Perindopril, Amlodipine, and Indapamide combination significantly lowers Blood Pressure: Brisighella Heart Study

Italy: Triple combination of perindopril/amlodipine/indapamide lowers blood pressure (BP) and preserves patients' metabolic profile better than all other triple antihypertensive medication, recent results of the Brisighella Heart Study have found.

The study which has been published in the latest issue of the Journal of Clinical Medicine is one of the first kinds of study on the long-term effects of different triple antihypertensive treatment strategies in real clinical practice.

The outcome will have a great impact on the management of cardiovascular disease (CVD) since a 5 mmHg reduction in systolic blood pressure is known to decrease the risk for major cardiovascular (CV) events (MACE) by about 10%, regardless of the previous history of CVD and even in patients with normal to high-normal BP.

The use of combination therapy with renin-angiotensin system (RAS) inhibitors, calcium antagonists, diuretics, and the addition of a third agent (usually a diuretic) to the RAS modulator and calcium antagonist for BP control and CV risk is backed by indirect evidence and small clinical trials.

With the given background, the Brisighella Heart Study was carried out in order to evaluate clinical, laboratory, and hemodynamic effects in the long term of different triple combination antihypertensive medications.

For the analysis, the researchers considered the data of a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. In the analysis, 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/thiazidelike diuretics were excluded.

The remaining participants were divided into three categories depending on whether they are 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 group of age- and sex-matched volunteers were made as controls and included patients receiving other antihypertensive treatments. The comparison was done of the long-term (12 years) effects of the different antihypertensive treatments among the pre-defined group.

Based on the study, the researchers reported the following findings:

• During the observation period, there was a trend towards an increase in both systolic and diastolic blood pressure (BP) in all the investigated subgroups.
• The combination treatment with renin-angiotensin system (RAS) modulators, CCBs, and thiazide/thiazide-like diuretics was associated with significantly lower diastolic BP and more strictly controlled lipid pattern than other triple combinations of anti-hypertensive medications.
• Perindopril/Amlodipine/Indapamide was associated with significantly lower diastolic BP and more strictly control lipid patterns.
• Patients treated with Perindopril/Amlodipine/Indapamide showed a better protective metabolic profile than any other antihypertensive combinations with no impact on total cholesterols and no impact on uric acids.
• Most importantly, better target organ protection and a lower number of MACE were observed compared to the ARB-based single-pill combination.
• Patients treated with Perindopril/Amlodipine/Indapamide did not experience any age-related increase in serum levels of total cholesterol.
• The percentage of people reaching a BP < 140/90 mmHg was 65% among ACE-inhibitors/CCBs/Thiazide-treated subjects, compared with 59% among subjects treated with ARBs/CCBs/Thiazide and compared with 69% among subjects in treatment with Perindopril/Amlodipine/Indapamide, compared with 58% among subjects treated with any other considered combination antihypertensive medications.
• 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.

"These results are in line with previous findings from large clinical trials, showing no negative metabolic effects of the triple-drug therapy Perindopril/Amlodipine/Indapamide," the paper concluded.

"Perindopril/Amlodipine/Indapamide combo is associated with a more protective metabolic profile than any other considered combination antihypertensive medications.

Giving an explanation for this, the authors wrote, "it was seen that their use is not related to any age-related increase in serum levels of total cholesterol. Also, during the follow-up, they neither developed type 2 diabetes nor had a need for a greater number of antihypertensive drugs to improve BP control,"

In conclusion, the study found combination treatment with RAS modulators, amlodipine, and thiazides/thiazide-like diuretics is mildly but significantly better than other combinations of antihypertensive drugs for lowering BP, and has a better impact on serum lipids. Perindopril/amlodipine/indapamide is associated with a better metabolic profile than any other considered combination of antihypertensive medications

Reference: Cicero, A., Fogacci, F., Rizzoli, E., D'Addato, S., & Borghi, C. (2021). Long-Term Impact of Different Triple Combination Antihypertensive Medications on Blood Pressure Control, Metabolic Pattern and Incident Events: Data from the Brisighella Heart Study. Journal of clinical medicine, 10(24), 5921. https://doi.org/10.3390/jcm10245921