|Abstract / Summary
This thesis investigated the prognosis of THR patients over the last two decades. Ten studies were based on Danish cohorts of THR patients, whereas one study examined THR patients operated on in four Nordic countries: Denmark, Sweden, Norway, and Finland. As the overall aim of this thesis was to improve our understanding of the long-term clinical course of patients undergoing THR surgery, the occurrence of a broad range of adverse outcomes, including revision surgery, VTE, MI, stroke, bleeding, infection, and death was examined. The thesis further identified patients who are at increased risk of developing these outcomes in both the short- and long-term post-operative periods in order to create a basis for preventing adverse outcomes, refine patient selection and treatment, and improve the quality of THR surgery.
THR surgery is now one of the most commonly performed surgical procedures in Western countries, with increasing rates worldwide over the last two decades, including a 30% increase in Denmark from 1996-2002 (study I). Direct comparison of THR rates from different countries is complicated by a lack of generally accepted standardization methods as recognized in study I. In contrast, during the same time period in Denmark, the rate of THR due to RA was reduced by 30% (study I), which is in accordance with reports from other countries.
Several studies have predicted that the overall demand for THR surgery will further increase based on anticipated changes in patient demographics alone, as well as on the surgical activity in previous years (study I). On the other hand, the newest data show that the incidence of THR in Denmark has been stable over the years 2010-2013, which may be partly attributable to lower OA disease activity in the general population or more extensive pharmacological treatment, neither of which has been confirmed in the literature.
One feared post-THR complication is revision surgery, which has been studied extensively since the insertion of the first hip implants. A number of factors have been associated with the risk of revision surgery. However, there is a possible contradiction regarding the direction of associations depending on whether short- or long-term risk was studied, which has not been widely acknowledged before this thesis. For example, we observed that, during the short-term post-operative period, older patients have a higher risk of any revision due to their increased risk of falling and sustaining a fracture or dislocation. On the other hand, younger patients were at a higher risk of revision during the long-term period (study II) due to implant loosening. Similarly, in the short-term post-operative period, pediatric diseases were associated with an increased risk of any revision compared to OA due to the increased risk of dislocations, but no difference in revision risk was observed in the long-term period (study II). During a median follow-up time of approximately 5 years, 3.1% of all Danish primary THR patients underwent revision due to any cause (study II) and 0.7% due to joint infection (study IV).
Two studies observed that a high comorbidity level prior to surgery has a profound impact on short-term revision risk (study II). A novel finding of this thesis was that high comorbidity also affects the long-term revision risk (study II), which has been confirmed by several recent studies. Due to the increasing burden of a variety of comorbidities in THR patients, their association with revision risk and the underlying mechanisms merit further research. To offer some possible explanations for how comorbidity affects revision risk, this thesis focused in more detail on THR patients with diabetes, which has a high and increasing prevalence in both the general population and the THR population. Diabetes increased the risk of revision due to infection, particularly in patients with diabetes for less than 5 years prior to THR, those with complications due to diabetes, and those with cardiovascular comorbidities prior to surgery (study V). These findings were also confirmed recently. However, the effect of the quality of glycemic control on the risk of revision due to infection has not yet been addressed in detail. Other prognostic factors for revision due to infection remain to be identified, as several reports indicate increasing rates of revision due to deep infection.
Uncemented implants are supposed to solve the problem of aseptic loosening with cemented implants and wear of the acetabular bearing side. Uncemented implants are successful in achieving this goal when they are used in patients younger than 55 years of age (study III), but not in patients over 65 years. However, we still need to solve mechanical and technical problems with uncemented implants, which lead to short-term revisions irrespective of age (study III).
The 90-day risk of symptomatic VTE among Danish THR patients receiving pharmacological thromboprophylaxis is only 1% (studies VIII and X). THR was associated with an increased excess risk of developing symptomatic VTE up to one year after surgery compared to the general population without THR, irrespective of gender, age, or comorbidity prior to THR (study IX). There is clear evidence of an association between previous VTE or history of cardiovascular diseases and risk of post-operative VTE in THR patients (study VIII). However, only sparse data exist regarding the general effect of comorbidity on VTE risk. A high CCI score before surgery has been shown to substantially increase VTE risk in Danish settings (study VIII and X), but not in select clinics in the United States. Study VIII observed that THR patients with RA have a lower 90-day risk of VTE compared to THR patients with primary OA. However, this finding was not confirmed in a recent meta-analysis based on two studies and further research is needed.
Evidence from non-randomized cohort study XI based on real life THR patients indicates that the risks of developing VTE, VTE/death, or major bleeding do not differ between extended and short-term thromboprophylaxis.
Approximately 1 in 200 THR patients develop MI or ischemic stroke within 90 days of surgery (study X). The risk of MI and stoke is elevated for 6 weeks following THR compared to the general population without THR.
The risk of major bleeding complications associated with THR was stable from 1997 to 2011 (study X), and was approximately 0.5% within 90 post-operative days. Despite more aggressive thromboprophylaxis (study XI), major bleeding still occurred infrequently and was less common than VTE (study X). Study X reported for the first time several prognostic factors for major bleeding in THR patients, including male gender, older age, high comorbidity level, and use of general anesthesia. Approximately 32% Danish THR patients received treatment with allogeneic blood transfusion, although the treatment is associated with an adverse prognosis following THR surgery (study VI).
As expected, THR surgery is associated with an increased risk of any death within the first 30 days after surgery (study VII). However, in general, 90 days after surgery, patients who underwent THR due to OA showed similar or even lower any cause mortality (study VII) compared to the general population, which persisted in the long term (study VII). A novel finding of this thesis was that THR surgery seems to be associated with increased 90 days mortality, particularly due to MI and VTE, among younger patients and those without comorbidity before surgery compared to matched persons from the general population without THR (study VII). Treatment with THR is overall well optimized, as shown by the decreased in-hospital mortality and 90-day mortality rates in several developed countries (study X). The steady-state occurrence of cardiovascular complications was observed over the last 15 years, from 1997 to 2011 (study X) suggesting that that there may still be room for clinical improvement.