Background
Methods
Data sources
Study Selection
Data Extraction and Quality Assessment
Data Analysis
Results
Description of Included Studies and Quality Assessment
Patients Randomised Post Elective CABG | Patients Randomized with ACS or symptomatic CAD - CABG Subgroup | ||||||||
---|---|---|---|---|---|---|---|---|---|
Clopidogrel 300 then 75 mg/d vs placebo | Clopidogrel 75 mg/d | Clopidogrel 75 mg/d vs placebo | Clopidogrel 75 mg/d | Clopidogrel 75 mg/d | Clopidogrel 300 then 75 mg/d vs placeboa | Clopidogrel 300 then 75 mg/d vs placebo | Ticagrelor 180 then 90 mg bid vs Clopidogrel 300 then 75 mg/d | Prasugrel 60 then 10 mg/d vs Clopidogrel 300 then 75 mg/d | |
ASA Dose (mg/d) | 325 then 81 | 100 | 162 | 100 | 300 | 325 | 75-325 | 75-100 | 75-162 |
Trial | Sun et al. [16] | Gao et al. [15] | CASCADE [21] | CRYSSA [22] | Gasparovic [23] | CREDO [18] | CURE [19] | PLATO [17] | TRITON- TIMI 38 [11] |
n = CABG/total patients | n = 100/100 | n = 249/249 | n = 113/113 | n = 300/300 | n = 224/224 | n = 83/2116 | n = 2072/12562 | n = 1261 (1899)/18624 | n = 346 (485)/13608 |
Trial Characteristics | |||||||||
No. of Centres | 1 | 1 | 2 | 1 | 1 | 99 | 428 | 862 | 707 |
Enrolment period | Nov 2006 – Feb 2008 | Dec 2007 – Dec 2008 | May 2006 – Jul 2008 | Dec 2006 – Oct 2009 | Jun 2010 – Feb 2013 | Jun 1999 – Apr 2001 | Dec 1998 – Sep 2000 | Oct 2006 – Jul 2008 | Nov 2004 – Jan 2007 |
Treatment/Follow Up Post Randomization | 30 (all)/49 (median) d | 3 months (all) | 12 months (all) | 12 months (all) | 6 months (all) | 12 months (all) | 9 months (mean) | 224 days [7.5 months] (median) | 14.5 months (median) |
Median Time to CABG Post Randomization | (Randomized At Time of CABG) | n/r (index CABG instead of PCI) | 25.5 days (IQR 12–70.5) | ~20 days | 100 days [50] | ||||
Treatment/Follow Up Post CABG | 30 (all)/49 (median) d | 3 months (all) | 12 months (all) | 12 months (all) | 12 months (all) | ~12 months (all) | ~8 months (mean) | ~200 days [6.7 months] (median) | ~11.2 months (median) |
Funding | Public/ Industry | Public | Public/Industry | n/r | n/r | Industry | Industry | Industry | Industry |
Patients | n = 99 | n = 224 | n = 113 | n = 300 | n = 219 | n = 83 | n = 2072 | n = 1261 | n = 346 |
Mean Age (years) | 65 | 59 | 67 | 59 | 65 | 61 | 64 | 64 | 61 |
% Male | 90 | 83 | 89 | 74 | 75 | 74 | 70 | 79 | 77 |
BMI | 31 | 26 | 28 | 26 | 29 | 29 | 27 | n/r (28b) | |
Diabetes | 35 % | 40 % | 29 % | 0 % (excl) | 38 % | 22 % | 27 % | 32 % | 28 % |
Hypertension | 70 % | 59 % | 50 % | 46 % | 96 % | 75 % | 61 % | 68 % | 64 % |
Smoker | 59.6 % (current/ former) | 55.8 % (history of) | 13.2 % | n/r | 36 % | 33 % (within 1 year) | 64.5 % (current /former) | 31.2 % | n/r (38 %b) |
COPD | n/r | n/r | 8.1 % | ||||||
Dyslipidemia | 76 % | 38 % | 88 % | 56 % | 96 % | 71 % | n/r | 54 % | n/r (56 %b) |
Prev MI | 39 % | 47 % | n/r | 36 % | n/r | 37 % | 36 % | 20 % | n/r (18 %b) |
