Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Interaction between nonsteroidal anti-inflammatory drug intake and calcium-channel blocker-based antihypertensive treatment in the Syst-Eur trial

Journal of Human Hypertension volume 15, pages 613–618 (2001)Cite this article

Abstract

Objective: To assess the relationship between chronic intake of nonsteroidal anti-inflammatory drugs (NSAID) and outcome, in particular (gastrointestinal) bleeding and to investigate whether the effect of chronic NSAID intake was similar in untreated and treated elderly hypertensives.

Methods: Eligible patients (⩾60 years, with systolic blood pressure 160–219 mm Hg and diastolic blood pressure <95 mm Hg) were randomised to active treatment or placebo. Active treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both, titrated or combined to reduce the sitting systolic blood pressure by at least 20 mm Hg to below 150 mm Hg. Patients never taking NSAIDs (n = 2882) were compared with patients on chronic NSAID intake (n= 861), defined as reporting NSAID intake on at least 50% of the patient forms.

Results: There was a tendency towards lower mortality (relative hazard rate (95% confidence interval (CI), 0.77 (0.56–1.06)) and higher incidence of bleeding (1.13 (0.63–2.05) with chronic NSAID intake. Although there was no significant interaction between calcium-channel blocker (CCB)-based treatment and chronic NSAID intake for any of the end points, chronic NSAID intake tended to be associated with a lower incidence of bleeding on active treatment as compared to placebo (P-value of the interaction term = 0.07).

Conclusion: The effect of chronic NSAID intake on outcome was similar in patients on active treatment based on a dihydropyridine CCB or on placebo. However, chronic NSAID intake might have a less deleterious effect on bleeding on active treatment as compared to placebo.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Hansson L et alEffects of intensive blood-pressure lowering and low-dose aspirin inpatients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial Lancet 1998 351 1755–1762

    Article  CAS  Google Scholar 

  2. Antiplatelet Trialists’ Collaboration Collaborative overview of randomised trials of antiplatelet therapy – I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories ofpatients BMJ 1994 308 81–106

    Article  Google Scholar 

  3. Hennekens CH et alAspirin and other antiplatelet agents in the secondary and primary prevention of cardiovascular disease Circulation 1989 80 749–756

    Article  CAS  Google Scholar 

  4. The SALT collaborative group Swedish aspirin low-dose trial (SALT)of 75 mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events Lancet 1991 338 1345–1349

    Article  Google Scholar 

  5. Garcia Rodriguez LA, Cattaruzzi C, Troncon MG, Agostinis L Risk of hospitalization for upper gastrointestinal tract bleeding associated with ketorolac, other nonsteroidal anti-inflammatory drugs, calcium antagonists, and other antihypertensive drugs Arch Intern Med 1995 158 33–39

    Article  Google Scholar 

  6. Gabriel SE, Jaakkimainen L, Bombardier C Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A meta-analysis Ann Intern Med 1991 115 787–796

    Article  CAS  Google Scholar 

  7. Griffin MR et alNonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons Ann Intern Med 1991 114 257–263

    Article  CAS  Google Scholar 

  8. Weil J et alProphylactic aspirin and risk of peptic ulcer bleeding BMJ 1995 310 827–830

    Article  CAS  Google Scholar 

  9. Langman MJS et alRisks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs Lancet 1994 343 1075–1078

    Article  CAS  Google Scholar 

  10. Hawkey CJ Non-steroidal anti-inflammatory drugs and peptic ulcers BMJ 1990 300 278–284

    Article  CAS  Google Scholar 

  11. Hawkey CJ Non-steroidal anti-inflammatory druggastropathy: causes and treatment Gastroenterology 1996 31 124–127

    Google Scholar 

  12. Smalley WE, Ray WA, Daugherty JR, Griffin MR No association between calcium channel blocker use and confirmed bleeding peptic ulcer Am J Epidemiol 1998 148 350–354

    Article  CAS  Google Scholar 

  13. Legault C et alNimodipine neuroprotection in cardiac valve replacement – report of an early terminated trial Stroke 1996 27 593–598

