The Efficacy And Safety Of Rivaroxaban In The Prevention And Treatment For Thrombo-embolic Diseases In The Very Old Patients

Background: As the aging population grows, the incidences of thrombotic diseasesin the old population continue to increase including arterial and venous thrombosis,pulmonary embolism, cerebral embolism secondary to atrial fibrillation (AF) and so on.Prospective epidemiological investigations showed that the prevalence of venousthrombosis reached9.7%in the old hospitalized patients and the prevalence ofpulmonary embolism was also reached1.9%, so the very old population should beclassified as the population at high risk of venous thromboembolism. Currently, mostmedical hospitalized patients did not undergo reasonable venous thromboembolism(VTE) prophylaxis. Literatures also showed that only40%of high-risk patients receivedthrombosis prophylaxis in the advanced countries, and it was only13%to20%in China.Timely and reasonable antithrombotic therapy especially anticoagulant therapy is themost important measure for the prevention and treatment of serious thrombotic events.Anticoagulant drugs widely used presently are unfractionated heparin, low molecularweight heparin and warfarin. Although these anticoagulant drugs could play and hadplayed an important role in the prevention and treatment of thrombotic diseases, thereare many disadvantages in clinical applications. Heparin can neither oral nor desirablefor long-term use. Warfarin not only could interact with a variety of drugs or foods butalso has a very narrow safety window and the dose must be adjusted frequentlyaccording to international normalized ratio (INR). Therefore, new drugs were urged todevelop to meet the demands of good efficacy, safety and convenient administering foranticoagulant therapy. Novel oral anticoagulant drugs such as rivaroxaban were themost promising agent among them.Objective: The aim of this study was to evaluate the effects and safety of rivaroxabanin the prevention and treatment of thromboembolic diseases in the very old patientscompared with warfarin. Methods: There were two parts in this study. The first part was done to evaluate thetreatment effects and safety of rivaroxaban in the very old patients suffered from acutevenous thrombosis. The second part was done to evaluate the preventive effects andsafety of rivaroxaban in the very old patients at high risk of thrombo-embolic diseases.All enrolled patients were followed up for12months. During that period, thehemoglobin, platelets, coagulation, liver and kidney function were monitored at baseline,1month,3months,6months and12months respectively after treatment. The primaryefficacy endpoints included all-cause mortality, recurrent or new venous thrombosis,pulmonary embolism，cerebrovascular and cardiovascular events. The primary safetyendpoints included major and clinically relevant non-major bleeding, liver and kidneyfunction worsening.In the first part,82venous thrombosis patients treated in our hospital from March2012to March2014were enrolled with an average age of81.5±5.6years old. Theenrolled patients were randomized into rivaroxaban group with39patients (30malesand9females) and warfarin group with43patients (34males and9females). Therivaroxaban group was given low molecular weight heparin and oral rivaroxaban10mg,1/d for the first3days, than oral rivaroxaban10mg,1/d was continued to be given alone.The warfarin group was given individual dose of warfarin and low molecular weightheparin therapy for the first several days until INR got to1.6to2.5(the average INR2.04±0.42), than oral warfarin was continued to be given and INR was monitored to keepINR stabilize at1.6to2.5.In the second part,90patients from March2012to March2014at high risk of venousthrombosis in our hospital were enrolled, with an average age of82.4±5.5years old. Allenrolled patients were also randomized into rivaroxaban group with44patients (34males and10females) and warfarin group with46patients (38males and8females).The rivaroxaban group was given oral rivaroxaban10mg,1/d. The warfarin group wasgiven titrated dose of warfarin and INR monitored constantly to keep INR stabilize at1.6to2.5. Results:1. In the first part, thrombi were all disappeared in the rivaroxaban and warfaringroups. There were no recurrent or new venous thrombosis, pulmonary embolism anddeaths in the two groups. At1st,3rd,6th and12th month in warfarin group, the averageINR was1.98±0.44、2.04±0.53、2.03±0.49and2.01±0.46respectively. Duringfollow up,1case of acute coronary syndrome occurred at6th month in the warfaringroup with a rate of2.33%;3cases of positive fecal occult blood occurred at6th monthin the rivaroxaban group with a rate of7.69%;3cases of positive fecal occult blood at3rd month and6th month respectively in the warfarin group with a rate of13.95%, butthe differences of efficacy and safety were not statistically significant between the twogroups. Hemoglobin, platelet, coagulation, liver and kidney function had no significantchanges both in rivaroxaban group and warfarin group during follow up.2. In the second part, there were also no deaths among the patients at high risk ofthrombosis. At1st,3rd,6th and12th month in warfarin group, the average INR was2.02±0.46、1.98±0.54、2.03±0.56and2.04±0.46. During follow up,1case ofasymptomatic venous thrombosis occurred at6th month and12month respectively inthe rivaroxaban group with the incidence of4.55%;2cases and3cases of asymptomaticvenous thrombosis at3rd month and6th month occurred respectively,2cases ofpulmonary embolism at6th month in warfarin group with the incidence of15.22%.1case of hemoptysis occurred at3rd month and2cases of positive fecal occult bloodoccurred at6th month in rivaroxaban group with the rate of6.82%;2cases of positivefecal occult blood at3rd month and6th month after therapy respectively in warfaringroup with the rate of8.70%. The differences of efficacy and safety were notstatistically significant between the two groups. Hemoglobin, platelet, coagulation, liverand kidney function had no significant changes both in rivaroxaban group and warfaringroup during follow up.Conclusions: Oral rivaroxaban is an effective way for the treatment and preventionfor thrombo-embolic diseases in the very old patients.10mg daily of rivaroxaban is thesafety and effective dose for the prevention and treatment for thromboembolic diseasesin the very old patients. The efficacy of rivaroxaban was equal to warfarin, and it was safer, more convenient to administer, as well as better compliance.