Advertisement

Adherence to Triple-Free-Drug Combination Therapies Among Patients With Cardiovascular Disease

Published:February 06, 2020DOI:https://doi.org/10.1016/j.amjcard.2020.01.036
      Combination therapies are often needed to modify the concomitant risk factors for cardiovascular disease. Nonadherence to cardiovascular medications is a relevant concern, especially in polytherapy. We conducted a population-based, cohort study with the aim of quantifying the level of adherence and its related determinants in patients exposed to free 3-drug combination therapies, namely concurrent use of angiotensin-converting-enzyme inhibitor (ACEi), calcium channel blocker (CCB), and statin or of ACEi, statin, and low-dose aspirin. Within Health Search Database, we selected a cohort of adult patients concurrently prescribed with ACEi, CCB, and statin, as well as those prescribed with ACEi, statin and low-dose aspirin, from the January 1, 2002 to the December 31, 2014. Adherent patients were concurrent users of triple free pill regimen with a proportion of days covered ≥80% during 1-year follow-up; demographics and clinical determinants of 1-year adherence were identified by multivariate logistic regression. We found that more than half of patients prescribed with triple free drug combination therapy with ACEi plus CCB plus statin or ACEi plus statin plus low-dose aspirin, were found to be nonadherent to these treatments. Males and patients at high/very-high cardiovascular risk were more likely to be adherent, whereas depression and atrial fibrillation were associated with nonadherence. Our findings indicate that sex, cardiovascular risk, presence of atrial fibrillation, and depression can influence adherence to polytherapy. In conclusion, given that patients suffering from multiple cardiovascular risk factors are at higher risk of fatal events, strategies are needed to improve medication adherence to combination therapies.
      To read this article in full you will need to make a payment

      References

      1. Anon. World Health Statistics 2009. Table 2: cause-specific mortality and morbidity. Available at: https://www.who.int/whosis/whostat/EN_WHS09_Table2.pdf. Accessed on September 26, 2019.

        • Lonn E
        • Bosch J
        • Teo KK
        • Pais P
        • Xavier D
        • Yusuf S
        The polypill in the prevention of cardiovascular diseases: key concepts, current status, challenges, and future directions.
        Circulation. 2010; 122: 2078-2088
        • Marengoni A
        • Melis RJF
        • Prados Torres A
        • Onder G
        Multimorbidity: epidemiology and models of care.
        Biomed Res Int. 2016; 20167029027
        • Cimmaruta D
        • Lombardi N
        • Borghi C
        • Rosano G
        • Rossi F
        • Mugelli A
        Polypill, hypertension and medication adherence: the solution strategy?.
        Int J Cardiol. 2018; 252: 181-186
        • Bahiru E
        • Cates AN de
        • Farr MR
        • Jarvis MC
        • Palla M
        • Rees K
        • Ebrahim S
        • Huffman MD
        Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular diseases.
        Cochrane Database Syst Rev. 2017; 3CD009868
        • Castellano JM
        • Sanz G
        • Fernandez Ortiz A
        • Garrido E
        • Bansilal S
        • Fuster V
        A polypill strategy to improve global secondary cardiovascular prevention: from concept to reality.
        J Am Coll Cardiol. 2014; 64: 613-621
        • Cricelli C
        • Mazzaglia G
        • Samani F
        • Marchi M
        • Sabatini A
        • Nardi R
        • Ventriglia G
        • Caputi AP
        Prevalence estimates for chronic diseases in Italy: exploring the differences between self-report and primary care databases.
        J Public Health Med. 2003; 25: 254-257
        • Filippi A
        • Vanuzzo D
        • Bignamini AA
        • Mazzaglia G
        • Cricelli C
        • Catapano AL
        The database of Italian general practitioners allows a reliable determination of the prevalence of myocardial infarction.
        Ital Heart J. 2005; 6: 311-314
      2. ENCePP. Resources Database. Available at: http://www.encepp.eu/encepp/resourcesDatabase.jsp. Accessed on January 24, 2020.

