title: Achieved anticoagulation vs prosthesis selection for mitral mechanical valve replacement: a population-based outcome study.
abstract: BACKGROUND
  Thromboembolic events (TEs) are frequent after mechanical mitral valve replacement (MVR), but their association to anticoagulation quality is unclear and has never been studied in a population-based setting with patients who have a complete anticoagulation record.
  
  
  METHODS
  We compiled a complete record of all residents of Olmsted County, MN, who underwent mechanical MVR between 1981 and 2004, for all TE, bleeding episodes, and international normalized ratios (INRs) measured from prosthesis implantation.
  
  
  RESULTS
  In the 112 residents (mean [+/- SD] age, 57 +/- 16 years; 60% female residents) who underwent mechanical MVR, 19,647 INR samples were obtained. While INR averaged 3.02 +/- 0.57, almost 40% of INRs were < 2 or > 4.5. Thirty-four TEs and 28 bleeding episodes occurred during a mean duration of 8.2 +/- 6.1 years of follow-up. There was no trend of association of INR (average, SD, growth variance rate, or intensity-specific incidence of events) with TE. Previous cardiac surgery (p = 0.014) and ball prosthesis (hazard ratio [HR], 2.92; 95% CI, 1.43 to 5.94; p = 0.003) independently determined TE. With MVR using a ball prosthesis, despite higher anticoagulation intensity (p = 0.002), the 8-year rate of freedom from TE was considerably lower (50 +/- 9% vs 81 +/- 5%, respectively; p < 0.0001). Compared with expected stroke rates in the population, stroke risk was elevated with non-ball prosthesis MVR (HR 2.6; 95% CI, 1.3 to 5.2; p = 0.007) but was considerable with ball prosthesis MVR (HR 11.7; 95% CI, 7.5 to 18.4; p < 0.0001). INR variability (SD) was higher with a higher mean INR value (p < 0.0001). INR variability (HR 2.485; 95% CI, 1.11 to 5.55; p = 0.027) and cancer history (p < 0.0001) independently determined bleeding rates.
  
  
  CONCLUSIONS
  This population-based comprehensive study of anticoagulation and TE post-MVR shows that, in these closely anticoagulated patients, anticoagulation intensity was highly variable and not associated with TE incidence post-MVR. Higher anticoagulation intensity is linked to higher variability and, thus, to bleeding. The MVR-ball prosthesis design is associated with higher TE rates notwithstanding higher anticoagulation intensity, and its use should be retired worldwide.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
authors.forename: Thierry
authors.initials: T
authors.lastname: Le Tourneau
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Lim
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Inamo
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
authors.forename: Fletcher A
authors.initials: FA
authors.lastname: Miller
authors.affiliation: Section of Biostatistics, Mayo Clinic, Rochester, MN.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Mahoney
authors.affiliation: Division of Cardiovascular Surgery, Mayo Clinic, Rochester, MN.
authors.forename: Hartzell V
authors.initials: HV
authors.lastname: Schaff
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN. Electronic address: sarano.maurice@mayo.edu.
authors.forename: Maurice
authors.initials: M
authors.lastname: Enriquez-Sarano
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006350:Heart Valve Prosthesis / Q000009:adverse effects*; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008910:Minnesota; D008943:Mitral Valve / Q000601:surgery*; D017063:Outcome Assessment, Health Care; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011474:Prosthesis Design / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*; D013923:Thromboembolism / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin