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Semin Thromb Hemost 2020; 46(08): 908-918
DOI: 10.1055/s-0040-1716874
Review Article

Sulodexide versus Control and the Risk of Thrombotic and Hemorrhagic Events: Meta-Analysis of Randomized Trials

Behnood Bikdeli
1   Brigham and Women’s Hospital, Boston, Massachusetts
2   Harvard Medical School, Boston, Massachusetts
3   Center for Outcomes Research and Evaluation (CORE), Yale University School of Medicine, New Haven, Connecticut
4   Clinical Trials Center, Cardiovascular Research Foundation, New York, New York
,
Saurav Chatterjee
5   Hoffman Heart Institute, Saint Francis Hospital, University of Connecticut, Hartford, Connecticut
,
Ajay J. Kirtane
1   Brigham and Women’s Hospital, Boston, Massachusetts
4   Clinical Trials Center, Cardiovascular Research Foundation, New York, New York
,
Sahil A. Parikh
1   Brigham and Women’s Hospital, Boston, Massachusetts
4   Clinical Trials Center, Cardiovascular Research Foundation, New York, New York
,
Giuseppe M. Andreozzi
6   Angiology Care Unit, University of Padova, Padova, Italy
,
Nihar R. Desai
3   Center for Outcomes Research and Evaluation (CORE), Yale University School of Medicine, New Haven, Connecticut
7   Section of Cardiovascular Medicine, Yale School of Medicine, Yale University, New Haven, Connecticut
,
Dominic P. Francese
4   Clinical Trials Center, Cardiovascular Research Foundation, New York, New York
,
C Michael Gibson
2   Harvard Medical School, Boston, Massachusetts
8   Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts
,
Gregory Piazza
1   Brigham and Women’s Hospital, Boston, Massachusetts
2   Harvard Medical School, Boston, Massachusetts
,
Samuel Z. Goldhaber
1   Brigham and Women’s Hospital, Boston, Massachusetts
2   Harvard Medical School, Boston, Massachusetts
,
John W. Eikelboom
9   Division of Hematology and Thromboembolism, McMaster University, Hamilton, Ontario, Canada
,
Harlan M. Krumholz
3   Center for Outcomes Research and Evaluation (CORE), Yale University School of Medicine, New Haven, Connecticut
7   Section of Cardiovascular Medicine, Yale School of Medicine, Yale University, New Haven, Connecticut
10   Department of Health Policy and Management, Yale School of Public Health, Yale University, New Haven, Connecticut
,
Gregg W. Stone
4   Clinical Trials Center, Cardiovascular Research Foundation, New York, New York
11   The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
› Author Affiliations Funding No external funding was sought for this study. Dr. Bikdeli was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), through grant number T32 HL007854 (07/2017–06/2018).
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Abstract

Thrombotic cardiovascular disease (myocardial infarction [MI], stroke, and venous thromboembolism [VTE]) remains a major cause of death and disability. Sulodexide is an oral glycosaminoglycan containing heparan sulfate and dermatan sulfate. We conducted a systematic review and meta-analysis to determine the cardiovascular efficacy, and safety of sulodexide versus control in randomized controlled trials (RCTs). We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs reporting cardiovascular outcomes in patients receiving sulodexide versus control (placebo or no treatment). Outcomes included all-cause mortality, cardiovascular mortality, MI, stroke, deep vein thrombosis (DVT), pulmonary embolism, and bleeding. We used inverse variance random-effects models with odds ratio (OR) as the effect measure. After screening 360 records, 6 RCTs including 7,596 patients (median follow-up duration: 11.6 months) were included. Patients were enrolled for history of MI, VTE, peripheral arterial disease, or cardiovascular risk factors plus nephropathy. Use of sulodexide compared with control was associated with reduced odds of all-cause mortality (OR 0.67, 95% confidence interval [CI] 0.52–0.85, p = 0.001), cardiovascular mortality (OR 0.44, 95% CI 0.22–0.89, p = 0.02), and MI (OR 0.70, 95% CI 0.51–0.96, p = 0.03), and nonsignificantly reduced odds of stroke (OR 0.78, 95% CI 0.45–1.35, p = 0.38). Sulodexide was associated with significantly reduced odds of VTE (OR 0.44, 95% CI 0.24–0.81, p = 0.008), including DVT (OR 0.41, 95% CI 0.26–0.65, p < 0.001), but not pulmonary embolism (OR 0.92, 95% CI 0.40–2.15, p = 0.86). Bleeding events were not significantly different in the two groups (OR 1.14, 95% CI 0.47–2.74, p = 0.48). In six RCTs across a variety of clinical indications, use of sulodexide compared with placebo or no treatment was associated with reduced odds of all-cause mortality, cardiovascular mortality, MI, and DVT, without a significant increase in bleeding. Additional studies with this agent are warranted.

Keywords

sulodexide - cardiovascular - venous thromboembolism - myocardial infarction - bleeding


Publication History

Article published online:
21 October 2020

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