Improving Adherence to Ticagrelor in Patients After Acute Coronary Syndrome: Results from the PROGRESS Trial

Author(s): Mario Crisci, Felice Gragnano, Marco Di Maio, Vincenzo Diana, Elisabetta Moscarella, Ivana Pariggiano, Dario Di Maio, Claudia Concilio, Vittorio Taglialatela, Fabio Fimiani, Arturo Cesaro, Plinio L. Cirillo, Paolo Calabrò*

Journal Name: Current Vascular Pharmacology

Volume 18 , Issue 3 , 2020


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Graphical Abstract:


Abstract:

Background: Dual antiplatelet therapy (DAPT) with aspirin and ticagrelor is recommended for at least 12 months in patients after an acute coronary syndrome (ACS). However, its underuse and premature discontinuation are common in clinical practice. We aimed to investigate the impact of a dedicated follow-up strategy with clinical visits and counselling on adherence levels to ticagrelor in patients after ACS.

Methods: PROGRESS (PROmotinG dual antiplatelet therapy adheREnce in the setting of acute coronary Syndromes) is a prospective, randomized trial enrolling 400 ACS patients treated with ticagrelor. Patients were randomized to be followed-up in a dedicated outpatient clinic (In-person follow-up group, [IN-FU], n=200), or with scheduled for phone interviews only (Telephone follow-up group [TEL-FU], n=200), to assess ticagrelor adherence and related complications. DAPT disruption was defined as an interruption of the administration of the drug due to complications or other reasons of non-adherence, and divided according to the duration into short (1-5 days), temporary (6-30 days) and permanent (≥30 days) disruption. The primary endpoint was the rate of DAPT disruption at 1-year follow-up.

Results: The rate of ticagrelor disruption at 1 year follow-up was higher in the TEL-FU group than in the IN-FU group (19.6 vs 5.5%; p<0.0001). The IN-FU group reported a significantly lower rate of short (3.0 vs 8.5%; p=0.012) and permanent (2.0 vs 9.6%; p=0.012) disruption than TEL-FU group. The rate of major bleeding did not differ significantly between the 2 groups (p=0.450).

Conclusion: The PROGRESS trial showed a net reduction in DAPT disruption in patients followed-up with clinical (in-person) follow-up visits in a dedicated outpatient clinic compared with those scheduled for phone interviews only.

Keywords: Ticagrelor, adherence, acute coronary syndrome, bleeding, disruption, dual antiplatelet therapy.

