Table 4.
IRs (per 100 patient-years) and RRs for cardiac, vascular, and respiratory AEs
| HandiHaler®
|
Respimat®
|
Total
|
|||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Placebo n=8,343 |
Tiotropium n=9,647 |
RR (95% CI) | Placebo n=3,283 |
Tiotropium n=3,282 |
RR (95% CI) | Placebo n=11,626 |
Tiotropium n=12,929 |
RR (95% CI) | |||||||
| n (%) | IR | n (%) | IR | n (%) | IR | n (%) | IR | n (%) | IR | n (%) | IR | ||||
| Cardiac disordersa | 778 (9.3) | 7.22 | 785 (8.1) | 6.40 | 0.89 (0.80, 0.98)b | 183 (5.6) | 7.31 | 217 (6.6) | 8.25 | 1.13 (0.93, 1.38) | 961 (8.3) | 7.24 | 1,002 (7.8) | 6.73 | 0.93 (0.85, 1.02) |
| AF/flutterc | 145 (1.7) | 1.26 | 147 (1.5) | 1.13 | 0.91 (0.72, 1.14) | 24 (0.7) | 0.93 | 22 (0.7) | 0.82 | 0.86 (0.48, 1.54) | 169 (1.5) | 1.20 | 169 (1.3) | 1.07 | 0.90 (0.73, 1.12) |
| Cardiac arrestc | 31 (0.4) | 0.27 | 23 (0.2) | 0.17 | 0.68 (0.40, 1.17) | 3 (0.1) | 0.12 | 7 (0.2) | 0.26 | 2.28 (0.59, 8.81) | 34 (0.3) | 0.24 | 30 (0.2) | 0.19 | 0.82 (0.50, 1.34) |
| Cardiac failured | 256 (3.1) | 2.24 | 231 (2.4) | 1.77 | 0.80 (0.67, 0.96)b | 40 (1.2) | 1.56 | 38 (1.2) | 1.41 | 0.90 (0.58, 1.41) | 296 (2.5) | 2.12 | 269 (2.1) | 1.71 | 0.81 (0.69, 0.96)b |
| Ischemic heart diseasee | 215 (2.6) | 1.89 | 225 (2.3) | 1.75 | 0.92 (0.76, 1.11) | 32 (1.0) | 1.25 | 54 (1.6) | 2.01 | 1.61 (1.04, 2.49)b | 247 (2.1) | 1.77 | 279 (2.2) | 1.79 | 1.01 (0.85, 1.19) |
| MIf | 114 (1.4) | 0.99 | 112 (1.2) | 0.85 | 0.87 (0.67, 1.14) | 21 (0.6) | 0.82 | 16 (0.5) | 0.59 | 0.73 (0.38, 1.39) | 135 (1.2) | 0.95 | 128 (1.0) | 0.81 | 0.85 (0.67, 1.09) |
| Palpitationsc | 59 (0.7) | 0.51 | 74 (0.8) | 0.56 | 1.09 (0.77, 1.55) | 29 (0.9) | 1.13 | 40 (1.2) | 1.49 | 1.33 (0.82, 2.14) | 88 (0.8) | 0.62 | 114 (0.9) | 0.72 | 1.17 (0.88, 1.55) |
| Supraventricular tachycardiac | 27 (0.3) | 0.23 | 32 (0.3) | 0.24 | 1.06 (0.64, 1.78) | 21 (0.6) | 0.82 | 16 (0.5) | 0.59 | 0.73 (0.38, 1.39) | 48 (0.4) | 0.34 | 48 (0.4) | 0.30 | 0.92 (0.61, 1.37) |
| Tachycardiac | 52 (0.6) | 0.45 | 64 (0.7) | 0.49 | 1.05 (0.73, 1.53) | 27 (0.8) | 1.05 | 18 (0.5) | 0.67 | 0.64 (0.35, 1.17) | 79 (0.7) | 0.56 | 82 (0.6) | 0.52 | 0.92 (0.67, 1.25) |
| Ventricular tachycardia/fibrillationc | 27 (0.3) | 0.23 | 19 (0.2) | 0.14 | 0.64 (0.35, 1.16) | 2 (0.1) | 0.08 | 3 (0.1) | 0.11 | 1.39 (0.24, 8.26) | 29 (0.2) | 0.20 | 22 (0.2) | 0.14 | 0.69 (0.40, 1.21) |
