First-line eradication of Helicobacter pylori: Are the standard triple therapies obsolete? A different perspective

Table 1 Topics of meta-analyses of Helicobacter pylori eradication between 1992-2010

Topics of meta-analysis	No. of studies
First-line triple therapies	25
PPI-based therapies	22
Ranitidine bismuth citrate-based therapies	3
Bismuth-based quadruple therapies	2
Non-bismuth-based quadruple therapies	1
Histamine H2 receptor blockers + two different antibiotics	5
Rescue (second- and third-line) therapies	3
Sequential therapies	4
Alternative therapies	4
Eradication in functional dyspepsia	20
Eradication in peptic ulcer	10
Effect of CagA status on eradication	1
Gastric cancer prevention	5
Eradication in children	2
Eradication in prevention of NSAID-ulcers	1
Eradication in extradigestive diseases	5
Effect of probiotics on eradication results	5
Eradication and antimicrobial resistance	4
Effect of CYP polymorphism on eradication	2
Adverse effects of eradication	4
Multiple topics	11
Total	113

PPI: Proton pump inhibitors; NSAID: Nonsteroidal anti-inflammatory drugs; CYP: Cytochrome P450 isoenzyme.

Table 2 First-line standard triple therapies for Helicobacter pylori eradication: chronological order and results of meta-analyses

