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Wells G, Coyle D, Cameron C, et al. Safety, Effectiveness, and Cost-Effectiveness of New Oral Anticoagulants Compared with Warfarin in Preventing Stroke and Other Cardiovascular Events in Patients with Atrial Fibrillation [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2012 Apr 9.
A summary of study level results are shown in Table 48. Information on follow-up time and control event rate are provided alongside the relative and absolute risk. With the exception of dabigatran 110 mg, all treatments achieved statistically significant reductions in all-cause stroke/SE relative to adjusted-dose warfarin (Table 46). The use of dabigatran 150 mg produced the largest effects, with a reduction in odds of all-cause stroke/SE (OR [95% CI]: 0.65 [0.52 to 0.81]) and a corresponding absolute risk reduction of six fewer events per 1,000 patients treated each year. Relative to adjusted-dose warfarin, the reduction in odds for dabigatran 110 mg, apixaban 5 mg, and rivaroxaban 20 mg ranged from 0.78 to 0.90, with an absolute risk reduction of two to three fewer events per 1,000 patients treated each year.
Summary of Study-level Results for All-Cause Stroke/Systemic Embolism Compared with Adjusted-Dose Warfarin.
Both Bayesian and frequentist evidence networks were comprised of three RCTs — ARISTOTLE, RE-LY, ROCKET-AF — representing four treatments, each relative to adjusted-dose warfarin (N = 50,276). The first network meta-analysis was unadjusted, not taking any possible differences in the patient populations across the studies into consideration. A summary of the unadjusted results for the fixed-effects Bayesian MTC are shown in Table 49, along with model fit statistics. With the exception of dabigatran 110 mg and rivaroxaban, all treatments achieved statistically significant reductions in the odds of all-cause stroke/SE relative to adjusted-dose warfarin. The use of dabigatran 150 mg produced the largest effects, with a reduction in odds of stroke/ SE (OR [95% CrI]: 0.65 [0.52 to 0.81]) relative to adjusted-dose warfarin. Data on the probability of an event in the warfarin arm provides a reflection of potential heterogeneity across studies, which are partially adjusted for in Section 8.12.1.3. Complete results from the MTC meta-analysis for all possible comparisons are presented in Table 24. The estimates of effect derived from fixed-effects Bayesian MTC analyses aligned closely with study level results and frequentist network meta-analysis results (see Table 49) in both direction and magnitude. The point estimates for the Bayesian random-effects MTC analysis were similar to those reported in the Bayesian fixed-effects MTC, although the credible intervals were much wider (see Appendix 7.11).
Summary of Unadjusted Fixed-Effects Bayesian MTC Results for All-cause Stroke/Systemic Embolism Compared with Adjusted-Dose Warfarin.
Figure 12 shows the distribution of the probabilities, considered from a descriptive statistics perspective, of each treatment being ranked at each of the possible five ranking positions for the unadjusted Bayesian MTC meta-analysis. Dabigatran 150 mg had the highest probability of being best at reducing all-cause stroke/SE; apixaban and rivaroxaban have the highest probability of being second and third best, respectively; whereas dabigatran 110 mg and adjusted-dose warfarin have the highest probability of being fourth and fifth best, respectively.
Rankogram for Unadjusted Fixed-Effects Bayesian MTC Results for All-cause Stroke/Systemic Embolism Compared with Adjusted-Dose Warfarin. b.i.d. = twice daily; MTC = mixed treatment comparison; q.d. = once daily.
A summary of results from a subgroup analysis by TTR are reported in Table 50. Odds ratios are derived from a Bayesian fixed-effects MTC analysis, whereas absolute risk reduction results are based on study-level results. For TTR < 66%, dabigatran 150 mg had a strong trend in reducing the odds of all-cause stroke/SE relative to adjusted-dose warfarin (OR [95% CrI]: 0.54 [0.40 to 0.74]), with an absolute risk reduction of nine fewer events per 1,000 treated each year relative to adjusted-dose warfarin. Relative to adjusted-dose warfarin, the reduction in odds for the other treatments ranged from 0.80 to 0.91 with absolute risk reduction ranging from two to four per 1,000 treated each year. For TTR ≥ 65%, no treatments had a strong trend in reducing the odds of all-cause stroke/SE relative to adjusted-dose warfarin. Relative to adjusted-dose warfarin, the reduction in odds for all treatments ranged from 0.80 to 0.91.
