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Published in: Advances in Therapy 1/2024

Open Access 21-10-2023 | Perindopril | Original Research

A Retrospective Observational Real-Word Analysis of the Adherence, Healthcare Resource Consumption and Costs in Patients Treated with Bisoprolol/Perindopril as Single-Pill or Free Combination

Authors: Stefano Masi, Zhanna Kobalava, Chiara Veronesi, Elisa Giacomini, Luca Degli Esposti, Konstantinos Tsioufis

Published in: Advances in Therapy | Issue 1/2024

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Abstract

Introduction

The present real-world analysis aims to compare the drug utilization, hospitalizations and direct healthcare costs related to the use of single-pill combination (SPC) or free-equivalent combination (FEC) of perindopril and bisoprolol (PER/BIS) in a large Italian population.

Methods

This observational retrospective analysis was based on administrative databases covering approximately 7 million subjects across Italy. All adult subjects receiving PER/BIS as SPC or FEC between January 2017–June 2020 were included. Subjects were followed for 1 year after the first prescription of PER/BIS as FEC (± 1 month) or SPC. Before comparing the SPC and FEC cohorts, propensity score matching (PSM) was applied to balance the baseline characteristics. Drug utilization was investigated as adherence (defined by the proportion of days covered, PDC) and persistence (evaluated by Kaplan-Meier curves). Hospitalizations and mean annual direct healthcare costs (due to drug prescriptions, hospitalizations and use of outpatient services) were analyzed during follow-up.

Results

The original cohort included 11,440 and 6521 patients taking the SPC and FEC PER/BIS combination, respectively. After PSM, two balanced SPC and FEC cohorts of 4688 patients were obtained (mean age 70 years, approximately 50% male, 24% in secondary prevention). The proportion of adherent patients (PDC ≥ 80%) was higher for those on SPC (45.5%) than those on FEC (38.6%), p < 0.001. The PER/BIS combination was discontinued by 35.8% of patients in the SPC cohort and 41.7% in the FEC cohort (p < 0.001). The SPC cohort had fewer cardiovascular (CV) hospitalizations (5.3%) than the free-combination cohort (7.4%), p < 0.001. Mean annual total healthcare costs were lower in the SPC (1999€) than in the FEC (2359€) cohort (p < 0.001).

