Early Anticoagulation is Associated with Reduced Mortality for Acute Pulmonary Embolism

Sean B. Smith, MD; Jeffrey B. Geske, MD; Jennifer M. Maguire, MD; Nicholas A. Zane, BA; Rickey E. Carter, PhD; Timothy I. Morgenthaler, MD, FCCP

Disclosures

CHEST. 2010;137(6):1382-1390.

Conclusions

We provide novel data regarding how the timing of anticoagulation relates to mortality for patients with acute PE. Delayed anticoagulation in our cohort was a risk factor associated with increased mortality. Further investigations are warranted to elucidate the influence of certain demographics and comorbidities, but we nevertheless advocate that quality improvement measures be considered to expedite management of acute PE.

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Funding/Support
This study was supported by the National Center for Research Resources, a component of the National Institutes of Health (NIH) [Grant 1 UL1 RR024150-01] and the NIH Roadmap for Medical Research. The Center for Translation Science Activities at Mayo Clinic has NIH funding.

Abbreviations
aPTT = activated partial thromboplastin time; CAD = coronary artery disease; CHF = congestive heart failure; DVT = deep vein thrombosis; IQR = interquartile range; LMWH = low-molecular-weight heparin; OR = odds ratio; PE = pulmonary embolism; SBP = systolic BP; VTE = venous thromboembolism

Author Contributions
Dr Smith: contributed to collecting and analyzing the data.
Dr Geske: contributed to collecting and analyzing the data.
Dr Maguire: contributed to collecting and analyzing the data.
Mr Zane: contributed to collecting and analyzing the data.
Dr Carter: contributed to providing statistical support.
Dr Morgenthaler: contributed to providing review, guidance, and manuscript preparation.

Financial/nonfinancial disclosures
The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors
The contents of this article are solely the responsibility of the authors and do not necessarily represent the official view of National Center for Research Resources or NIH. Information on the National Center for Research Resources is available at https://www.ncrr.nih.gov/. Information on Reengineering the Clinical Research Enterprise can be obtained from https://nihroadmap.nih.gov/clinicalresearch/.

Cite this: Early Anticoagulation is Associated with Reduced Mortality for Acute Pulmonary Embolism - Medscape - Jun 01, 2010.

