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Review
Stroke paradox with SGLT-2 inhibitors: a play of chance or a viscosity-mediated reality?
  1. Konstantinos P Imprialos1,
  2. Chrysoula Boutari1,
  3. Konstantinos Stavropoulos1,
  4. Michael Doumas2,
  5. Asterios I Karagiannis1
  1. 1Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
  2. 2George Washington University, Washington DC, USA
  1. Correspondence to Dr Konstantinos Stavropoulos, Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, St. Konstantinoupoleos 49, Thessaloniki 54642, Greece; konvstavropoulos{at}hotmail.com

Abstract

Diabetes mellitus is a major risk factor for cardiovascular morbidity and mortality. Current therapeutic strategies have not provided constant beneficial cardiovascular-related results. Sodium–glucose co-transporters 2 (SGLT-2) inhibitors have emerged as a novel antidiabetic class of drugs that exert favourable results in a variety of other cardiovascular risk factors too, such as increased blood pressure and body weight. The Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) study was the first trial that evaluated cardiovascular outcomes in patients with diabetes with the use of empagliflozin, a member of this new class of drugs. Empagliflozin was associated with remarkable reduction of cardiovascular morbidity and mortality and all-cause death. On the contrary, stroke incidence was slightly increased, although the result did not reach statistical significance. It could be assumed that a drug providing such beneficial effects on cardiovascular outcomes, would have also the same impact in stroke risk. This finding could theoretically be attributed to ‘play of chance’. However, an increase of haematocrit was observed in EMPA-REG and other SGLT-2 inhibitors studies. Accumulating evidence suggests a direct association between increased haematocrit and stroke risk. Could this ‘stroke paradox’ be a result of the increased haematocrit levels noted with SGLT-2 inhibitors? The aim of this review is to critically assess both possibilities, given that increased stroke rates (if indeed true) should not be neglected and unattended.

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Footnotes

  • Contributors KPI, CB and KS performed the initial search and evaluation of the literature, and prepared the manuscript. MD supervised the preparation of the manuscript and AIK performed the overall evaluation of the final manuscript.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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