RENAL-ASSOCIATED ESCAPE EFFECT OF ANTIHYPERTENSIVE THERAPY IN HYPERTENSIVE PATIENTS RECEIVING NONSTEROIDAL ANTI-INFLAMMA‑ TORY DRUGS (“PANDA” TRIAL)

Objective. The subanalysis of the study “PANDA” (the study of renal function in patients with acute nonspecific pain in lower back during therapy with nonsteroidal anti-inflammatory drugs (NSAID)) is the study of renal-associated escape effect of antihypertensive therapy in patients with arterial hypertension (HTN) receiving NSAID. Design and methods. We included 407 patients receiving one of the following NSAIDs for 14 days: meloxicam (15 mg/day), etoricoxib (60 mg/day), nimesulide (200 mg/day) or celecoxib (200 mg/day). Five visits were performed. During the visits blood pressure (BP), glomerular filtration rate (GFR), blood levels of cystatin C were assessed. Results. At first step, all parameters were evaluated in the whole group (n = 407). As the second step, we analyzeds the indicators in 4 groups depending on the NSAID type. At the third stage (subanalysis) we allocated 3 groups of patients: 1 group (n = 62) — patients with a history of HTN and diabetes mellitus, group 2 (n = 173) patients with HTN, and group 3 (n = 172) — patients without HTN and diabetes mellitus. Conclusions. In patients with acute nonspecific back pain, with a history of HTN, NSAID intake is associated with the certain changes in BP, GFR and cystatin-С. Therefore, we can discuss a renal-associated escape effect of antihypertensive therapy. It is the most evident on the 7th day of NSAID therapy. All changes of the studied parameters should be considered as a class-effect adverse reactions of NSAIDs, without any benefits in relation to specific medications.

nonsteroidal anti-inflammatory drugs, glomerular filtration rate, cystatin C, arterial hypertension, blood pressure, decreased effectiveness of antihypertensive drugs

1. Croff L. Prostanoid biology and its therapeutic targeting. In Kelley’s Textbook of Rheumatology. Ed. by Firestein GS, Budd RC, Gabriel SE, McInnes IB, O’Dell JR. 9th edition. Philadelphia: Saunders. 2013:871–893.

2. Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev. 2004;56(3):387. doi:10.1124/pr.56.3.3

3. Llorens O, Perez JJ, Palomar A, Mauleon D. Differential binding mode of diverse cyclooxygenase inhibitors. J Mol Graph Model. 2002;20(5):359–371.

4. Allison SJ. Hypertension: Haematopoietic COX-2 in salt-sensitive hypertension. Nat Rev Nephrol. 2016;12(1):3. doi:10.1038/nrneph.2015.182

5. Winkelmayer WC, Waikar SS, Mogun H, Solomon DH. Nonselective and cyclooxygenase-2-selective NSAIDs and acute kidney injury. Am J Med. 2008;121(12):1092–1098. doi:10.1016/j.amjmed.2008.06.035

6. Lanza FL, Chan FK, Quigley EM. Practice Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009;104(3):728–38. doi:10.1038/ajg.2009.115

7. Lanas A, Carrera-Lasfuentes P, Arguedas Y, García S, Bujanda L, Calvet X et al. Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulant. Clin Gastroenterol Hepatol. 2015;13(5):906–912. doi:10.1016/j.cgh.2014.11.007

8. Lapi F, Azoulay L, Yin H, Nessim SJ, Suissa S. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal antiinflammatory drugs and risk of acute kidney injury: nested case-control study. Br Med J. 2013;346: e8525. doi:10.1136/bmj.e8525

9. Taubert КА. Cardiology patient pages: can patients with cardiovascular disease take nonsteroidal antiinflammatory drugs? Circulation. 2008;117(17):322–324. doi:10.1161/ CIRCULATIONAHA.107.749135

10. Li H, Hortmann M, Daiber A, Oelze M, Ostad MA, Schwarz PM et al. Cyclooxygenase 2-selective and nonselective nonsteroidal anti-inflammatory drugs induce oxidative stress by up-regulating vascular NADPH oxidases. J Pharmacol Exp Ther. 2008;326(3):745–53. doi:10.1124/jpet.108.139030

11. Vázquez-Meza H, de Piña MZ, Pardo JP, Riveros-Rosas H, Villalobos-Molina R, Piña E. Non-steroidal antiinflammatory drugs activate NADPH oxidase in adipocytes and raise the H2O2 pool to prevent cAMP-stimulated protein kinase a activation and inhibit lipolysisю. BMC Biochem. 2013;30(14):13. doi:10.1186/1471– 2091–14–13

