Table 3.
Characteristics of warfarin users, by antihyperlipidemic exposure group, and measures of association for the primary analysis
| Statins | Fibrates | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| pravastatin | atorvastatin | fluvastatin | lovastatin | rosuvastatin | simvastatin | fenofibrate | gemfibrozil | ||
| Ns (unless otherwise noted) | |||||||||
| Users, concomitant with warfarin | 20,238 | 79,391 | 2,793 | 14,316 | 11,763 | 94,738 | 7,807 | 5,645 | |
| Person-years of follow-up | 1,555 | 6,119 | 215 | 1,104 | 896 | 7,268 | 564 | 415 | |
| GIB/ICH outcomes within 30 days of cohort entry | 192 | 778 | 23 | 104 | 100 | 1,073 | 58 | 73 | |
| GIB outcomes within 30 days of cohort entry | 166 | 685 | * | 91 | 87 | 955 | 51 | * | |
| ICH outcomes within 30 days of cohort entry | 26 | * | * | * | * | * | * | * | |
| Both outcomes (contemporaneously) within 30 days of cohort entry | 0 | * | * | * | * | * | * | * | |
| Unadjusted incidence rate of GIB/ICH, per 100 person-years | 12.3 | 12.7 | 10.7 | 9.4 | 11.2 | 14.8 | 10.3 | 17.6 | |
| Measures of Association | |||||||||
| Unadjusted hazard ratio for GIB/ICH within 30 days of cohort entry (95% CI) | 1.00 (reference) | 1.03 (0.88-1.21) | 0.87 (0.56-1.34) | 0.76 (0.60-0.97) | 0.90 (0.71-1.15) | 1.20 (1.03-1.39) | 0.83 (0.62-1.12) | 1.42 (1.09-1.86) | |
| Adjusted hazard ratio for GIB/ICH within 30 days of cohort entry (95% CI); see • in Figure 2 | 1.00 (reference) | 0.99 (0.84-1.16) | 1.13 (0.73-1.75) | 0.99 (0.78-1.27) | 0.87 (0.68-1.11) | 1.02 (0.87-1.19) | 1.03 (0.76-1.38) | 1.79 (1.36-2.35) | |
| Demographics | Group | % (unless otherwise noted) | |||||||
| Event triggering concomitant use (see Figure 1) | combination triggered | 6.2 | 7.0 | 5.2 | 7.3 | 4.0 | 8.4 | 2.6 | 4.5 |
| warfarin triggered | 59.7 | 61.1 | 63.5 | 60.3 | 64.5 | 63.2 | 60.1 | 52.1 | |
| antihyperlipidemic triggered | 34.1 | 31.9 | 31.3 | 32.4 | 31.5 | 28.4 | 37.3 | 43.4 | |
| Age in years at cohort entry, continuous | Median (Q1-Q3) | 71.4 (61.1-79.0) | 70.7 (60.3-78.6) | 71.4 (61.8-79.1) | 73.7 (64.7-80.9) | 70.8 (60.4-78.4) | 71.2 (61.0-79.4) | 67.0 (54.5-76.6) | 66.1 (53.8-75.4) |
| Sex | female | 63.7 | 63.4 | 70.1 | 64.9 | 63.9 | 62.7 | 59.2 | 55.2 |
| Race | white | 54.8 | 55.0 | 58.1 | 51.4 | 52.3 | 52.4 | 66.9 | 56.7 |
| black | 15.0 | 15.2 | 13.4 | 14.5 | 12.8 | 17.3 | 6.4 | 8.6 | |
| hispanic/latino- | 0.3 | 0.3 | 0.4 | 0.3 | 0.2 | 0.3 | 0.3 | 0.4 | |
| other/unknown | 29.9 | 29.5 | 28.2 | 33.8 | 34.7 | 30.1 | 26.4 | 34.3 | |
| State of residence | CA | 40.9 | 39.3 | 45.1 | 49.7 | 27.0 | 31.7 | 27.5 | 48.1 |
| FL | 12.9 | 8.9 | 13.8 | 14.3 | 24.9 | 15.2 | 18.4 | 15.0 | |
