The Results of ACES (Antihypertensive Combinations' Long Term Efficacy Comparing Study): Analysis of Metabolic Effects of Antihypertensive Combination Therapies

Abstract

Background: More than 50 % of hypertensive patients have lipid disorders, and one-third of hypertensive patients have impaired glucose metabolism. Owing to the high prevalence of metabolic risk factors and/or comorbidities, antihypertensives with favorable or neutral metabolic effects are preferred. Based on the available evidence, diuretics and β-blockers are heterogeneous regarding their metabolic effects.

Objective: The aim of ACES (Antihypertensive Combinations' Long Term Efficacy Comparing Study) was to compare the efficacy and metabolic effects of a carvedilol/indapamide free combination, a fixed-dose combination of perindopril/amlodipine, and a fixed combination of perindopril/indapamide in everyday practice.

Methods: This study was a 6-month, multi-center, prospective, observational, non-interventional, open-label clinical study. The data of 9124 outpatients (4898 female, 4226 male; mean age 61.7 ± 11.7 years) with mild, moderate, or severe essential (primary) hypertension with one or more metabolic risk factors were subjected to statistical analysis. At visits one (day 1), three (month 3), and four (month 6), the following metabolic parameters were monitored: fasting blood glucose, glycosylated hemoglobin, estimated glomerular filtration rate, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, and serum potassium, sodium, creatinine, and uric acid levels. A total of 3888 patients took perindopril/amlodipine, while 2992 took perindopril/indapamide, and 2244 took a combination of carvedilol/indapamide. Statistical analysis was carried out using the one-paired t test and the Chi square test; the two-sided level of significance was set at 0.05.

Results: The observed changes in the main metabolic parameters were favorable and similar in all therapeutic groups: fasting blood glucose decreased by 5.5-5.5-5.5 %, total cholesterol by 9.0-10.2-9.9 %, and triglycerides by 12.7-15.4-13.8 % (respectively in perindopril/amlodipine, perindopril/indapamide and carvedilol/indapamide groups).

Conclusions: Based on our findings, we conclude that the metabolic profile of indapamide is very similar to the metabolically neutral and well-documented metabolic profiles of the calcium-channel blocker amlodipine and the vasodilator β-blocker carvedilol and that all the combinations studied had similar beneficial effects on the main metabolic parameters. The favorable changes of metabolic parameters are because of the discontinuation of active substances (e.g., conventional thiazides, second-generation β-blockers) used in the previous therapy, which were associated with unfavorable metabolic effects, and to the increase in the ratio of administered lipid-lowering drugs and oral antidiabetic drugs.