Background
Methods
Data source
Patient population
Covariates
Endpoints
Statistical analysis
Results
Patient characteristic
Reduced dose (75 mg twice daily) | Standard Dose (150 mg twice daily) | P-value | |
---|---|---|---|
Total number of patients | 1455 | 6580 | |
Age Category, years | < 0.001 | ||
65–69 | 7.1% | 18.0% | |
70 to 74 | 13.7% | 26.8% | |
75 to 79 | 18.8% | 25.4% | |
80 to 84 | 26.0% | 18.1% | |
85 to 89 | 16.8% | 7.1% | |
90 or over | 17.5% | 4.7% | |
Sex | < 0.001 | ||
Female | 56.3% | 47.9% | |
Male | 43.7% | 52.1% | |
Race Category | < 0.001 | ||
White | 84.1% | 87.5% | |
Black | 10.2% | 6.9% | |
Hispanic | 2.5% | 1.7% | |
Asian | 1.4% | 0.6% | |
Other | 1.9% | 3.2% | |
Smoking | 14.0% | 16.7% | 0.01 |
Alcohol use | 2.0% | 2.3% | < 0.001 |
Weight Category (based on ICD-9 and ICD-10 codes for BMI Category) | < 0.001 | ||
Under-Weight | 1.2% | 0.6% | |
Healthy or Overweight | 10.1% | 8.0% | |
Obese or Severe Obese | 20.1% | 23.9% | |
Not available | 68.5% | 67.5% | |
Comorbid Conditions | |||
Prior Stroke | 26.8% | 24.4% | 0.06 |
Prior major bleeding from Diagnosis | 26.7% | 24.5% | 0.07 |
Gastrointestinal bleeding | 0 | 13.0% | 0.24 |
Cerebral bleeding | 0 | 0.8% | 0.7 |
Diabetes | 50.7% | 48.9% | 0.2 |
Prior AMI | 8.0% | 5.2% | < 0.001 |
Liver Disease | 3.4% | 2.6% | 0.13 |
Heart Failure | 48.6% | 31.3% | < 0.001 |
Hypertension | 96.0% | 93.4% | < 0.001 |
Ischemic cardiomyopathy | 55.5% | 48.0% | < 0.001 |
Pulmonary | 16.6% | 11.4% | < 0.001 |
COPD | 36.4% | 31.8% | < 0.001 |
Transfusion from Procedure | 3.8% | 2.7% | 0.02 |
Revascularization | 17.3% | 15.0% | 0.03 |
Implantable Devices | 16.9% | 13.8% | 0.002 |
Valve Disease | 44.7% | 40.3% | 0.002 |
Renal Disease (ICD-9 and ICD-10 codes) | < 0.001 | ||
None or Mild (Stage I, II) | 53.4% | 81.7% | |
Moderate (Stage III) | 36.0% | 16.5% | |
Severe (Stage IV, V) | 10.6% | 1.7% | |
Concurrent Drugs (+/− 90 days of initiating DOAC) | |||
SSRI/SNRI | 33.5% | 31.0% | 0.05 |
Strong and moderate P-GP inhibitors | 21.4% | 22.7% | 0.28 |
P-GP inducers | 16.4% | 18.8% | 0.03 |
Strong P-GP and CYP3A4 dual inhibitors | 22.7% | 22.5% | 0.8 |
P-GP and CYP3A4 inducers | 16.4% | 18.8% | 0.03 |
ACE inhibitors | 70.1% | 68.0% | 0.12 |
Warfarin | 20.8% | 25.0% | < 0.001 |
Angiotensin receptor blockers | 41.0% | 39.3% | 0.2 |
Beta blockers | 92.1% | 89.1% | < 0.001 |
Calcium channel blockers | 66.8% | 63.8% | 0.03 |
Digoxin | 31.1% | 29.4% | 0.2 |
Proton pump inhibitors | 60.5% | 56.4% | 0.004 |
NSAIDs | 49.6% | 51.2% | 0.29 |
Antiplatelets | 32.0% | 26.5% | < 0.001 |
Insulin | 17.0% | 12.9% | < 0.001 |
Statins | 79.6% | 79.4% | 0.86 |
Antiarrhythmics | 47.3% | 48.0% | 0.6 |
Estimated Glomerular Filtration rate (ml/min/1.73 m2) | < 0.001 | ||
< 30 | 12.3% | 2.5% | |
30–60 | 62.2% | 45.8% | |
60–90 | 23.8% | 46.0% | |
> = 90 | 1.8% | 5.7% | |
