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Mechanism of Action, Efficacy, and Adverse Events of Calcium Antagonists in Hypertrophic Scars and Keloids: A Systematic Review

Verhiel, Svenna MD; Piatkowski de Grzymala, Andrzej MD; van der Hulst, Rene MD, PhD

doi: 10.1097/DSS.0000000000000506
Review Article

BACKGROUND Pathological scars often cause major cosmetic and functional consequences, which make effective treatment important. Intralesional therapies are widely used, with corticosteroid injection considered to be first choice. An emerging and promising treatment option is the calcium antagonist verapamil.

OBJECTIVE To provide a comprehensive evidence-based review of current evidence on mechanism of action, efficacy, and adverse events of calcium antagonists in treatment of hypertrophic scars and keloids.

METHODS AND MATERIALS A Cochrane Library and PubMed search was performed for the literature pertaining to treatment with calcium antagonists in pathological scars. Articles were categorized into two groups: mechanism of action or efficacy and adverse events.

RESULTS Six in vitro studies were included in the first subgroup. Calcium antagonists have been found to reduce extra cellular matrix production, induce procollagenase synthesis, and inhibit interleukin-6, vascular endothelial growth factor, and proliferation of fibroblasts. Eight studies with a median level of evidence of 3.5 (range: 2–4) were included in the second category. A good efficacy with no major side effects was reported for calcium antagonists.

CONCLUSION Important methodological shortcomings of the available literature were identified. Interesting results have been reported, but further large scale, high-quality studies are needed to optimally evaluate efficacy of treatment with calcium antagonists.

Department of Plastic, Reconstructive and Hand Surgery, Maastricht University Medical Center, Maastricht, the Netherlands

Address correspondence and reprint requests to: Svenna Verhiel, MD, Department of Plastic, Reconstructive and Hand Surgery, Rooseveltlaan 211-1, 1079AS Amsterdam, the Netherlands, or e-mail:

The authors have indicated no significant interest with commercial supporters.

© 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.
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