Results from Fixed-Effects Bayesian MTC Sub-Group Analysis for All-Cause Stroke/Systemic Embolism Compared with Adjusted-Dose Warfarin by TTR.
Figure 13 shows the distribution of probabilities, considered from a descriptive statistics perspective, of each treatment being ranked at each of the possible five ranking positions for the Bayesian MTC meta-analysis by TTR subgroup. For TTR< 66%, dabigatran 150 mg has the highest probability of being best at reducing all-cause stroke/SE; apixaban and rivaroxaban have the highest probability of being second and third best, respectively; whereas dabigatran 110 mg and adjusted-dose warfarin have the highest probability of being fourth and fifth best, respectively — the same ordering that was found based on the unadjusted analysis. For TTR ≥ 66%, rivaroxaban has the highest probability of being best; apixaban and dabigatran 150 mg have a similar probability of being second or third best, respectively; whereas dabigatran 110 mg and adjusted-dose warfarin have the highest probability of being fourth and fifth best, respectively (Figure 13).
A summary of results from a subgroup analyses by age are reported in Table 51. Odds ratios are derived from Bayesian fixed-effects MTC analyses, whereas absolute risk reductions are based on study-level results. For age < 75 years, dabigatran 150 mg had a strong trend of reducing the odds of all-cause stroke/SE relative to adjusted-dose warfarin (OR [95% CrI]: 0.64 [0.46 to 0.87]), with an absolute risk reduction of 5 fewer per 1,000 treated each year. Relative to adjusted-dose warfarin, the reduction in odds for other treatments ranged from 0.85 to 0.94, with absolute risk reduction ranging from one to five fewer. For age ≥ 75 years, apixaban, dabigatran 150 mg, and rivaroxaban all had strong trends in reducing the odds of all-cause stroke/SE relative to adjusted-dose warfarin. Relative to adjusted-dose warfarin, the reduction in odds for dabigatran 110 mg was 0.89.
Results from Fixed-Effects Bayesian MTC Sub-Group Analysis for All-cause Stroke/Systemic Embolism Compared with Adjusted-Dose Warfarin By Age.
Figure 14 shows the distribution of probabilities, considered from a descriptive statistics perspective, of each treatment being ranked at each of the possible five ranking positions for the Bayesian MTC meta-analysis by age sub-groups. For age < 75 years, dabigatran 150 mg has the highest probability of being best at reducing all-cause stroke/SE; apixaban and rivaroxaban have the highest probability of being second and third best, respectively; whereas dabigatran 110 mg and adjusted-dose warfarin have the highest probability of being fourth and fifth best, respectively. For age ≥ 75 years, dabigatran 150 mg and rivaroxaban have a similar probability of being best; apixaban has the highest probability of being third best; whereas dabigatran 110 mg and adjusted-dose warfarin have the highest probability of being fourth and fifth best, respectively (Figure 14).
Rankograms for Fixed-Effects Bayesian MTC for All-Cause Stroke/Systemic Embolism Compared with Adjusted-Dose Warfarin By Age. b.i.d. = twice daily; MTC = mixed treatment comparison; q.d. = once daily; SE = systemic embolism; y = year.
A summary of results from a subgroup analysis by CHADS2 score is reported in Table 52. Odds ratios are derived from Bayesian fixed-effects MTC analyses, whereas ARR results are based on study-level results. For CHADS2 < 2, dabigatran 150 was associated with a strong trend to reducing the odds of all-cause stroke/SE relative to adjusted-dose warfarin. Relative to adjusted-dose warfarin, the reduction in odds for apixaban and dabigatran 110 mg was 0.86 and 1.00, respectively. The corresponding ARR were low. For rivaroxaban, results were not available, as no patients with a CHADS2 < 2 were recruited into the study. For CHADS2 ≥ 2, apixaban and dabigatran 150 mg were associated with strong trends in reducing the odds of all-cause stroke/SE relative to adjusted-dose warfarin. Relative to adjusted-dose warfarin, the reduction in odds for dabigatran 110 mg and rivaroxaban was 0.89 and 0.88, respectively. The ARR ranged from 2 to 6 for CHADS2 ≥ 2.