CCI(Charlson Comorbodity Index), mean (standard deviation) | 5.52 (3.75) | 4.17(3.47) | < 0.001 |
Reduced Dose (15 mg daily) | Standard Dose (20 mg daily) | P-value | |
---|---|---|---|
Total number of patients | 6467 | 13,245 | |
Age Category, years | < 0.001 | ||
65–69 | 7.9% | 18.2% | |
70 to 74 | 14.8% | 29.0% | |
75 to 79 | 20.7% | 25.6% | |
80 to 84 | 25.4% | 17.0% | |
85 to 89 | 19.8% | 7.8% | |
90 or over | 11.4% | 2.4% | |
Sex | < 0.001 | ||
Female | 57.1% | 46.2% | |
Male | 42.9% | 53.8% | |
Race Category | < 0.001 | ||
White | 85.2% | 85.8% | |
Black | 9.0% | 8.0% | |
Hispanic | 2.2% | 1.6% | |
Asian | 0.8% | 0.8% | |
Other | 2.8% | 3.8% | |
Smoking | 20.2% | 22.8% | < 0.001 |
Alcohol | 2.3% | 3.2% | < 0.001 |
Weight Category (based on ICD-9 and ICD-10 codes for BMI Category) | < 0.001 | ||
Under-Weight | 2.3% | 1.3% | |
Healthy or Overweight | 19.1% | 14.3% | |
Obese or Severe Obese | 26.2% | 31.2% | |
Not available | 52.4% | 53.2% | |
Comorbid Conditions | |||
Prior Stroke | 28.2% | 22.4% | < 0.001 |
Prior major bleeding from Diagnosis | 26.6% | 23.9% | < 0.001 |
Gastrointestinal bleeding | 15.2% | 13.5% | 0.002 |
Cerebral bleeding | 1.3% | 0.8% | < 0.001 |
Diabetes | 51.0% | 47.7% | < 0.001 |
Prior AMI | 9.0% | 5.7% | < 0.001 |
Liver Disease | 2.9% | 3.1% | 0.35 |
Heart Failure | 35.6% | 24.3% | < 0.001 |
Hypertension | 94.6% | 92.1% | < 0.001 |
Ischemic cardiomyopathy | 47.7% | 40.2% | < 0.001 |
Pulmonary | 15.9% | 11.1% | < 0.001 |
COPD | 36.3% | 31.4% | < 0.001 |
Transfusion from Procedure | 5.0% | 2.3% | < 0.001 |
Revascularization | 16.5% | 13.7% | < 0.001 |
Implantable Devices | 16.7% | 12.5% | < 0.001 |
Valve Disease | 40.6% | 36.4% | 0.002 |
Renal Disease (ICD-9 and ICD-10 codes) | < 0.001 | ||
None or Mild (Stage I, II) | 54.8% | 83.9% | |
Moderate (Stage III) | 37.5% | 14.5% | |
Severe (Stage IV, V) | 7.7% | 1.5% | |
Concurrent Drugs (+/− 90 days of initiating DOAC) | |||
SSRI/SNRI | 33.7% | 29.1% | < 0.001 |
Strong and moderate P-GP inhibitors | 18.3% | 18.5% | 0.63 |
P-GP inducers | 18.5% | 16.5% | < 0.001 |
Strong P-GP and CYP3A4 dual inhibitors | 22.7% | 20.8% | 0.002 |
P-GP and CYP3A4 inducers | 18.5% | 16.5% | < 0.001 |
ACE inhibitors | 67.4% | 64.3% | < 0.001 |
Warfarin | 15.0% | 16.1% | 0.045 |
Angiotensin receptor blockers | 40.0% | 36.7% | < 0.001 |
Beta blockers | 88.1% | 86.5% | 0.015 |
Calcium channel blockers | 64.5% | 59.4% | < 0.001 |
Digoxin | 23.1% | 20.8% | < 0.001 |
Proton pump inhibitors | 58.3% | 52.3% | < 0.001 |
NSAIDs | 52.9% | 50.1% | < 0.001 |
Antiplatelets | 30.2% | 24.3% | < 0.001 |
Insulin | 14.3% | 10.8% | < 0.001 |
Statins | 79.3% | 77.6% | 0.006 |
Antiarrhythmics | 40.4% | 43.1% | < 0.001 |
Estimated Glomerular Filtration rate (ml/min/1.73 m2) | < 0.001 | ||
< 30 | 7.5% | 1.3% | |
30–60 | 61.1% | 35.2% | |
60–90 | 28.8% | 56.7% | |
