dual antiplatelet therapy

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DAPT SOUMYA KANTI DUTTAIPGMER ICVS KOLKATA

The term and acronym DAPT has been used to specifically refer to combination antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor). Most contemporary studies of DAPT have compared either shorter (3 to 6 months) or longer (18 to 48 months) duration of therapy with 12 months of DAPT, which is the recommended or minimal duration of therapy formost patients in ACC/AHA and European Society of Cardiology guidelines published between 2011 and 2014.

Three critical questions on DAPT areIn patients treated with newer (non-first) generation DES for (1) SIHD or (2) ACS, compared with 12 months of DAPT, is 36 months of DAPT as effective in preventing stent thrombosis, preventing MACE and/or reducing bleeding complications? In patients treated with newer (non-first) generation DES, compared with 12 months of DAPT, does >12 (1848) months of DAPT result in differences in mortality rate, decreased MACE, decreased stent thrombosis, and/or increased bleeding?In post-MI (NSTEMI or STEMI) patients who are clinically stable and >12 months past their event, does continued DAPT, compared with aspirin monotherapy, result in differences in mortality rate, decreased nonfatal MI, decreased MACE, and/or increased bleeding?

Antiplatelet AgentsOral P2Y12 Inhibitors++++++Bleeding Risk

82011 ACC/AHA/SCAI Guideline for PCI

The duration of P2Y12 inhibitor therapy should generally be as follows:

DURATIONIII

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IIaIIaIIaIIbIIbIIbIIIIIIIIIB In patients receiving a stent (BMS or DES) during PCI for ACS, P2Y12 inhibitor therapy should be given for at least 12 months. Options include clopidogrel 75 mg daily,prasugrel 10 mg daily or ticagrelor 90mg twice daily

b. In patients receiving DES for non-ACS indication, clopidogrel should be given for at least 12 months if patients are not at high risk for bleeding.

c. In patients receiving BMS for a non-ACS indication, clopidogrel should be given for a minimum of 1 month and ideally up to 12 months (unless patient is at increased risk for bleeding;then it should be given for a minimum of 2 weeks)Circulation 2011;124:e574-651III


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Randomized Trials of DAPT DurationTrialPatientsTestRandomization1 EPProlonged DAPT StudiesREAL/ZEST Late2701 DES1 vs. 2 yrsA vs. A+CSuperiorityD/MI2 yrs after randDAPTN=20,645 (15,245 DES) (5,400 BMS)1 vs. 2.5 yrs*A+P vs. DAPT (clop or pras)NI and SupD/MI/CVAST, BleedingPRODIGYN=1,800 DES, BMS6 mos vs. 2 yrsA vs. A+CSuperiorityD/MI/CVAAbbreviated DAPT StudiesEXCELLENTN=1,443 SES and EES6 vs. 12 mosA vs. A+CNoninferiorityD/MI/TVRISAR-SAFE**N=6,000DES6 vs. 12 mos*A+P vs. A+CNoninferiorityD/MI/CVA/ST/TIMI MBITALICN=3,700EES6 vs. 12 mosA vs. A+CNoninferiorityD/MI/CVA/Urg Revasc/MBOPTIMIZEN=3,120ZES3 vs. 12 mosA vs. A+CNoninferiorityD/MI/CVA/MBRESETN=2,148E-ZES vs RZES, SES, EES3 vs. 12 mosA+C vs. A+CCVD/MI/ST/ID-TVR, Bleed

*Plus a 3 month washout periodStrategy not DAPT duration **2014-2015

The Will this trial change my practice? sessions at PCR 2015Will this trial change my practice? The Dual Antiplatelet Therapy (DAPT) study 12 or 30 months of dual antiplatelet therapy after drug-eluting stentsShould the DAPT study shift the standard of care from 12 months to 30 months in patients who receive a DES? Does the increased risk of bleeding essentially offset the benefits? To whom would you recommend continued DAPT? In whom would you avoid it?

DAPTDES PCI: MACCE for DAPT vs. placebo: 4.3% vs. 5.9%, p < 0.001; MI: 2.1% vs. 4.1%, p < 0.001; stent thrombosis: 0.4% vs. 1.4%, p < 0.001; all-cause mortality: 2.0% vs. 1.5%, p = 0.05; GUSTO moderate/severe bleeding: 2.5% vs. 1.6%, p = 0.001BMS PCI: MACCE for DAPT vs. placebo: 4.0% vs. 4.7%, p = 0.72; MI: 2.7% vs. 3.1%, p = 0.74; stent thrombosis: 0.5% vs. 1.1%, p = 0.24; all-cause mortality: 1% vs. 1.2%, p = 0.83

Trial design: Patients undergoing DES/BMS PCI, no ischemic/bleeding complications, and with documented compliance at 1 year, were randomized to receive another 18 months of dual antiplatelet therapy (DAPT) or placebo. Patients were followed for 18 months.ResultsConclusionsMauri L, et al. N Engl J Med 2014;371:2155-66 DAPT DES (n = 5,020)MACCEProlonged DAPT ~30 months following DES PCI results in lower stent thrombosis/recurrent MIs compared with 12-month DAPT, although bleeding and all-cause mortality were higher; BMS subset showed a less impressive treatment effectPlacebo DES (n = 4,941)%

(p < 0.001)%

(p = 0.72) DAPT BMS (n = 842)Placebo BMS PCI(n = 845)

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Studies of Shorter-Duration DAPT: After Stent Implantation five RCTs of patients treated with elective DES implantation have compared shorter-duration (3 to 6 months) DAPT with 12 months of DAPT.The trials primarily enrolled low-risk (non-ACS) patients, with only a small proportion having had a recent MI. The main endpoints of these noninferiority trials were composite ischemic events and stent thrombosis. These studies, as well as several meta-analyses did not find any increased risk of stent thrombosis with shorter-duration DAPT in patients currently being treated with newergeneration (e.g., everolimus- or zotarolimus-eluting) DES.

Extended DAPTprolonged or extended DAPT for an additional 18 to 36 months after DES found an absolute decrease in late stent thrombosis and ischemic complications of 1% to 2% and an absolute increase in bleeding complications of 1% . Extended DAPT resulted in a 0.7% absolute reduction in very late stent thrombosis, a 2.0% absolute reduction in MI, a 1.6% absolute reduction in major adverse cardiac events (MACE), a 0.9% absolute increase in moderate or severe bleeding.

Mortality in prolonged DAPT30 months of DAPT versus 12 months of DAPT in DES treated patients, which was due to significantly increased deaths from noncardiovascular causes (most commonly cancer), with no increase in cardiovascular deaths, and no significant increase in fatal bleeding.OPTIDUAL (Optimal Dual Antiplatelet Therapy) trial, found numerically or statistically significant increased risk of all cause (though not cardiovascular) death associated with prolonged duration of DAPT

Increased Ischemic Risk/Risk of Stent Thrombosis (may favor longer-duration DAPT) Increased ischemic risk Advanced age Multiple prior MIs Extensive CAD Diabetes mellitus CKDIncreased risk of stent thrombosis Diabetes mellitus Left ventricular ejection fraction

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