The association of high-normal international-normalized-ratio (INR) with mortality in patients referred for coronary angiography

PLoS One. 2019 Aug 15;14(8):e0221112. doi: 10.1371/journal.pone.0221112. eCollection 2019.

Abstract

Aims: The international-normalized-ratio (INR) is typically used to monitor patients on warfarin or related oral anticoagulant therapy. The aim of our study was to investigate the association of the INR with mortality in coronary artery disease (CAD) patients not on oral anticoagulant therapy.

Methods and results: Between 1997 to 2000 the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study enrolled 3316 patients of German ancestry that had been referred for coronary angiography. We excluded patients on coumarin therapy (n = 222) and patients with an INR more than 5 standard deviations (SD) away from the mean (n = 30). During a median follow-up of 9.9 years, 884 patients died, 547 patients from cardiovascular causes. After adjustment for cardiovascular risk factors the INR was associated with all-cause mortality in all patients and the CAD positive group with HRs (95% CI) of 1.14(1.07-1.21) and 1.16(1.09-1.23) per 1-SD increase, respectively. Adjustment for NT-proBNP rendered the association insignificant.

Conclusion: In LURIC, the INR was positively associated with mortality in patients with prevalent CAD not on oral anticoagulant therapy as well as in patients without CAD. Adjustment for NT-proBNP abolished the association suggesting clinical or subclinical heart failure strongly contributing to increased INR and higher mortality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Coronary Angiography*
  • Coronary Artery Disease* / blood
  • Coronary Artery Disease* / diagnostic imaging
  • Coronary Artery Disease* / drug therapy
  • Coronary Artery Disease* / mortality
  • Female
  • Follow-Up Studies
  • Heart Failure* / blood
  • Heart Failure* / diagnostic imaging
  • Heart Failure* / drug therapy
  • Heart Failure* / mortality
  • Humans
  • International Normalized Ratio*
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors

Grants and funding

This work was supported by a grant from the 7th Framework Program of the European Union (RiskyCAD, grant agreement number 305739) to MEK and WM (https://ec.europa.eu/research/fp7/index_en.cfm). The funding institution had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Furthermore, the funder SYNLAB Holding Deutschland GmbH provided support in the form of salaries for author W.M. and the funder MediClin Medical Care Centre GmbH provided support in the form of salaries for author T.S., but they did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.