Table 1. Baseline Characteristics of Patients Based on In-Hospital and 30-d Mortality
Characteristics	All Patients (N = 400)	Hospital Survivors (n = 388)	Hospital Nonsurvivors (n = 12)	30-d Survivors (n = 362)	30-d Nonsurvivors (n = 30)
Age, y (IQR)	68.0 (54.0–76.0)	68.0 (54.3–76.8)	72.5 (48.3–75.8)	68.0 (54.0–76.0)	73.0 (60.8–79.0)
Male sex	195 (48.8)	191 (49.2)	4 (33.3)	177 (48.9)	14 (46.7)
Heparin in ED	280 (70.0)	276 (71.1)	4 (33.3)^a	262 (72.4)	12 (40.0)^b
Hours to aPTT (IQR)	10.8 (7.7–17.3)	10.7 (7.7–16.6)	20.9 (8.4–28.8)^b	10.8 (7.8–16.5)	16.3 (5.3–28.6)^a
aPTT within 24 h	325 (85.8)	320/371 (86.3)	5/8 (62.5)	301/347 (86.7)	18/26 (69.2)^c
Temperature, °C (IQR)	36.8 (36.2–37.3)	36.8 (36.2–37.3)	36.5 (35.7–37.3)	36.9 (36.2–37.3)	36.6 (36.2–37.0)
Heart rate, bpm (IQR)	92 (77–107)	92 (77–107)	102 (90–120)	91 (77–106)	102 (84–119)
Tachycardia	152 (38.4)	144 (37.1)	8 (66.7)^c	130 (35.9)	18 (60.0)^a
SBP, mm Hg (IQR)	135 (118–155)	135 (120–156)	105 (101–119)^b	135 (120–155)	122 (104–145)
Hypotension	24 (6.9)	23 (5.9)	1 (8.3)	20 (5.5)	3 (10.0)
Respiratory rate (IQR)	20 (18–24)	20 (18–24)	24 (20–30)	20 (18–24)	22 (20–28)
Wells score (IQR)	4.5 (2.5–6.0)	4.5 (2.5–6.0)	3.5 (1.5–6.8)	4.5 (2.5–5.6)	5.5 (2.5–7.0)^c
Leukocytosis	171 (42.9)	161 (41.5)	10 (83.3)^a	148 (40.9)	19 (63.3)^c
d-dimer > 500 ng/mL	160/192 (83.3)	153/185 (82.7)	7/7 (100)	143/175 (81.7)	15/15 (100)
Troponin > 0.01 ng/mL	87/312 (27.9)	81/301 (26.9)	6/11 (54.6)	75/284 (26.4)	11/23 (47.8)^c
Active nicotine use	40 (10.0)	40 (10.3)	0 (0)	36 (9.9)	3 (10.0)
CAD	81 (20.3)	80 (20.6)	1 (8.3)	78 (21.6)	3 (10.0)
CHF	36 (9.0)	34 (8.8)	2 (16.7)	31 (8.6)	5 (16.7)
CAD or CHF	101 (25.3)	98 (25.3)	3 (25.0)	94 (26.0)	7 (23.3)
COPD	42 (10.5)	38 (9.8)^c	4 (33.3)^c	36 (9.9)^c	6 (20.0)
Malignancy	129 (32.3)	124 (32.0)	5 (41.7)	110 (30.4)	16 (53.3)^c
History of VTE	71 (17.8)	69 (17.8)	2 (16.7)	64 (17.7)	5 (16.7)
Current DVT	62/214 (29.0)	61/211 (28.9)	1/3 (33.3)	55/199 (27.6)	6/12 (50.0)
Immobile/recent surgery	169 (42.3)	162 (41.8)	7 (58.3)	146 (40.3)	19 (63.3)^c
Coagulation disorder	22 (5.5)	22 (5.7)	0 (0)	22 (6.1)	0 (0)
Oral contraceptive use	23 (5.7)	22 (5.7)	1 (8.3)	22 (6.1)	1 (3.3)
Hospital days (IQR)	4.6 (2.1–6.9)	4.6 (2.1–7.0)	5.4 (1.4–6.6)	4.4 (2.1–6.9)	5.7 (3.5–7.9)
ICU admission	77 (19.3)	69 (17.8)	8 (66.7)^b	63 (17.4)	12 (40.0)^a
ICU days (IQR)	2.0 (1.0–3.0)	2.0 (1.0–3.0)	1.5 (1.0–4.5)	2.0 (1.0–3.0)	1.5 (1.0–4.5)
Hemorrhagic events	21 (5.3)	18 (4.6)	3 (25.0)	16 (4.4)^c	4 (13.3)
Intubation	11 (2.8)	9 (2.3)	2 (16.7)^c	9 (2.5)	2 (6.7)
Recurrent VTE in 90 d	6/391 (1.5)	6/379 (1.6)	0/12 (0.0)	6/357 (1.7)	0 (0)

Data are presented as No. (%) unless otherwise indicated. aPTT = activated partial thromboplastin time; bpm = beats per minute; CAD = coronary artery disease; CHF = congestive heart failure; DVT = deep vein thrombosis; IQR = interquartile range; SBP = systolic blood pressure; VTE = venous thromboembolism.
^a P < .01.
^b P < .001.
^c P < .05.

