Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Sep 1;41(9):1466-1473.
doi: 10.1097/HJH.0000000000003497. Epub 2023 Jul 5.

Adherence and related cardiovascular outcomes to single pill vs. separate pill administration of antihypertensive triple-combination therapy

Federico Rea  1   2 , Gabriella Morabito  1   2 , Laura Savaré  1   3   4 , Atul Pathak  5 , Giovanni Corrao  1   2 , Giuseppe Mancia  6   7
Affiliations

Adherence and related cardiovascular outcomes to single pill vs. separate pill administration of antihypertensive triple-combination therapy

Federico Rea et al. J Hypertens. .

Abstract

Objective: To compare adherence to antihypertensive treatment between patients prescribed a three-drug single-pill combination (SPC) of perindopril/amlodipine/indapamide (P/A/I) vs. the combination of an angiotensin-converting enzyme inhibitor (ACEI), a calcium-channel blocker (CCB), and a diuretic (D) as a two-drug SPC plus a third drug given separately.

Methods: Using the healthcare utilization database of the Lombardy Region (Italy), the 28 210 patients, aged at least 40 years, who were prescribed P/A/I SPC during 2015-2018 were identified and the date of the first prescription was defined as the index date. For each patient prescribed the SPC, a comparator who started ACEI/CCB/D treatment as a two-pill combination was considered. Adherence to the triple combination was assessed over the year after the index date as the proportion of the follow-up days covered by prescription (PDC). Patients who had a PDC >75% were defined as highly adherent to drug therapy. Log-binomial regression models were fitted to estimate the risk ratio of treatment adherence in relation to the drug treatment strategy.

Results: About 59 and 25% of SPC and two-pill combination users showed high adherence, respectively. Compared with patients under a three-drug two-pill combination, those who were treated with the three-drug SPC had a higher propensity to be highly adherent to the triple combination (2.38, 95% confidence interval: 2.32-2.44). This was the case regardless of the sex, age, comorbidities, and number of co-treatments.

Conclusions: In a real-life setting, patients under three-drug SPC exhibited more frequently a high adherence to antihypertensive treatment than those prescribed a three-drug two-pill combination.

PubMed Disclaimer

Conflict of interest statement

Giovanni Corrao received research support from the European Community (EC), the Italian Medicines Agency (AIFA), Italian Ministry of Health, and the Italian Ministry of Education, University and Research (MIUR). He took part to a variety of projects that were funded by pharmaceutical companies (i.e., Novartis, GSK, Roche, AMGEN, BMS and Servier). He also received honoraria as member of Advisory.

Giuseppe Mancia received honoraria for participation as speaker/chairman in national/international meetings from Bayer, Boehringer Ingelheim, CVRx, Daiichi Sankyo, Ferrer, Medtronic, Menarini Int., Merck, Novartis, Recordati and Servier.

Other authors have no disclosures.

Figures

FIGURE 1
FIGURE 1
Risk ratios (RR), and 95% confidence intervals (CI), estimating the association between high adherence to treatment (PDC > 75%) and single-pill combination vs. the two-pill combination. Three categories were considered for the clinical profile according to the Multisource Comorbidity Score (MCS): good (0 ≤ MCS ≤ 4), intermediate (5 ≤ MCS ≤ 14), and poor (MCS ≥ 15).
FIGURE 2
FIGURE 2
Risk ratios (RR), and 95% confidence intervals (CI), estimating the association between low adherence to treatment (PDC < 25%) and single-pill combination vs. the two-pill combination. Three categories were considered for the clinical profile according to the Multisource Comorbidity Score (MCS): good (0 ≤ MCS ≤ 4), intermediate (5 ≤ MCS ≤ 14), and poor (MCS ≥ 15).
FIGURE 3
FIGURE 3
Risk ratios (RR), and 95% confidence intervals (CI), estimating the association between treatment discontinuation and single-pill combination vs. the two-pill combination. Three categories were considered for the clinical profile according to the Multisource Comorbidity Score (MCS): good (0 ≤ MCS≤4), intermediate (5 ≤ MCS ≤ 14), and poor (MCS ≥ 15).
FIGURE 4
FIGURE 4
Hazard ratios (HR), and 95% confidence intervals (CI), for cardiovascular hospitalization associated with adherence to antihypertensive drugs, after adjustment for the baseline characteristics. Meta-analytic procedures were used for summarized estimates. Adherence categories are: very low (PDC < 25%), low (25% ≤ PDC < 50%), intermediate (50 ≤ PDC ≤ 75%), and high (PDC >75).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al. . ESC National Cardiac Societies; ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2021; 42:3227–3337. - PubMed
    1. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. . Authors/Task Force Members. 2018 ESC/ESH Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: the Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens 2018; 36:1953–2041. - PubMed
    1. Du LP, Cheng ZW, Zhang YX, Li Y, Mei D. The impact of fixed-dose combination versus free-equivalent combination therapies on adherence for hypertension: a meta-analysis. J Clin Hypertens (Greenwich) 2018; 20:902–907. - PMC - PubMed
    1. Burnier M, Egan BM. Adherence in hypertension. Circ Res 2019; 124:1124–1140. - PubMed
    1. Schulz M, Krueger K, Schuessel K, Friedland K, Laufs U, Mueller WE, et al. . Medication adherence and persistence according to different antihypertensive drug classes: a retrospective cohort study of 255,500 patients. Int J Cardiol 2016; 220:668–676. - PubMed

Publication types

MeSH terms