1. Vascular Overviews Group
Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials
Vascular Overviews Group
15-March-2018

2. PRISMA Diagram 32826 articles identified 10260 through MEDLINE search
22555 through EMBASE search
11 through manual search
8155 duplicates removed
24671 identified for screening
22035 excluded on the basis of title and abstract
2636 full-text articles assessed for eligibility
1286 articles (including 1286 trials) excluded, plus an additional 17 trials reported in articles that also contained an eligible trial.
These 1303 trials were excluded for the
following primary reasons:
- 229 trials not randomised
- 92 trials too short (<2 weeks for prevention
or healing trials)
- 411 unsuitable or confounded comparison
- 508 different-dose or within-class
comparison
- 20 trials of children (<18 years)
- 13 trials in critical care settings
- 10 review articles
- 5 ongoing trials
- 4 variceal indication
- 11 articles unobtainable*
1350 eligible articles, including
1212 eligible trials†
*Full-text copies of these articles were unobtainable from all available sources including the British Library.
†Some trials were published in more than one article (and, conversely, a few articles reported results from more than one trial).

3. Gastroprotectant vs control Gastroprotectant vs gastroprotectant**
Availability of data for measuring the effects of gastroprotectants
Prevention Trials
Healing Trials
Acute Bleeding Trials
Trials (%)
Participants (%)
Gastroprotectant vs control
Endoscopic ulcer*
162 (28)
31580 (29)
207 (89)
22086 (92) -
Symptomatic ulcer*
73 (13)
21505 (19)
Mortality+
185 (32)
57472 (52)
43 (18)
6243 (26)
31 (86)
7596 (97)
Further bleeding, endoscopy, surgery or transfusion
33 (92)
7662 (98)
Bleeds, perforations or obstructions
115 (20)
41764 (38)
No data available for any of the above outcomes
259 (45)
33122 (30)
18 (8)
1250 (5)
2 (6)
106 (1)
Total
580
110626
233
24033 36
7826
Gastroprotectant vs gastroprotectant**
22 (14)
5781 (18)
150 (90)
25494 (90)
15 (9)
3199 (10)
61 (38)
10716 (33)
68 (41)
11739 (41)
16 (89)
3478 (96)
17 (94)
3518 (97)
41 (26)
8065 (24)
74 (46)
16813 (51)
14 (8)
2661 (9)
1 (6)
122 (3)
160
32959
167
28306 18
3640
* Duodenal, gastric or any (i.e, not subdivided). ** Only comparisons between two different class of gastroprotectants were included for analysis. + Cause-specific or total (i.e, all-cause) mortality. Trials with no events reported in both arms contributed to this table. In addition, there were 29 trials in which the number randomised was not reported.

4. Prevention trials - effects of gastroprotectants on endoscopic ulcers
0.1
0.25
0.5 1 2
Prevention trials - effects of gastroprotectants on endoscopic ulcers
No.
Events/Patients (%)
Allocated
GPT
control
Odds Ratio (95 or 99% CI)
Less likely
with GPT
More likely
Any
PPI 29
314/6541 (4.8%)
937/4912 (19.1%)
0.20 ( ) P A 22
228/3427 (6.7%)
435/2532 (17.2%)
0.26 ( )
H2RA
105
1347/8074 (16.7%)
2298/6187 (37.1%)
0.32 ( )
Any GPT
152
1889/18042 (10.5%)
3502/13255 (26.4%)
0.27 ( )
p<0.0001
(Heterogeneity c =
39.5, p<0.0001)
Duodenal
59/3846 (1.5%)
286/3042 (9.4%)
0.14 ( ) PA 17
96/3187 (3.0%)
132/2324 (5.7%)
0.41 ( ) 81
1008/6939 (14.5%)
1709/5083 (33.6%)
0.29 ( )
116
1163/13972 (8.3%)
2085/10073 (20.7%)
0.27 ( )
39.0, p<0.0001)
Gastric 19
212/4150 (5.1%)
501/3356 (14.9%)
0.26 ( )
127/3323 (3.8%)
310/2440 (12.7%)
0.22 ( ) 39
327/3857 (8.5%)
572/2845 (20.1%)
0.39 ( ) 74
666/11330 (5.9%)
1257/8277 (15.2%)
0.30 ( )
25.0, p<0.0001)
99% or
95% CI c c

