Efficacy and safety of dual antiplatelet therapy after complex PCI
Selected in the Journal of the American College of Cardiology by D. Milasinovic
Giustino G, Chieffo A, Palmerini T, Valgimigli M, Feres F, Abizaid A, Costa RA, Hong MK, Kim BK, Jang Y, Kim HS, Park KW, Gilard M, Morice MC, Sawaya F, Sardella G, Genereux P, Redfors B, Leon MB, Bhatt DL, Stone GW, Colombo A
J Am Coll Cardiol. 2016 Oct 25;68(17):1851-1864
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What is known
The issue of optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug eluting stents (DES) has not been settled. Recent studies have indicated the potential of longer-term DAPT (≥12 months) to reduce ischemic events, albeit at the cost of increased major bleeding. Hence, when deciding on DAPT duration, individualized approach seems to be warranted, taking into account patient's risk factors for ischemia vs. bleeding. However, the contemporary risk assessment tools do not include angiographic complexity of the underlying coronary artery disease (CAD).
The effect of reducing MACE with longer-term(≥ 12 months) compared with short-term DAPT (3-6 months) is greater in patients undergoing complex PCI.
- Patient-level pooled analysis (n=9577) from 6 randomized trials that compared 3-6 vs. ≥12 months of DAPT after PCI with DES
- Complex PCI was defined as at least one of the following: 3-vessel PCI, ≥3 stents implanted, ≥3 lesions treated, two-stent bifurcation PCI, total stent length >60mm or PCI of chronic total occlusion (CTO)
- Primary efficacy endpoint was MACE (cardiac death, myocardial infarction (MI) or definite/probable stent thrombosis (ST)) and primary safety endpoint was major bleeding
- At median follow-up of 392 days, patients with complex vs. non-complex PCI had higher crude rate of MACE (5.4% vs. 2.9%, p<0.001), and a tendency toward more major bleeding (1.0% vs. 0.6%, p=0.06).
- After adjusting for known ischemia and bleeding predictors, complex PCI remained independently associated with higher MACE rate (HR 1.98, p<0.001), albeit without significantly impacting the risk of major bleeding (HR 1.52, p=0.19)
- Among different components of complex PCI, bifurcation PCI with implantation of two stents was most consistently associated with increased risk of ischemic events (HR 2.76, p<0.001, for MACE)
- In patients undergoing complex PCI, MACE was reduced with longer vs. shorter DAPT (4.1% vs. 6.8%, respectively), whereas duration of DAPT had no bearing on the occurrence of ischemic events after non-complex PCI (MACE rate was 2.9% with both longer and shorter DAPT) (p=0.01 for interaction between PCI complexity and DAPT duration for MACE)
- Major bleeding was increased with longer DAPT after both complex and non-complex PCI (p=0.96 for interaction between PCI complexity and DAPT duration for major bleeding)
This study showed that longer DAPT reduced ischemic events after complex PCI with new-generation DES (85% in the pooled trials), but not in patients undergoing non-complex PCI, whereas major bleeding was increased with longer DAPT regimen irrespective of PCI complexity.
Clinical relevance of the study’s findings is twofold. First, a considerable proportion of PCI patients seem to undergo complex interventions (18% in the present analysis with pooled data from randomized trials, a likely underestimate of everyday practice), which seem to be associated with increased risk of ischemic complications. Second, as hitherto developed scoring systems like DAPT and risk scores from PARIS registry are based mainly on clinical characteristics, the addition of angiographic and procedure-related variables may improve ischemic risk stratification and by extension aid decision-making on duration of DAPT.
However, at least three clinically important questions seem to remain open.
First, the present study used a preconceived and not data-derived definition of complex PCI. Thereby, the only two PCI-related variables from the contemporary DAPT risk score, stent diameter <3mm and stenting of vein grafts, were not included in the present study’s definition of complex PCI.
Second, conceptually, complex PCI mainly addresses the risk of stent-related ischemic complications and may only serve as a surrogate of the underlying severity CAD. However, occurrence of MACE is to a considerable extent non-stent related (in the PROSPECT trial, almost a half of ischemic adverse events were not related to previously treated lesions). In this respect, the angiographic completeness of revascularization, which has been quantified by residual SYNTAX score and linked to increased risk of MACE, seems to be left unaddressed when focusing only on PCI-related features without taking into account the underlying complexity of CAD.
Third, since the present analysis evaluated short vs. longer DAPT with clopidogrel, the effects of prolonged antiplatelet regimen with newer, more potent agents, such as ticagrelor, need further elucidation, especially in the light of recent data indicating potential benefit of prolonged ticagrelor use in patients with prior MI (PEGASUS TIMI-54 trial).
Do you incorporate PCI-related variables in your everyday decision-making on duration of DAPT? If yes, what type(s) of PCI would you consider prolonging DAPT for?