Advertisement

Secondary prevention of acute coronary events with antiplatelet agents (SPACE-AA): One-year real-world effectiveness and safety cohort study in the French nationwide claims database

      Highlights

      • In real-life, clopidogrel was used in older patients compared with ticagrelor or prasugrel.
      • Prasugrel was used mostly after percutaneous intervention.
      • There were fewer deaths in ticagrelor users than in matched clopidogrel users.
      • There was no difference between ticagrelor and matched prasugrel users, or between clopidogrel and matched prasugrel users.

      Abstract

      Background and aims

      We aimed to compare the effectiveness of ticagrelor vs. clopidogrel or prasugrel on recurrence of acute coronary syndromes (ACS) in real-life conditions, as requested by regulatory authorities at the time of marketing.

      Methods

      We performed a cohort study in SNDS, the French national healthcare database. All patients with a hospital admission for ACS in 2013 were followed one year. Patients on ticagrelor, clopidogrel or prasugrel were matched 1:1 using age, gender, index ACS type, and high-dimensional propensity scores (hdPS). Outcomes were ACS, stroke, all-cause death, and major bleeding, compared within matched groups using Cox proportional hazards models analysis during treatment.

      Results

      54,048 ACS were hospitalized in 2013. At discharge, 19,796 were dispensed clopidogrel, 8242 prasugrel, and 13,916 ticagrelor. Per group, 9224 ticagrelor vs. clopidogrel, 6752 ticagrelor vs. prasugrel, and 4676 prasugrel vs. clopidogrel patients were matched. Compared to clopidogrel, ticagrelor was associated with a lower hazard ratio of death 0.73 [0.59–0.90] and composite criterion (0.88, 95% CI [0.79–0.99] but not ACS 0.92 [0.80–1.06], stroke (0.96 [017-5.53]) or major bleeding (1.02 [0.82–1.26]). Prasugrel was not different from ticagrelor or clopidogrel for any outcome, in matched patients.

      Conclusions

      Ticagrelor in real-life conditions in matched populations was associated with a lower risk of all-cause death than clopidogrel, and a lower risk of composite outcome, as in the main pivotal clinical trial. Ticagrelor and prasugrel were not different, nor were prasugrel and clopidogrel.

