Skip to main content
Log in

Randomised, Double-Blind, Placebo-Controlled Trial of Ivabradine in Patients with Acute Coronary Syndrome: Effects of the I f Current Inhibitor Ivabradine on Reduction of Inflammation Markers in Patients with Acute Coronary Syndrome—RIVIERA Trial Study Design and Rationale

  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Purpose

Elevated levels of serum inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) represent independent risk factors for further cardiovascular events. In an atherosclerosis model, selective heart rate (HR) reduction with ivabradine has been shown to decrease markers of vascular oxidative stress, to improve endothelial function, and to reduce atherosclerotic plaque formation. We hypothesized that the addition of ivabradine to standard medical therapy has a beneficial effect on markers of inflammatory stress in acute coronary syndromes (ACS) patients.

Methods

RIVIERA is a unicenter, randomized, double-blind, placebo-controlled trial involving 1,270 patients of either gender admitted to hospital with non ST elevation ACS. The primary study aim is to evaluate the effects of ivabradine therapy, initiated at the time of hospital admission, on hs-CRP levels. There is also a combined secondary endpoint i.e. to assess the effects of ivabradine on the occurrence of death, nonfatal myocardial infarction, recurrent symptomatic ischemia, urgent revascularization, and cardiac arrest at 30-days and 1-year follow up.

Conclusion

We hypothesize that ivabradine therapy, when started immediately after hospital admission for ACS, will result in the reduction of hs-CRP levels and the improvement of cardiovascular outcome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Ross T. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993;362:801–9.

    Article  PubMed  CAS  Google Scholar 

  2. Morrow DR, Rifai N, Antman EM, et al. C-reactive protein is a potent predictor of mortality independently of and in combination with troponin T in acute coronary syndromes: a TIMI 11A substudy. J Am Coll Cardiol. 1998;31:1460–5.

    Article  PubMed  CAS  Google Scholar 

  3. Phillips AN, Neaton JD, Cook DG, et al. Leukocyte count and risk of major coronary heart disease events. Am J Epidemiol. 1992;136:59–70.

    PubMed  CAS  Google Scholar 

  4. Ridker PM, Cushman M, Stampfer MJ, et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973–9.

    Article  PubMed  CAS  Google Scholar 

  5. Huikuri HV, Malkikallio TH, Airaksinen KEJ, et al. Power-law relationship of heart rate variability as a predictor of mortality in the elderly. Circulation 1998;97:2031–6.

    PubMed  CAS  Google Scholar 

  6. Tsuji H, Larson MG, Venditti FJ, et al. Impact of heart rate variability on risk for cardiac events: the Framingham Heart Study. Circulation 1996;94:2850–5.

    PubMed  CAS  Google Scholar 

  7. Hikuri HV, Jokinen V, Syvanne M, for the Lipid Coronary Angioplasty Trial (LOCAT) study Group, et al. Heart rate variability and progression of coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 1999;19:1979–85.

    Google Scholar 

  8. Kannel WB, Kannel CE, Paffenbarger R. Heart rate and cardiovascular mortality in the Framingham study. Am Heart J. 1987;113:1489–94.

    Article  PubMed  CAS  Google Scholar 

  9. Sajadich A, Nielsen OW, Rasmussen V, et al. Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease. Eur Heart J. 2004;25:363–70.

    Article  Google Scholar 

  10. Heidland UE, Strauer BE. Left ventricular muscle mass and elevated heart rate are associated with coronary plaque disruption. Circulation 2001;104:1477–82.

    Article  PubMed  CAS  Google Scholar 

  11. Mangoni ME, Nargeot J. Properties of the hyperpolarization-activated current (I f ) in isolated mouse sino-atrial cells. Cardiovasc Res. 2001;52:51–64.

    Article  PubMed  CAS  Google Scholar 

  12. Bois P, Bescond J, Renaudon B, et al. Mode of action of bradycardic agent, S 16257, on ionic currents of rabbit sinoatrial node cells. Br J Pharmacol. 1996;118:1051–7.

    PubMed  CAS  Google Scholar 

  13. Gardiner SM, Kemp PA, March JE, et al. Acute and chronic cardiac and regional haemodynamic effects of the novel bradycardic agent, S16257, in conscious rats. Br J Pharmacol. 1995;115:579–86.

    PubMed  CAS  Google Scholar 

  14. Tardif JC, Ford I, Tendera M, et al. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J. 2005;26:2529–36.

    Article  PubMed  CAS  Google Scholar 

  15. Borer JS, Fox K, Jaillon P, et al. Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double blind, multicentered, placebo-controlled trial. Circulation 2003;107:817–23.

    Article  PubMed  Google Scholar 

  16. Custodis F, Baumhakel M, Schlimmer N, et al. Heart rate reduction by ivabradine reduces oxidative stress, improves endothelial function, and prevents atherosclerosis in apolipoprotein E deficient mice. Circulation 2008;117:2377–87.

    Article  PubMed  CAS  Google Scholar 

  17. Bassand JP, Hamm CW, Ardissino D, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: the Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology. Eur Heart J. 2007;28:1598–660.

    Article  PubMed  CAS  Google Scholar 

  18. Kaski JC, Consuegra-Sanchez L, Fernandez-Berges DJ, et al. SIESTA Investigators. Elevated serum neopterin levels and adverse cardiac events at 6 months follow-up in Mediterranean patients with non-ST-segment elevation acute coronary syndrome. doi:10.1016/j.atherosclerosis.2008.01.009.

  19. O’Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics 1979;35:549–56.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alberto Dominguez-Rodriguez.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dominguez-Rodriguez, A., Fard, S.S., Abreu-Gonzalez, P. et al. Randomised, Double-Blind, Placebo-Controlled Trial of Ivabradine in Patients with Acute Coronary Syndrome: Effects of the I f Current Inhibitor Ivabradine on Reduction of Inflammation Markers in Patients with Acute Coronary Syndrome—RIVIERA Trial Study Design and Rationale. Cardiovasc Drugs Ther 23, 243–247 (2009). https://doi.org/10.1007/s10557-009-6164-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-009-6164-9

Key words

Navigation