Table 3.
Hazard ratio (95% confidence interval) estimates for AF comparing bisphosphonate users to matched nonusers
|
Database |
MarketScan (US) |
Ingenix (US) |
THIN (UK) |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Index drug | ALN or RIS | ALN | RIS | ALN or RIS | ALN | RIS | ALN or RIS | ALN | RIS |
| Unadjusted | 0.92 (0.87–0.98) | 0.91 (0.84–0.98) | 0.94 (0.85–1.03) | 0.96 (0.85–1.09) | 1.06 (0.91–1.24) | 0.78 (0.62–0.97) | 0.93 (0.78–1.12) | 0.99 (0.80–1.21) | 0.92 (0.87–0.98) |
| Adjusted | 0.92 (0.85–0.99)a | 0.93 (0.85–1.02) | 0.90 (0.80–1.01) | 1.00 (0.87–1.16) | 1.12 (0.94–1.34) | 0.79 (0.62–1.03) | 0.97 (0.79–1.20) | 1.02 (0.81–1.28) | 0.86 (0.54–1.37) |
| BIS Rx ≥ 2 | 0.86 (0.79–0.93)a | 0.89 (0.80–0.98)a | 0.82 (0.72–0.93)a | 0.96 (0.82–1.13) | 1.09 (0.90–1.33) | 0.71 (0.52–0.95)a | 0.98 (0.79–1.23) | 1.03 (0.80–1.31) | 0.88 (0.54–1.44) |
| Age | |||||||||
| ≥70 | 0.95 (0.88–1.04) | 0.96 (0.86–1.06) | 0.93 (0.81–1.06) | 1.01 (0.84–1.20) | 1.17 (0.95–1.44) | 0.71 (0.51–0.99) | 1.07 (0.86–1.33)b | 1.14 (0.89–1.45)b | 0.88 (0.55–1.43) |
| <70 | 0.85 (0.74–0.98) | 0.87 (0.74–1.03) | 0.83 (0.67–1.03) | 1.03 (0.80–1.32) | 1.05 (0.79–1.39) | 0.93 (0.64–1.35) | 0.33 (0.13–0.82)b | 0.35 (0.15–0.83)b | 0.67 (0.18–2.48) |
| Heart disease | |||||||||
| Yes | 0.94 (0.81–1.09) | 0.92 (0.76–1.11) | 0.97 (0.78–1.22) | 0.97 (0.69–1.36) | 1.10 (0.71–1.69) | 0.75 (0.43–1.32) | 0.51 (0.24–1.08) | 0.37 (0.16–0.88)b | 2.04 (0.32–12.80) |
| No | 0.91 (0.84–0.99) | 0.94 (0.84–1.04) | 0.87 (0.76–1.00) | 1.01 (0.86–1.18) | 1.12 (0.93–1.36) | 0.80 (0.60–1.06) | 1.03 (0.83–1.28) | 1.12 (0.88–1.42)b | 0.84 (0.53–1.35) |
| Vascular disease | |||||||||
| Yes | 1.75 (1.55–1.97)b | 1.69 (1.44–1.98)b | 1.83 (1.52–2.20)b | 1.98 (1.45–2.71)b | 2.30 (1.58–3.34)b | 1.39 (0.77–2.51)b | 1.09 (0.70–1.71) | 1.06 (0.64–1.73) | 1.10 (0.36–3.34) |
| No | 0.74 (0.68–0.80)b | 0.77 (0.69–0.85)b | 0.70 (0.61–0.80)b | 0.91 (0.78–1.06)b | 1.04 (0.86–1.26)b | 0.71 (0.54–0.94)b | 0.95 (0.76–1.19) | 1.01 (0.78–1.30) | 0.82 (0.50–1.34) |
| Blood pressure drugs | |||||||||
| Yes | 1.00 (0.92–1.09)b | 1.03 (0.92–1.16) | 0.96 (0.84–1.10)b | 1.04 (0.86–1.25) | 1.18 (0.94–1.47) | 0.77 (0.55–1.09) | 1.01 (0.79–1.30) | 1.07 (0.81–1.41) | 0.88 (0.51–1.51) |
| No | 0.78 (0.69–0.88)b | 0.77 (0.66–0.90) | 0.80 (0.65–0.97)b | 0.97 (0.79–1.20) | 1.05 (0.81–1.36) | 0.85 (0.59–1.22) | 0.87 (0.62–1.21) | 0.93 (0.64–1.34) | 0.66 (0.30–1.44) |
| Fracture | |||||||||
| Yes | 1.05 (0.84–1.31) | 1.20 (0.90–1.60) | 0.93 (0.47–1.84) | 1.41 (0.90–2.21) | 1.74 (1.00–3.05) | 0.85 (0.60–1.21) | 0.82 (0.45–1.50) | 0.93 (0.47–1.84) | 1.00 (0.47–2.15) |
