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Bisphosphonates and risk of atrial fibrillation: a meta-analysis.

Kim SY, Kim MJ, Cadarette SM, Solomon DH - Arthritis Res. Ther. (2010)

Bottom Line: Egger's and Begg's tests did not suggest an evidence of publication bias (P = 0.90, 1.00 respectively).Few studies compared risk between bisphosphonates or by dosing.Our study did not find an association between bisphosphonate exposure and AF.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Rheumatology, Allergy and Immunology, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. skim62@partners.org

ABSTRACT

Introduction: Bisphosphonates are the most commonly used drugs for the prevention and treatment of osteoporosis. Although a recent FDA review of the results of clinical trials reported no clear link between bisphosphonates and serious or non-serious atrial fibrillation (AF), some epidemiologic studies have suggested an association between AF and bisphosphonates.

Methods: We conducted a meta-analysis of non-experimental studies to evaluate the risk of AF associated with bisphosphonates. Studies were identified by searching MEDLINE and EMBASE using a combination of the Medical Subject Headings and keywords. Our search was limited to English language articles. The pooled estimates of odds ratios (OR) as a measure of effect size were calculated using a random effects model.

Results: Seven eligible studies with 266,761 patients were identified: three cohort, three case-control, and one self-controlled case series. Bisphosphonate exposure was not associated with an increased risk of AF [pooled multivariate OR 1.04, 95% confidence interval (CI) 0.92-1.16] after adjusting for known risk factors. Moderate heterogeneity was noted (I-squared score = 62.8%). Stratified analyses by study design, cohort versus case-control studies, yielded similar results. Egger's and Begg's tests did not suggest an evidence of publication bias (P = 0.90, 1.00 respectively). No clear asymmetry was observed in the funnel plot analysis. Few studies compared risk between bisphosphonates or by dosing.

Conclusions: Our study did not find an association between bisphosphonate exposure and AF. This finding is consistent with the FDA's statement.

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Related in: MedlinePlus

Selection of studies included in the analysis.
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Figure 2: Selection of studies included in the analysis.

Mentions: The electronic search retrieved 160 potentially relevant references (Figure 2). A manual search of bibliographies of relevant review papers and the published abstracts of the annual meetings of the American College of Rheumatology and the International Conference on Pharmacoepidemiology (2008 to 2009) identified five additional references. On initial screening, 156 of 165 were excluded based on titles and abstracts. Nine full-text articles were subsequently retrieved for detailed evaluation. Of those, seven studies - three cohort, three case-control, and one self-controlled case series [7,14-19] - representing data from 266,761 patients were finally included in the meta-analysis and two systematic reviews [20,21] were excluded. The characteristics of the included studies and of their participants are summarized in Tables 1 and 2. The self-controlled case series study by Grosso and colleagues [16] was considered as a case-control study for analysis.


Bisphosphonates and risk of atrial fibrillation: a meta-analysis.

Kim SY, Kim MJ, Cadarette SM, Solomon DH - Arthritis Res. Ther. (2010)

Selection of studies included in the analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875664&req=5

Figure 2: Selection of studies included in the analysis.
Mentions: The electronic search retrieved 160 potentially relevant references (Figure 2). A manual search of bibliographies of relevant review papers and the published abstracts of the annual meetings of the American College of Rheumatology and the International Conference on Pharmacoepidemiology (2008 to 2009) identified five additional references. On initial screening, 156 of 165 were excluded based on titles and abstracts. Nine full-text articles were subsequently retrieved for detailed evaluation. Of those, seven studies - three cohort, three case-control, and one self-controlled case series [7,14-19] - representing data from 266,761 patients were finally included in the meta-analysis and two systematic reviews [20,21] were excluded. The characteristics of the included studies and of their participants are summarized in Tables 1 and 2. The self-controlled case series study by Grosso and colleagues [16] was considered as a case-control study for analysis.

Bottom Line: Egger's and Begg's tests did not suggest an evidence of publication bias (P = 0.90, 1.00 respectively).Few studies compared risk between bisphosphonates or by dosing.Our study did not find an association between bisphosphonate exposure and AF.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Rheumatology, Allergy and Immunology, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. skim62@partners.org

ABSTRACT

Introduction: Bisphosphonates are the most commonly used drugs for the prevention and treatment of osteoporosis. Although a recent FDA review of the results of clinical trials reported no clear link between bisphosphonates and serious or non-serious atrial fibrillation (AF), some epidemiologic studies have suggested an association between AF and bisphosphonates.

Methods: We conducted a meta-analysis of non-experimental studies to evaluate the risk of AF associated with bisphosphonates. Studies were identified by searching MEDLINE and EMBASE using a combination of the Medical Subject Headings and keywords. Our search was limited to English language articles. The pooled estimates of odds ratios (OR) as a measure of effect size were calculated using a random effects model.

Results: Seven eligible studies with 266,761 patients were identified: three cohort, three case-control, and one self-controlled case series. Bisphosphonate exposure was not associated with an increased risk of AF [pooled multivariate OR 1.04, 95% confidence interval (CI) 0.92-1.16] after adjusting for known risk factors. Moderate heterogeneity was noted (I-squared score = 62.8%). Stratified analyses by study design, cohort versus case-control studies, yielded similar results. Egger's and Begg's tests did not suggest an evidence of publication bias (P = 0.90, 1.00 respectively). No clear asymmetry was observed in the funnel plot analysis. Few studies compared risk between bisphosphonates or by dosing.

Conclusions: Our study did not find an association between bisphosphonate exposure and AF. This finding is consistent with the FDA's statement.

Show MeSH
Related in: MedlinePlus