Author	Databases, abstracts1	Study period	No. of studies	No. of patients	Eradication rate [ITT, (%) mean + 95% CI]	Duration of treatment (d)	Comments
Bazzoli et al[11]	Medline	1993-1996	14	507	LAC: 80.6	7	L and O are equally efficient
					OAC: 69.6
Laheij et al[12]	Medline, abstracts	1983-1998	644	53 228	PPI + A + C: 80.09 (NS)	7-14
Huang et al[13]	Medline, PubMed, abstracts	1986-1998	82	6123	PPI + A + C: 89.5.6 (86.9-92.0)	7	C 500 mg b.i.d. achieved the best result
					PPI + A + M: 90.8% (87.0-94.5)
Gisbert et al[14]	PubMed	1986-1999	22	2862	PPI + A + C: 81 (76-85)	7	PAC and PAN have similar efficiency
					PPI + A + N: 84 (79-89)
Gisbert et al[15]	PubMed + abstracts	1995-1999	12	1170	RBC + A + C: 76.6 (72-81)	7	RBC + AC and PPI + AC have similar efficiency, RBC + CN has higher efficiency than PPI + CN
					RBC + CN: 87.2 (83-91)
					PPIAC: 73.7 (69-78)
					PPIAN: 74.9 (71-84)
Calvet et al[16]	Medline + abstracts	1990-1999	21	1349	PPI + 2AB		Triple therapies of 14 d are superior to 7, but not 10 d regimens
					76 (68-86)	7
					82 (77-86)	10
					84 (79-8)	14
Janssen et al[17]	Medline + abstracts	1994-2000	47	3541	RBC + A + C: 81 (71-96)	5-10	PPI + AC and NC are equally effective, RBCNC is superior to RBCAC
					RBC + N + C: 88 (78-94)
					PPI + A + C: 79 (24-95)
					PPI + N + C: 79 (42-100)
Vallve et al[18]	Medline + abstract	1996-2000	13	2391	Single dose PPI: 77.7 (72-77)	7	Single dose PPI triple regimens are less efficient
					Double dose PPI: 83.9 (81-85)
Vergara et al[19]	Medline + abstracts	1995-2002	134	3293	O: 74.7 (NS)	7	PPIs are similar in standard triple therapy
					L: 74.7 (NS)
					R: 77.9 (NS)
					E: 87.9 (NS)
Gené et al[20]	PubMed, abstracts	1995-2002	5	1118	Triple therapy: 79 (74-81)	7-10	The effectiveness of triple and quadruple therapies is similar
					Quadruple therapy: 80 (77-84)
Gisbert et al[21]	Medline, Embase, CINAHL, CCTR	1996-2002	7	2226	RAC: 79 (76-82)	7-14	R, O and L achieved similar results
					OAC: 77 (74-80)
					LAC: 77 (75-79)
Gisbert et al[22]	Medline, congress abstracts	1997-2003	12	1137	P + 2AB: 83 (78-88)	7	P, O and L achieved similar results
					O, L + 2AB: 81 (77-86)
Gisbert et al[23]	Medline, congress abstracts	1999-2003	4	816	E + 2AB: 85 (81-89)	7	E + 2AB has comparable efficacy with O + 2AB
					O + 2AB: 82 (78-86)
Gisbert et al[24]	Medline, Embase, CINAHLISIWS + congress abstracts	1997-2004	14	4435	RBC + C + A: 79.5 (72.2-83.7)	7-10-14	RBC or PPI + A + C are comparable, RBC + C + N is superior to PPI + C + N
					PPI + C + A: 78.1 (73.6-84.1)	7-10-14
					RBC + C + N: 87.4 (82.8-93.6)	7-10-14
					PPI + C + N: 79.9 (73.6-84.8)	7-10-14
Padol et al[25]	Medline, Embase, CCTR	1996-2005	17	1569	PPI + 2AB	7-14	O, but not L and R effect is influenced by CYP2C19 status
					PM: 88.9 (81.2-97.6)
					HomEM: 70.9 (64.3-77.4)
					HetEM: 82.7 (75.3-89.2)
Suzuki et al[26]	PubMed	1998-2005	14	1529	CagA +: 84% (79-89%)	7-14	Presence of CagA is predictive for a successful eradication
					CagA-: 73% (65-82)
Wang et al[27]	Medline, Embase, CCTR	2000-2005	11	2159	E + 2AB: 86%	7	E, O and P are of comparable efficiency
					PPI + 2AB: 81%
Buzás et al[28]	Abstracts	1997-2004	75	15 634	PPI + 2AB: 81.4% (78.5-84.5)	7	PPIs, RBC + 2AB and quadruple regimens are equally efficient as first-line therapies
					RBC + 2AB: 78.5% (70.5-84.3)
					PPI + 2AB + bismuth: 82.6% (76.0-89.2)
Fuccio et al[29]	Medline, Embase, CCTR, abstracts	1996-2007	21	4831	PPI + 2AB:		Extending triple therapy to 10-14 d is not useful
					75% (72-77)	7
					80.7% (75.2-85.7)	10
					78.2% (74.3-82.6)	14
Villoria et al[30]	PubMed, ISIWS, Embase, CCTR CINAH, abstracts	1990-2007	6	1703	High-dose PPI: 82% (78-84)	7	High-dose PPIs are 8% more effective than standard doses in 7 d therapies
					Standard dose PPI: 74% (NS)
Zhao et al[31]	Medline, PubMed, Embase, ISIWB, CCTR, Chinese Databases	1999-2007	20	3330	PMs: 91.6 (83-99)	7-10-14	O and L effects are dependent on CYP2C19 genotype, R effect is not dependent
					HetEMs: 85.5 (79.6-92.3)
					HomEMs: 74.6 (70.1-79.8)
Essa et al[32]	PubMed, Embase, CCTR + abstracts	1990-2008	9	1054	Triple therapies: 76.8 (72.2-81.2)	5-10	Concomitant quadruple therapy is superior to standard triple therapy
					Concomitant quadruple therapy: 89.7% (86.8-92.1)	7
Luther et al[33]	Medline, Embase, Google Scholar, CCTR, ACP Journal Club	1996-2009	9	1679	PPI + AC: 77.0 (71-84)	7	Triple and quadruple therapies yielded similar suboptimal results
					PPI + 2AB +
					Bi: 78.3 (71.7-84.6)

¹Abstracts of the Digestive Diseases Week, United European Digestive Week and European Helicobacter Study Group annual meetings. Abbreviations: A: Amoxicillin; AB: Antibiotic; Bi: Bismuth compound C: Clarithromycin; CCTR: Cochrane Controlled Trials Register; CI: 95% confidence interval; E: Esomeprazole; ISIWB: Institute of Scientific Information Web of Science; ITT: Intention-to-treat; HetEM: Heterozygous extensive metabolizers; HomEM: Homozygous extensive metabolizers; L: Lansoprazole; N: Nitroimidazole; P: Pantoprazole; PM: Poor metabolizers; PPI: Proton pump inhibitor; O: Omeprazole; R: Rabeprazole; RBC: Ranitidine bismuth citrate.