Results from Fixed-Effects Bayesian MTC Sub-Group Analysis for All-Cause Stroke/Systemic Embolism Compared with Adjusted-Dose Warfarin By CHADS2.
Figure 15 shows the distribution of probabilities, considered from a descriptive statistics perspective, of each treatment being ranked at each of the possible five ranking positions based on the Bayesian MTC meta-analysis for the sub-group CHADS2 ≥ 2 for the ITT analysis population. For CHADS2 ≥ 2 and per ITT population, dabigatran 150 mg has the highest probability of being best at reducing all-cause stroke/SE, apixaban has the highest probability of being second best, rivaroxaban has the highest probability of being third best, whereas dabigatran 110 mg and adjusted-dose warfarin have the highest probability of being fourth and fifth best, respectively (Figure 15).
A summary of study level results are shown in Table 53, with information on follow-up time and control event rate provided alongside relative and absolute risks. Apixaban and dabigatran 110 mg achieved statistically significant reductions in major bleed relative to adjusted-dose warfarin (Table 53). The use of apixaban produced the largest effects, with a reduction in odds of major bleed (OR [95% CI]: 0.69 [0.60 to 0.80]) and a corresponding absolue risk reduction of eight fewer events per 100 treated each year.
Summary of Study-Level Results for Major Bleeding Compared with Adjusted-Dose Warfarin.
Both Bayesian and frequentist evidence networks were comprised of three RCTs — ARISTOTLE, RE-LY, ROCKET-AF— representing four treatments, each relative to adjusted-dose warfarin (N = 50,276). A summary of unadjusted results for the fixed-effects Bayesian MTC are shown in Table 54, along with model fit statistics. Apixaban and dabigatran 110 mg achieved statistically significant reductions in the odds of major bleed relative to adjusted-dose warfarin. The use of apixaban produced the largest effects, with a reduction in odds of major bleeding (OR [95% CrI]: 0.70 [0.61 to 0.81]) relative to adjusted-dose warfarin. Relative to adjusted-dose warfarin, the reduction in odds for other treatments ranged from 0.81 to 1.03. There were no statistically significant differences between agents, the exception being dabigatran 110 mg versus 150 mg (OR [95% CrI]: 0.81 [0.70 to 0.93]). Data on the probability of an event in the warfarin arm provide a reflection of potential heterogeneity across studies, which are partially adjusted for in Section 8.12.2.3. Complete results from the MTC meta-analysis for all possible comparisons are presented in Table 24. The estimates of effects derived from fixed-effects Bayesian MTC analyses aligned closely with study level results and frequentist network meta-analysis results (see Table 54) in both direction and magnitude. The point estimates for the Bayesian random-effects MTC meta-analysis were similar to those reported in the Bayesian fixed-effects MTC, although the credible intervals were much wider (see Appendix 7.11).
Summary of Unadjusted Fixed-Effects Bayesian MTC Results for Major Bleed Compared with Adjusted-Dose Warfarin.
Figure 16 shows the distribution of probabilities, considered from a descriptive statistics perspective, of each treatment being ranked at each of the possible five ranking positions for unadjusted Bayesian MTC meta-analyses. Apixaban has the highest probability of being best at reducing all major bleeding. Dabigatran 110 mg and 150 mg have the highest probability of being second and third best, whereas adjusted-dose warfarin and rivaroxaban have the highest probability of being fourth and fifth best, respectively.
Rankogram for Unadjusted Fixed-Effects Bayesian MTC Results for Major Bleeding Compared with Adjusted-Dose Warfarin. b.i.d. = twice daily; FE = fixed effects; MTC = mixed treatment comparison; q.d. = once daily..