| No | 0.90 (0.81–1.11) | 0.90 (0.81–0.99) | 0.98 (0.75–1.27) | 0.95 (0.81–1.11) | 1.06 (0.88–1.28) | 0.90 (0.80–1.02) | 0.94 (0.74–1.19) | 0.98 (0.75–1.27) | 0.76 (0.58–1.00) |
| Follow-up (days) since index | |||||||||
| <90 | 0.94 (0.83–1.07) | 0.95 (0.80–1.12) | 0.93 (0.76–1.14) | 1.33 (1.02–1.75) | 1.37 (0.99–1.91) | 1.24 (0.77–1.99) | 1.00 (0.57–1.77) | 1.11 (0.59–2.08) | 0.67 (0.17–2.65) |
| 90–179 | 0.86 (0.73–1.01) | 0.83 (0.67–1.03) | 0.90 (0.70–1.16) | 1.23 (0.92–1.66) | 1.33 (0.92–1.94) | 1.05 (0.65–1.71) | 0.87 (0.50–1.49) | 0.95 (0.53–1.71) | 0.54 (0.12–2.42) |
| 180–364 | 0.93 (0.81–1.07) | 0.92 (0.77–1.10) | 0.94 (0.75–1.17) | 0.77 (0.59–1.02) | 0.95 (0.69–1.31) | 0.45 (0.25–0.81) | 0.88 (0.59–1.30) | 0.83 (0.53–1.30) | 1.07 (0.44–2.64) |
| ≥365 | 0.92 (0.82–1.04) | 0.97 (0.84–1.13) | 0.84 (0.69–1.03) | 0.89 (0.70–1.12) | 1.02 (0.77–1.37) | 0.68 (0.44–1.04) | 1.04 (0.79–1.37) | 1.12 (0.82–1.53) | 0.90 (0.50–1.64) |
| # of BIS prescriptions | |||||||||
| 1 | 1.13 (1.01–1.28) | 1.11 (0.95–1.30) | 1.16 (0.97–1.40) | 1.47 (1.16–1.86) | 1.62 (1.21–2.19) | 1.20 (0.80–1.80) | 1.05 (0.64–1.74) | 1.12 (0.64–1.96) | 0.80 (0.25–2.56) |
| 2–10 | 0.83 (0.76–0.91) | 0.83 (0.74–0.94) | 0.83 (0.72–0.96) | 0.88 (0.73–1.07) | 0.97 (0.77–1.22) | 0.73 (0.52–1.03) | 0.85 (0.65–1.12) | 0.93 (0.69–1.26) | 0.58 (0.29–1.15) |
| ≥11 | 0.91 (0.73–1.13) | 1.08 (0.83–1.40) | 0.61 (0.41–0.92) | 0.78 (0.52–1.16) | 1.10 (0.69–1.74) | 0.29 (0.11–0.75) | 1.23 (0.82–1.83) | 1.26 (0.80–2.00) | 1.31 (0.57–2.98) |
| Per 1 more | 0.98 (0.97–0.99)c | 0.99 (0.98–1.00) | 0.97 (0.95–0.99)c | 0.99 (0.97–1.00) | 1.00 (0.98–1.02) | 0.96 (0.93–0.99)c | 1.00 (0.99–1.02) | 1.00 (0.98–1.02) | 1.02 (0.99–1.06) |
Notes:
a
P < 0.05 for likelihood ratio test;
b
P < 0.05 for test of interaction or effect modification;
c
P < 0.05 for trend test, with number of bisphosphonate prescriptions as a continuous variable. Model adjusted variables: history of angina, congestive heart failure, diabetes, any hospitalizations, hypertension, myocardial infarction, osteoporosis, renal diseases, stroke, thrombosis, prescriptions for ACE inhibitors, angiotensin receptor blockers, anticoagulants, beta-blockers, calcium channel blockers, medications for cardiac ischemia, estrogens, diuretics, statins, and total number of all prescriptions.
Abbreviations: AF, atrial fibrillation; ALN, alendronate; BIS, bisphosphonate; HR, hazard ratio; NA, not applicable; RIS, risedronate; Rx, prescription.