> =90 | 2.6% | 6.8% | |
CCI(Charlson Comorbodity Index), mean (standard deviation) | 5.05(3.65) | 3.71(3.34) | < 0.001 |
Low dose eligible that received low dose Dabigatran (n = 442) | Low dose eligible that received standard dose Dabigatran (n = 959) | P value | Before Matching Standardized Difference | After Matching (N = 366 vs 366) Standardized Difference | |
---|---|---|---|---|---|
Year | 0.001 | ||||
2010–2012 | 57.7% | 69.3% | 0.244 | 0.228 | |
2013 | 16.1% | 10.3% | 0.170 | 0.289 | |
2014 | 10.9% | 8.1% | 0.093 | 0.047 | |
2015 | 7.7% | 6.5% | 0.048 | 0 | |
2016–2017 | 7.7% | 5.7% | 0.078 | 0.011 | |
Region | 0.1 | ||||
Midwest | 15.4% | 12.4% | 0.086 | 0.008 | |
Northeast | 0.5% | 1.4% | 0.096 | 0.141 | |
South | 73.3% | 76.7% | 0.080 | 0 | |
West | 10.9% | 9.5% | 0.045 | 0.035 | |
Age Category | < 0.001 | ||||
65–69 | 7.9% | 14.0% | 0.195 | 0 | |
70 to 74 | 16.5% | 24.2% | 0.192 | 0 | |
75 to 79 | 18.6% | 28.5% | 0.235 | 0 | |
80 to 84 | 25.1% | 19.3% | 0.140 | 0 | |
85 to 89 | 13.1% | 7.8% | 0.174 | 0 | |
90 or over | 18.8% | 6.3% | 0.385 | 0 | |
Sex | 0.2 | ||||
Female | 57.9% | 54.3% | 0.072 | 0 | |
Male | 42.1% | 45.7% | |||
Race Category | |||||
White | 84.2% | 85.0% | 0.023 | 0 | |
Black | 10.4% | 8.9% | 0.052 | 0 | |
Hispanic | 2.5% | 2.4% | 0.006 | 0 | |
Other | 0 | ||||
Smoking | 0.04 | ||||
Yes | 11.5% | 15.7% | 0.123 | 0.055 | |
No | 88.5% | 84.3% | |||
Weight Category (based on ICD-9 and ICD-10 codes for BMI Category) | 0.02 | ||||
Underweight | 1.6% | 0.6% | 0.092 | 0 | |
Healthy or Overweight | 8.6% | 6.3% | 0.089 | 0.062 | |
Obese or Severe Obese | 20.4% | 26.3% | 0.140 | 0.013 | |
Others | 69.5% | 66.8% | 0.056 | 0.024 | |
Comorbid Conditions | |||||
Prior Stroke | 26.7% | 27.4% | 0.8 | 0.016 | 0.042 |
Prior major bleeding | 29.0% | 28.2% | 0.8 | 0.018 | 0.006 |
Diabetes | 55.0% | 54.0% | 0.7 | 0.019 | 0.077 |
Prior AMI | 10.6% | 6.2% | 0.003 | 0.162 | 0.147 |
Liver Disease | 2.9% | 3.2% | 0.8 | 0.017 | 0 |
Heart Failure | 56.8% | 40.7% | < 0.001 | 0.327 | 0.265 |
Hypertension | 98.2% | 96.1% | 0.04 | 0.124 | 0.082 |
Ischemic cardiomyopathy | 60.4% | 57.2% | 0.3 | 0.064 | 0.089 |
Pulmonary | 18.8% | 13.3% | 0.008 | 0.148 | 0.066 |
COPD | 37.8% | 36.2% | 0.6 | 0.033 | 0.034 |
Transfusion from Procedure | 5.4% | 4.3% | 0.3 | 0.054 | 0.051 |
Revascularization | 18.6% | 17.8% | 0.7 | 0.019 | 0.043 |
Implantable Devices | 20.1% | 17.5% | 0.2 | 0.067 | 0 |
Valve Disease | 45.9% | 42.0% | 0.2 | 0.079 | 0.099 |
Concurrent Drugs (+/− 90 days of initiating DOAC) | |||||
SSRI/SNRI | 32.6% | 36.5% | 0.15 | 0.083 | 0.023 |
Strong and moderate p-gp inhibitors | 53.5% | 79.9% | < 0.001 | 0.580 | 0.068 |
Warfarin | 22.6% | 31.0% | 0.001 | 0.189 | 0.153 |
Strong p-gp and cyp3a4 dual inhibitors | 35.7% | 47.5% | < 0.001 | 0.241 | 0.089 |
ACE inhibitors | 74.0% | 72.7% | 0.6 | 0.029 | 0.044 |