      Graphical abstract

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Deeks E.D.
        Ticagrelor: a review of its use in the management of acute coronary syndromes.
        Drugs. 2011; 71: 909-933
        • Husted S.
        • van Giezen J.J.
        Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist.
        Cardiovasc Ther. 2009; 27: 259-274
        • Cannon C.P.
        • Harrington R.A.
        • James S.
        • Ardissino D.
        • Becker R.C.
        • Emanuelsson H.
        • et al.
        Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study.
        Lancet. 2010; 375: 283-293
        • Wallentin L.
        • Becker R.C.
        • Budaj A.
        • Cannon C.P.
        • Emanuelsson H.
        • Held C.
        • et al.
        Ticagrelor versus clopidogrel in patients with acute coronary syndromes.
        N. Engl. J. Med. 2009; 361: 1045-1057
        • Motovska Z.
        • Hlinomaz O.
        • Miklik R.
        • Hromadka M.
        • Varvarovsky I.
        • Dusek J.
        • et al.
        Prasugrel versus ticagrelor in patients with acute myocardial infarction treated with primary percutaneous coronary intervention: multicenter randomized PRAGUE-18 study.
        Circulation. 2016; 134: 1603-1612
        • Gosling R.
        • Yazdani M.
        • Parviz Y.
        • Hall I.R.
        • Grech E.D.
        • Gunn J.P.
        • et al.
        Comparison of P2Y12 inhibitors for mortality and stent thrombosis in patients with acute coronary syndromes: single center study of 10 793 consecutive 'real-world' patients.
        Platelets. 2017; 28: 1-7
        • Bavishi C.
        • Panwar S.
        • Messerli F.H.
        • Bangalore S.
        Meta-analysis of comparison of the newer oral P2Y inhibitors (prasugrel or ticagrelor) to clopidogrel in patients with non-ST-elevation acute coronary syndrome.
        Am. J. Cardiol. 2015; 116: 809-817
        • Lee Y.S.
        • Jin C.D.
        • Kim M.H.
        • Guo L.Z.
        • Cho Y.R.
        • Park K.
        • et al.
        Comparison of prasugrel and ticagrelor antiplatelet effects in Korean patients presenting with ST-segment elevation myocardial infarction.
        Circ. J. 2015; 79: 1248-1254
        • Steiner S.
        • Moertl D.
        • Chen L.
        • Coyle D.
        • Wells G.A.
        Network meta-analysis of prasugrel, ticagrelor, high- and standard-dose clopidogrel in patients scheduled for percutaneous coronary interventions.
        Thromb. Haemostasis. 2012; 108: 318-327
        • Briasoulis A.
        • Telila T.
        • Palla M.
        • Siasos G.
        • Tousoulis D.
        P2Y12 receptor antagonists: which one to choose? A systematic review and meta-analysis.
        Curr. Pharmaceut. Des. 2016; 22: 4568-4576
        • Montalescot G.
        • Wiviott S.D.
        • Braunwald E.
        • Murphy S.A.
        • Gibson C.M.
        • McCabe C.H.
        • et al.
        Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial.
        Lancet. 2009; 373: 723-731
        • Bezin J.
        • Duong M.
        • Lassalle R.
        • Droz C.
        • Pariente A.
        • Blin P.
        • et al.
        The national healthcare system claims databases in France, SNIIRAM and EGB: powerful tools for pharmacoepidemiology.
        Pharmacoepidemiol. Drug Saf. 2017; 26: 954-962
        • Schneeweiss S.
        • Rassen J.A.
        • Glynn R.J.
        • Avorn J.
        • Mogun H.
        • Brookhart M.A.
        High-dimensional propensity score adjustment in studies of treatment effects using health care claims data.
        Epidemiology. 2009; 20: 512-522
        • Bezin J.
        • Girodet P.O.
        • Rambelomanana S.
        • Touya M.
        • Ferreira P.
        • Gilleron V.
        • et al.
        Choice of ICD-10 codes for the identification of acute coronary syndrome in the French hospitalization database.
        Fundam. Clin. Pharmacol. 2015; 29: 586-591
        • Bezin J.
        • Groenwold R.H.
        • Ali M.S.
        • Lassalle R.
        • Robinson P.
        • de Boer A.
        • et al.
        Comparative effectiveness of recommended versus less intensive drug combinations in secondary prevention of acute coronary syndrome.
        Pharmacoepidemiol. Drug Saf. 2017; 26: 285-293
        • Blin P.
        • Dureau-Pournin C.
        • Lassalle R.
        • Jove J.
        • Thomas-Delecourt F.
        • Droz-Perroteau C.
        • et al.
        Outcomes in Post-Myocardial Infarction patients similar to those of the PEGASUS-TIMI 54 trial: a cohort study in the French national claims database.
