Variability in anticoagulation control predicts thromboembolism after mechanical cardiac valve replacement: a 23-year population-based study.
OBJECTIVE
To assess optimal control of blood anticoagulation to maximize antithrombotic protection after mechanical cardiac valve replacement.


METHODS
A population-based study of 96 patients with a mean follow-up of 7.7 years (range, 1 month to 23 years) was performed in Olmsted County, Minnesota, and 10,301 prothrombin time (PT) ratios were determined after mechanical heart valve replacement.


METHODS
PT ratios were analyzed in a new time-dependent Cox proportional-hazards model by defining an algorithm for comparing variability in PT ratios at each month of follow-up and relating these to thromboembolic events. The new method was compared with several conventional time-independent definitions.


RESULTS
During 740 person-years of follow-up, 19 of 96 patients (20%) had 27 thromboembolic events. Of these 19 patients, 8 (42%) had events within 3 months after valve replacement. Freedom from any thromboembolic event was 72% at 15 years. The event rate was high (7.5% per year) during high variability and low (0.9% per year) during low variability in the PT ratio. This relationship was lost when time dependence was removed. More PT ratios were less than 1.5 during high (27%) than during low (19%) variability. Several conventional definitions of adequacy of anticoagulation that averaged PT ratios before a thromboembolic event or throughout follow-up or that compared the proportion of PT ratios above or below a fixed ratio did not define or only partially defined different thromboembolic risks.


CONCLUSIONS
Periods of high and low variability of PT ratios define high and low risk of thromboembolism, respectively.
Huber
K C
KC
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic Rochester, MN 55905, USA.
Gersh
B J
BJ
Bailey
K R
KR
Schaff
H V
HV
Hodge
D O
DO
Cha
R H
RH
Chesebro
J H
JH
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D005260:Female; D006350:Heart Valve Prosthesis / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011517:Prothrombin Time; D013923:Thromboembolism / Q000097:blood* / Q000209:etiology / Q000517:prevention & control; D013997:Time Factors
D000925:Anticoagulants