Angiotensin receptor blockers | 46.6% | 45.9% | 0.8 | 0.015 | 0.066 |
Beta blockers | 95.2% | 92.9% | 0.09 | 0.099 | 0.165 |
Calcium channel blockers | 69.7% | 67.5% | 0.4 | 0.048 | 0.098 |
Digoxin | 28.7% | 33.8% | 0.06 | 0.109 | 0.083 |
Proton pump inhibitors | 64.7% | 63.2% | 0.6 | 0.032 | 0.119 |
NSAIDs | 52.7% | 55.4% | 0.4 | 0.053 | 0.055 |
Antiplatelets | 35.3% | 31.3% | 0.13 | 0.085 | 0.099 |
Insulin | 22.9% | 17.6% | 0.02 | 0.130 | 0.206 |
Statins | 80.8% | 83.3% | 0.24 | 0.066 | 0.007 |
Renal Disease | |||||
Moderate (GFR 30–60 ml/min/1.73 m2) | 45.7% | 74.9% | < 0.001 | 0.6245 | 0.0439 |
Severe (GFR < 30 ml/min/1.73 m2) | 54.3% | 25.1% |
Standard dose eligible that received low dose Dabigatran (n = 1013) | Standard dose eligible that received standard dose Dabigatran (n = 5621) | P value | Before Matching Standardized Difference | After Matching (N = 1001 vs 1001) Standardized Difference | |
---|---|---|---|---|---|
Year | < 0.001 | ||||
2010–12 | 50.0% | 55.7% | 0.116 | 0.198 | |
2013 | 18.6% | 13.6% | 0.137 | 0.174 | |
2014 | 11.6% | 11.4% | 0.008 | 0.032 | |
2015 | 10.9% | 10.1% | 0.026 | 0.047 | |
2016–17 | 9.0% | 9.3% | 0.009 | 0.040 | |
Region | 0.8 | ||||
Midwest | 12.3% | 12.9% | 0.017 | 0.024 | |
Northeast | 1.7% | 1.5% | 0.018 | 0.016 | |
South | 73.7% | 74.3% | 0.012 | 0.009 | |
West | 12.2% | 11.4% | 0.027 | 0.006 | |
Age Category | < 0.001 | ||||
65–69 | 6.7% | 18.7% | 0.365 | 0 | |
70 to 74 | 12.5% | 27.3% | 0.3755 | 0 | |
75 to 79 | 19.0% | 24.9% | 0.143 | 0 | |
80 to 84 | 26.4% | 17.9% | 0.206 | 0 | |
85 to 89 | 18.5% | 6.9% | 0.351 | 0 | |
90 or over | 17.0% | 4.4% | 0.415 | 0 | |
Sex | < 0.001 | ||||
Female | 55.6% | 46.8% | 0.176 | 0 | |
Male | 44.4% | 53.2% | |||
Race Category | < 0.001 | ||||
White | 84.0% | 87.9% | 0.113 | 0 | |
Black | 10.1% | 6.6% | 0.126 | 0 | |
Hispanic | 2.5% | 1.6% | 0.059 | 0 | |
Asian | 1.2% | 0.6% | 0.066 | 0 | |
Other | 2.3% | 3.3% | 0.060 | 0 | |
Smoker | 15.0% | 16.8% | 0.15 | 0.049 | 0.037 |
Weight Category (based on ICD-9/ ICD-10 codes for BMI) | 0.003 | ||||
Under Weight | 1.1% | 0.6% | 0.057 | 0.031 | |
Healthy or Overweight | 10.8% | 8.3% | 0.082 | 0.013 | |
Obese or Severe Obese | 20.0% | 23.4% | 0.084 | 0.054 | |
Others | 68.1% | 67.6% | 0.010 | 0.061 | |
Comorbid Conditions | |||||
Prior Stroke | 26.9% | 23.9% | 0.04 | 0.067 | 0.011 |
Prior Major Bleeding | 25.8% | 23.9% | 0.2 | 0.044 | 0.042 |
Diabetes | 48.9% | 48.0% | 0.6 | 0.018 | 0.066 |
Prior AMI | 6.9% | 5.0% | 0.01 | 0.082 | 0.103 |
Liver Disease | 3.6% | 2.5% | 0.07 | 0.059 | 0.126 |
Heart Failure | 45.0% | 29.7% | < 0.001 | 0.320 | 0.274 |
Hypertension | 95.1% | 93.0% | 0.01 | 0.089 | 0.088 |
Ischemic Cardiomyopathy | 53.4% | 46.4% | < 0.001 | 0.140 | 0.110 |
Pulmonary Circulatory Disease | 15.6% | 11.0% | < 0.001 | 0.135 | 0.083 |
COPD | 35.7% | 31.0% | 0.003 | 0.1 | 0.115 |
Blood Transfusion | 3.2% | 2.4% | 0.18 | 0.044 | 0 |
Revascularization | 16.8% | 14.5% | 0.05 | 0.063 | 0.075 |
Implantable cardiac device | 15.5% | 13.1% | 0.04 | 0.068 | 0.011 |
Valve Disease | 44.1% | 40.0% | 0.015 | 0.083 | 0.024 |
Concurrent Drugs (+/− 90 days of initiating DOAC) | |||||
SSRI/SNRI | 34.0% | 30.0% | 0.01 | 0.085 | 0.126 |
Strong and moderate p-gp inhibitors | 7.3% | 12.9% | < 0.001 | 0.188 | 0.135 |
Warfarin | 19.9% | 24.0% | 0.004 | 0.099 | 0.237 |
Strong p-gp and cyp3a4 dual inhibitors | 17.0% | 18.2% | 0.3 | 0.0325 | 0.032 |
ACE inhibitors | 68.4% | 67.2% | 0.45 | 0.0257 | 0.081 |
Angiotensin receptor blockers | 38.6% | 38.1% | 0.8 | 0.0094 | 0.010 |
Beta blockers | 90.7% | 88.4% | 0.03 | 0.0759 | 0.108 |
Calcium channel blockers | 65.5% | 63.2% | 0.15 | 0.0488 | 0.040 |
Digoxin | 32.1% | 28.7% | 0.03 | 0.0741 | 0.002 |
Proton pump inhibitors | 58.7% | 55.2% | 0.04 | 0.0707 | 0.008 |
NSAIDs | 48.3% | 50.4% | 0.2 | 0.0433 | 0.04 |
Antiplatelets | 30.5% | 25.7% | 0.0015 | 0.1064 | 0.093 |
Insulin | 14.5% | 12.1% | 0.03 | 0.072 | 0.137 |
Statins | 79.1% | 78.7% | 0.8 | 0.009 | 0.079 |
Renal Disease | < 0.001 | ||||
None or Mild | 33.6% | 57.2% | 0.489 | 0.255 | |
Moderate (GFR 30–60 ml/min/1.73 m2) | 66.4% | 42.8% | |||
Severe (GFR < 30 ml/min/1.73 m2) | 0.0% | 0.0% |
Low dose eligible that received low dose Rivaroxaban (n = 3916) | Low dose eligible that received standard dose Rivaroxaban (n = 3904) | P value | Before Matching Standardized Difference | After Matching (N = 2703 vs 2703) Standardized Difference | |
---|---|---|---|---|---|
Year | 0.2 | ||||
2010–2012 | 7.2% | 6.7% | 0.021 | 0.028 | |
2013 | 18.3% | 17.6% | 0.017 | 0.0308 | |
2014 | 23.0% | 23.0% | 0.002 | 0.016 | |
2015 | 22.9% | 21.8% | 0.024 | 0.003 | |
2016–2017 | 28.6% | 30.9% | 0.050 | 0.058 | |
Region | 0.04 | ||||
Midwest | 15.2% | 13.0% | 0.064 | 0.084 | |
Northeast | 1.2% | 1.1% | 0.009 | 0.016 | |
South | 73.0% | 75.0% | 0.044 | 0.028 | |
West | 10.5% | 10.9% | 0.013 | 0.061 | |
Age Category | < 0.001 | ||||
65–69 | 7.5% | 14.5% | 0.225 | 0 | |
70 to 74 | 14.0% | 26.0% | 0.302 | 0 | |
75 to 79 | 20.1% | 25.8% | 0.135 | 0 | |
80 to 84 | 25.5% | 19.7% | 0.139 | 0 | |
85 to 89 | 20.5% | 10.1% | 0.291 | 0 | |
90 or over | 12.4% | 3.9% | 0.311 | 0 | |
Sex | 0.0008 | ||||
Female | 56.0% | 52.3% | 0.076 | 0 | |
Male | 44.0% | 47.7% | |||
Race Category | 0.7 | ||||
White | 84.5% | 83.4% | 0.031 | 0 | |
Black | 10.2% | 10.7% | 0.017 | 0 | |
Hispanic | 2.0% | 2.2% | 0.011 | 0 | |
Asian | 0.7% | 0.8% | 0.015 | 0 | |
Other | 2.7% | 3.0% | 0.019 | 0 | |
Smoker | 19.6% | 22.5% | 0.001 | 0.073 | 0.033 |
Weight Category (ICD9/ICD-10 codes for BMI) | < 0.0001 | ||||
Under Weight | 1.9% | 1.2% | 0.053 | 0.025 | |
Healthy or Overweight | 18.4% | 16.1% | 0.062 | 0.008 | |
Obese or Severe Obese | 28.9% | 35.4% | 0.139 | 0.079 | |