A summary of results from a subgroup analyses by TTR are reported in Table 55. Odds ratios were derived from Bayesian fixed-effects MTC meta-analyses, whereas absolute risk reduction results were based on study-level results. For TTR < 66%, apixaban, dabigatran 110 mg, and dabigatran 150 mg were all associated with a strong trend in reducing the odds of major bleeding relative to adjusted-dose warfarin, with absolute risk reduction ranging from 9 to 11 fewer per 1,000 treated each year. Relative to adjusted-dose warfarin, rivaroxaban was associated with a reduction in odds of 0.92, with an absolute risk reduction of two fewer per 1,000 treated each year. For TTR ≥ 66%, apixaban was associated with a strong trend in reducing the odds of major bleeding relative to adjusted-dose warfarin. Relative to adjusted-dose warfarin, rivaroxaban had a trend of an increase in the odds of major bleeding (OR [95% CrI]: 1.30 [1.01 to 1.69]), and dabigatran 110 mg and 150 mg had an odds of 0.86 and 1.15, respectively. The absolute risk reduction ranged from six fewer to 11 more per 1,000 treated each year.
Results from fixed-effects Bayesian MTC Sub-Group Analysis for Major Bleeding Compared with Adjusted-Dose Warfarin by TTR.
Figure 17 shows the distribution of probabilities, considered from a descriptive statistics perspective, of each treatment being ranked at each of the possible five ranking positions for the TTR sub-groups. For TTR < 66%, apixaban has the highest probability of being best at reducing major bleeding; dabigatran 110 mg and dabigatran 150 mg have the highest probability of being second and third best, respectively; whereas rivaroxaban and adjusted-dose warfarin have the highest probability of being fourth and fifth best, respectively. For TTR ≥ 66%, apixaban has the highest probability of being best at reducing major bleeding; dabigatran 110 mg and adjusted-dose warfarin have the highest probability of being second and third best, respectively; whereas dabigatran 150 mg and rivaroxaban have the highest probability of being fourth and fifth best, respectively (Figure 17).
A summary of the results from a subgroup analyses by age are reported in Table 56. Odds ratios are derived from Bayesian fixed-effects MTC meta-analyses, whereas absolute risk reduction results are based on study-level results. For age < 75 years, apixaban, dabigatran 110 mg and dabigatran 150 mg all were associated with a strong trend in reducing the odds of major bleeding relative to adjusted-dose warfarin. Relative to adjusted-dose warfarin, the reduction in odds for rivaroxaban was 0.93. The absolute risk reductions ranged between two and eleven fewer per 1,000 treated each year relative to adjusted-dose warfarin. For age ≥ 75 years, apixaban was associated with a strong trend in reducing the odds of major bleeding relative to adjusted-dose warfarin. Relative to adjusted-dose warfarin, the other treatments were associated with an odds ranging from 1.03 to 1.20. With the exception of apixaban, the benefits diminished for age ≥ 75 years compared to age < 75 years, with absolute risk reduction ranging from 15 fewer to eight more per 1,000 treated each year for age ≥ 75 years.
Results from Fixed-Effects Bayesian MTC Sub-Group Analysis for Major Bleeding Compared with Adjusted-Dose Warfarin By Age.
Figure 18 shows the distribution of probabilities, considered from a descriptive statistics perspective, of each treatment being ranked at each of the possible five ranking positions for subgroup analyses by age. For age < 75 years, dabigatran 110 mg has the highest probability of being best at reducing major bleeding; dabigatran 150 mg and apixaban have the highest probability of being second and third best, respectively; whereas rivaroxaban and adjusted-dose warfarin have the highest probability of being fourth and fifth best, respectively. For age ≥ 75 years, apixaban has the highest probability of being best at reducing major bleeding, adjusted-dose warfarin has the highest probability of being second best, whereas dabigatran 110 mg, rivaroxaban and dabigatran 150 mg appear to have the highest likelihood of being third, fourth, and fifth best, respectively (Figure 18).
Rankograms for Fixed-Effects Bayesian MTC for Major Bleeding Compared with Adjusted-Dose Warfarin by Age. b.i.d. = twice daily; MTC = mixed treatment comparison; q.d. = once daily;y = years.
