On-X Aortic Valve: 50% Closer to a Normal INR1

On-X Aortic Valve patients with an INR of 1.5–2.0 had a >60% reduction in bleeding events and no increase in TE compared to patients with an INR of 2.0–3.0.* All other bileaflet aortic valve anticoagulation should be managed at an INR of 2.0–3.0.2

INR vs. Event Rate3

INR vs. Event Rate

*Reduce INR after 3 months standard therapy.4

Study Objective4,6

Study Design

  • IDE study
  • Prospective
  • Randomized
  • Multi-center (36 US centers)

Primary Endpoint of the Study

Sum of the following:

  • Thromboembolism (TE)
  • Thrombosis
  • Bleeding events

Method4

In the AVR high-risk group of the study, patients with elevated risk factors for thromboembolism were randomized to receive lower dose warfarin therapy (Test Group INR 1.5 – 2.0), or continue standard warfarin therapy (Control Group INR 2.0 - 3.0), 3 months after mechanical aortic valve replacement. All patients received home INR monitoring.

Table 1. Study Design

AVR high-risk (with reduced anticoagulation) TEST GROUP

Closed 185 766.2

Standard INR of between 2.0 and 3.0 and aspirin therapy for the first 3 months then reduced to a target of between 1.5 and 2.0. (warfarin plus aspirin 81mg per day)

AVR high-risk (with standard anticoagulation) CONTROL GROUP

Closed 190 878.6

Standard INR of between 2.0 and 3.0 maintained with warfarin plus aspirin 81mg per day

High-Risk AVR Patient Inclusion Criteria

Chronic atrial fibrillation, left ventricular ejection fraction <30%, enlarged left atrium >50mm diameter, spontaneous echocardiographic contrasts in the left atrium, vascular pathology features, neurological events, hypercoagulability, left or right ventricular aneurysm, lack of platelet response to aspirin or clopidogrel, and women receiving estrogen replacement therapy.

High-Risk AVR Patient Exclusion Criteria

Right-sided valve replacement, mitral valve replacement, double (aorta plus mitral) valve replacement, patients with active endocarditis at implantation, previous confirmed or suspected thromboembolic event or thrombophlebitis occurring or resolving within the last year prior to enrollment, and patients who are in an emergency state.

Results4

The follow-up duration average was 3.82 (878.6 patient years [pt-yrs] for control and 766.2 pt-yrs for test). The mean INR was 2.50 ± 0.63 for the control and 1.89 ± 0.49 for the test group (P <0.001) (Figure 1). The 60% test group experienced significantly lower major bleeding rates (1.57% vs 3.87%pt-yrs; P=0.007). The incidence of stroke, transient ischemic 50% attack, total neurologic events, and all-cause mortality were similar between the two groups. The Primary Endpoint of the study was met 40% (Table 2).

Table 2. AVR High-Risk Post-Randomization Event Comparison


Table 2. AVR High-Risk Post-Randomization Event Comparison

Conclusion

INR can be safely maintained at 1.5 – 2.0* in On-X Aortic Valve patients. Combined with low dose aspirin, this therapy reduces the risk of bleeding by >60% compared to the standard INR range of 2.0 to 3.0, without an increase in TE events1 (Table 2).

 

* Reduce INR after 3 months standard therapy.4

References

  1. Normal INR is considered 1. WHO Expert Committee on Biological Standardization, 33rd Report, World Health Organization, 1983. http://apps.who.int/iris/bitstream/10665/39217/1/WHO_TRS_687.pdf, downloaded on 06/29/2016.
  2. Nishimura et al., 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135:e1159–e1195.
  3. Data on file.
  4. On-X Prosthetic Heart Valve Instructions for Use.
  5. Levine M et al., Monitoring of international normalized ratios: comparison of community nurses with family physicians. Can Fam Physician 2012;58:e465-71.
  6. Puskas J, Gerdisch M, Nichols D, et al. Reduced anticoagulation after mechanical aortic valve replacement: Interim results from the Prospective Randomized On-X® Valve Anticoagulation Clinical Trial randomized
    Food and Drug Administration investigational device exemption trial. J Thorac Cardiovasc Surg. 2014;147(4):1201-1211.

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