Others | 50.8% | 47.3% | 0.070 | 0.062 | |
Comorbid Conditions | |||||
Prior Stroke | 29.1% | 25.1% | < 0.001 | 0.089 | 0.051 |
Prior major bleeding | 27.6% | 28.0% | 0.6 | 0.011 | 0.026 |
Diabetes | 55.9% | 57.2% | 0.2 | 0.027 | 0.021 |
Prior AMI | 10.4% | 6.7% | < 0.001 | 0.132 | 0.119 |
Liver Disease | 3.2% | 3.5% | 0.4 | 0.019 | 0.017 |
Heart Failure | 41.2% | 31.6% | < 0.001 | 0.201 | 0.151 |
Hypertension | 96.8% | 95.3% | < 0.001 | 0.076 | 0.030 |
Cardiomyopathy | 50.4% | 44.6% | < 0.001 | 0.115 | 0.100 |
Pulmonary Circulatory Dis | 17.2% | 14.2% | < 0.001 | 0.082 | 0.021 |
COPD | 38.5% | 37.0% | 0.17 | 0.031 | 0.054 |
Prior Blood Transfusion | 5.8% | 3.5% | < 0.001 | 0.107 | 0.083 |
Revascularization | 17.7% | 15.4% | 0.007 | 0.061 | 0.079 |
Implantable Cardiac Device | 18.3% | 14.8% | < 0.001 | 0.094 | 0.078 |
Valve Disease | 42.2% | 38.1% | < 0.001 | 0.084 | 0.064 |
Concurrent Drugs (+/− 90 days of initiating DOAC) | |||||
SSRI/SNRI | 34.0% | 33.3% | 0.5 | 0.014 | 0.034 |
Strong and moderate p-gp inhibitors | 19.9% | 24.5% | < 0.001 | 0.110 | 0.012 |
Warfarin | 16.1% | 19.6% | < 0.001 | 0.092 | 0.124 |
Pgp inducers | 17.9% | 18.0% | 0.9 | 0.003 | 0.018 |
Strong p-gp and cyp3a4 dual inhibitors | 26.1% | 35.1% | < 0.001 | 0.194 | 0.009 |
P-gp and cyp3a4 inducers | 17.9% | 18.1% | 0.9 | 0.003 | 0.017 |
Ace inhibitors | 70.6% | 69.6% | 0.34 | 0.022 | 0.025 |
Angiotensin receptor blockers | 43.9% | 43.8% | 0.86 | 0.004 | 0.004 |
Beta blockers | 89.7% | 89.0% | 0.32 | 0.023 | 0.019 |
Calcium channel blockers | 67.6% | 64.4% | =0.003 | 0.067 | 0.026 |
Digoxin | 23.0% | 23.3% | 0.7 | 0.008 | 0.003 |
Proton pump inhibitors | 59.6% | 59.2% | 0.7 | 0.008 | 0.026 |
NSAIDS | 52.6% | 53.3% | 0.5 | 0.015 | 0.022 |
Antiplatelets | 31.8% | 28.4% | 0.001 | 0.074 | 0.067 |
Insulin | 18.0% | 17.1% | 0.27 | 0.025 | 0.087 |
Statins | 81.8% | 81.6% | 0.79 | 0.006 | 0.024 |
Renal Disease | |||||
None or mild | 3.6% | 17.1% | < 0.0001 | 0.452 | 0.058 |
Moderate (GFR 30–60 ml/min/1.73 m2) | 83.3% | 77.4% | 0.149 | 0.039 | |
Severe (GFR < 30 ml/min/1.73 m2) | 13.1% | 5.5% | 0.262 | 0.002 |
Standard dose eligible that received low dose Rivaroxaban (n = 2551) | Standard dose eligible that received standard dose Rivaroxaban (n = 9341) | P value | Before Matching Standardized Difference | After Matching (N = 2397 vs 2397) Standardized Difference | |
---|---|---|---|---|---|
Year | 0.06 | ||||
2010–2012 | 8.2% | 7.1% | 0.0439 | 0.0031 | |
2013 | 17.9% | 17.1% | 0.0204 | 0.0098 | |
2014 | 23.8% | 22.7% | 0.0256 | 0.0248 | |
2015 | 21.4% | 22.7% | 0.0312 | 0.0051 | |
2016–2017 | 28.7% | 30.4% | 0.0379 | 0.0284 | |
Region | 0.12 | ||||
Midwest | 15.1% | 14.4% | 0.0178 | 0.1713 | |
Northeast | 1.1% | 1.3% | 0.0229 | 0.1515 | |
South | 73.1% | 72.0% | 0.0254 | 0.2038 | |
West | 10.8% | 12.3% | 0.0476 | 0.0186 | |