A summary of results from subgroup analyses by CHADS2 are reported in Table 57. The ORs are derived from Bayesian fixed-effects MTC meta-analyses, absolute risk reduction results are based on study-level results. For CHADS2 < 2, apixaban and dabigatran 110 mg had a strong trend in reducing the odds of major bleeding relative to adjusted-dose warfarin. Relative to adjusted-dose warfarin, the reduction in odds for dabigatran 150 mg was 0.77. The absolute risk reduction s ranged from 7 to 10 fewer per 1,000 patients treated each year relative to adjusted-dose warfarin. Results were not available for rivaroxaban, as patients with CHADS2 < 2 were not included in the study. For CHADS2 ≥ 2, apixaban was associated with a strong trend in reducing the odds of major bleeding relative to adjusted-dose warfarin. Relative to adjusted-dose warfarin, the reduction in odds for all treatments ranged from 0.74 to 1.03. The absolute risk reduction ranged from eight fewer to one more per 1,000 patients treated each year for CHADS2 ≥ 2.
Results from Fixed-Effects Bayesian MTC Sub-Group Analysis for Major Bleeding Compared with Adjusted-Dose Warfarin by CHADS2.
Figure 19 shows the distribution of probabilities, considered from a descriptive statistics perspective, of each treatment being ranked at each of the possible five ranking positions for CHADS2 ≥ 2. Apixaban has the probability of being best at reducing major bleeding; dabigatran 110 mg has the highest probability of being second best; whereas dabigatran 150 mg, adjusted-dose warfarin, and rivaroxaban have the highest probability of being third, fourth, and fifth best, respectively (Figure 19).
Rankograms for Fixed-Effects Bayesian MTC for Major Bleeding Compared with Adjusted-Dose Warfarin for CHADS2 ≥ 2. b.i.d. = twice daily; MTC = mixed treatment comparison; q.d. = once daily.
A summary of study level results are shown in Table 58, with information on follow-up time and control event rate provided alongside relative and absolute risks including the number needed to treat. Apixaban approached a statistically significant reduction in all-cause mortality relative to adjusted-dose warfarin (OR [95% CI]: 0.89 [0.79 to 0.998]) with corresponding absolute risk reductions of four fewer deaths per 1,000 treated each year relative to adjusted-dose warfarin. Relative to adjusted-dose warfarin, the reduction in odds for dabigatran 110 mg, apixaban 5 mg, and rivaroxaban 20 mg ranged from 0.88 to 0.92, with absolute risks ranging from three to four fewer.
Summary of Study-Level Results for All-Cause Mortality Compared with Adjusted-Dose Warfarin.
Both Bayesian and frequentist evidence networks were comprised of three RCTs — ARISTOTLE, RE-LY, ROCKET-AF — representing four treatments, each relative to adjusted-dose warfarin (N = 50,276). A summary of unadjusted results for the fixed-effects Bayesian MTC are shown in Table 59, along with model fit statistics. There were no statistically significant differences between agents and adjusted-dose warfarin; however, apixaban approached statistical significance (OR [95% CrI]: 0.90 [0.80 to 1.00]). Data on probability of an event in the warfarin arm is also provided to reflect potential heterogeneity across studies. The estimates of effects derived from fixed-effects Bayesian MTC analyses aligned closely with study level results and frequentist network meta-analysis results (see Table 59) in both direction and magnitude. The point estimates for the Bayesian random-effects MTC meta-analysis were similar to those reported in the Bayesian fixed-effects MTC, although the credible intervals were much wider (see Appendix 7.11).
Summary of Unadjusted Fixed-Effects Bayesian MTC Results for All-cause Mortality Compared with Adjusted-Dose Warfarin.
Figure 20 shows the distribution of probabilities, considered from a descriptive statistics perspective, of each treatment being ranked at each of the possible five ranking positions for unadjusted Bayesian MTC meta-analyses. Dabigatran 150 mg and apixaban had the highest probability of being best and second best at reducing all-cause mortality. Dabigatran 110 mg and rivaroxaban had the highest probability of being third and fourth best, whereas adjusted-dose warfarin had the highest probability of being fifth best.
