TABLE 1.
Characteristics of the included studies and patients.
| Study name | RCT Type/ Design |
Treatment | Comparator | Population | Total (N) | Mean age (yr) | Male N/(%) | Duration comparison (mo) | Follow up (mo) | Time of randomization | Time from PCI to randomization |
| Dapt study | |||||||||||
| Mauri et al. (8) | Double-Blind Superiority | Thienopyridine drug plus ASA (75–162 mg daily) | Placebo plus ASA (75 -162 mg daily) | Patients older than 18 years of age who were candidates for DAPT after treatment with FDA-approved drug-eluting stents | 9961 | 61.7 | 7435/ (74.64%) |
12 vs. 30 = 18 | 33 | 12 mo. after PCI | 12 mo. |
| Clopidogrel 75 mg daily | |||||||||||
| NCT00977938 | Prasugrel✧10 mg daily | ||||||||||
| Themis | |||||||||||
| Steg et al. (13) | Double-Blind Superiority |
Ticagrelor* (60 mg twice daily) plus ASA (75–150 mg daily). |
Placebo plus ASA (75–150 mg daily) | Patients who were 50 years of age or older and who had stable CAD (a history of previous PCI or CABG or documentation of angiographic stenosis of at least 50% in at least one coronary artery) and type 2 diabetes mellitus | 19220 | 66 | 13189/ (68.62%) |
Median of 39.9 | At enrollment | Median of 3.3 yr. | |
| NCT01991795 | |||||||||||
| Compass | |||||||||||
| Connolly et al. (14) | Double-Blind Superiority | Rivaroxaban (2.5 mg twice daily) plus ASA (100 mg once daily) | Placebo twice daily and ASA (100 mg daily). | Patients who were at least 65 years old with a diagnosis of CAD, patients had to have either MI within 20 years, multi-vessel CAD, history of stable or unstable angina, previous multi-vessel PCI, or previous multi-vessel CABG | 16574 | 69 | 13192 (79.59%) |
Mean of 1.95 yr. : 23.4 | After a 30-day run-in period since enrollment | Mean of 5.4 yr. | |
| NCT01776424 | |||||||||||
| Optidual | |||||||||||
| Helft et al. (7) | Open Label Superiority | Clopidogrel (75 mg daily) plus ASA (75–160 mg daily) | ASA (75–160 mg daily) | Patients had symptoms of stable angina, silent ischemia, ACS (unstable angina, NSTEMI, STEMI) with ≥ 1 lesion with stenosis ≥ 50% located in a native vessel ≥ 2.25 mm in diameter and who were implanted with ≥ 1 DES of any type | 1385 | 64.1 | 1115/ (80.50%) |
12 ± 3 vs. 48 ± 3 = 36 | Median of 33.4 (IQR, 18.9–36.5) | 12 ± 3 mo. after PCI | 12 ± 3 mo. |
| NCT00822536 | |||||||||||
| Pegasus-timi | |||||||||||
| Bonaca et al. (15) | Double-Blind Superiority | Ticagrelor (90/60 mg twice daily) plus ASA (75–150 mg daily) | Placebo plus ASA (75–150 mg daily) | Patients had spontaneous MI 1 to 3 years before enrollment, were at least 50 years of age, and had one of the following additional high-risk features: age of 65 years or older, diabetes mellitus requiring medication, a second prior spontaneous MI, multivessel CAD, or chronic renal dysfunction: defined as an estimated creatinine clearance of less than 60 ml/min. | 21162 | 65.3 | 16102/ (76.10%) |
Median of 33 (IQR, 28 to 37) | At enrollment | Median of 1.6 yr. | |
| Ticagrelor (90 mg twice daily) plus ASA (75–150 mg daily) | |||||||||||
| Ticagrelor (60 mg twice daily) plus ASA (75–150 mg daily) | |||||||||||
| NCT01225562 | |||||||||||
