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Better outcome with longer dual antiplatelet treatment in real-life ACS population

22-10-2013 • Varenhorst et al., Eur Heart J. Oct 2013


Duration of dual antiplatelet treatment with clopidogrel and aspirin in patients with acute coronary syndrome.

 
Varenhorst C, Jensevik K, Jernberg T et al.
Eur Heart J. 2013 Oct 11. [Epub ahead of print]
 

Background

Dual antiplatelet treatment (DAPT) with aspirin and P2Y12 receptor inhibitor is given to patients with acute coronary syndrome (ACS), whether they are treated invasively or non-invasively. Guidelines recommend treatment of 9-12 months after ACS and up to 12 months after drug-eluting stents placement, although no trial has supported extended DAPT.
Recent trials have suggested no net clinical benefit of treatment with DAPT longer than 6-12 months after drug-eluting stent implantation. These trials had, however, limited power and did not specifically include ACS patients [1-3].
Premature discontinuation of clopidogrel is known to induce stent thrombosis [4-6]. On the other hand, recent trials with newer generation drug-eluting stents have suggested low event rates despite a relatively short DAPT duration [3,7]. Register studies show no evidence of a reduction of ischaemic adverse events when continuing clopidogrel treatment for longer than six months [8].
The Swedish Websystem for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) is a national register of all patients hospitalized for ACS in Sweden [9].The SWEDEHEART register was used to evaluate the effect of different DAPT durations (depending on dispensed clopidogrel tablets) with clopidogrel and aspirin on clinical outcome in ACS patients.
 

Main results

  • The combined primary endpoint of death/stroke or re-infarction occurred less often in the >3 months’ DAPT group than in the 3 months’ DAPT group (654 vs. 858 patients, HR: 0.70, 95%CI: 0.63-0.77, P<0.0001). The association remained statistically significant after adjustment for potential confounders. The difference in calculated incidence per 1000 person-years was 45 vs. 65 events.
  • When comparing the primary endpoint in the >6 and the 6 months groups, HR was 0.70 (95%CI: 0.56-0.87, P=0.0012), and remained significant after adjustment for baseline characteristics.
    Significant interactions between DAPT duration and revascularisation at index hospitalisation were seen for the comparisons of >3 vs. 3 months and >6 vs. 6 months for the combined endpoint.
  • Only for the individual endpoint of re-infarction, a statistically significant lower event rate was seen in the >3 months’ group as compared to the 3 months’ group (adjHR: 0.83, 95%CI: 0.70-0.98, P=0.03). No differences between these treatment periods was seen for individual end-points all-cause death and stroke.
  • Patients in the >3 months’ group had a higher hazard of post-ACS revascularisation than after 3 months’ DAPT duration (adj HR: 1.37, 95%CI: 1.21-1.56, P<0.0001).
  • Risk of bleeding was higher with longer DAPT duration (316 vs. 180 reported bleeds, adjHR: 1.56, 95%CI: 1.18-2.07 for >3 vs. 3 months). Bleeds were mostly gastrointestinal (76.1%), and 12.9% were intracranial bleeds. The calculated risk of bleeding was 11 events per 1000 person-years in the >3 months’ group, and 8 events per 1000 person-years in the 3 months’ DAPT group.
 

Conclusion

This first large outcome analysis of varying DAPT durations in patients discharged with ACS, shows that DAPT of >3 months is associated with a statistically significantly lower incidence of death/stroke or re-infarction than DAPT of 3 months. Bleeding risk was higher at DAPT for longer than 3 months than for 3 months, but the overall incidence was low.
 

References

1. Valgimigli M, Campo G, Monti M et al. Shortversus long-termduration of dual-antiplatelet therapy after coronary stenting: a randomized multicenter trial. Circulation 2012;125:2015–2026.
2. Park S-J, Park D-W, Kim Y-H et a.. Duration of dual antiplatelet therapy after implantation of drug-eluting stents.NEngl JMed 2010;362:1374–1382.
3. Gwon H-C, Hahn J-Y, Park KW, et al. Six-month versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: the Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) randomized, multicenter study. Circulation 2012;125:505–513.
4. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293: 2126–2130.
5. Eisenstein EL, Anstrom KJ, Kong DF, et al. Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA 2007;297:159–168.
6. Spertus JA, Kettelkamp R, Vance C, et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation 2006; 113:2803–2809.
7. Leon MB, Mauri L, Popma JJ, et al. A randomized comparison of the ENDEAVOR zotarolimus-eluting stent versus the TAXUS paclitaxel-eluting stent in de novo native coronary lesions 12-month outcomes from the ENDEAVOR IV trial. J Am Coll Cardiol 2010;55:543–554.
8. KimuraT,MorimotoT, NakagawaY, et al. Antiplatelet therapy and stent thrombosis after sirolimus-eluting stent implantation. Circulation 2009;119:987–995.
9. Jernberg T, Attebring MF, Hambraeus K et al. The Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART). Heart (British Cardiac Society) 2010;96: 1617–1621.  


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ACSantiplateletclopidogrelDAPTJames SSWEDEHEARTVarenhorst C

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