        • Levi M
        • Pasqua A
        • Cricelli I
        • Cricelli C
        • Piccinni C
        • Parretti D
        • Lapi F
        Patient adherence to olmesartan/amlodipine combinations: fixed versus extemporaneous combinations.
        J Manag Care Spec Pharm. 2016; 22: 255-262
        • Xie L
        • Frech-Tamas F
        • Marrett E
        • Baser O
        A medication adherence and persistence comparison of hypertensive patients treated with single-, double- and triple-pill combination therapy.
        Curr Med Res Opin. 2014; 30: 2415-2422
        • Conroy RM
        • Pyörälä K
        • Fitzgerald AP
        • Sans S
        • Menotti A
        • De Backer G
        • De Bacquer D
        • Ducimetière P
        • Jousilahti P
        • Keil U
        • Njølstad I
        • Oganov RG
        • Thomsen T
        • Tunstall-Pedoe H
        • Tverdal A
        • Wedel H
        • Whincup P
        • Witheimsen L
        • Graham IM
        Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project.
        Eur Heart J. 2003; 24: 987-1003
        • ISTAT
        Retribuzioni Orarie Dei Dipendenti Del Settore Privato.
        2019 (Available at:) (Accessed on January 24, 2020)
        • Geest S De
        • Sabaté E
        Adherence to long-term therapies: Evidence for action.
        Eur J Cardiovasc Nurs. 2003; 2: 323
        • Abegaz TM
        • Shehab A
        • Gebreyohannes EA
        • Bhagavathula AS
        • Elnour AA
        Nonadherence to antihypertensive drugs.
        Medicine (Baltimore). 2017; 96: e5641
        • Corrao G
        • Parodi A
        • Nicotra F
        • Zambon A
        • Merlino L
        • Cesana G
        • Mancia G
        Better compliance to antihypertensive medications reduces cardiovascular risk.
        J Hypertens. 2011; 29: 610-618
        • Chowdhury R
        • Khan H
        • Heydon E
        • Shroufi A
        • Fahimi S
        • Moore C
        • Stricker B
        • Mendis S
        • Hofman A
        • Mant J
        • Franco OH
        Adherence to cardiovascular therapy: a meta-analysis of prevalence and clinical consequences.
        Eur Heart J. 2013; 34: 2940-2948
        • Lemstra M
        • Alsabbagh W
        Proportion and risk indicators of nonadherence to antihypertensive therapy: a meta-analysis.
        Patient Prefer Adherence. 2014; 8: 211
        • Manteuffel M
        • Williams S
        • Chen W
        • Verbrugge RR
        • Pittman DG
        • Steinkellner A
        Influence of patient sex and gender on medication use, adherence, and prescribing alignment with guidelines.
        J Women's Heal. 2014; 23: 112-119
        • Lewey J
        • Shrank WH
        • Bowry ADK
        • Kilabuk E
        • Brennan TA
        • Choudhry NK
        Gender and racial disparities in adherence to statin therapy: a meta-analysis.
        Am Heart J. 2013; 165: 665-678.e1
        • Poluzzi E
        • Strahinja P
        • Lanzoni M
        • Vargiu A
        • Silvani MC
        • Motola D
        • Gaddi A
        • Vaccheri A
        • Montanaro N
        Adherence to statin therapy and patients’ cardiovascular risk: a pharmacoepidemiological study in Italy.
        Eur J Clin Pharmacol. 2008; 64: 425-432
        • Gehi A
        • Haas D
        • Pipkin S
        • Whooley MA
        Depression and medication adherence in outpatients with coronary heart disease: findings from the Heart and Soul Study.
        Arch Intern Med. 2005; 165: 2508-2513
        • Stoehr GP
        • Lu S-Y
        • Lavery L
        • Bilt JV
        • Saxton JA
        • Chang C-CH
        • Ganguli M
        Factors associated with adherence to medication regimens in older primary care patients: the Steel Valley Seniors Survey.
        Am J Geriatr Pharmacother. 2008; 6: 255-263
        • Brieger D
        • Chow C
        • Gullick J
        • Hyun K
        • D'Souza M
        • Briffa T
        • CONCORDANCE Investigators
        Improving patient adherence to secondary prevention medications 6 months after an acute coronary syndrome: observational cohort study.
        Intern Med J. 2018; 48: 541-549
        • Keenan J
        Improving adherence to medication for secondary cardiovascular disease prevention.
        Eur J Prev Cardiol. 2017; 24: 29-35
        • Anon. Novartis Europharm Limited
        Exforge HCT Film-Coated Tablets: EU Summary of Product Characteristics.
        2014 (Available at:) (Accessed on September 27, 2018)
        • Anon. Les Laboratoires Servier
        Triveram Film-Coated Tablets: IT Summary of Product Characteristics.
        2016 (Available at:) (Accessed on September 27, 2018)
        • World Health Organisation
        Global action plan for the prevention and control of noncommunicable diseases 2013-2020.
        World Heal Organ. 2013; (Available at:)
        • Williams B
        • Mancia G
        • Spiering W
        • Agabiti Rosei E
        • Azizi M
        • Burnier M
        • Clement DL
        • Coca A
        • de Simone G
        • Dominiczak A
        • Kahan T
        • Mahfoud F
        • Redon J
        • Ruilope L
        • Zanchetti A
        • Kerins M
        • Kjeldsen SE
        • Kreutz R
        • Laurent S
        • Lip GYH
        • McManus R
        • Narkiewicz K
        • Ruschitzka F
        • Schmieder RE
        • Shlyakhto E
        • Tsioufis C
        • Aboyans V
        • Desormais I
        • De Backer G
        • Heagerty AM
        • Agewall S
        • Bochud M
        • Borghi C
        • Boutouyrie P
        • Brguljan J
        • Bueno H
        • Caiani EG
        • Carlberg B
        • Chapman N
        • Cífková R
        • Cleland JGF
        • Collet J-P
        • Coman IM
        • Leeuw PW de
        • Delgado V
        • Dendale P
        • Diener H-C
        • Dorobantu M
        • Fagard R
        • Farsang C
        • et al.
        2018 ESC/ESH Guidelines for the management of arterial hypertension.
        Eur Heart J. 2018; 39: 3021-3104
        • Lapi F
        • Lucenteforte E
        • Moschini M
        • Bonaiuti R
        • Pirro M Di
        • Barchielli A
        • Benemei S
        • Belladonna M
        • Nesti N
        • Coppini R
        • Taras M
        • Vannacci A
        • Ungar A
        • Mugelli A
        Representativeness of the “Fiesole Misurata”; study database for use in pharmaco-epidemiological investigations on adherence to antihypertensive medications.
        Aging Clin Exp Res. 2013; 25: 433-445