12. US Food and Drug Administration. Thrombotic cardiovascular events associated with NSAID use: regulatory history and results of literature search (RCTs), in proceedings of the joint meeting of the arthritis advisory committee and drug safety and risk management advisory committee. 2014. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMate-rials/Drugs/ArthritisAdvisoryCommittee/UCM383180.pdf

13. Fosbøl EL, Gislason GH, Jacobsen S, Folke F, Hansen ML, Schramm TK et al. Risk of myocardial infarction and death associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) among healthy individuals: a nationwide cohort study. Clin Pharmacol Ther. 2009;85(2):190–7. doi:10.1038/clpt.2008.204

14. Bacic-Vrca V, Marusic S, Erdeljic V, Falamic S, Gojo-Tomic N, Rahelic D. The incidence of potential drug-drug interactions in elderly patients with arterial hypertension. Pharm World Sci. 2010;32(6):815–21. doi:10.1007/s11096–010–9442–5

15. Andrassy KM. Comments on KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2013;84(3):622–3. doi:10.1038/ki.2013.243

16. Рекомендации по лечению артериальной гипертонии. ESH/ESC 2013. Российский кардиологический журнал. 2014;1(105):7–94. [The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Russian Journal of Cardiology. 2014;1(105):7–94. In Russian].

17. Campbell WB, Gomez-Sanchez CE, Adams BV, Schmitz JM, Itskovitz HD. Attenuation of angiotensin II and III-induced aldosterone release by prostaglandin synthesis inhibitors. J Clin Invest. 1979;64(6):1552–1557. doi:10.1172/JCI109615

18. Kramer HJ, Glänzer K, Düsing R. Role of prostaglandins in the regulation of renal water excretion. Kidney Int. 1981;19 (6):851–859.

19. Walker RM, Brown RS, Stoff JS. Role of renal prostaglandins during antidiuresis and water diuresis in man. Kidney Int. 1982;21 (2):365–370.

20. Nasjletti A. Arthur C. Corcoran Memorial Lecture. The role of eicosanoids in angiotensin-dependent hypertension. Hypertension. 1998;31(1 Pt 2):194–200.

21. Wilson SL, Poulter NR. The effect of non-steroidal anti-inflammatory drugs and other commonly used nonnarcotic analgesics on blood pressure level in adults. J Hypertens. 2006;24 (8):1457–1469. doi:10.1097/01.hjh.0000239278.82196.a5

22. Schlondorff D. Renal complications of nonsteroidal antiinflammatory drugs. Kidney Int. 1993;44(3):643–653.

23. Zadražil J. Nonsteroidal antiinflammatory drugs and the kidney. Vnitř Lék. 2006;52(7–8):686–90.

24. Gavrilescu CM, Felea MG, Barbu R, Duma O, Bodescu MM, Midilina Bodescul M et al. Assessment of adverse drug reactions as cardiovascular risk factors. Rev Med Chir Soc Med Nat Iasi. 2016;120(1):48–54.

25. Pavlicević I, Kuzmanić M, Rumboldt M, Rumboldt Z. Interaction between antihypertensives and NSAIDs in primary care: a controlled trial. Can J Clin Pharmacol. 2008;15(3):372–82.

26. Hersh EV, Pinto A, Moore PA. Adverse drug interactions involving common prescription and over-the-counter analgesic agents. Clin Ther. 2007;29(Suppl):2477–97. doi:10.1016/j. clinthera.2007.12.003

27. Cheng HF, Harris RC. Renal effects of non-steroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors. Curr Pharm Des. 2005;11(14):1795–1804. doi:10.2174/1381612053764922

28. Whelton A, Lefkowith JL, West CR, Verburg KM. Cardiorenal effects of celecoxib as compared with the nonsteroidal anti-inflammatory drugs diclofenac and ibuprofen. Kidney Int. 2006;70(8):1495–1502. doi:10.1038/sj.ki.5001766

29. Hernanz R, Briones AM, Salaices M, Alonso MJ. New roles for old pathways? A circuitous relationship between reactive oxygen species and cyclo-oxygenase in hypertension. Clin Sci (Lond). 2014;126(2):111–121. doi:10.1042/CS20120651

30. Yu Y, Ricciotti E, Scalia R, Tang SY, Grant G, Yu Z et al. Vascular COX-2 modulates blood pressure and thrombosis in mice. Sci Transl Med. 2012;4(132):132–54. doi:10.1126/ scitranslmed.3003787

31. Facemire CS, Griffiths R, Audoly LP, Koller BH, Coffman TM. The impact of microsomal prostaglandin E synthase 1 on blood pressure is determined by genetic background. Hypertension. 2010;55 (2):531–538. doi:10.1161/HYPERTENSIONAHA.109.145631