| NY | 23.9 | 27.9 | 17.5 | 19.2 | 32.8 | 28.6 | 22.8 | 17.8 | |
| OH | 9.4 | 12.0 | 8.7 | 6.7 | 7.8 | 11.5 | 16.6 | 9.7 | |
| PA | 12.8 | 11.9 | 14.9 | 10.2 | 7.6 | 12.9 | 14.7 | 9.4 | |
| Calendar year of cohort entry | 2000 | 7.4 | 5.4 | 11.3 | 1.3 | 0.0 | 2.2 | 1.9 | 7.0 |
| 2001 | 8.9 | 7.2 | 11.5 | 1.1 | 0.0 | 3.3 | 3.3 | 8.7 | |
| 2002 | 9.1 | 8.1 | 14.7 | 1.6 | 0.0 | 3.8 | 4.5 | 9.2 | |
| 2003 | 10.0 | 8.8 | 13.9 | 4.4 | 0.7 | 4.3 | 6.0 | 9.1 | |
| 2004 | 8.3 | 9.4 | 11.1 | 5.8 | 4.4 | 3.9 | 6.0 | 7.3 | |
| 2005 | 7.3 | 11.2 | 10.1 | 7.8 | 6.2 | 5.5 | 8.1 | 7.5 | |
| 2006 | 7.8 | 15.2 | 13.9 | 25.8 | 13.1 | 9.1 | 12.6 | 11.5 | |
| 2007 | 5.2 | 10.0 | 5.2 | 13.7 | 10.6 | 10.6 | 10.3 | 8.5 | |
| 2008 | 5.7 | 7.4 | 3.7 | 9.2 | 8.8 | 10.8 | 8.8 | 6.4 | |
| 2009 | 8.4 | 6.1 | 2.6 | 10.4 | 15.8 | 14.4 | 11.6 | 8.5 | |
| 2010 | 10.4 | 5.7 | 1.1 | 10.0 | 20.5 | 17.0 | 14.5 | 8.6 | |
| 2011 | 11.3 | 5.4 | 0.9 | 8.7 | 20.0 | 15.1 | 12.5 | 7.7 | |
| Medicare enrolled | Yes | 80.1 | 78.6 | 79.3 | 86.6 | 78.1 | 79.2 | 77.1 | 71.4 |
| Nursing home residence, ever during baseline | 16.5 | 20.3 | 14.5 | 21.8 | 12.7 | 24.7 | 18.9 | 17.9 | |
| Healthcare utilization intensity measures, in baseline period† | Group | Measures of Central Tendency | |||||||
| # prescriptions dispensed | Median (Q1-Q3) | 61.0 (33.0-98.0) | 63.0 (33.0-102) | 52.0 (25.0-85.0) | 47.0 (20.0-85.0) | 69.0 (39.0-109) | 64.0 (34.0-104) | 80.0 (45.0-126) | 66.0 (33.0-108) |
| # unique drugs dispensed | 15.0 (10.0-22.0) | 16.0 (10.0-23.0) | 13.0 (8.0-20.0) | 13.0 (7.0-19.0) | 17.0 (10.0-24.0) | 16.0 (10.0-23.0) | 17.0 (11.0-25.0) | 16.0 (10.0-23.0) | |
| # inpatient diagnosis codes | 6.0 (0.0-15.0) | 7.0 (0.0-15.0) | 3.0 (0.0-9.0) | 1.0 (0.0-9.0) | 7.0 (0.0-16.0) | 9.0 (0.0-18.0) | 6.0 (0.0-14.0) | 4.0 (0.0-11.0) | |
| # unique inpatient diagnosis codes | 6.0 (0.0-11.0) | 6.0 (0.0-11.0) | 3.0 (0.0-9.0) | 1.0 (0.0-9.0) | 7.0 (0.0-12.0) | 8.0 (0.0-14.0) | 6.0 (0.0-11.0) | 3.0 (0.0-9.0) | |
| # outpatient diagnosis codes | 84.0 (39.0-161) | 90.0 (45.0-171) | 68.0 (30.0-122) | 50.0 (3.0-120) | 88.0 (40.0-177) | 89.0 (36.0-182) | 91.0 (44.0-171) | 74.0 (33.0-150) | |
| # unique outpatient diagnosis codes | 25.0 (14.0-38.0) | 26.0 (16.0-38.0) | 22.0 (12.0-32.0) | 17.0 (2.0-31.0) | 26.0 (14.0-40.0) | 26.0 (13.0-40.0) | 26.0 (15.0-38.0) | 22.0 (12.0-35.0) | |
| # outpatient CPT-4/HCPCS procedure codes | 95.0 (44.0-174) | 101 (51.0-183) | 77.0 (38.0-140) | 61.0 (11.0-136) | 100 (46.0-188) | 97.0 (40.0-187) | 104 (49.0-184) | 87.0 (39.0-166) | |