Rankogram for Unadjusted Fixed-Effects Bayesian MTC Results for All-Cause Mortality. b.i.d. = twice daily; MTC = mixed treatment comparison; q.d. = once daily.
A summary of study level results are shown in Table 60, with information on follow-up time and control event rate provided alongside relative and absolute risks including the number needed to treat benefit. All treatments were associated with a statistically significant reduction in intracranial bleeding with ORs ranging from 0.30 to 0.65 and corresponding absolute risk reductions ranging from three to five fewer per 1,000 treated each year.
Summary of Study-level Results for Intracranial Bleeding Compared with Adjusted-Dose Warfarin.
Both Bayesian and frequentist evidence networks were comprised of 3 RCTs — ARISTOTLE, RE-LY, ROCKET-AF — representing four treatments, each relative to adjusted-dose warfarin (N = 50,276). A summary of unadjusted results for the fixed-effects Bayesian MTC are shown in Table 61, along with model fit statistics. All treatments were associated with a statistically significant difference in intracranial bleeding compared with adjusted-dose warfarin, with ORs ranking from 0.30 to 0.66. Data on probability of an event in the warfarin arm is also provided to reflect potential heterogeneity across studies. The estimates of effect derived from fixed-effects Bayesian MTC analyses aligned closely with study level results and frequentist network meta-analysis results (see Table 61) in both direction and magnitude. The point estimates for the Bayesian random-effects MTC meta-analysis were similar to those reported in the Bayesian fixed-effects MTC, although the credible intervals were much wider (see Appendix 7.11).
Summary of Unadjusted Fixed-Effects Bayesian MTC Results for Intracranial Bleeding Compared with Adjusted-Dose Warfarin.
Figure 21 shows the distribution of probabilities, considered from a descriptive statistics perspective, of each treatment being ranked at each of the possible five ranking positions for unadjusted Bayesian MTC meta-analyses. Dabigatran 110 mg had the highest probability of being associated with reduced intracranial bleeding. Dabigatran 150 mg and apixaban were second and third best, whereas rivaroxaban and adjusted-dose warfarin were fourth and fifth best, respectively.
Rankogram for Unadjusted Fixed-Effects Bayesian MTC Results for Intracranial Bleeding. b.i.d. = twice daily; MTC = mixed treatment comparison; q.d. = once daily.
A summary of study level results are shown in Table 62, with information on follow-up time and control event rate provided alongside relative and absolute risks including the number needed to treat to benefit . No treatments were associated with a statistically significant reduction in MI relative to adjusted-dose warfarin. The ORs for other treatments ranged from 0.88 to 1.31, with corresponding absolute risk reductions ranging from one fewer to two more per 1,000 treated per year.
Summary of Study-Level Results for Myocardial Infarction Compared with Adjusted-Dose Warfarin.
Both Bayesian and frequentist evidence networks were comprised of 3 RCTs — ARISTOTLE, RE-LY, ROCKET-AF — representing four treatments, each relative to adjusted-dose warfarin (N = 50,276). A summary of unadjusted results for the fixed-effects Bayesian MTC are shown in Table 63, along with model fit statistics. No treatments were associated with a statistically significant reduction in MI relative to adjusted-dose warfarin. The ORs for treatments ranged from 0.80 to 1.32. Data on probability of an event in the warfarin arm is also provided to reflect potential heterogeneity across between studies. The estimates of effects derived from fixed-effects Bayesian MTC analyses aligned closely with study level results and frequentist network meta-analysis results (see Table 63) in both direction and magnitude. The point estimates for the Bayesian random-effects MTC meta-analysis were similar to those reported in the Bayesian fixed-effects MTC, although the credible intervals were much wider (see Appendix 7.11).
Summary of Unadjusted Fixed-Effects Bayesian MTC Results for Myocardial Infarction Compared with Adjusted-Dose Warfarin.