Table 2. Odds Ratios for In-Hospital and 30-d Mortality Based on Baseline Characteristics
Characteristics	Hospital Mortality			30-d Mortality
Characteristics	OR	95% CI	P Value	OR	95% CI	P Value
Age, y	1.00	0.97–1.04	.422	0.28	0.04–1.65	.910
Male sex	0.52	0.15–1.74	.382	0.91	0.43–1.93	.851
Heparin in ED	0.20	0.06–0.69	.009	0.25	0.12–0.55	<.001
aPTT within 24 h	0.27	0.06–1.15	.091	0.34	0.14–0.84	.037
Temperature, °C	1.50	0.56–3.70	.203	1.29	0.73–2.25	.183
Tachycardia	4.46	1.17–17.09	.025	2.88	1.32–6.29	.009
Hypotension	1.72	0.21–14.33	.478	2.13	0.58–7.75	.212
Respiratory rate	0.95	0.88–1.07	.837	0.96	0.91–1.03	.873
Wells score	0.84	0.06–12.25	.553	0.17	0.03–0.96	.044
Leukocytosis	7.02	1.52–32.46	.006	2.49	1.15–5.38	.021
d-dimer > 500 ng/mL	3.18	0.18–57.01	.603	7.02	0.41–120.38	.079
Troponin > 0.01 ng/mL	3.26	0.97–10.97	.079	2.55	1.08–6.03	.029
Active nicotine use	0.25	0.01–4.23	.619	1.01	0.29–3.48	1.000
CAD	0.35	0.04–2.75	.473	0.40	0.12–1.37	.163
CHF	2.08	0.44–9.89	.295	2.14	0.76–5.97	.177
CAD or CHF	0.99	0.26–3.72	1.000	0.87	0.36–2.09	.832
COPD	4.61	1.32–16.01	.028	2.26	0.87–5.90	.116
Malignancy	1.52	0.47–4.89	.535	2.62	1.23–5.55	.010
History of VTE	0.92	0.20–4.31	1.000	0.93	0.34–2.52	1.000
Current DVT	1.23	0.11–13.81	1.000	2.62	0.81–8.46	.110
Immobile/recent surgery	1.95	0.61–6.26	.374	2.56	1.12–5.53	.012
Alternative diagnosis	0.56	0.18–1.78	.367	0.86	0.40–1.84	.698
Coagulation disorder	0.65	0.04–11.36	1.000	0.25	0.01–4.19	.397
Oral contraceptive use	1.51	0.19–12.25	.514	0.53	0.07–4.10	1.000
Hospital days	1.02	0.97–1.20	.390	1.00	0.97–1.05	.574
ICU admission	9.25	2.71–31.60	<.001	3.16	1.45–6.90	.006
Hemorrhagic events	6.85	1.71–27.50	.020	3.33	1.04–10.68	.057
Intubation	8.42	1.61–44.11	.039	2.80	0.58–13.60	.203

Unit ORs are recorded for continuous variables. OR = odds ratio. See Table 1 for expansion of other abbreviations.

Table 3. Baseline Characteristics Associated With the Timing of Heparin Administration
Characteristic	Heparin in ED (n = 280)	Heparin After Admission (n = 120)	OR	95% CI	P Value
Age, y (IQR)	62.5 (48.3–73.0)	75.0 (68.0–81.0)	0.94	0.92–0.96	<.001
Wells score (IQR)	4.5 (3.0–6.0)	3.0 (1.5–5.5)	1.22	1.11–1.34	<.001
CAD	43 (15.4%)	38 (31.7%)	0.39	0.24–0.65	<.001
CHF	13 (4.6%)	23 (19.2%)	0.21	0.10–0.42	<.001
COPD	20 (7.1%)	22 (18.3%)	0.34	0.18–0.66	.002
Troponin > 0.01 ng/mL	47 (16.8%)	40 (33.3%)	0.48	0.29–0.80	.005
D-dimer > 500 ng/mL	105/133(78.9%)	55/59 (93.2%)	0.27	0.09–0.82	.020
Alternative diagnosis less likely	201 (71.8%)	53 (44.2%)	3.21	2.06–5.01	<.001

Unit ORs are recorded for continuous variables. See Tables 1 and 2 for expansion of abbreviations.

Table 4. Baseline Characteristics Associated With the Timing of Therapeutic aPTT
Characteristic	aPTT <24 h (n = 325)	aPTT >24 h (n = 54)	OR	95% CI	P Value
Age, y (IQR)	67.0 (53.0–76.0)	74.0 (63.0–81.0)	1.03	1.01–1.06	.002
CAD	59 (18.2%)	20 (37.0%)	0.38	0.20–0.70	.003
Alternative diagnosis less likely	215 (66.2%)	26 (48.1%)	2.10	1.18–3.76	.014

Unit ORs are recorded for continuous variables. See Tables 1 and 2 for expansion of abbreviations.

Table 5. Multiple Logistic Regression Models of 30-d Mortality
Variable	Model 1			Model 2
Variable	OR	95% CI	P Value	OR	95% CI	P Value
Heparin in ED	0.22	0.08–0.60	.003	…	…	…
Therapeutic aPTT <24h	…	…	…	0.49	0.18–1.53	.207
ICU admission	3.65	1.47–8.84	.006	2.36	0.84–6.13	.098
Propensity score^a	0.43	0.04–3.75	.457	20.42	0.23–1368	.182

Receiving heparin in the ED and achieving a therapeutic aPTT within 24 h of arrival had significant covariance, so two models were created. See Tables 1 and 2 for expansion of abbreviations.
^aEach model used the propensity score for the respective first variable (ie, either the score for receiving heparin in the ED or achieving a therapeutic aPTT within 24 h).

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