Introduction
Methods
Setting and study population
Data quality control
Outcomes
Health-related quality of life
Mortality
Analyses and statistics
Missing data and sensitivity analysis
Results
Patient characteristics
Baseline, % | Total N = 1399 | Active cancer | Baseline, % | Total N = 1399 | Active cancer | ||
---|---|---|---|---|---|---|---|
No, N = 1279 | Yes, N = 120 | No, N = 1279 | Yes, N = 120 | ||||
Age, years, mean (SD) | 62.3 (17.1) | 61.8 (17.4) | 67.2 (11.5)* | Comorbidities | |||
Male | 53.2 | 52.4 | 61.7 | Active cancer | 8.6 | 0 | 100 |
BMI, mean (SD) | 28.16 (6.0) | 28.4 (5.9) | 25.7 (5.5)* | Hypertension | 46.3 | 46.6 | 43.3 |
Highest graduation | Congestive heart failure | 5.9 | 5.9 | 6.7 | |||
Primary school | 32.0 | 31.7 | 35 | Vascular disease | 7.1 | 6.8 | 10* |
Secondary school | 41.8 | 41.9 | 40.8 | Dyslipidemia | 26.4 | 26.2 | 28.3 |
Above | 21.9 | 22.1 | 20 | Diabetes | 11.2 | 10.8 | 15 |
Marital status | Chronic venous insufficiency | 14.2 | 14.5 | 10.8 | |||
Single | 14.2 | 16.0 | 9.2 | Renal disease | 6.4 | 6.7 | 4.2 |
Married/living as married | 62.2 | 61.2 | 72.5 | Liver disease | 2.6 | 2.0 | 9.2* |
Separated/divorced | 5.3 | 5.7 | 0.8 | Chronic respiratory disease | 10.7 | 10.3 | 15 |
Widowed | 14.4 | 14.4 | 15 | Arthritis | 6.0 | 6.3 | 2.5 |
Other | 1.2 | 1.3 | 0 | Bone fracture/soft tissue trauma | 10.0 | 10.3 | 5.8 |
Country | Lower extremity paralysis | 1.1 | 1.2 | 0 | |||
France | 25.2 | 25.5 | 21.7 | Thrombophilia | 5.1 | 5.5 | 0.8* |
DACH | 17.2 | 18.3 | 5.8 | Cardiovascular disease | 16.8 | 16.7 | 18.3 |
Italy | 23.7 | 22.7 | 35* | Alcohol use | 15.6 | 16.3 | 7.5* |
Spain | 23.4 | 22.4 | 34.2* | Smoking history | 33.1 | 32.0 | 45.8* |
UK | 10.5 | 11.2 | 3.3 | Risk factors (within past 3 month or ongoing) | |||
Previous clinical event (within 3 yr. prior to enroll.) | Prolonged immobilization | 17.8 | 17.9 | 16.7 | |||
Myocardial infarction | 3.7 | 3.8 | 3.3 | >5 day in bed | 11.8 | 11.5 | 15 |
Coronary artery disease | 3.8 | 3.8 | 3.3 | Varicose veins | 17.5 | 18.2 | 10 |
Percutaneous coronary intervention | 2.4 | 2.4 | 2.5 | Major surg. or trauma | 14.0 | 13.9 | 15 |
Atrial fibrillation | 4.7 | 4.5 | 7.5 | PE symptoms present | |||
Transient ischemic attack | 2.65 | 2.66 | 2.5 | Dyspnea | 75.6 | 76.2 | 70* |
Stoke | 2.7 | 2.8 | 1.7 | Chest pain | 45.5 | 47.2 | 28.3* |
Bleeding event | 4.2 | 4.0 | 6.7 | Cough | 16.8 | 16.7 | 18.3 |
Clinical factors | Hemoptysis | 3.4 | 3.6 | 1.7 | |||
Previous VTE event | 20.2 | 20.9 | 13.3 | Syncope | 8.2 | 8.3 | 6.7 |
With concomitant DVT | 46.5 | 45.5 | 57.5* | Palpitations | 7.9 | 7.7 | 9.2 |
Provoked | 27.5 | 27.3 | 30 | Fever | 7.8 | 7.9 | 6.7 |
Baseline treatment | Cyanosis | 2.2 | 2.1 | 3.3 | |||
Use of heparin | 85.4 | 85.4 | 84.9 | Tachypnea | 16.2 | 16.0 | 17.5 |
