Original Study Fall-Risk-Increasing Drugs: A Systematic Review and Meta-Analysis: I. Cardiovascular Drugs Max de Vries MB a, b , Lotta J. Seppala MSc a, b , Joost G. Daams MA, MD, PhD c , Esther M.M. van de Glind MD, PhD a, b , Tahir Masud MD, PhD d , Nathalie van der Velde MD, PhD a, b, *, on behalf of the EUGMS Task and Finish Group on Fall-Risk-Increasing Drugs a Department of Internal Medicine, Section of Geriatric Medicine, Academic Medical Center, University of Amsterdam, The Netherlands b Amsterdam Public Health research institute, Amsterdam, The Netherlands c Medical library, Academic Medical Center, Amsterdam, The Netherlands d Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom Keywords: Aged accidental falls cardiovascular medication diuretics digoxin statins abstract Background and objective: Use of certain medications is recognized as a major and modifiable risk factor for falls. Although the literature on psychotropic drugs is compelling, the literature on cardiovascular drugs as potential fall-risk-increasing drugs is conflicting. The aim of this systematic review and meta- analysis is to provide a comprehensive overview of the associations between cardiovascular medica- tions and fall risk in older adults. Methods: Design: A systematic review and meta-analysis. Data sources: Medline, Embase, and PsycINFO. Key search concepts were “fall,”“aged,”“causality,” and “medication.” Studies that investigated cardio- vascular medications as risk factors for falls in participants 60 years old or participants with a mean age of 70 or older were included. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratios (ORs) separately. Results: In total, 131 studies were included in the qualitative synthesis. Meta-analysis using adjusted ORs showed significant results (pooled OR [95% confidence interval]) for loop diuretics, OR 1.36 (1.17, 1.57), and beta-blocking agents, OR 0.88 (0.80, 0.97). Meta-analysis using unadjusted ORs showed significant results for digitalis, OR 1.60 (1.08, 2.36); digoxin, OR 2.06 (1.56, 2.74); and statins, OR 0.80 (0.65, 0.98). Most of the meta-analyses resulted in substantial heterogeneity that mostly did not disappear after stratification for population and setting. In a descriptive synthesis, consistent associations were not observed. Conclusion: Loop diuretics were significantly associated with increased fall risk, whereas beta-blockers were significantly associated with decreased fall risk. Digitalis and digoxin may increase the risk of falling, and statins may reduce it. For the majority of cardiovascular medication groups, outcomes were inconsistent. Furthermore, recent studies indicate that specific drug properties, such as selectivity of beta-blockers, may affect fall risk, and drug-disease interaction also may play a role. Thus, studies addressing these issues are warranted to obtain a better understanding of drug-related falls. Ó 2018 AMDA e The Society for Post-Acute and Long-Term Care Medicine. Falls form a significant and growing public health concern. About a third of the population older than 65 years experience at least 1 fall annually, and 1 of 55 of these falls is injurious. 1 Consequently, falls are the leading cause of injury-related emergency room visits and injury- related deaths in older adults. 2 Furthermore, falls are associated with premature institutionalization, decreased quality of life, impaired mobilization, and a substantial rise in health care costs. 3,4 Use of certain medications is recognized as a major risk factor for falls. Primarily, the association between psychotropic drugs and falls is Max de Vries and Lotta J. Seppala are coefirst authors. Conflicts of interest statement: This work was supported by the Clementine Brigitta Maria Dalderup fund which is an Amsterdam University fund. The sponsor played no part in the design, methods, data collection, analysis, and preparation of this paper. There is no conflict of interest in this regard. * Address correspondence to Nathalie van der Velde, MD, PhD, Academic Medical Center, Department Internal Medicine, Geriatrics F4 129, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands. E-mail address: n.vandervelde@amc.uva.nl (N. van der Velde). JAMDA journal homepage: www.jamda.com https://doi.org/10.1016/j.jamda.2017.12.013 1525-8610/Ó 2018 AMDA e The Society for Post-Acute and Long-Term Care Medicine. JAMDA 19 (2018) 371.e1e371.e9