| Lee et al. (16) | Open Label Superiority | Clopidogrel (75 mg daily) plus ASA (100–200 mg daily) | ASA (100-200 mg daily) | Patients had undergone implantation with DES at least 12 months before enrolment, no MACE (MI, stroke, or repeat revascularization) or major bleeding since implantation, DAPT on board | 5045 | 62.4 | 3498/ (69.33%) |
12 vs. 36 = 24 | Median of 42.0 (IQR, 24.7–50.7) | 12-18 mo. after PCI | 12 mo. |
|
NCT01186146 |
|||||||||||
| Prodigy | |||||||||||
| Valgimigli et al. (17) | Open Label Superiority | Clopidogrel (75 mg daily) plus ASA (80–160 mg daily) | ASA (80–160 mg daily) | Patients undergoing elective, urgent, or emergent coronary angioplasty with intended stent implantation | 1970 | 67.8 | 1511/ (76.70%) |
6 vs. 24 = 18 | 24 | 30 ± 5 days after PCI | 30 ± 5 days |
| NCT00611286 | |||||||||||
| Dadjou et al. (20) | Open Label | Clopidogrel (75 mg daily) plus ASA (75 mg daily) | ASA (75 mg daily) | Patients who were referred for elective, urgent, or emergency coronary angioplasty with intended stent implantation | 1010 | 60 | 647 (64.05%) | Less vs. more than 12 | More than 36 | Randomization at index PCI | |
| NCT02327741 | |||||||||||
| Real-late/Zest late | |||||||||||
| Park et al. (18) | Open Label Superiority | Clopidogrel (75 mg daily) plus ASA (100–200 mg daily) | ASA (100 mg daily) | Patients who had received drug-eluting stents and had been free of major adverse cardiac or cerebrovascular events and major bleeding for a period of at least 12 months to receive clopidogrel plus aspirin or aspirin alone. | 2701 | 61.9 | 1883/ (69.71%) |
12 vs. 36 = 24 | Median of 33.2 (IQR, 28.1–37.6) | 12 mo. after PCI with the placement of DES | 12 mo. |
|
NCT00484926, NCT00590174 |
|||||||||||
| Smart-date & | |||||||||||
| Hahn et al. (19) | Open Label Non-inferiority | P2Y12 inhibitor** plus ASA (100 mg daily) | ASA (100–200 mg daily) | Patients had unstable angina, NSTEMI, or STEMI, with at least one lesion in a native coronary vessel with reference diameter of 2.25–4.25 mm and stenosis >50% amenable for PCI with stents. | 2712 | 62.1 | 2044/ (75.36%) |
6 vs. 12.6 to 18 | Median of 17.7 (IQR, 12.6–18.0) | Randomization at index PCI | |
| Clopidogrel (75 mg daily) plus ASA (100 mg daily) | 2191& | 1651/ (75.36%) |
|||||||||
| NCT01701453 | |||||||||||
| Trilogy^ | |||||||||||
| Roe et al. (12) | Double-Blind Superiority | Prasugrel (10 mg daily) plus ASA | Clopidogrel (75 mg daily) plus ASA | Patients (age < 75) with unstable angina or NSETMI who do not undergo revascularization | 7243 | 62 | 4644/ (64.12%) |
6 to 30 months | Median of 17.1 (IQR, 10.4-24.4) | Within 10 days of the index event | Excluded |
| NCT00699998 | |||||||||||
✧ Dose of 5 mg daily recommended in patients who weighed less than 60 kg.
* Patients converted to dosage regimen of 60 mg twice daily after median exposure of 7.7 months to the 90 mg dose.
**Clopidogrel 75 mg daily or prasugrel 10mg daily or Ticagrelor 90 mg twice daily.
& Due to missing data referred to patients randomly assigned to another P2Y12 inhibitor separately, only available data on clopidogrel was included in the analysis.
^The comparator in this trial is considered also as intervention.