Prev stroke/TIA | 5.1 % | 4.9 % | n/r | n/r | n/r | n/r | 3.9 % | 3.9 %/3.1 % | 7.8 % |
Periph Vasc Dz | 5.1 % | n/r | n/r | n/r | n/r | 6.2 % | 9.7 % | 7.6 % | 7.0 % |
Chronic Renal Disease | excl Cr >130 μM | n/r | n/r | excl Cr >177 μM | n/r | n/r | n/r | 4.8 % | n/r (11 % CrCl < 60 mL/minb) |
Mean LVEF | n/r | 60 % | 54 % | 54 % | 53 % | ||||
CHF | 0 % (excl) | 20.3 % | n/r | n/r | 7.3 % | 4.1 % | 10.7 % | ||
Severe LV dysfunction | 38 %(Gr 3 LV) | 0 % (excl) | n/r | n/r | n/r | n/r | Excluded | 3.9 % (EF ≤ 30 %) | |
1 % (Gr 4 LV) | |||||||||
Previous PCI | n/r | 13 % | 16 % | n/r | 17 % | 7.4 % | 10 % | n/r | |
Previous CABG | n/r | 0 % (excl) | 0 % (excl) | n/r | n/r | 8.5 % | 4.6 % | 1.5 % | 2.9 % |
3VD | 54 % | n/r | 77 % | n/r | |||||
LM | 24.2 % | n/r | 48 % | n/r | |||||
ST depression | 54.2 % | ||||||||
ST elevation | 2.7 % | 33.0 % (persistent) | |||||||
Abnormal ECG | 95.2 % | ||||||||
Diagnosis: UA | 73.9 % | 64.1 % (UA/NSTEMI) | |||||||
Diagnosis: MI | 26.1 % (all NSTEMI) | 35.9 % (STEMI) | |||||||
Abnormal ECG/enzymes | 97.7 % | ||||||||
CABG | |||||||||
% Off-pump CABG | 0 % | 58.0 % | 3.6 % | 100 % | 0 % | ||||
% arterial conduits | 100 % | 100 % | 100 % | 100 % | 93 % | ||||
Grafts or adiseased vessels | 4.0 | 3.1 | 3.5 ± 0.7 | 3.2 ± 0.6 | n/r | 1–2 (31 %) | a1 (14.4 %) | ||
3–4 (60 %) | a2 (61.5 %) | ||||||||
≥5 (8 %) | a3 (20.5 %) | ||||||||
Median (IQR) days to CABG (all) | 25.5 (12–70.5) | ~20 | 100(36) | ||||||
CABG pre-d/c | 49 % | 57 % | 4.3 % | ||||||
Median (IQR) days to CABG pre-d/c | 13 (8–21) vs 12 (8–19) | ||||||||
CABG post-d/c | 51 % | 43 % | 95.7 % | ||||||
Median (IQR) days to CABG post d/c | 67.5 (38–141) vs 73 (36–129) | ||||||||
Days off study drug before CABG | 17 (9–33) | ≤2d (30.1 %) 3-5d (43.8 %) >5 (26.1 %) | ≤2d (25.1 %) 3-5d (29.0 %) >5 (45.4 %) | ||||||
Restarted treatment post CABG | 76.1 % (66 never discontinued + 1451 resumed/1928; 78 data unavailable) | 66.4 % | 61.8 % (214/346); additional 21/173 prasugrel and 16/173 clopidogrel patients resumed open label clopidogrel | ||||||
Days off study drug after CABG | 10 (6–25) | <7d (35.9 %) | n/r | ||||||
7–14(16.8 %) | |||||||||
>14d (10.0 %) |
Trial | Blinded | Concealed allocation | Intention to treat analysis | Not stopped early for benefit | < 5 % Randomized Patients with Missing Outcome Data |
---|---|---|---|---|---|
Yes | Yes (central randomization) | Yes | Yes | Yes (0.1 %: 13/12,562 overall; 0 % of CABG) | |
Yes | Yes (central randomization) | Yes | Yes | Yes (0.03 %: 5/18,624 overall) | |
Yes | Yes (central randomization) | Yes | Yes | Yes (0.1 %: 14/13,608 overall) | |
Yes | Yes | Yes | Yes | Yes (0 %) | |
CRYSSA [22] | No | Yes | Yes | Yes | Yes (0.3 %: 1/300) |
CASCADE [21] | Yes | Yes | Yes | Yes | Yes (0 %) |
Gao 2010 [15] | No | Unclear | Yes | Yes | Yes (3.7 %: 9/249) |
Sun 2010 [16] | Yes | Yes | Yes | Yes | Yes (1.0 %: 1/100) |
Gasparovic 2014 [23] | No | Yes | Yes | Yes | Yes (2.2 %: 5/224) |