5. Prevention trials - effects of gastroprotectants on symptomatic ulcers
0.1
0.25
0.5 1 2
Prevention trials - effects of gastroprotectants on symptomatic ulcers
No.
Events/Patients (%)
Allocated
GPT
control
Odds Ratio (95 or 99% CI)
Less likely
with GPT
More likely
Any
PPI 8
28/2585 (1.1%)
152/2587 (5.9%)
0.15 ( ) PA 4
14/4619 (0.3%)
41/4673 (0.9%)
0.38 ( )
H2RA 39
481/2653 (18.1%)
943/2184 (43.2%)
0.27 ( )
Any GPT 51
523/9857 (5.3%)
1136/9444 (12.0%)
0.25 ( )
p<0.0001
(Heterogeneity =
12.7, p=0.0018)
Duodenal
1/60 (1.7%)
44/63 (69.8%)
0.05 ( )
7/4404 (0.2%)
14/4439 (0.3%)
0.52 ( ) 29
404/2204 (18.3%)
786/1734 (45.3%)
0.26 ( ) 31
412/6668 (6.2%)
844/6236 (13.5%)
0.25 ( )
19.6, p<0.0001)
Gastric -
7/4444 (0.2%)
17/4482 (0.4%)
0.44 ( ) 6
64/228 (28.1%)
97/224 (43.3%)
0.48 ( )
71/4672 (1.5%)
114/4706 (2.4%)
0.47 ( )
0.0, p=0.85)
99% or
95% CI c c c

6. 0.1
0.5 1
2.5
Prevention trials - effects of gastroprotectants on ulcer complications and all-cause mortality
No.
Events/Patients (%)
Allocated
GPT
control
Odds Ratio (95 or 99% CI)
Less likely
with GPT
More likely
Bleeds
PPI 18
14/5910 (0.2%)
88/4937 (1.8%)
0.21 ( ) PA 3
33/4464 (0.7%)
53/4489 (1.2%)
0.63 ( )
H2RA 29
43/3631 (1.2%)
84/2779 (3.0%)
0.49 ( )
Any GPT 49
90/14139 (0.6%)
221/12130 (1.8%)
0.40 ( )
p<0.0001
(Heterogeneity 2 =
15.3, p=0.0005)
Perforations
1/1917 (0.1%)
2/981 (0.2%)
0.31 ( )
1/4700 (0.0%)
8/4594 (0.2%)
0.19 ( )
0/49 (0.0%)
1/50 (2.0%) 5
2/6666 (0.0%)
10/5470 (0.2%)
0.21 ( )
p=0.0089
0.2, p=0.92)
Obstructions
1/1938 (0.1%)
1/1935 (0.1%)
0/4404 (0.0%)
3/4439 (0.1%)
0.14 ( )
3/394 (0.8%)
6/404 (1.5%)
0.52 ( ) 4
4/6736 (0.1%)
10/6778 (0.1%)
0.43 ( )
p=0.12
1.4, p=0.49)
All-cause mortality
37/7471 (0.5%)
31/5352 (0.6%)
1.01 ( )
17/4853 (0.4%)
20/4752 (0.4%)
0.81 ( )
420/3520 (11.9%)
445/2959 (15.0%)
0.83 ( ) 51
474/15844 (3.0%)
496/13063 (3.8%)
0.85 ( )
p=0.11
0.5, p=0.77)
99% or
95% CI c c c c

7. ulcers, bleeds and all-cause mortality, subdivided by use of NSAIDs
0.1
0.25
0.5 1
2.5
Prevention trials - effects of gastroprotectants on endoscopic and symptomatic
ulcers, bleeds and all-cause mortality, subdivided by use of NSAIDs
No.
tNSAID/
COXIB/
aspirin use
Events/Patients (%)
Allocated
GPT
control
Odds Ratio (95 or 99% CI)
Less likely
with GPT
More likely
Any endoscopic ulcer
NSAID use 51
660/11409 (5.8%)
1220/8068 (15.1%)
0.27 ( )
No NSAID use 34
397/2089 (19.0%)
784/1674 (46.8%)
0.26 ( ) T
otal 85
1057/13498 (7.8%)
2004/9742 (20.6%)
0.27 ( )
p<0.0001
(Heterogeneity 2 =
0.2, p=0.62)
Any symptomatic ulcer 9
23/6871 (0.3%)
95/6917 (1.4%)
0.28 ( ) 17
162/1369 (11.8%)
449/1127 (39.8%)
0.21 ( ) 26
185/8240 (2.2%)
544/8044 (6.8%)
0.22 ( )
2.0, p=0.16)
Bleeds 21
50/11706 (0.4%)
146/10106 (1.4%)
0.35 ( ) 10
8/648 (1.2%)
24/555 (4.3%)
0.28 ( ) 31
58/12354 (0.5%)
170/10661 (1.6%)
0.34 ( )
0.3, p=0.56)
All-cause mortality
38/11944 (0.3%)
34/9826 (0.3%)
0.95 ( ) 5
5/466 (1.1%)
2/462 (0.4%)
2.34 ( ) 22
43/12410 (0.3%)
36/10288 (0.3%)
1.03 ( )
p=0.90
1.3, p=0.25)
99% or
95% CI c c c c