[1]
Gaziano TA, Opie LH, Weinstein MC. Cardiovascular disease prevention with a multidrug regimen in the developing world: a cost-effectiveness analysis. Lancet 2006; 368(9536): 679-86.
[http://dx.doi.org/10.1016/S0140-6736(06)69252-0] [PMID: 16920473]
[2]
Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2016; 37(3): 267-315.
[http://dx.doi.org/10.1093/eurheartj/ehv320] [PMID: 26320110]
[3]
Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American college of cardiology/American heart association task force on clinical practice guidelines. J Am Coll Cardiol 2016; 68(10): 1082-115.
[http://dx.doi.org/10.1016/j.jacc.2016.03.513] [PMID: 27036918]
[4]
Wallentin L, Becker RC, Budaj A, et al. PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361(11): 1045-57.
[http://dx.doi.org/10.1056/NEJMoa0904327] [PMID: 19717846]
[5]
Ilardi F, Gargiulo G, Schiattarella GG, et al. Effects of carvedilol versus metoprolol on platelet aggregation in patients with acute coronary syndrome: the PLATE-BLOCK study. Am J Cardiol 2018; 122(1): 6-11.
[http://dx.doi.org/10.1016/j.amjcard.2018.03.004] [PMID: 29747861]
[6]
Hamm CW, Bassand JP, Agewall S, et al. ESC Committee for Practice Guidelines. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011; 32(23): 2999-3054.
[http://dx.doi.org/10.1093/eurheartj/ehr236] [PMID: 21873419]
[7]
Valgimigli M, Bueno H, Byrne RA, et al. 2017 focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur Heart J 2018; 39: 213-60.
[http://dx.doi.org/10.1093/eurheartj/ehx419] [PMID: 28886622]
[8]
Calabrò P, Gragnano F, Di Maio M, et al. Epidemiology and management of patients with acute coronary syndromes in contemporary real-world practice: evolving trends from the EYESHOT study to the START-ANTIPLATELET registry. Angiology 2018; 69(9): 795-802.
[http://dx.doi.org/10.1177/0003319718760917] [PMID: 29544348]
[9]
Bianchi R, D’Acierno L, Crisci M, et al. From femoral to radial approach in coronary intervention. Angiology 2017; 68(4): 281-7.
[http://dx.doi.org/10.1177/0003319716656714] [PMID: 27401210]
[10]
Ferreira-González I, Marsal JR, Ribera A, et al. Double antiplatelet therapy after drug-eluting stent implantation: risk associated with discontinuation within the first year. J Am Coll Cardiol 2012; 60(15): 1333-9.
[http://dx.doi.org/10.1016/j.jacc.2012.04.057] [PMID: 22999716]
[11]
Mathews R, Wang TY, Honeycutt E, et al. Persistence with secondary prevention medications after acute myocardial infarction: Insights from the TRANSLATE-ACS study. Am Heart J 2015; 170(1): 62-9.
[http://dx.doi.org/10.1016/j.ahj.2015.03.019] [PMID: 26093865]
[12]
Cutlip DE, Baim DS, Ho KK, et al. Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials. Circulation 2001; 103(15): 1967-71.
[http://dx.doi.org/10.1161/01.CIR.103.15.1967] [PMID: 11306525]
[13]
Valgimigli M, Garcia-Garcia H, Vrijens B, et al. Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: a consensus report from the Non-adherence Academic Research Consortium (NARC). Eur Heart J 2019; 40(25): 2070-85.
[http://dx.doi.org/10.1093/eurheartj/ehy377]
[14]
Ferdinand KC, Senatore FF, Clayton-Jeter H, et al. Improving Medication Adherence in Cardiometabolic Disease: Practical and Regulatory Implications. J Am Coll Cardiol 2017; 69(4): 437-51.
[http://dx.doi.org/10.1016/j.jacc.2016.11.034] [PMID: 28126162]
[15]
Shalansky SJ, Levy AR, Ignaszewski AP. Self-reported Morisky score for identifying nonadherence with cardiovascular medications. Ann Pharmacother 2004; 38(9): 1363-8.
[http://dx.doi.org/10.1345/aph.1E071] [PMID: 15238622]
[16]
Ho PM, Bryson CL, Rumsfeld JS. Medication adherence: its importance in cardiovascular outcomes. Circulation 2009; 119(23): 3028-35.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.108.768986] [PMID: 19528344]
[17]
Rossini R, Baroni M, Musumeci G, Gavazzi A. Oral antiplatelet therapy after drug-eluting stent implantation: adherence and side-effects. J Cardiovasc Med (Hagerstown) 2013; 14(2): 81-90.
[http://dx.doi.org/10.2459/JCM.0b013e328356a545] [PMID: 22885533]
[18]
Zeymer U, James S, Berkenboom G, et al. Differences in the use of guideline-recommended therapies among 14 European countries in patients with acute coronary syndromes undergoing PCI. Eur J Prev Cardiol 2013; 20(2): 218-28.
[http://dx.doi.org/10.1177/2047487312437060] [PMID: 22345684]
[19]
Goodman SG, Nicolau JC, Requena G, et al. Longer-term oral antiplatelet use in stable post-myocardial infarction patients: Insights from the long Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease (TIGRIS) observational study. Int J Cardiol 2017; 236: 54-60.
[http://dx.doi.org/10.1016/j.ijcard.2017.02.062] [PMID: 28268087]
[20]
Halvorsen S, Jortveit J, Hasvold P, Thuresson M, Øie E. Initiation of and long-term adherence to secondary preventive drugs after acute myocardial infarction. BMC Cardiovasc Disord 2016; 16: 115.
[http://dx.doi.org/10.1186/s12872-016-0283-6] [PMID: 27246583]
[21]
Becker RC, Bassand JP, Budaj A, et al. Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J 2011; 32(23): 2933-44.
[http://dx.doi.org/10.1093/eurheartj/ehr422] [PMID: 22090660]
[22]
Arnold SV, Spertus JA, Jones PG, Xiao L, Cohen DJ. The impact of dyspnea on health-related quality of life in patients with coronary artery disease: results from the PREMIER registry. Am Heart J 2009; 157(6): 1042-9.e1.
[http://dx.doi.org/10.1016/j.ahj.2009.03.021] [PMID: 19464415]
[23]
Storey RF, Bliden KP, Patil SB, et al. Incidence of dyspnea and assessment of cardiac and pulmonary function in patients with stable coronary artery disease receiving ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET study. J Am Coll Cardiol 2010; 56(3): 185-93.
[http://dx.doi.org/10.1016/j.jacc.2010.01.062] [PMID: 20620737]
[24]
Cattaneo M, Faioni EM. Why does ticagrelor induce dyspnea? Thromb Haemost 2012; 108(6): 1031-6.
[PMID: 23070079]
[25]
Levin LÅ, Wallentin L, Bernfort L, et al. Health-related quality of life of ticagrelor versus clopidogrel in patients with acute coronary syndromes-results from the PLATO trial. Value Health 2013; 16(4): 574-80.
[http://dx.doi.org/10.1016/j.jval.2013.01.013] [PMID: 23796291]
[26]
Claeys MJ, Beauloye C, Pourbaix S, et al. Real world insights on the initiation and treatment duration of oral antiplatelets in acute coronary syndromes: a retrospective cohort study. Eur Heart J Cardiovasc Pharmacother 2017; 3: 189-97.
[http://dx.doi.org/10.1093/ehjcvp/pvw043] [PMID: 28122973]
[27]
Gragnano F, Natale F, Concilio C, et al. Adherence to proprotein convertase subtilisin/kexin 9 inhibitors in high cardiovascular risk patients: an Italian single-center experience. J Cardiovasc Med (Hagerstown) 2018; 19(2): 75-7.
[http://dx.doi.org/10.2459/JCM.0000000000000611] [PMID: 29251697]


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Article Details

VOLUME: 18
ISSUE: 3
Year: 2020
Published on: 24 May, 2019
Page: [294 - 301]
Pages: 8
DOI: 10.2174/1570161117666190524123225
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