The results were revealed for 5 clinical trials of rivaroxaban in 2018. Over 28,000 subjects were given rivaroxaban in these clinical trials. The dose of rivaroxaban used in these trials ranged from 2.5 mg bid to 15 mg bid.
The COMPASS study1,2 recruits 24,824 subjects. The inclusion criteria of the subjects for this study were stable multivessel Coronary Artery Disease or Peripheral Arterial Disease or both and the age > 65 years along with more than or equal to 2 vascular beds involved or 2 additional risk factors. 8313 patients were randomized to receive rivaroxaban, at a dose of 2.5 mg bid along with aspirin 100 mg OD. The comparator arm consists of 8261 patients and was given 100 mg aspirin OD. The primary endpoint of the study was cardiovascular death, myocardial infarction, and stroke. The study concludes that the risk of cardiovascular death, stroke, and myocardial infarction was reduced in the rivaroxaban arms. The result also indicates a reduction in the peripheral events by half in the group with peripheral arterial disease. However, there was an increased risk of bleeding in both the arms of the rivaroxaban group. It may indicate that patients with a high risk of bleeding may be selected out before initiating the rivaroxaban therapy.
COMMANDER HF3 trial comprises 5,022 patients. The inclusion criteria were Chronic heart failure with left ventricle ejection fraction < 40% and coronary artery disease and brain Natriuretic peptide; ≥ 200 pg/ml or N-terminal pro-brain Natriuretic peptide≥ 800 pg/ml and worsening heart failure within 21 days. The dose administered in the rivaroxaban arm was 2.5 mg bid along with standard care. 2,515 subjects were randomized in the comparator arm and were given a placebo and standard care. The primary endpoints were All-cause death, myocardial infarction, and stroke. The trial concluded that the rivaroxaban was not able to reduce the risk of myocardial infarction, stroke, and all-cause death in patients with recently exacerbated CHF.
Another trial, the NAVIGATE ESUS4 trial comprises 7,213 subjects. The inclusion criteria of this trial were Ischemic CVA (7 days-6 months) and age > 49 years. The patients should have no lacunae, no extracranial/ intracranial stenosis > 50%, and no embolic source + 20 hours EKG. If the age of the patients is 50-59 years, they should also have at least 1 additional risk factor. The dose of rivaroxaban used in the trial was 15 mg OD in 3,609 patients. The comparator arm comprises 3604 patients who were administered 100 mg aspirin. The primary endpoint of the study was systemic embolism or first recurrent stroke. The trial concluded that as compared with aspirin, 15 mg rivaroxaban was unable to reduce the risk of systemic embolism or first recurrent stroke in patients over the age of 49 years with ischemic stroke of unknown origin.
MARINER5 recruits 12,019 patients. The inclusion criteria include age ≥ 40 years, with hospitalized for 3-10 days. The patients should have to IMPROVE score ≥ 4 or a score of 2 or 3 with a D-dimer ≥ 2 × upper limit of normal. The patient received low molecular weight heparin or unfractionated heparin in the hospital. The primary endpoint is symptomatic venous thromboembolism or death due to venous thromboembolism. The dose of rivaroxaban was 10 mg OD in patients with healthy kidney function and 7.5 mg if creatine clearance 30-50 ml/min. The therapy was for 45 days post-discharge. 6,012 patients in the comparator arm received a placebo. The study concluded that rivaroxaban was not effective in reducing the risk of venous thromboembolism or thrombotic death.
SELECT-D6 clinical trial was done on 406 patients. The inclusion criteria include active cancer with symptomatic or asymptomatic venous thromboembolism. The primary endpoint was the recurrence of venous thromboembolism. The patients in the rivaroxaban arm were given 15 mg bid for three weeks then 20 mg OD. The comparator arm received dalteparin. The study concluded that rivaroxaban was inferior to dalteparin in reducing the recurrence of cancer-associated thrombosis.
It is important to note that anticoagulant therapy is effective in reducing thrombosis; however, there is an increased risk of bleeding making it a decisive factor for continuing therapy. The therapy should be given after analyzing the condition of the patient. Further, not all patients with cardiovascular risks should be given rivaroxaban. The dose of rivaroxaban should be decided based on the type of risk in the patient along with the current condition.