| # unique outpatient CPT-4/HCPCS procedure codes | 45.0 (24.0-69.0) | 47.0 (27.0-70.0) | 38.0 (20.0-60.0) | 30.0 (4.0-55.0) | 48.0 (25.0-74.0) | 45.0 (21.0-71.0) | 47.0 (25.0-70.0) | 41.0 (20.0-64.0) | |
| Other investigator predefined covariates, in baseline period | Group | % | |||||||
| GIB/ICH | Yes | 2.8 | 3.1 | 2.2 | 1.9 | 2.5 | 3.5 | 2.3 | 2.8 |
| Coagulation defect | 10.9 | 11.0 | 10.2 | 7.5 | 10.8 | 9.7 | 12.6 | 11.5 | |
| Liver disease | 13.2 | 13.1 | 9.7 | 8.6 | 14.4 | 13.1 | 15.1 | 14.5 | |
| Kidney disease | 33.9 | 35.1 | 25.3 | 25.9 | 35.7 | 37.7 | 36.3 | 31.7 | |
| Obesity | 13.7 | 14.4 | 12.0 | 11.4 | 17.2 | 16.4 | 18.5 | 15.2 | |
| Ulcer | 4.8 | 4.9 | 4.4 | 2.9 | 4.4 | 4.5 | 4.5 | 4.9 | |
| Esophagitis/gastritis/duodenitis | 28.7 | 29.0 | 24.7 | 21.5 | 34.9 | 30.9 | 33.3 | 25.6 | |
| Esophageal varices | 0.2 | 0.1 | 0.0 | 0.1 | 0.1 | 0.2 | 0.1 | 0.2 | |
| Diabetes mellitus | 50.0 | 53.4 | 46.4 | 41.5 | 52.7 | 52.9 | 58.5 | 55.7 | |
| Non-warfarin anticoagulant, oral | 0.1 | 0.0 | 0.0 | 0.1 | 0.2 | 0.1 | 0.1 | 0.1 | |
| Non-warfarin anticoagulant, subcutaneous/injectable | 6.1 | 6.1 | 3.9 | 6.2 | 7.9 | 7.6 | 9.0 | 6.9 | |
| Antiplatelet agent, oral | 17.5 | 19.1 | 13.1 | 13.8 | 25.4 | 20.9 | 16.7 | 11.6 | |
| ASA/NSAID, oral | 40.5 | 42.4 | 35.8 | 33.0 | 43.9 | 40.6 | 37.4 | 38.2 | |
| Gastroprotective agent, oral | 51.1 | 51.7 | 43.6 | 43.9 | 56.7 | 53.0 | 56.9 | 50.7 | |
| Selective COX-2 inhibitor | 17.5 | 17.5 | 20.0 | 6.2 | 10.5 | 10.4 | 13.0 | 14.0 | |
| Drug that can interact with warfarin, oral | 72.3 | 72.3 | 68.0 | 63.3 | 73.9 | 71.2 | 89.9 | 74.2 | |
| Clinically relevant CYP2C9/3A4/1A2 inhibitor | 56.7 | 54.9 | 50.9 | 47.5 | 54.7 | 53.4 | 58.4 | 56.6 | |
| Clinically relevant CYP2C9/3A4/1A2 inducer | 11.8 | 13.0 | 11.4 | 9.7 | 12.3 | 11.5 | 14.3 | 13.6 | |
ASA = aspirin; CI = confidence interval; CPT-4 = Current Procedural Terminology-4; COX = cyclooxygenase; CYP = cytochrome P450; GIB = gastrointestinal bleeding; ICH = intracranial hemorrhage; NSAID = nonsteroidal anti-inflammatory drug; Q = quartile
*
cell suppressed to comply with Centers for Medicare and Medicaid Services privacy policy
†
the following healthcare utilization covariates were excluded from presentation the table, as their median values were zero for the majority of antihyperlipidemics: # inpatient ICD-9 procedure codes; # unique inpatient ICD-9 procedure codes; # inpatient CPT-4/HCPCS procedure codes; # unique inpatient CPT-4/HCPCS procedure codes; # outpatient ICD-9 procedure codes; # unique outpatient ICD-9 procedure codes; # other setting ICD-9 diagnosis codes; # unique other setting ICD-9 diagnosis codes; # other setting ICD-9 procedure codes; # unique other setting ICD-9 procedure codes