Age Category | < 0.0001 | ||||
65–69 | 8.5% | 19.7% | 0.3266 | 0 | |
70 to 74 | 15.9% | 30.3% | 0.3453 | 0 | |
75 to 79 | 21.6% | 25.5% | 0.0916 | 0 | |
80 to 84 | 25.3% | 15.9% | 0.2337 | 0 | |
85 to 89 | 18.8% | 6.9% | 0.3622 | 0 | |
90 or over | 9.8% | 1.7% | 0.3544 | 0 | |
Sex | < 0.0001 | ||||
Female | 58.7% | 43.7% | 0.3044 | 0 | |
Male | 41.3% | 56.3% | |||
Race Category | < 0.0001 | ||||
White | 86.2% | 86.8% | 0.0164 | 0 | |
Black | 7.3% | 6.9% | 0.0144 | 0 | |
Hispanic | 2.4% | 1.3% | 0.0813 | 0 | |
Asian | 1.1% | 0.8% | 0.0304 | 0 | |
Other | 3.0% | 4.2% | 0.065 | 0 | |
Smoker | 21.1% | 23.0% | 0.05 | 0.044 | 0.003 |
Weight Category (based on ICD-9/ICD-10 codes for BMI) | < 0.0001 | ||||
Under | 2.9% | 1.4% | 0.1038 | 0.0682 | |
Healthy or Overweight | 20.1% | 13.6% | 0.1737 | 0.2328 | |
Obese or Severe Obese | 22.1% | 29.4% | 0.1684 | 0.0561 | |
Others | 55.0% | 55.6% | 0.0126 | 0.2406 | |
Comorbid Conditions | |||||
Prior Stroke | 26.9% | 21.3% | < 0.001 | 0.1295 | 0 |
Prior major bleeding | 25.2% | 22.2% | 0.001 | 0.071 | 0 |
Diabetes | 43.4% | 43.8% | 0.76 | 0.0069 | 0.1063 |
Prior AMI | 7.0% | 5.3% | 0.001 | 0.0701 | 0 |
Liver Disease | 2.4% | 2.9% | 0.14 | 0.0337 | 0.0139 |
Heart Failure | 27.0% | 21.3% | < 0.001 | 0.1339 | 0 |
Hypertension | 91.2% | 90.8% | 0.57 | 0.0128 | 0.0474 |
Cardiomyopathy | 43.5% | 38.3% | < 0.001 | 0.1063 | 0.1134 |
Pulmonary Circulatory dis | 13.9% | 9.8% | < 0.001 | 0.1277 | 0.0414 |
COPD | 33.0% | 29.1% | < 0.001 | 0.0846 | 0.0972 |
Prior blood transfusion | 3.7% | 1.8% | < 0.001 | 0.1173 | 0.0855 |
Revascularization | 14.7% | 13.0% | 0.02 | 0.0495 | 0.08 |
Implantable Devices | 14.1% | 11.6% | < 0.001 | 0.0766 | 0.0553 |
Valve Disease | 38.1% | 35.7% | 0.02 | 0.051 | 0.0347 |
Concurrent Drugs (+/− 90 days of initiating DOAC) | |||||
SSRI/SNRI | 33.3% | 27.4% | < 0.001 | 0.1289 | 0.0682 |
Strong and moderate p-gp inhibitors | 15.7% | 16.1% | 0.67 | 0.0096 | 0 |
Warfarin | 13.2% | 14.6% | 0.08 | 0.0391 | 0.1199 |
Pgp inducers | 19.5% | 15.8% | < 0.001 | 0.097 | 0 |
Strong p-gp and cyp3a4 dual inhibitors | 17.3% | 14.8% | 0.002 | 0.069 | 0.0232 |
P-gp and cyp3a4 inducers | 19.5% | 15.8% | < 0.001 | 0.097 | 0 |
Ace inhibitors | 62.4% | 62.1% | 0.77 | 0.0066 | 0.006 |
Angiotensin receptor blockers | 33.8% | 33.8% | 0.98 | 0.0005 | 0.0222 |
Beta blockers | 85.7% | 85.4% | 0.74 | 0.0075 | 0.042 |
Calcium channel blockers | 59.6% | 57.3% | 0.03 | 0.0475 | 0.0179 |
Digoxin | 23.4% | 19.8% | <.001 | 0.0892 | 0.0403 |
Proton pump inhibitors | 56.2% | 49.5% | < 0.001 | 0.1356 | 0.0753 |
NSAIDS | 53.2% | 48.7% | < 0.001 | 0.091 | 0.133 |
Antiplatelets | 27.9% | 22.5% | < 0.001 | 0.1229 | 0.0785 |
Insulin | 8.5% | 8.2% | 0.54 | 0.0136 | 0.0247 |
Statins | 75.4% | 75.9% | 0.6 | 0.0114 | 0.0608 |
Renal Disease | |||||