Use of VKA | 57.4 | 61.5 | 13.5* | Tachycardia | 16.7 | 16.4 | 19.2 |
Use of NOACs | 21.2 | 22.7 | 5.9* | Cardiogenic shock | 1.5 | 1.4 | 2.5 |
Others | 7.6 | 8.0 | 3.3 |
Missing data
Health-related quality of life
Without VTE/bleeding events (n = 1191, Obs = 4024) | With VTE/bleeding events (n = 1191, Obs = 3875) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Coef. | Std. Err. | p > z | [95% Conf. | Interval] | Coef. | Std. Err. | p > z | [95% Conf. | Interval] | |
Patients without ACTIVE cancer | ||||||||||
Constant | 0.974 | 0.044 | < 0.001 | 0.888 | 1.060 | 0.970 | 0.044 | < 0.001 | 0.884 | 1.057 |
Age | − 0.001 | 0.000 | 0.006 | − 0.002 | 0.000 | − 0.001 | 0.000 | 0.011 | − 0.002 | 0.000 |
Male | 0.105 | 0.013 | < 0.001 | 0.079 | 0.131 | 0.105 | 0.013 | < 0.001 | 0.079 | 0.131 |
Body mass index | − 0.004 | 0.001 | 0.001 | − 0.006 | − 0.002 | − 0.004 | 0.001 | 0.001 | − 0.006 | − 0.002 |
Previous stroke | − 0.115 | 0.040 | 0.004 | − 0.192 | − 0.037 | − 0.120 | 0.040 | 0.003 | − 0.199 | − 0.042 |
Prolong immobilization | − 0.074 | 0.021 | < 0.001 | − 0.114 | − 0.034 | − 0.072 | 0.021 | 0.001 | − 0.112 | − 0.031 |
> 5 day in bed | − 0.071 | 0.024 | 0.003 | − 0.118 | − 0.023 | − 0.068 | 0.024 | 0.005 | − 0.116 | − 0.021 |
Varicose veins | 0.036 | 0.017 | 0.037 | 0.002 | 0.070 | 0.038 | 0.017 | 0.03 | 0.004 | 0.072 |
Vascular disease | − 0.092 | 0.027 | 0.001 | − 0.145 | − 0.039 | − 0.090 | 0.027 | 0.001 | − 0.143 | − 0.036 |
Dyslipidemia | 0.040 | 0.015 | 0.010 | 0.010 | 0.070 | 0.038 | 0.015 | 0.014 | 0.008 | 0.068 |
Diabetes mellitus | − 0.059 | 0.022 | 0.007 | − 0.101 | − 0.016 | − 0.055 | 0.022 | 0.011 | − 0.098 | − 0.013 |
Chronic respiratory disease | − 0.057 | 0.022 | 0.009 | − 0.100 | − 0.015 | − 0.059 | 0.022 | 0.007 | − 0.102 | − 0.016 |
Arthritis | − 0.068 | 0.026 | 0.008 | − 0.119 | − 0.018 | − 0.065 | 0.026 | 0.013 | − 0.116 | − 0.014 |
Bone fracture/soft tissue trauma | − 0.073 | 0.022 | 0.001 | − 0.116 | − 0.030 | − 0.074 | 0.022 | 0.001 | − 0.117 | − 0.031 |
VTE event during follow-up | Not included | − 0.061 | 0.043 | 0.158 | − 0.145 | 0.024 | ||||
Bleeding event during follow-up | Not included | − 0.050 | 0.022 | 0.027 | − 0.094 | − 0.006 |
Without VTE/bleeding events (n = 110, Obs = 321) | With VTE/bleeding events (n = 110, Obs = 296) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Coef. | Std. Err. | p > z | [95% Conf. | Interval] | Coef. | Std. Err. | p > z | [95% Conf. | Interval] | |
Patients with ACTIVE cancer | ||||||||||
Constant | 1.236 | 0.161 | < 0.001 | 0.921 | 1.552 | 1.237 | 0.165 | 0 < 0.001 | 0.914 | 1.560 |
Age | − 0.008 | 0.002 | 0.001 | − 0.012 | − 0.003 | − 0.008 | 0.002 | 0.001 | − 0.013 | − 0.003 |