| Vascular disordersa | 610 (7.3) | 5.65 | 670 (6.9) | 5.48 | 0.98 (0.88, 1.09) | 128 (3.9) | 5.09 | 122 (3.7) | 4.60 | 0.90 (0.70, 1.15) | 738 (6.3) | 5.54 | 792 (6.1) | 5.32 | 0.96 (0.87, 1.07) |
| Aneurysmc | 41 (0.5) | 0.35 | 53 (0.5) | 0.40 | 1.16 (0.77, 1.75) | 5 (0.2) | 0.19 | 7 (0.2) | 0.26 | 1.32 (0.42, 4.13) | 46 (0.4) | 0.32 | 60 (0.5) | 0.38 | 1.18 (0.80, 1.74) |
| Hypertensionc | 386 (4.6) | 3.49 | 393 (4.1) | 3.12 | 0.89 (0.77, 1.03) | 81 (2.5) | 3.20 | 97 (3.0) | 3.65 | 1.14 (0.85, 1.53) | 467 (4.0) | 3.43 | 490 (3.8) | 3.21 | 0.93 (0.82, 1.06) |
| Strokec | 96 (1.2) | 0.83 | 114 (1.2) | 0.87 | 1.07 (0.81, 1.41) | 17 (0.5) | 0.66 | 13 (0.4) | 0.48 | 0.73 (0.35, 1.49) | 113 (1.0) | 0.80 | 127 (1.0) | 0.80 | 1.02 (0.79, 1.32) |
| Respiratory, thoracic, and mediastinal disordersa | 3,676 (44.1) | 60.44 | 3,786 (39.2) | 51.15 | 0.81 (0.78, 0.85)b | 1,490 (45.4) | 83.64 | 1,346 (41.0) | 68.38 | 0.82 (0.76, 0.88)b | 5,166 (44.4) | 65.69 | 5,132 (39.7) | 54.77 | 0.81 (0.78, 0.85)b |
| COPD exacerbationc | 2,951 (35.4) | 42.70 | 2,907 (30.1) | 34.48 | 0.80 (0.76, 0.84)b | 1,147 (34.9) | 57.82 | 949 (28.9) | 42.84 | 0.74 (0.68, 0.80)b | 4,098 (35.2) | 46.07 | 3,856 (29.8) | 36.22 | 0.78 (0.75, 0.81)b |
| Pneumoniac | 543 (6.5) | 4.92 | 591 (6.1) | 4.74 | 0.95 (0.84, 1.07) | 100 (3.0) | 3.94 | 99 (3.0) | 3.71 | 0.95 (0.72, 1.25) | 643 (5.5) | 4.74 | 690 (5.3) | 4.56 | 0.95 (0.85, 1.06) |
| Respiratory failurec | 215 (2.6) | 1.87 | 189 (2.0) | 1.45 | 0.80 (0.66, 0.97)b | 28 (0.9) | 1.09 | 26 (0.8) | 0.96 | 0.89 (0.52, 1.52) | 243 (2.1) | 1.73 | 215 (1.7) | 1.36 | 0.81 (0.67, 0.97)b |
Notes:
a
Primary SOC.
b
Significantly different from 1.
c
PV endpoint (see Table S1 for details).
d
SMQ cardiac failure (narrow).
e
SMQ ischemic heart disease sub-SMQ other ischemic heart disease (broad).
f
SMQ ischemic heart disease sub-SMQ MI (broad).
Abbreviations: AE, adverse event; AF, atrial fibrillation; CI, confidence interval; COPD, chronic obstructive pulmonary disease; IR, incidence rate; MI, myocardial infarction; PV, pharmacovigilance; RR, rate ratio; SMQ, standardized Medical Dictionary for Regulatory Activities queries; SOC, system organ class.