Long-term effect of the triple combination of perindopril, indapamide, and amlodipine on left ventricular hypertrophy in hypertension

Left ventricular hypertrophy in hypertensive patients

Left ventricular hypertrophy is a compensatory mechanism in response to increased wall stress in this part of the heart. Echocardiographic screening has shown that LVH is almost non-existent in healthy individuals, but is present in 7–40% of hypertensive patients, and even up to 50% of these patients if they are over 65 years old. Reducing the left ventricular mass index (LVMI) during antihypertensive treatment represents an important prognostic factor for the occurrence of fatal and non-fatal events. According to several studies, regression of LVH can be achieved using specific classes of antihypertensive agents, namely angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs or sartans), and calcium channel blockers (CCBs), either in monotherapy or in combination.

Study design and patient population

The interventional study included 184 patients with grade 2 essential hypertension, i.e., systolic blood pressure (sBP) > 140 mmHg and diastolic BP (dBP) > 90 mmHg, who had no history of cardiovascular events and whose hypertension was inadequately controlled by prior treatment with a fixed-dose combination of a renin-angiotensin-aldosterone system (RAAS) blocker and a diuretic.

Patients were randomized in a 1:1 ratio and subsequently received either a fixed-dose triple combination of perindopril/indapamide/amlodipine in various doses (5/1.2/5, or 10/2.5/5, or 10/2.5/10 mg once daily depending on initial BP values) or a free triple combination of any RAAS blocker, diuretic, and CCB. Blood pressure measured in the office and via 24-hour monitoring, echocardiographic examinations, and 24-hour BP variability (expressed as the standard deviation of daytime sBP) were monitored at baseline and during treatment.

Baseline characteristics of the treatment groups were comparable. Patients in the free combination group used ACEi in 65% of cases and ARBs in 35%.

Results

Both groups experienced a significant decrease in office-measured and 24-hour monitored BP as well as BP variability over the 14-month follow-up period. However, the resulting BP variability was significantly lower with the fixed triple combination compared to the free combination of antihypertensive agents (14.0 vs. 16.1; p < 0.005).

Similarly, the final LVMI value was lower in the group treated with the fixed triple combination than in the other study arm. The reduction in LVMI was 8.3% in the fixed-dose combination arm compared to 2.0% in the free combination group (p < 0.0001). LVH regression reached 43.5% in the fixed-dose combination group, but only 30.4% in the free combination group (p < 0.05).

Conclusion

Despite comparable blood pressure reductions, the fixed combination of perindopril/indapamide/amlodipine in a single tablet taken once daily reduced LVMI more than the free combination of RAAS blocker, diuretic, and CCB. It also achieved greater regression of LVH. According to the study authors, this may be due to the pleiotropic effects of the administered antihypertensive agents and the lower BP variability achieved with the fixed combination.

The arginine salt-based perindopril evaluated in this study is bioequivalent to the erbumine salt-based perindopril.

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Source: Mazza A., Townsend D. M., Schiavon L. et al. Long-term effect of the perindopril/indapamide/amlodipine single-pill combination on left ventricular hypertrophy in outpatient hypertensive subjects. Biomed Pharmacother 2019; 120: 109539, doi: 10.1016/j.biopha.2019.109539.