    Article  CAS  Google Scholar 

  14. Pahor M et alRisk of gastrointestinal haemorrhage with calcium antagonists in hypertensive persons over 67 years old Lancet 1996 347 1061–1065

    Article  CAS  Google Scholar 

  15. Pilotto A et alRole of Helicobacter pylori infection on upper gastrointestinal bleeding in the elderly Dig Dis Sci 1997 42 586–591

    Article  CAS  Google Scholar 

  16. Kelly JP et alMajor upper gastrointestinal bleeding and the use of calcium channel blockers Lancet 1999 353 559–559

    Article  CAS  Google Scholar 

  17. Suissa S et alAntihypertensive drugs and the risk of gastro-intestinal bleeding Am J Med 1998 105 230–235

    Article  CAS  Google Scholar 

  18. Weil J et alPeptic ulcer bleeding: accessory risk factors and interactions with non-steroidal anti-inflammatory drugs Gut 2000 46 27–31

    Article  CAS  Google Scholar 

  19. Desboeuf K, Lapeyre-Mestre M, Montastruc J-L Risk of gastrointestinal haemorrhage with calcium antagonists Br J Clin Pharmacol 1998 46 87–89

    Google Scholar 

  20. Staessen JA et alRandomised double-blind comparison of placebo and active treatment for olderpatients with isolated systolic hypertension Lancet 1997 350 757–764

    Article  CAS  Google Scholar 

  21. Amery A et alSyst-Eur. A multicentre trial on the treatment of isolated systolic hypertension in the elderly: objectives, protocol, and organization Aging 1991 3 287–302

    CAS  PubMed  Google Scholar 

  22. Staessen JA et alSubgroup and per-protocol analysis of the randomized european trial on isolated systolic hypertension in the elderly Arch Intern Med 1998 158 1681–1691

    Article  CAS  Google Scholar 

  23. Forbes CD et alSecondary stroke prevention with low-dose aspirin, sustained releae dipyramidole alone and in combination Thrombosis Res 1998 92 S1–S6

    Article  CAS  Google Scholar 

  24. Jick H, Porter J Drug-induced gastro-intestinal bleeding Lancet 1978 2 87–89

    Article  CAS  Google Scholar 

  25. Cullen DJE et alPeptic ulcer bleeding in the elderly: relative roles of Helicobacter pylori and non-steroidal anti-inflammatory drugs Gut 1997 41 459–462

    Article  CAS  Google Scholar 

  26. Altman R, Scazziota A, Dujovne C Diltiazem potentiates the inhibitory effect of aspirin on platelet aggregation Clin Pharmacol Ther 1988 44 320–325

    Article  CAS  Google Scholar 

  27. Onoda JM, Sloane BF, Honn KV Antithrombogenic effects of calcium channel blockers: synergism with prostacyclin and tromboxane synthase inhibitors Thrombosis Res 1984 34 367–378

    Article  CAS  Google Scholar 

  28. Greer IA, Walker JJ, Calder AA, Forbes CD Aspirin with an adrenergic or calcium-channel blocking agent as a new combination therapy for arterial thrombosis Lancet 1985 1 351–352

    Article  CAS  Google Scholar 

  29. Odawara A et alInhibitory effect of clentiazem (TA-3090) on platelet aggregation – alone and in combination with aspirin or ticlopidine Thrombosis Res 1994 75 109–119

    Article  CAS  Google Scholar 

  30. Tison P et alEffects of dihydropyridines and their combination with aspirin on blood pressure and circadian platelet activity inpatients with essential hypertension Am J Hypertens 1994 7 46S–49S

    Article  CAS  Google Scholar 

  31. Zucker ML et alEffect of diltiazem and low-dose aspirin on platelet aggregation and ATP release induced by paired agonists Thrombosis and Haemostasis 1993 70 332–335

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The Syst-Eur trial was a concerted action of the BIOMED Research Program sponsored by the European Union. The trial was carried out in consultation with the World Health Organization, the International Society of Hypertension, the European Society of Hypertension and the World Hypertension League. The trial was sponsored by Bayer AG (Wuppertal, Germany). The National Fund for Scientific Research (Brussels, Belgium) provided additional support. Study medication was donated by Bayer AG and Merck Sharpe and Dohme Inc, West Point, PA.