8. Healing trials - effects of gastroprotectants on ulcer healing
0.5 1 2 5
Healing trials - effects of gastroprotectants on ulcer healing
No.
Events/Patients (%)
Allocated
GPT
control
Odds Ratio (95 or 99% CI)
Less likely
with GPT
More likely
Endoscopic ulcer healing
PPI 24
1650/1925 (85.7%)
650/1033 (62.9%)
5.22 ( ) PA 37
1501/2452 (61.2%)
751/1729 (43.4%)
2.27 ( )
H2RA
148
5714/7533 (75.9%)
2676/5670 (47.2%)
3.80 ( )
Any GPT
207
8865/11910 (74.4%)
4050/8373 (48.4%)
3.49 ( )
p<0.0001
(Heterogeneity =
62.0, p<0.0001)
Endoscopic duodenal ulcer healing 17
950/1095 (86.8%)
426/672 (63.4%)
5.91 ( ) 19
866/1458 (59.4%)
382/953 (40.1%)
2.21 ( ) 97
3924/5154 (76.1%)
1786/3929 (45.5%)
4.09 ( )
131
5740/7707 (74.5%)
2567/5495 (46.7%)
3.73 ( )
53.4, p<0.0001)
Endoscopic gastric ulcer healing 4
648/774 (83.7%)
179/306 (58.5%)
4.47 ( ) 16
435/698 (62.3%)
252/577 (43.7%)
2.60 ( ) 45
1306/1675 (78.0%)
773/1421 (54.4%)
3.05 ( ) 65
2389/3147 (75.9%)
1204/2304 (52.3%)
3.09 ( )
6.9, p=0.0325)
99% or
95% CI c c c

9. Acute UGI bleeding treatment trials - effects of gastroprotectants on
0.25
0.5 1 2
Acute UGI bleeding treatment trials - effects of gastroprotectants on
further bleeding, need for blood transfusion and endoscopic interventions
No.
Events/Patients (%)
Allocated
GPT
control
Odds Ratio (95 or 99% CI)
Less likely
with GPT
More likely
Further bleeding
PPI 12
192/2234 (8.6%)
311/2198 (14.1%)
0.57 ( )
H2RA 18
320/1487 (21.5%)
376/1478 (25.4%)
0.79 ( )
Any GPT 30
512/3721 (13.8%)
687/3676 (18.7%)
0.68 ( )
p<0.0001
(Heterogeneity =
6.5, p=0.0107)
Blood transfusion 5
449/974 (46.1%)
542/967 (56.0%)
0.67 ( )
266/434 (61.3%)
259/426 (60.8%)
1.01 ( ) 10
715/1408 (50.8%)
801/1393 (57.5%)
0.75 ( )
p=0.0003
6.2, p=0.0130)
Endoscopic interventions 8
140/1890 (7.4%)
234/1906 (12.3%)
0.56 ( ) -
0.56 ( )
99% or
95% CI c c

10. Acute UGI bleeding treatment trials - effects of gastroprotectants on
0.25
0.5 1 2
Acute UGI bleeding treatment trials - effects of gastroprotectants on
surgery and all-cause mortality
No.
Events/Patients (%)
Allocated
GPT
control
Odds Ratio (95 or 99% CI)
Less likely
with GPT
More likely
Surgery
PPI 12
120/2234 (5.4%)
187/2198 (8.5%)
0.62 ( )
H2RA 15
197/1331 (14.8%)
239/1349 (17.7%)
0.81 ( ) An
y GPT 27
317/3565 (8.9%)
426/3547 (12.0%)
0.72 ( )
p<0.0001
(Heterogeneity =
2.9, p=0.09)
All-cause mortality
84/2234 (3.8%)
86/2198 (3.9%)
0.98 ( ) 17
95/1526 (6.2%)
113/1525 (7.4%)
0.83 ( ) 29
179/3760 (4.8%)
199/3723 (5.3%)
0.90 ( )
p=0.31
0.5, p=0.46)
99% or
95% CI c c