Figure 22 shows the distribution of probabilities, considered from a descriptive statistics perspective, of each treatment being ranked at each of the possible five ranking positions for unadjusted Bayesian MTC meta-analyses. Rivaroxaban and apixaban had the highest probability of being best and second best at reducing MI, adjusted-dose warfarin had the highest probability of being third best, and dabigatran 150 mg and dabigatran 110 mg had the highest probability of being fourth and fifth best, respectively.
A summary of study level results are shown in Table 64, with information on follow-up time and control event rate provided alongside relative and absolute risks. No treatments were associated with a statistically significant reduction in major GI bleeding relative to adjusted-dose warfarin. However, dabigatran 150 mg (OR [95% CI]: 1.45 [1.13 to 1.85]) and rivaroxaban (OR [95% CI]: 1.60 [1.29 to 1.98]) were associated with a statistically significant increase in major GI bleeding, with corresponding absolute risk increase of four and eight events per 1,000 treated per year, respectively.
Summary of Study-Level Results for Major Gastrointestinal Bleeding Compared with Adjusted-Dose Warfarin.
Both Bayesian and frequentist evidence networks were comprised of three RCTs — ARISTOTLE, RE-LY, ROCKET-AF — representing four treatments, each relative to adjusted-dose warfarin (N = 50,276). A summary of unadjusted results for the fixed-effects Bayesian MTC are shown in Table 65, along with model fit statistics. No treatments were associated with a statistically significant reduction in major GI bleeding relative to adjusted-dose warfarin. However, dabigatran 150 mg (OR [95% CrI]: 0.1.45 [1.14 to 1.86]) and rivaroxaban (OR [95% CrI]: 1.61 [1.30 to 1.99]) were associated with a statistically significant increase in major GI bleeding. Data on probability of an event in the warfarin arm is also provided to reflect potential heterogeneity across studies. The estimates of effect derived from fixed-effects Bayesian MTC analyses aligned closely with study level results and frequentist network meta-analysis results (see Table 65) in both direction and magnitude. The point estimates for the Bayesian random-effects MTC meta-analysis were similar to those reported in the Bayesian fixed-effects MTC, although the credible intervals were much wider (see Appendix 7.11).
Summary of Unadjusted Fixed-Effects Bayesian MTC Results for Major Gastrointestinal Bleeding Compared with Adjusted-Dose Warfarin.
Figure 23 shows the distribution of probabilities, considered from a descriptive statistics perspective, of each treatment being ranked at each of the possible five ranking positions for unadjusted Bayesian MTC meta-analyses. Apixaban and adjusted-dose warfarin had the highest probability of being best and second best at reducing major GI bleeding. Dabigatran 110 mg and 150 had the highest probability of being third and fourth best, respectively, whereas rivaroxaban had the highest probability of being fifth best.
Rankogram for Unadjusted Fixed-Effects Bayesian MTC Results for Major Gastrointestinal Bleeding. b.i.d. = twice daily; MTC = mixed treatment comparison; q.d. = once daily
There was insufficient information on ischemic/uncertain stroke or SE, life-threatening bleeds, and cardiovascular mortality for network meta-analyses to be conducted. No studies reported information on ischemic/uncertain stroke or systemic embolism. No data was available on life-threatening bleeds in ARISTOTLE and ROCKET-AF. In RE-LY, 1.85% of patients who received warfarin had a life-threatening bleed compared with 1.24% and 1.45% of patients receiving dabigatran 110 mg and 150 mg, respectively. Raw data was not available for cardiovascular mortality from ARISTOTLE. The risk of cardiovascular mortality was lower in patients receiving dabigatran 110 mg (2.43%) and 150 mg (2.28%) in RE-LY, compared with those receiving warfarin (2.69%). In ROCKET-AF, the risk of cardiovascular mortality was lower in patients receiving rivaroxaban (2.41%) compared with those receiving warfarin (2.73%).
Except where otherwise noted, this work is distributed under the terms of a Creative Commons Attribution-NonCommercial- NoDerivatives 4.0 International licence (CC BY-NC-ND), a copy of which is available at http://creativecommons.org/licenses/by-nc-nd/4.0/
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