Conclusion

In a real-world setting, patients treated with PER/BIS SPC showed higher adherence, lower risk of drug discontinuation, reduced risk of CV hospitalization, and lower healthcare costs than those on FEC of the same drugs.
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Literature
1.
go back to reference Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study. J Am Coll Cardiol. 2020;76:2982–3021.PubMedPubMedCentralCrossRef Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study. J Am Coll Cardiol. 2020;76:2982–3021.PubMedPubMedCentralCrossRef
2.
go back to reference Dzau VJ, Antman EM, Black HR, Hayes DL, Manson JE, Plutzky J, et al. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part I: pathophysiology and clinical trial evidence (risk factors through stable coronary artery disease). Circulation. 2006;114:2850–70.PubMedCrossRef Dzau VJ, Antman EM, Black HR, Hayes DL, Manson JE, Plutzky J, et al. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part I: pathophysiology and clinical trial evidence (risk factors through stable coronary artery disease). Circulation. 2006;114:2850–70.PubMedCrossRef
3.
go back to reference Dzau VJ, Antman EM, Black HR, Hayes DL, Manson JE, Plutzky J, et al. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part II: clinical trial evidence (acute coronary syndromes through renal disease) and future directions. Circulation. 2006;114:2871–91.PubMedCrossRef Dzau VJ, Antman EM, Black HR, Hayes DL, Manson JE, Plutzky J, et al. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part II: clinical trial evidence (acute coronary syndromes through renal disease) and future directions. Circulation. 2006;114:2871–91.PubMedCrossRef
4.
go back to reference Cody RJ. The sympathetic nervous system and the renin-angiotensin-aldosterone system in cardiovascular disease. Am J Cardiol. 1997;80:9J-14J.PubMedCrossRef Cody RJ. The sympathetic nervous system and the renin-angiotensin-aldosterone system in cardiovascular disease. Am J Cardiol. 1997;80:9J-14J.PubMedCrossRef
5.
go back to reference Seravalle G, Grassi G. Sympathetic nervous system and hypertension: new evidences. Auton Neurosci. 2022;238: 102954.PubMedCrossRef Seravalle G, Grassi G. Sympathetic nervous system and hypertension: new evidences. Auton Neurosci. 2022;238: 102954.PubMedCrossRef
6.
go back to reference Mancia G, Kjeldsen SE, Kreutz R, Pathak A, Grassi G, Esler M. Individualized beta-blocker treatment for high blood pressure dictated by medical comorbidities: indications beyond the 2018 European Society of cardiology/European Society of hypertension guidelines. Hypertension. 2022;79:1153–66.PubMedCrossRef Mancia G, Kjeldsen SE, Kreutz R, Pathak A, Grassi G, Esler M. Individualized beta-blocker treatment for high blood pressure dictated by medical comorbidities: indications beyond the 2018 European Society of cardiology/European Society of hypertension guidelines. Hypertension. 2022;79:1153–66.PubMedCrossRef
7.
go back to reference van Vark LC, Bertrand M, Akkerhuis KM, Brugts JJ, Fox K, Mourad J-J, et al. Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients. Eur Heart J. 2012;33:2088–97.PubMedPubMedCentralCrossRef van Vark LC, Bertrand M, Akkerhuis KM, Brugts JJ, Fox K, Mourad J-J, et al. Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients. Eur Heart J. 2012;33:2088–97.PubMedPubMedCentralCrossRef
8.
go back to reference Mancia Chairperson G, Kreutz Co-Chair R, Brunström M, Burnier M, Grassi G, Januszewicz A, et al. 2023 ESH Guidelines for the management of arterial hypertension the task force for the management of arterial hypertension of the European Society of Hypertension Endorsed by the European Renal Association (ERA) and the International Society of Hypertension (ISH). J Hypertens. 2023;2:2. Mancia Chairperson G, Kreutz Co-Chair R, Brunström M, Burnier M, Grassi G, Januszewicz A, et al. 2023 ESH Guidelines for the management of arterial hypertension the task force for the management of arterial hypertension of the European Society of Hypertension Endorsed by the European Renal Association (ERA) and the International Society of Hypertension (ISH). J Hypertens. 2023;2:2.
9.
go back to reference Chowdhury R, Khan H, Heydon E, Shroufi A, Fahimi S, Moore C, et al. Adherence to cardiovascular therapy: a meta-analysis of prevalence and clinical consequences. Eur Heart J. 2013;34:2940–8.PubMedCrossRef Chowdhury R, Khan H, Heydon E, Shroufi A, Fahimi S, Moore C, et al. Adherence to cardiovascular therapy: a meta-analysis of prevalence and clinical consequences. Eur Heart J. 2013;34:2940–8.PubMedCrossRef
10.
go back to reference Kolandaivelu K, Leiden BB, O’Gara PT, Bhatt DL. Non-adherence to cardiovascular medications. Eur Heart J. 2014;35:3267–76.PubMedCrossRef Kolandaivelu K, Leiden BB, O’Gara PT, Bhatt DL. Non-adherence to cardiovascular medications. Eur Heart J. 2014;35:3267–76.PubMedCrossRef
11.