        Br. J. Clin. Pharmacol. 2017; 83: 2056-2065
        • Puymirat E.
        • Riant E.
        • Aissoui N.
        • Soria A.
        • Ducrocq G.
        • Coste P.
        • et al.
        Beta blockers and mortality after myocardial infarction in patients without heart failure: multicentre prospective cohort study.
        BMJ. 2016; 354: i4801
        • Bannay A.
        • Chaignot C.
        • Blotiere P.O.
        • Basson M.
        • Weill A.
        • Ricordeau P.
        • et al.
        The best use of the Charlson comorbidity index with electronic health care database to predict mortality.
        Med. Care. 2016; 54: 188-194
        • Rassen J.A.
        • Glynn R.J.
        • Brookhart M.A.
        • Schneeweiss S.
        Covariate selection in high-dimensional propensity score analyses of treatment effects in small samples.
        Am. J. Epidemiol. 2011; 173: 1404-1413
        • Austin P.C.
        Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples.
        Stat. Med. 2009; 28: 3083-3107
        • Bezin J.
        • Pariente A.
        • Lassalle R.
        • Dureau-Pournin C.
        • Abouelfath A.
        • Robinson P.
        • et al.
        Use of the recommended drug combination for secondary prevention after a first occurrence of acute coronary syndrome in France.
        Eur. J. Clin. Pharmacol. 2014; 70: 429-436
        • Ibanez B.
        • James S.
        • Agewall S.
        • Antunes M.J.
        • Bucciarelli-Ducci C.
        • Bueno H.
        • et al.
        ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC).
        Eur. Heart J. 2017; 39 (2018): 119-177
        • Pareek M.
        • Bhatt D.L.
        Ticagrelor for patients with acute coronary syndromes: PLATOnic affair or lasting SWEDEHEART?.
        Eur. Heart J. 2016; 37: 3343-3346
        • Sahlen A.
        • Varenhorst C.
        • Lagerqvist B.
        • Renlund H.
        • Omerovic E.
        • Erlinge D.
        • et al.
        Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry.
        Eur. Heart J. 2016; 37: 3335-3342
        • Schneeweiss S.
        • Eddings W.
        • Glynn R.J.
        • Patorno E.
        • Rassen J.
        • Franklin J.M.
        Variable selection for confounding adjustment in high-dimensional covariate spaces when analyzing healthcare databases.
        Epidemiology. 2017; 28: 237-248
        • Blin P.
        • Philippe F.
        • Bouee S.
        • Laurendeau C.
        • Torreton E.
        • Gourmelin J.
        • et al.
        Outcomes following acute hospitalised myocardial infarction in France: an insurance claims database analysis.
        Int. J. Cardiol. 2016; 219: 387-393
        • Jernberg T.
        • Attebring M.F.
        • Hambraeus K.
        • Ivert T.
        • James S.
        • Jeppsson A.
        • et al.
        The Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART).
        Heart. 2010; 96: 1617-1621
        • Tunstall-Pedoe H.
        • Kuulasmaa K.
        • Mahonen M.
        • Tolonen H.
        • Ruokokoski E.
        • Amouyel P.
        Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA project populations. Monitoring trends and determinants in cardiovascular disease.
        Lancet. 1999; 353: 1547-1557
        • Serebruany V.
        • Cherepanov V.
        • Dukhanin A.
        Significant excess of early deaths after prehospital ticagrelor: the ATLANTIC trial challenge.
        Thromb. Haemostasis. 2015; 114: 7-8
        • Serebruany V.L.
        • Cherepanov V.
        • Tomek A.
        • Kim M.H.
        Among antithrombotic agents, prasugrel, but not ticagrelor, is associated with reduced 30 day mortality in patients with ST-elevated myocardial infarction.
        Int. J. Cardiol. 2015; 195: 104-110
        • Lhermusier T.
        • Lipinski M.J.
        • Tantry U.S.
        • Escarcega R.O.
        • Baker N.
        • Bliden K.P.
        • et al.
        Meta-analysis of direct and indirect comparison of ticagrelor and prasugrel effects on platelet reactivity.
        Am. J. Cardiol. 2015; 115: 716-723
        • Giroud M.
        • Hommel M.
        • Benzenine E.
        • Fauconnier J.
        • Bejot Y.
        • Quantin C.
        • et al.
        Positive predictive value of French hospitalization discharge codes for stroke and transient ischemic attack.
        Eur. Neurol. 2015; 74: 92-99
        • Gilleron V.
        • Gasnier-Duparc N.
        • Hebbrecht G.
        Certification des comptes: une incitation à la traçabilité des processus de contrôle.
        Revue Hospitaliere de France. 2018; 582: 42-46