ESC Congress 2017 In Review – Focus on Arrhythmias - 9B

if bleeding is the major risk, they should consider triple
therapy for 1 month, followed by dual therapy up to 12
months; beyond 12 months, they can prescribe OACs.
The guidelines also recommend only dual therapy for
patients at high risk of bleeding.8
The RE-DUAL PCI trial has also shown that AF
patients receiving triple therapy after PCI may be able
to avoid aspirin by taking dual therapy with dabigatran
and a P2Y12 inhibitor.9 These data were presented in the
Late-Breaking Science in PCI session by Christopher P.
Cannon, MD, Harvard Medical School and Baim Institute
for Clinical Research, Boston, USA, and were simultaneously published in the New England Journal of Medicine.
In the study, 2725 AF patients who had undergone PCI
with stent placement were randomised to receive either
triple therapy (warfarin, a P2Y12 inhibitor [clopidogrel or
ticagrelor], and aspirin) or dual therapy (dabigatran 110
mg or 150 mg BID, plus clopidogrel or ticagrelor).
Dabigatran 110 mg with a P2Y12 inhibitor almost halved
major and clinically relevant nonmajor bleeds over 14
months when compared with triple therapy (Figure 2).
Dual therapy using dabigatran 150 mg was also associated with fewer bleeds (Figure 2). For the composite efficacy endpoint of time to death, thromboembolic events
(myocardial infarction, stroke, or systemic embolism),
or unplanned revascularisation, dual therapy with dabigatran was noninferior to triple therapy with warfarin.
Though the trial was properly powered to assess noninferiority for 2 composite efficacy endpoints, it was not
powered to assess differences in individual components
of this endpoint for the combined doses or for each individual dose.
These dabigatran dual-therapy regimens use doses
approved for stroke prevention, said Dr Cannon, and offer
clinicians 2 new options for managing AF patients post PCI.

Todd Villines, MD, Walter Reed National Military
Medical Center, Bethesda, USA, noted that all NOACs have
shown favourable safety and efficacy profiles compared
with warfarin in AF patients. Only dabigatran 150 mg has
shown reductions in the rate of ischaemic strokes, he
said, which comprise most of the ischaemic events in AF
patients.10-11 But the NOACs as a class consistently reduce
the rate of haemorrhagic stroke.10-14
However, Dr Villines acknowledges that clinicians
still need to choose among the 4 NOACs. And while data
from head-to-head trials are not available for these
agents, emerging data from large scale real-world studies can inform decision-making. For example, studies
comparing dabigatran with apixaban have shown these
agents to have similar bleeding risks;15 however, data
have shown an association between an increased risk
of bleeding with rivaroxaban as compared with dabigatran16. It is possible that this association could also contribute to the association between an increase in the
risk of mortality with rivaroxaban seen in patients > 75
years old as compared with dabigatran.16
The real-world data thus appear to suggest some differences in safety between the NOACs, Dr Villines concluded.
References
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Calkins H, Willems S, Gerstenfeld EP, et al. N Engl J Med. 2017;376:1627-36.
Pollack CV Jr, Reilly PA, van Ryn J, et al. N Engl J Med. 2017;377:431-41.
Calkins H, Hindricks G, Cappato R, et al. Heart Rhythm. 2017; doi: 10.1016/j.hrthm.2017.05.012.
Dewilde WJ, Oirbans T, Verheugt FW, et al. Lancet. 2013 381:1107-15.
D'Ascenzo F, Taha S, Moretti C, et al. Am J Cardiol. 2015;115:1185-93.
Gibson CM, Mehran R, Bode C, et al. Am Heart J. 2015;169:472-78.
Gibson CM, Mehran R, Bode C, et al. N Engl J Med. 2016;375:2423-34.
Valgimigli M, Bueno H, Byrne RA, et al. Eur Heart J. 2017; doi: 10.1093/eurheartj/ehx419.
Cannon CP, Bhatt DL, Oldgren J, et al. N Engl J Med. 2017; doi:10.1056/NEJMoa1708454.
Connolly SJ, Ezekowitz MD, Yusuf S, et al. N Engl J Med. 2010;363:1875-6.
Connolly SJ, Wallentin L, Yusuf S. N Engl J Med. 2014;371:1464-5.
Granger CB, Alexander JH, McMurray JJ, et al. N Engl J Med. 2011;365:981-92.
Patel MR, Mahaffey KW, Garg J, et al. N Engl J Med. 2011;365:883-91.
Giugliano RP, Ruff CT, Braunwald E, et al. N Engl J Med. 2013;369:2093-104.
Lip GY, Keshishian A, Kamble S, et al. Thromb Haemost. 2016;116:975-86.
Graham DJ, Reichman ME, Wernecke M, et al. JAMA Intern Med. 2016;176:1662-71.

Figure 2. Rates of Major Bleeding or Clinically Relevant Nonmajor Bleeding in RE-DUAL PCI
40
35

Probability of Event (%)

HR, 0.52 (95% CI, 0.42-0.63)
Noninferiority P < .0001
P < .0001

HR, 0.72 (95% CI, 0.58-0.88)
Noninferiority P < .0001
P < .002

Warfarin
triple therapy

Dabigatran 110 mg
dual therapy

Dabigatran 150 mg
dual therapy

180

270

360

450

Time to First Event (days)

540

630

750

180

270

360

450

540

630

750

Time to First Event (days)

From The New England Journal of Medicine, Cannon CP et al, Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. EPub 28 August 2017.
Copyright © 2017 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

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