go back to reference Moise N, Schwartz J, Bring R, Shimbo D, Kronish IM. Antihypertensive drug class and adherence: an electronic monitoring study. Am J Hypertens. 2015;28:717–21.PubMedCrossRef Moise N, Schwartz J, Bring R, Shimbo D, Kronish IM. Antihypertensive drug class and adherence: an electronic monitoring study. Am J Hypertens. 2015;28:717–21.PubMedCrossRef
12.
go back to reference Kronish IM, Woodward M, Sergie Z, Ogedegbe G, Falzon L, Mann DM. Meta-analysis: impact of drug class on adherence to antihypertensives. Circulation. 2011;123:1611–21.PubMedPubMedCentralCrossRef Kronish IM, Woodward M, Sergie Z, Ogedegbe G, Falzon L, Mann DM. Meta-analysis: impact of drug class on adherence to antihypertensives. Circulation. 2011;123:1611–21.PubMedPubMedCentralCrossRef
13.
go back to reference Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, et al. 2020 international society of hypertension global hypertension practice guidelines. Hypertension. 2020;75:1334–57.PubMedCrossRef Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, et al. 2020 international society of hypertension global hypertension practice guidelines. Hypertension. 2020;75:1334–57.PubMedCrossRef
14.
go back to reference Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018;39:3021–104.PubMedCrossRef Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018;39:3021–104.PubMedCrossRef
15.
go back to reference Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41:111–88.PubMedCrossRef Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41:111–88.PubMedCrossRef
16.
go back to reference Mancia G, Rea F, Corrao G, Grassi G. Two-drug combinations as first-step antihypertensive treatment. Circ Res. 2019;124:1113–23.PubMedCrossRef Mancia G, Rea F, Corrao G, Grassi G. Two-drug combinations as first-step antihypertensive treatment. Circ Res. 2019;124:1113–23.PubMedCrossRef
17.
go back to reference Parati G, Kjeldsen S, Coca A, Cushman WC, Wang J. Adherence to single-pill versus free-equivalent combination therapy in hypertension. Hypertension. 2021;77:692–705.PubMedCrossRef Parati G, Kjeldsen S, Coca A, Cushman WC, Wang J. Adherence to single-pill versus free-equivalent combination therapy in hypertension. Hypertension. 2021;77:692–705.PubMedCrossRef
18.
go back to reference Degli Esposti L, Perrone V, Veronesi C, Gambera M, Nati G, Perone F, et al. Modifications in drug adherence after switch to fixed-dose combination of perindopril/amlodipine in clinical practice. Results of a large-scale Italian experience. The amlodipine-perindopril in real settings (AMPERES) study. 2018;34:1571–7. Degli Esposti L, Perrone V, Veronesi C, Gambera M, Nati G, Perone F, et al. Modifications in drug adherence after switch to fixed-dose combination of perindopril/amlodipine in clinical practice. Results of a large-scale Italian experience. The amlodipine-perindopril in real settings (AMPERES) study. 2018;34:1571–7.
19.
go back to reference Borghi C, Jayagopal PB, Konradi A, Bortolotto LA, Degli Esposti L, Perrone V, et al. Adherence to triple single-pill combination of perindopril/indapamide/amlodipine: findings from real-world analysis in Italy. Adv Ther. 2023;40:1765–72.PubMedPubMedCentralCrossRef Borghi C, Jayagopal PB, Konradi A, Bortolotto LA, Degli Esposti L, Perrone V, et al. Adherence to triple single-pill combination of perindopril/indapamide/amlodipine: findings from real-world analysis in Italy. Adv Ther. 2023;40:1765–72.PubMedPubMedCentralCrossRef
20.
go back to reference Zhang Z, Kim HJ, Lonjon G, Zhu Y. Written on behalf of AME Big-Data Clinical Trial Collaborative Group. Balance diagnostics after propensity score matching. Ann Transl Med. 2019;7:16.PubMedPubMedCentralCrossRef Zhang Z, Kim HJ, Lonjon G, Zhu Y. Written on behalf of AME Big-Data Clinical Trial Collaborative Group. Balance diagnostics after propensity score matching. Ann Transl Med. 2019;7:16.PubMedPubMedCentralCrossRef
21.
go back to reference Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, et al. 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41:407–77.PubMedCrossRef Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, et al. 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41:407–77.PubMedCrossRef
22.
go back to reference McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42:3599–726.PubMedCrossRef McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42:3599–726.PubMedCrossRef
23.
go back to reference Foch C, Allignol A, Hohenberger T, Boutmy E, Schaefer S, Hostalek U. Effectiveness of bisoprolol versus other β-blockers and other antihypertensive classes: a cohort study in the clinical practice research Datalink. J Compar Effectiv Res. 2022;11:423–36.CrossRef Foch C, Allignol A, Hohenberger T, Boutmy E, Schaefer S, Hostalek U. Effectiveness of bisoprolol versus other β-blockers and other antihypertensive classes: a cohort study in the clinical practice research Datalink. J Compar Effectiv Res. 2022;11:423–36.CrossRef
24.
