Patient characteristics and stroke and bleeding events in nonvalvular atrial fibrillation patients treated with apixaban and vitamin K antagonists: a Spanish real-world study

Abstract

Aim: To compare the risk of stroke, systemic thromboembolism and bleeding, in patients initiating apixaban or acenocoumarol for the treatment of nonvalvular atrial fibrillation. Methods: An observational, retrospective study was performed using medical records of patients who initiated apixaban or acenocoumarol between 2015 and 2017. Propensity score matching was used to match patients; stroke, systemic thromboembolism, major and minor bleeding events were compared between the matched patients. Results: Patients who were prescribed apixaban had a lower rate of systemic embolism/stroke (hazard ratio [HR] = 0.54; 95% CI: 0.38–0.78; p = 0.001), minor bleeding (HR = 0.64; 95% CI: 0.52–0.79; p < 0.001) and major bleeding (HR = 0.51; 95% CI: 0.37–0.72; p < 0.001). Conclusion: Patients prescribed apixaban for the treatment of nonvalvular atrial fibrillation had lower rates of thromboembolic events and minor/major bleeding than patients on acenocoumarol.

Apixaban for Stroke Prevention in Atrial Fibrillation: Why are Event Rates Higher in Clinical Practice than in Randomized Trials?—A Systematic Review

“…1 and ►Table 2, available in the online version). [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] ►Table 1 describes the clinical characteristics of the patients who were treated with either apixaban or a VKA in the two types of studies. Patients treated with apixaban in observational studies were older (mean age 73.8 vs. 69.8 years), had higher CHA 2 DS 2 -VASc scores (mean 3.6 vs. 2.9), and were far more likely to receive the reduced dose (31.3% vs. 5.1%), than those enrolled in RCTs.…”

“…Patients treated with apixaban in observational studies were older (mean age 73.8 vs. 69.8 years), had higher CHA 2 DS 2 -VASc scores (mean 3.6 vs. 2.9), and were far more likely to receive the reduced dose (31.3% vs. 5.1%), than those enrolled in RCTs. [1][2][3][4]7,9,10,12,13,[15][16][17]19,20,47 Apixaban-treated patients prescribed 5 mg were older in observational studies than in RCTs (mean age 70.5 vs. 68.6 years), 7,9,11,14,16,21,48 whereas for those on 2.5 mg no important difference was observed (mean age 83.1 vs. 83.6 years). 7,9,11,16,18,21,48 We were unable to find data on CHA 2 DS 2 -VASc scores per dosing regimen of apixaban for patients enrolled in the RCTs.…”

“…Similarly, compared with patients treated with a VKA in RCTs, VKA-treated patients included in observational studies were older (mean age 76.8 vs. 69.7 years), and had higher CHA 2 DS 2 -VASc scores (mean 3.7 vs. 2.9). [2][3][4][7][8][9]15,16,[18][19][20] ►Table 2 shows the rates of S/SEE, ischemic stroke, major bleeding, ICH, and mortality of patients treated with either apixaban or a VKA in observational studies, compared with those in RCTs. Patients treated with apixaban in observational studies had higher rates of S/SEE (RR 1.62; 95% CI 1.19-1.64), major bleeding (RR 1.37; 95% CI 1.20-1.56), ICH (RR 1.61; 95% CI 1.17-2.20), and mortality (RR 1.91; 95% CI 1.73-2.11) than those treated with apixaban in RCTs.…”

“…Patients treated with apixaban in observational studies had higher rates of S/SEE (RR 1.62; 95% CI 1.19-1.64), major bleeding (RR 1.37; 95% CI 1.20-1.56), ICH (RR 1.61; 95% CI 1.17-2.20), and mortality (RR 1.91; 95% CI 1.73-2.11) than those treated with apixaban in RCTs. [1][2][3][4][5][6][7][8][9][10]12,13,[15][16][17]19,20 Patients treated with apixaban 5 mg twice daily in observational studies had higher rates of S/SEE (RR 1.40; 95% CI 1.14-1.73), major bleeding (RR 1.34; 95% CI 1.15-1.56), and mortality (RR 1.16; 95% CI 1.00-1.35) than those in RCTs. 6,7,11,14,16,21 A similar trend was observed for those treated with apixaban 2.5 mg twice daily: rates of S/SEE (RR 2.10; 95% CI 0.95-4.67), major bleeding (RR 1.18; 95% CI 0.70-1.99), and mortality (RR 1.19; 95% CI 0.89-1.58) were higher compared with patients on the same dose in RCTs, but the difference did not reach statistical significance.…”

“…22 On the other hand, recent data provide another potentially treatable cause for the higher rates of thromboembolic events in patients prescribed apixaban in clinical practice. Thus, several observational studies have reported that the 2.5-mg dose of apixaban is used much more frequently in clinical practice than in RCTs, 1,2,7,9,10,12,13,15,16,19,20 that approximately 50% of patients who receive this dose do not meet two or more of the ABC criteria (i.e., off-label use), [23][24][25][26][27][28][29][30][31] and that such use is associated with an increased risk of thromboembolic events. 23,29,[32][33][34] On these grounds, several authors and guidance documents advocate against the off-label use of the 2.5-mg dose in all patients.…”