In this nationwide cohort study, patients treated with bilateral TKA had a significantly lower rate of stroke (adjusted HR 0.79) than patients with unilateral TKA. These findings conflict with results in a previous study that showed no significant difference between unilateral TKA and bilateral TKA with respect to postoperative stroke evaluated in a single institution. Furthermore, subgroup analyses stratified based on the factors that affect outcome showed that patients treated with bilateral TKA had a lower risk of postoperative stroke than patients with unilateral TKA when the following variables were present: age (70–79 years), female sex, health insurance, history of hypertension drug use, and comorbidities such as CHF, connective tissue disease, and diabetes.
Sex differences are specific characteristics of postoperative stroke with respect to clinical manifestations and outcomes. In a general surgical population, the manifestations of postoperative stroke were found more frequently in female patients than in male patients. In contrast, when investigating different patient-related factors and their association with postoperative stroke, the risk of stroke after total joint arthroplasty was not significantly different between female and male patients. Notably, in the present study,the risk of stroke was significantly decreased in both male (HR 0.79) and female (HR 0.75) patients treated with bilateral TKA compared with subjects with unilateral TKA, indicating that Korean female patients treated with unilateral TKA have an increased risk of stroke. The mechanism by which the risk of stroke is increased in female patients remains unclear. Proposed explanations for the association between stroke and female sex include a higher rate of embolism in females than males and decreased sensitivity to anticoagulant agents.[18, 19] Another potential explanation is that a substantial number of female patients treated with unilateral TKA who required prophylactic anticoagulant agents might be at greater risk of stroke due to lack of use of prophylactic anticoagulant agents during the postoperative period compared with patients with bilateral TKA even though prophylaxis with universal anticoagulant agents is not generally recommended to patients undergoing TKA in South Korea because the incidence of postoperative stroke is relatively low.
CHF is a commonly reported cardiac complication after bilateral TKA because of suboptimal cardiopulmonary reserve in patients with preexisting comorbid medical conditions and in elderly patients, resulting in greater need for monitoring cardiopulmonary parameters, subsequently leading to a higher rate of admission to the intensive care unit patients treated with bilateral TKA than patients with unilateral TKA.[21, 22] Conversely, in previous studies with relatively small cohorts, significant differences were not reported in terms of cardiac complications between unilateral TKA and bilateral TKA.[23, 24] The large differences among study findings is likely caused by the small numbers of patients enrolled in individual studies. In the present study, a nationwide population-based cohort analysis of 210,128 patients treated with unilateral TKA and 163,719 patients with bilateral TKA was performed, and CHF was most strongly associated with new-onset stroke in patients treated with unilateral TKA. In the current study, patients who received bilateral TKAwere divided into two groups: patients who underwent SBTKA and had two primary TKA procedure codes entered on the same day and patients who underwent StBTKA and had two primary TKA procedure codes entered without discharge.These situations may better identify healthier patients or medically optimized patients who had received bilateral TKA, and the results adequately represent the real-world incidence and disease association.
This study had several limitations. First, the NHI claims database may contain incorrect diagnoses. To minimize this issue, patients with new-onset stroke were defined as subjects whose documented admission yielded principal diagnoses of stroke, patients who were administered relevant CT or MRI within one week after admission, or subjects who were undergoing surgical procedures for new-onset stroke. Second, lifestyle factors, such as smoking status, alcohol consumption, and dietary data, were not evaluated although they could affect the development of stroke. Moreover, we were unable to capture patients who died from a stroke. These seem important since some patients die before reaching the hospital. Third, not every patient needs a TKA on the opposite knee. Thus, all other kinds of unilateral patients who may have had bilateral osteoarthritis but were only treated with TKA on one side should be excluded from these analyses because it was too risky or too frail to operate the other side later. But, we could not adjust for potential confounders such as the severity levels of comorbidities because the Korean NHI claims database did not provide it and substantial criteria in deciding, which of the two modalities to recommend. Fourth, we do not have any information regarding postoperative outcomes such as infection, length of stay, blood transfusion, length-of-rehabilitation, range of motion, and functional outcome. Clinical information available in the Korean NHI claims database is insufficiently reported and thus have limited effect in this comparative analysis. Fifth, we have a likely biased sample in that those who are deemed eligible for bilateral TKA after screening are healthier than those who undergo unilateral TKA even though we have attempted to limit such bias with multivariate logistic regression analysis and propensity score matching. Finally, a one-year period may not be sufficient to exclude all pre-existing strokes. However, the possibility of selection bias in both unilateral and bilateral TKA groups was equal. Despite these limitations, to the best of our knowledge, this is the first nationwide epidemiological study in which the incidence and risk factors for stroke in patients treated with unilateral TKA or bilateral TKA were evaluated using matched control patients.