Table 2:

Benefits and harms of extended dual antiplatelet therapy (DAPT; > 12 mo) compared with standard DAPT (6–12 mo) among all trial participants*

Outcome†RCTs that provided outcome dataNo. events (no. participants)Extended DAPT v. standard DAPT: RR (95% CI); I2
> 12 mo6–12 mo
All-cause deathARCTIC-Interruption;6 ITALIC;7 OPTIDUAL;8 DES-LATE;9 PRODIGY;10 DAPT;11 NIPPON31234 (13 041)205 (12 941)1.07 (0.80–1.42); 45%
Cardiovascular deathITALIC;7 NIPPON;31 OPTIDUAL;8 DES-LATE;9 DAPT1197 (10 829)98 (10 732)0.98 (0.74–1.30); 0%
Noncardiovascular deathOPTIDUAL;8 DAPT;11 NIPPON3157 (7374)40 (7292)NE‡
Myocardial infarctionARCTIC-Interruption;6 ITALIC;7 OPTIDUAL;8 DES-LATE;9 DAPT;11 NIPPON31170 (12 316)291 (12 218)0.58 (0.48–0.70); 0%
StrokeARCTIC-Interruption;6 ITALIC;7 OPTIDUAL;8 DES-LATE;9 DAPT;11 NIPPON3188 (12 316)92 (12 218)0.94 (0.70–1.25); 0%
Definite STARCTIC-Interruption;6 OPTIDUAL;8 DES-LATE;9 PRODIGY;10 DAPT1132 (10 464)85 (10 361)0.49 (0.22–1.08); 46%
Probable or definite STARCTIC-Interruption;6 ITALIC;7 OPTIDUAL;8 DAPT;11 NIPPON3130 (9785)86 (9704)0.38 (0.21–0.67); 10%
Urgent revascularizationITALIC;7 ARCTIC-INT611 (1569)18 (1567)0.60 (0.24–1.54); 29%
MACCEARCTIC-Interruption;6 ITALIC;7 DES-LATE;9 DAPT;11 PRODIGY10443 (10 687)506 (10 590)0.95 (0.76–1.19); 55%
GI bleedingNIPPON318 (1887)9 (1886)0.89 (0.34–2.30); NA
TIMI major bleedingARCTIC-Interruption;6 ITALIC;7 OPTIDUAL;8 DES-LATE942 (4801)28 (4778)1.42 (0.88–2.29); 0%
TIMI minor bleedingITALIC;7 OPTIDUAL821 (1625)22 (1623)0.95 (0.53–1.72); 0%
GUSTO moderate bleedingDAPT;11 OPTIDUAL8102 (6563)60 (6483)1.68 (1.22–2.30); 0%
GUSTO severe bleedingDAPT;11 OPTIDUAL841 (6553)33 (6483)1.41 (0.90–2.20); 0%
GUSTO moderate or severe bleedingDAPT;11 OPTIDUAL8148 (6563)92 (6483)1.57 (1.17–2.11); 7%
BARC type 3 bleedingDAPT;11 OPTIDUAL;8 NIPPON31161 (8216)99 (8137)1.29 (0.76–2.22); 58%
BARC type 5 bleedingDAPT;11 OPTIDUAL;8 NIPPON3110 (8216)5 (8047)1.72 (0.62–4.47); 0%
BARC type 2, 3, 5 bleedingOPTIDUAL818 (701)20 (697)0.89 (0.48–1.68); NA

  • Note: BARC = Bleeding Academic Research Consortium, CI = confidence interval, GI = gastrointestinal, GUSTO = Global Use of Strategies to Open Occluded Coronary Arteries, MACCE = major adverse cardiovascular and cerebrovascular event, NA = not applicable, NE = not estimable, RCT = randomized controlled trial, RR = relative risk, TIMI = Thrombolysis In Myocardial Infarction, ST = stent thrombosis.

  • ↵* Corresponding forest plots are presented in Appendix 1 and Figure 2.

  • ↵† MACCE: composite outcome includes all-cause death, myocardial infarction or stroke. Bleeding outcome definitions were obtained from Mehran et al.28 These include GUSTO moderate bleeding: requiring blood transfusion but not resulting in hemodynamic compromise; GUSTO severe bleed: intracerebral hemorrhage or resulting in substantial hemodynamic compromise requiring treatment; BARC type 3 bleed (3a, 3b, 3c): overt bleeding plus hemoglobin drop of 3 to 5 g/dL, any transfusion with overt bleeding, overt bleeding plus hemoglobin drop of 5 g/dL, cardiac tamponade, bleeding requiring surgical intervention for control (excluding dental, nasal, skin, hemorrhoid), bleeding requiring intravenous vasoactive agents, intracranial hemorrhage, subcategories confirmed by autopsy or imaging or lumbar puncture, intraocular bleed compromising vision. BARC type 5 bleed: fatal bleed. TIMI minor bleed: clinically overt, resulting in hemoglobin drop of 3 to 5 g/dL. TIMI major bleed: any intracranial bleeding (excluding microhemorrhages [10 mm] evident only on gradient-echo MRI), clinically overt signs of hemorrhage associated with a drop in hemoglobin of 5 g/dL, fatal bleeding (bleeding that directly results in death within 7 d).

  • ↵‡ Data not pooled because of high heterogeneity (I2 > 75), with inconsistent direction of findings across trials.