go back to reference Sabidó M, Hohenberger T, Grassi G. Pharmacological intervention in hypertension using beta-blockers: real-world evidence for long-term effectiveness. Pharmacol Res. 2018;130:191–7.PubMedCrossRef Sabidó M, Hohenberger T, Grassi G. Pharmacological intervention in hypertension using beta-blockers: real-world evidence for long-term effectiveness. Pharmacol Res. 2018;130:191–7.PubMedCrossRef
25.
go back to reference Mancia G, Grassi G. Systolic and diastolic blood pressure control in antihypertensive drug trials. J Hypertens. 2002;20:1461–4.PubMedCrossRef Mancia G, Grassi G. Systolic and diastolic blood pressure control in antihypertensive drug trials. J Hypertens. 2002;20:1461–4.PubMedCrossRef
26.
go back to reference Tocci G, Ferrucci A, Pontremoli R, Ferri C, Rosei EA, Morganti A, et al. Blood pressure levels and control in Italy: comprehensive analysis of clinical data from 2000–2005 and 2005–2011 hypertension surveys. J Hum Hypertens. 2015;29:696–701.PubMedCrossRef Tocci G, Ferrucci A, Pontremoli R, Ferri C, Rosei EA, Morganti A, et al. Blood pressure levels and control in Italy: comprehensive analysis of clinical data from 2000–2005 and 2005–2011 hypertension surveys. J Hum Hypertens. 2015;29:696–701.PubMedCrossRef
27.
go back to reference Murray CJL, Aravkin AY, Zheng P, Abbafati C, Abbas KM, Abbasi-Kangevari M, et al. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet. 2020;396:1223–49.CrossRef Murray CJL, Aravkin AY, Zheng P, Abbafati C, Abbas KM, Abbasi-Kangevari M, et al. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet. 2020;396:1223–49.CrossRef
28.
go back to reference Vos T, Lim SS, Abbafati C, Abbas KM, Abbasi M, Abbasifard M, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396:1204–22.CrossRef Vos T, Lim SS, Abbafati C, Abbas KM, Abbasi M, Abbasifard M, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396:1204–22.CrossRef
29.
go back to reference Rea F, Cantarutti A, Merlino L, Ungar A, Corrao G, Mancia G. Antihypertensive treatment in elderly frail patients: evidence from a large Italian database. Hypertension. 2020;76:442–9.PubMedCrossRef Rea F, Cantarutti A, Merlino L, Ungar A, Corrao G, Mancia G. Antihypertensive treatment in elderly frail patients: evidence from a large Italian database. Hypertension. 2020;76:442–9.PubMedCrossRef
30.
go back to reference Naderi SH, Bestwick JP, Wald DS. Adherence to drugs that prevent cardiovascular disease: meta-analysis on 376,162 patients. Am J Med. 2012;125:882–7.PubMedCrossRef Naderi SH, Bestwick JP, Wald DS. Adherence to drugs that prevent cardiovascular disease: meta-analysis on 376,162 patients. Am J Med. 2012;125:882–7.PubMedCrossRef
31.
go back to reference Kirsch F, Becker C, Kurz C, Schwettmann L, Schramm A. Effects of adherence to pharmacological secondary prevention after acute myocardial infarction on health care costs—an analysis of real-world data. BMC Health Serv Res. 2020;20:1145.PubMedPubMedCentralCrossRef Kirsch F, Becker C, Kurz C, Schwettmann L, Schramm A. Effects of adherence to pharmacological secondary prevention after acute myocardial infarction on health care costs—an analysis of real-world data. BMC Health Serv Res. 2020;20:1145.PubMedPubMedCentralCrossRef
32.
go back to reference Rea F, Corrao G, Merlino L, Mancia G. Early cardiovascular protection by initial two-drug fixed-dose combination treatment vs monotherapy in hypertension. Eur Heart J. 2018;39:3654–61.PubMedCrossRef Rea F, Corrao G, Merlino L, Mancia G. Early cardiovascular protection by initial two-drug fixed-dose combination treatment vs monotherapy in hypertension. Eur Heart J. 2018;39:3654–61.PubMedCrossRef
33.
go back to reference Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41–55.CrossRef Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41–55.CrossRef
34.
go back to reference Corrao G, Mancia G. Research strategies in treatment of hypertension: value of retrospective real-life data. Eur Heart J. 2022;43:3312–22.PubMedCrossRef Corrao G, Mancia G. Research strategies in treatment of hypertension: value of retrospective real-life data. Eur Heart J. 2022;43:3312–22.PubMedCrossRef
35.
go back to reference Wang SV, Schneeweiss S, Initiative RCT-DUPLICATE, Franklin JM, Desai RJ, Feldman W, et al. Emulation of randomized clinical trials with nonrandomized database analyses: results of 32 clinical trials. JAMA. 2023;329:1376.PubMedPubMedCentralCrossRef Wang SV, Schneeweiss S, Initiative RCT-DUPLICATE, Franklin JM, Desai RJ, Feldman W, et al. Emulation of randomized clinical trials with nonrandomized database analyses: results of 32 clinical trials. JAMA. 2023;329:1376.PubMedPubMedCentralCrossRef
Metadata
Title
A Retrospective Observational Real-Word Analysis of the Adherence, Healthcare Resource Consumption and Costs in Patients Treated with Bisoprolol/Perindopril as Single-Pill or Free Combination
Authors
Stefano Masi
Zhanna Kobalava
Chiara Veronesi
Elisa Giacomini
Luca Degli Esposti
Konstantinos Tsioufis
Publication date
21-10-2023
Publisher
Springer Healthcare
Published in
Advances in Therapy / Issue 1/2024
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-023-02707-7

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