Previous stroke | − 0.762 | 0.313 | 0.015 | − 1.376 | − 0.148 | − 0.758 | 0.318 | 0.017 | − 1.382 | − 0.134 |
VTE event during follow-up | Not included | 0.069 | 0.182 | 0.704 | − 0.288 | 0.427 | ||||
Bleeding event during follow-up | Not included | − 0.076 | 0.091 | 0.400 | − 0.254 | 0.102 |
Mortality
PE | Baseline | Month 1 | Month 3 | Month 6 | Month 12 |
---|---|---|---|---|---|
All | |||||
Total | 1398 | 1388 | 1327 | 1307 | 1263 |
Death, n(%) | 14 (1.00) | 34 (2.45) | 59 (4.45) | 79 (6.04) | 102 (8.08) |
Reason for death | |||||
Missing/unknown | – | 2 (5.9) | 2 (3.4) | 4 (5.1) | 6 (5.9) |
VTE-related death | 5 (35.7) | 6 (17.6) | 7 (11.9) | 7 (8.9) | 7 (6.9) |
Cardiovascular death | 3 (21.4) | 5 (14.7) | 9 (15.3) | 12 (15.2) | 18 (17.6) |
Other | 6 (42.9) | 21 (61.8) | 41 (69.5) | 56 (70.9) | 71 (69.6) |
Without active cancer | |||||
Total | 1278 | 1270 | 1213 | 1194 | 1151 |
Death, n(%) | 11 (0.86) | 23 (1.81) | 38 (3.13) | 45 (3.8) | 54 (4.69) |
Reason for death | |||||
Missing/unknown | – | 1 (4.3) | 1 (2.6) | 3 (6.7) | 2 (3.7) |
VTE-related death | 5 (45.5) | 6 (26.1) | 6 (15.8) | 6 (13.3) | 6 (11.1) |
Cardiovascular death | 2 (18.2) | 4 (17.4) | 8 (21.1) | 11 (24.4) | 13 (24.1) |
Other | 4 (36.4) | 12 (52.2) | 23 (60.5) | 25 (55.6) | 30 (55.6) |
With active cancer | |||||
Total | 120 | 118 | 114 | 113 | 112 |
Death, n(%) | 3 (2.5) | 11 (9.32) | 21 (18.4) | 34 (30.1) | 48 (42.9) |
Reason for death | |||||
Missing/unknown | – | 1 (9.1) | 1 (4.8) | 1 (2.9) | 4 (8.3) |
VTE-related death | – | – | 1 (4.8) | 1 (2.9) | 1 (2.1) |
Cardiovascular death | 1 (33.3) | 1 (9.1) | 1 (4.8) | 1 (2.9) | 5 (10.4) |
Other | 2 (66.7) | 9 (81.8) | 18 (85.7) | 31 (91.2) | 41 (85.4) |
Baseline characteristics (n = 1183) | Baseline characteristics (excluding PE Symptomsa) and EQ-5D-5L index score (n = 1198) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Odds ratio | Std. err. | p value | [95% conf. | Interval] | Odds ratio | Std. err. | p value | [95% conf. | Interval] | |
Total PE cohort | ||||||||||
Constant | 0.017 | 0.018 | < 0.001 | 0.002 | 0.135 | 0.201 | 0.231 | 0.162 | 0.021 | 1.912 |
Age | 1.046 | 0.011 | < 0.001 | 1.025 | 1.068 | 1.043 | 0.011 | < 0.001 | 1.022 | 1.065 |
BMI | 0.905 | 0.025 | < 0.001 | 0.857 | 0.955 | 0.887 | 0.026 | < 0.001 | 0.837 | 0.939 |
Active cancer | 13.137 | 3.600 | < 0.001 | 7.678 | 22.478 | 12.348 | 3.495 | < 0.001 | 7.090 | 21.504 |
Prolong immobilization | 2.587 | 0.777 | 0.002 | 1.436 | 4.661 | |||||
Vascular disease | 2.361 | 0.789 | 0.010 | 1.226 | 4.545 | |||||
Previous AF | 2.531 | 1.007 | 0.020 | 1.16 | 5.52 | 2.871 | 1.159 | 0.009 | 1.301 | 6.334 |
Smoking history | 1.931 | 0.495 | 0.010 | 1.168 | 3.191 | 1.967 | 0.534 | 0.013 | 1.155 | 3.349 |
Palpitations | 2.276 | 0.874 | 0.032 | 1.072 | 4.831 | Not includeda | ||||
