eTable 1b. Expanded overview of studies of VKA-based triple therapy.
| RE-DUAL-PCI (32) | AUGUSTUS (34) | |||||
| Treatment regimen | VKA + | Dabi. 2 × 150 mg + | Dabi. 2 × 110 mg + | VKA + | Apixa. 2 × 5 mg + | |
| Clopi. 1 × 75 mg + | Clopi. 1 × 75 mg | Clopi. 1 × 75 mg | Clopi. 1 × 75 mg + | Clopi. 1 × 75 mg + | ||
| ASA ≤ 100 ng | ASA (81 mg) / placebo | ASA (81 mg) / placebo | ||||
| Outside the United States, patients ≥ 80 years (or, in Japan, ≥ 70 years) were randomized to triple therapy or dabi. 2 × 110 mg | Placebo (patients treated with P2Y12 inhibitors were randomized to, (1) VKA or apixa., (2) ASA or placebo) | |||||
| No. of patients randomized | 2725 | 4614 | ||||
| Dose reduction | None | None | Apixa. 2 × 2.5 mg if at least 2 of 3 apply: age ≥ 80 years, BW < 60 kg, serum creatinine ≥ 133 µmol/l | |||
| GFR exclusion | <30 ml/min | <30 ml/min | <30 ml/min | |||
| Time to randomization | 5 days | Within 14 days (median 6 days) | ||||
| Duration of triple ther. | 1 month if BMS, 3 months if DES | 6 months | ||||
| Study design | Open-label with blinded determination of endpoints | Open-label VKA/apixa. + double-blind ASA/placebo | ||||
| Follow-up | 14 months | 6 months | ||||
| CHADS-VASc score | 3.7 ± 1.5 | 3.9 ± 1.6 | ||||
| HAS-BLED score | 2.7 ± 0.7 | 2.9 ± 0.9 | ||||
| PCI with ACS/CCS/non-PCI ACS | 50.5/49.5/- | 37.3/38.8/23.9 | ||||
| Other P2Y12 inhibitors apart from clopidogrel, % | 9.7 | 13.1 | 13.6 | Overall 7.4 | ||
| TTR | 64% | 59% | ||||
| Bleeding endpoint | Major or clinically significant no-nmajor bleeds | Major and clinically significant bleeds after 6 months of treatment | ||||
| 26.9% dabi. 110 | 20.20% | 15.40% | Apixa. vs. VKA | 10.50% | 14.70% | |
| 25.7% dabi. 150 | ASA vs. Placebo | 16.10% | 9.00% | |||
| Major bleeds (TIMI) | 3.8% dabi. 110 | Apixa. vs. VKA | 1.70% | 2.10% | ||
| 3.9% dabi. 150 | 2.10% | 1.40% | ASA vs. placebo | 2.40% | 1.30% | |
| Composite efficacy endpoint | Thrombembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization combined for both dosages | Death or ischemic event (myocardial infarction, confirmed or probable stent thrombosis, stroke, urgent revascularization) | ||||
| 13.40% | 13.70% | Apixa. vs. VKA | 6.70% | 7.10% | ||
| ASA vs. placebo | 6.50% | 7.30% | ||||
| Myocardial infarction | 3.0% dabi. 110 | Apixa. vs. VKA | 3.10% | 3.50% | ||
| 2.9% dabi. 150 | 3.40% | 4.50% | ASA vs. placebo | 2.90% | 3.60% | |
| Overall mortality | 4.9% dabi. 110 | Apixa. vs. VKA | 3.30% | 3.20% | ||
| 4.6% dabi. 150 | 3.90% | 5.60% | ASA vs. placebo | 3.10% | 3.40% | |
ACS, acute coronary syndrome; ASA, acetylsalicylic acid; BMS, bare metal stent; BW, body weight; CCS, chronic coronary syndrome; clopi., clopidogrel; dabi., dabigatran; DES, drug-eluting stent; GFR, glomerular filtration rate; PCI, percutaneous coronary intervention; triple ther., triple therapy (with VKA, ASA, and P2Y12 inhibitors, mainly clopidogrel); TTR, time [of INR] in therapeutic range; VKA, vitamin K antagonist