all the investigated subgroups (p for trend <0.05), but in the subgroup of patients treated with Perindopril/Amlodipine/Indapamide, such increase was significantly lower than in the other groups (p < 0.05). The combination treatment with renin-angiotensin system (RAS) modulators, CCBs and thiazide/thiazide-like diuretics was associated with significantly lower diastolic BP (p < 0.05) and more strictly controlled lipid pattern than other triple combination of anti-hypertensive medications. Patients treated with Perindopril/Amlodipine/Indapamide did not experience any age-related increase in serum levels of total cholesterol. Moreover, during the follow up none of them developed type 2 diabetes, nor had a need for a greater number of antihypertensive drugs to improve BP control, mainly because of a more stable BP control. Based on our observations, combination treatment with RAS modulators, amlodipine and thiazides/thiazide-like diuretics is more effective than other triple antihypertensive medications for lowering the diastolic BP and has a better impact on serum lipids. Perindopril/Amlodipine/Indapamide is associated with more protective metabolic profile than any other considered combination antihypertensive medications.