EQ-5D-5L index score at baseline | Not included | 0.095 | 0.040 | < 0.001 |
Baseline characteristics (n = 1071) | Baseline characteristics (excluding PE Symptomsa) and EQ-5D-5L index score (n = 1090) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Odds ratio | Std. err. | p value | [95% conf. | Interval] | Odds ratio | Std. err. | p value | [95% conf. | Interval] | |
Patients without ACTIVE cancer | ||||||||||
Constant | 0.194 | 0.280 | 0.257 | 0.011 | 3.294 | 0.502 | 0.775 | 0.655 | 0.024 | 10.315 |
Age | 1.058 | 0.014 | < 0.001 | 1.030 | 1.086 | 1.054 | 0.014 | < 0.001 | 1.027 | 1.082 |
Body mass index | 0.796 | 0.035 | < 0.001 | 0.730 | 0.869 | 0.808 | 0.035 | < 0.001 | 0.742 | 0.881 |
Prolong immobilization | 2.570 | 0.866 | 0.005 | 1.328 | 4.975 | 2.053 | 0.737 | 0.045 | 1.016 | 4.148 |
Vascular disease | 3.580 | 1.353 | 0.001 | 1.707 | 7.510 | 2.493 | 1.014 | 0.025 | 1.124 | 5.531 |
Diabetes mellitus | 2.575 | 0.985 | 0.013 | 1.217 | 5.448 | 2.534 | 0.996 | 0.018 | 1.173 | 5.474 |
Cardiogenic shock | 17.573 | 11.213 | < 0.001 | 5.032 | 61.373 | Not includeda | ||||
EQ-5D-5L index score at baseline | Not included | 0.220 | 0.117 | 0.004 | 0.078 | 0.622 |
Baseline characteristics (n = 112) | Baseline characteristics (excluding PE Symptomsa) and EQ-5D-5L index score (n = 108) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Odds ratio | Std. err. | p value | [95% conf. | Interval] | Odds ratio | Std. err. | p value | [95% conf. | Interval] | |
Patients with ACTIVE cancer | ||||||||||
Constant | 0.311 | 0.101 | < 0.001 | 0.164 | 0.588 | 3.232 | 1.934 | 0.050 | 1.001 | 10.440 |
Smoking history | 2.964 | 1.246 | 0.010 | 1.300 | 6.758 | 3.346 | 1.514 | 0.008 | 1.379 | 8.122 |
Tachycardia | 6.295 | 3.633 | 0.001 | 2.031 | 19.510 | Not includeda | ||||
EQ-5D-5L index score at baseline | Not included | 0.035 | 0.031 | < 0.001 | 0.006 | 0.193 |
Discussion
Utility
Mortality
Strengths and limitations
Conclusion
Acknowledgements
Compliance with ethical standards
Conflict of interest
Ethical approval
Ethics boards
Country | Name/place | Date |
---|---|---|
Germany | Rhineland Palatinate | 11.01.2013 |
Austria | Österreichische Agentur für Gesundheit und Ernährungssicherheit GmbH | 08.07.2013 |
Switzerland | Basel Region Ethics Committee | 10.04.2013 |
France | Comité consultatif sur le traitement de l’information en matière de recherche dans le domaine de la santé Commission Nationale de l’Informatique et des Libertés Conseil National de l’Ordre des Médecins | 21.02.2013 15.04.2013 22.01.2013 |
Italy | Perugia Hospital Ethics Committee | 24.01.2013 |
Spain | Asturia Hospital Ethics Committee Agencia Española de Medicamentos y Productos Sanitarios | 27.03.2013 10.04.2013 |
United Kingdom | NRES Committee– Camden & Islington | 10.04.2013 |