Better outcome with longer dual antiplatelet treatment in real-life ACS populationVarenhorst et al., Eur Heart J. Oct 2013 - Eur Heart J. 2013 Oct 11. [Epub ahead of print]
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]
BackgroundDual 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 .
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 .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.
- 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.
ConclusionThis 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.
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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