None or mild | 100.0% | 100.0% | Not available due to perfect match | ||
Moderate (GFR 30–60 ml/min/1.73 m2) | |||||
Severe (GFR < 30 ml/min/1.73 m2) |
Outcomes
Stroke
Patients Eligible for low dose but taking standard dose vs. those taking low dose | Patients Eligible for Standard dose but taking low dose vs. those taking dose standard dose | |||||
---|---|---|---|---|---|---|
Received Low Dose Events (Events/year) | Received Standard Dose Events (Events/year) | 95% Confidence Interval, p-value | Received Low Dose Events (Events/year) | Received Standard Dose Events (Events/year) | 95% Confidence Interval, p-value | |
Ischemic Stroke | ||||||
Dabigatran | ||||||
Unadjusted | 25 (0.059) | 57 (0.043) | 0.77 (0.47–1.26; p = 0.3) | 59 (0.051) | 319 (0.042) | 1.2 (0.92–1.6, P = 0.17) |
Propensity Matched | 22 (0.059) | 28 (0.061) | 1.13 (0.63–2; p = 0.69) | 55 (0.049) | 88 (0.071) | 0.74 (0.53–1.04; p = 0.08) |
Rivaroxaban | ||||||
Unadjusted | 176 (0.057) | 161 (0.043) | 0.87 (0.7–1.1; p = 0.2) | 89 (0.040) | 256 (0.026) | 1.36 (1.07–1.7, P = 0.01) |
Propensity Matched | 103 (0.048) | 128 (0.053) | 1.24 (0.96–1.6; p = 0.1) | 78 (0.040) | 73 (0.030) | 1.13 (0.83–1.56, P = 0.43) |
Major Bleeding | ||||||
Dabigatran | ||||||
Unadjusted | 62 (0.1456) | 124 (0.093) | 0.69 (0.51–0.94; p = 0.02) | 82 (0.071) | 393 (0.051) | 1.35 (1.06–1.7, p = 0.01) |
Propensity Matched | 46 (0.1228) | 58 (0.1258) | 1.07 (0.7–1.58 P = 0.75) | 78 (0.069) | 92 (0.075) | 1.01 (0.74–1.37, P = 0.97) |
Rivaroxaban | ||||||
Unadjusted | 307 (0.099) | 294 (0.079) | 0.95 (0.8–1.1, P = 0.5) | 147 (0.067) | 426 (0.043) | 1.35 (1.12–1.6, P = 0.001) |
Propensity Matched | 197 (0.091) | 216 (0.089) | 1.12 (0.92–1.35, P = 0.26) | 131 (0.068) | 116 (0.048) | 1.2 (0.93–1.53, P = 0.21) |
GI Hemorrhage | ||||||
Dabigatran | ||||||
Unadjusted | 46 (0.108) | 100(0.075) | 0.75 (0.5–1.07, P = 0.1) | 67 (0.058) | 292 (0.038) | 1.47 (1.13–1.9, P = 0005) |
Propensity Matched | 33 (0.088) | 45 (0.098) | 1.16 (0.74–1.82, P = 0.53) | 63 (0.056) | 68 (0.055) | 1.08 (0.77–1.53, P = 0.66) |
Rivaroxaban | ||||||
Unadjusted | 243 (0.078) | 227 (0.061) | 0.93 (0.78–1.1, P = 0.4) | 111 (0.050) | 341 (0.034) | 1.28 (1.04–1.6, P = 0.02) |
Propensity Matched | 158 (0.073) | 166 (0.069) | 1.07 (0.86–1.32, P = 0.5) | 97 (0.050) | 96 (0.040) | 1.08 (0.82–1.43, P = 0.58) |
Intracranial Hemorrhage | ||||||
Dabigatran | ||||||
Unadjusted | < 11 | < 11 | 0.33 (0.12–0.9; p = 0.03) | < 11 | 52 (0.007) | 0.77 (0.33–1.8; p = 0.54) |
Propensity Matched | < 11 | < 11 | 0.63 (0.2–1.99; p = 0.43) | < 11 | 12(0.009) | 0.58 (0.22–1.54; p = 0.27) |
Rivaroxaban | ||||||
Unadjusted | 25 (0.008) | 26 (0.007) | 0.99 (0.57–1.7; p = 0.96) | 13 (0.006) | 38 (0.004) | 1.33 (0.7–2.5; p = 0.37) |
Propensity Matched | 17 (0.008) | 22 (0.009) | 1.26 (0.67–2.38; p = 0.47) | 12 (0.006) | < 11 | 1.57 (0.64–3.84; p = 0.32) |