Adverse events with bismuth salts for Helicobacter pylori eradication: Systematic review and meta-analysis

Table 1 Characteristics of included studies

Study	Country	No. of centres	Bismuth compound used1	Duration of bismuth therapy (days)	Total dose (mg/d) used	Method of collection of adverse event data	Generation of randomization schedule provided	Method of concealment of allocation provided	Double-blind
Bujanda 2001[15]	Spain and Portugal	Multi-centre	RBC	7	800	Unclear	Yes	No	Yes
Burette 1992[16]	Belgium	1	CBS	10	480	Unclear	No	No	No
Buzas 2001[17]	Hungary	1	RBC	7	800	Unclear	No	No	No
Carpintero 1997[18]	Spain	1	CBS	42	480	Unclear	Yes	No	No
Carvalho 1998[19]	Brazil	1	BSN	14	1200	Unclear	No	No	No
Catalano 2000[20]	Italy	1	RBC	10	800	Questionnaire	Yes	No	Yes
Chuang 2001[22]	Taiwan	1	RBC	7	800	Unclear	No	No	Yes
Dal Bo 1998[23]	Italy	1	TDB	14	480	Unclear	No	No	No
Danese 2001[24]	Italy	1	RBC	7	800	Validated questionnaire	No	No	No
Eberhardt 1990[25]	Germany	4	BSS	28	1800	Unclear	No	No	No
Fakheri 2004[26]	Iran	1	CBS	14	480	Unclear	Yes	No	No
Forne 1995[27]	Spain	1	CBS	7	480	Diary cards	No	Yes	No
Gasbarrini 2000[28]	Italy	1	RBC	7	800	Validated questionnaire	No	No	No
Georgopoulos 1999[29]	Greece	3	RBC	7	800	Unclear	No	No	No
Gisbert 2000[30]	Spain	1	RBC	7	800	Unclear	Yes	No	No
Graham 1998[31]	USA	111	RBC	28	800	Unclear	No	No	Yes
Hung 2002[32]	Hong Kong	3	RBC	7	800	Diary	Yes	Yes	No
Lanza 1989[33]	USA	1	BSS	21	2100	Unclear	No	No	Yes
Lanza 1998[34]	USA	47	RBC	28	800	Diary cards	No	No	Yes
Liu 1999[35]	China	1	TDB	7	480	Diary	No	No	No
Mao 2000[36]	Vietnam	1	RBC	10	400	Diary	No	No	No
Marshall 1988[7]	Australia	1	CBS	56	480	Unclear	No	No	Yes
Masci 1995[37]	Italy	1	CBS	28 to 56	480	Unclear	Yes	No	Yes
Nafeeza 1992[38]	Malaysia	1	CBS	28	480	Unclear	No	No	Yes
Pare 1999[39]	Multi-national	Multi-centre	RBC	28	800	Unclear	Yes	No	Yes
Perri 2002[40]	Italy	1	RBC	7	800	Questionnaire	No	No	No
Peterson 1996[41]	USA	38	RBC	28	800	Unclear	No	No	Yes
Rokkas 1988[42]	UK	1	CBS	56	480	Unclear	No	No	Yes
Spadaccini 1998[43]	Italy	1	RBC	7	800	Face-to-face interview	No	No	No
Spiliadis 1998[44]	Greece	3	CBS	14	1200	Unclear	No	No	No
Spinzi 2000[45]	Italy	6	RBC	7	800	Face-to-face interview	No	No	No
Sung 1998[46]	Hong Kong	1	RBC	7	800	Telephone interview	No	No	No
Whitehead 2000[47]	UK	1	CBS and BSN	28	Unclear	Unclear	Yes	Yes	Yes
Wong 2001[48]	Hong Kong	1	RBC	7	800	Diary	Yes	Yes	No
Xiao 2001[21]	China	Multi-centre	CBS	7	480	Diary	No	No	No

¹BSN: Bismuth subnitrate; BSS: Bismuth subsalicylate; CBS: Colloidal bismuth subcitrate; RBC: Ranitidine bismuth citrate; TDB: Tripotassium dictrato bismuthate.

Table 2 Crude adverse event rates, and relative risk of adverse events

Adverse event	Number of trials	Total number of patients	Number of patients in bismuth arms	Number of patients in comparison arms	Number of adverse events in bismuth arms (%)	Number of adverse events in comparison arms (%)	Relative risk of adverse events with bismuth versus comparison regimen (95% CI)
Any	25	3180	1585	1595	431 (27.2)	419 (26.3)	1.01 (0.87-1.16)
Abdominal pain	13	2439	1221	1218	63 (5.2)	61 (5.0)	1.06 (0.64-1.74)
Dark stools	4	467	233	234	39 (16.7)	5 (2.1)	5.06 (1.59-16.12)
Diarrhoea	22	3406	1761	1645	124 (7.0)	113 (6.9)	1.01 (0.72-1.42)
Dizziness	8	1630	867	763	54 (6.2)	49 (6.4)	1.18 (0.81-1.72)
Headache	14	2433	1276	1157	41 (3.2)	28 (2.4)	1.31 (0.81-2.11)
Metallic taste	14	2475	1260	1215	124 (9.8)	116 (9.6)	1.02 (0.81-1.28)
Nausea and/or vomiting	20	3417	1767	1650	111 (6.3)	86 (5.2)	1.16 (0.89-1.52)
Leading to withdrawal of therapy	28	3951	2033	1918	33 (1.6)	38 (2.0)	0.86 (0.54-1.37)