Trial Coordinators: RH Fagard, MD; JA Staessen, MD.

Regional Coordinators: GG Arabidze (deceased), MD (Bellorussia and the Russian Federation); WH Birkenhäger, MD (the Netherlands); CJ Bulpitt, MD (United Kingdom); M Carrageta, MD (Portugal); H Celis, MD (Belgium); F Forette, MD (France); J Kocemba, MD (Poland); G Leonetti, MD (Italy); C Nachev, MD (Bulgaria); ET O’Brien, MD (Ireland); E Ritz, MD (Germany); JL Rodicio, MD (Spain); J Rosenfeld, MD (Israel); J Tuomilehto, MD (Finland, Estonia and Lithuania).

Steering Committee: GG Arabidze (deceased), MD, P De Cort, MD; RH Fagard, MD; F Forette, MD; K Kawecka-Jaszcz, MD; G Leonetti, MD; C Nachev, MD; ET O’Brien, MD; JL Rodico, MD; J Rosenfeld, MD; J Tuomilehto, MD; J Webster, MD; Y Yodfat, MD.

Data Monitoring Committee: CJ Bulpitt, MD; AE Fletcher, PhD; JA Staessen, MD; L Thijs, BSc.

End-Point Committee: PW de Leeuw, MD; RH Fagard, MD; G Leonetti, MD; JC Petrie, MD.

Ethics Committee: WH Birkenhäger, MD; CT Dollery, MD; RH Fagard, MD.

Publication Committee: WH Birkenhäger, MD; CJ Bulpitt, MD; JA Staessen, MD; A Zanchetti, MD.

Coordinating Office: N Ausseloos; H Celis, MD; E Den Hond, DSc; L De Pauw, RN; P Drent; RH Fagard, MD; H Fan; T Nawrot, BSc; Y Piccart; JA Staessen, MD; Y Toremans; L Thijs, BSc; I Van Bael; S Van Hulle, RN; JG Wang, MD; R Wolfs.

Clinical Centres: The clinical investigators are listed in Staessen et al.17,19

Author information

Authors and Affiliations

  1. The Hypertensie en Cardiovasculaire Revalidatie Eenheid, Departement Moleculair en Cardiovasculair Onderzoek, Katholieke Universiteit Leuven, Leuven, Belgium

    H Celis, L Thijs, JA Staessen & RH Fagard

  2. Erasmus University, Rotterdam, The Netherlands

    WH Birkenhäger

  3. Care of the Elderly, Imperial College School of Medicine, Hammersmith Campus, London, UK

    CJ Bulpitt

  4. Departement Inwendige Geneeskunde, Rijksuniversiteit Maastricht, Maastricht, The Netherlands

    PW de Leeuw

  5. Istituto Auxologico Italiano and the Centro di Fisiologia Clinica e lpertensione, Ospedale Maggiore, Universitá di Milano, Italy

    G Leonetti

  6. Department of Internal Medicine, Alexandrov’s University Hospital, Sofia, Bulgaria

    C Nachev

  7. Department of Epidemiology and Health Promotion, National Public Health Institute and Department of Public Health, University of Helsinki, Helsinki, Finland

    J Tuomilehto

Authors
  1. H Celis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L Thijs
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. JA Staessen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. WH Birkenhäger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. CJ Bulpitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. PW de Leeuw
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G Leonetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C Nachev
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J Tuomilehto
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. RH Fagard
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

the Syst-Eur investigators

Corresponding author

Correspondence to H Celis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Celis, H., Thijs, L., Staessen, J. et al. Interaction between nonsteroidal anti-inflammatory drug intake and calcium-channel blocker-based antihypertensive treatment in the Syst-Eur trial. J Hum Hypertens 15, 613–618 (2001). https://doi.org/10.1038/sj.jhh.1001235

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jhh.1001235

Keywords

This article is cited by

Search

Advanced search

Quick links