Temporal trends in the use of antithrombotics at admission

Figures & data

Table 1. Baseline characteristics

	Users n = 50,625	Non-users n = 103,422	p-value
Female sex, n (%)	34,579 (68)	72,750 (70)	< 0.001
Age in years, mean (SD)	81.5 (8.8)	76.7 (13.5)	< 0.001^a
Charlson comorbidity index median (range)	1 (0–16)	0 (0–19)	< 0.001^a
n (%)
0	13,025 (26)	59,613 (58)	< 0.001
1	12,847 (25)	19,615 (19)
2	10,559 (21)	13,004 (13)
≥ 3	14,194 (28)	11,190 (11)
Atrial fibrillation/flutter, n (%)	10,251 (20)	3,743 (4)	< 0.001
Ischemic heart disease, n (%)	14,632 (29)	6,127 (6)	< 0.001
Valvular disease, n (%)	3,200 (6)	1,534 (2)	< 0.001
Artificial heart valve, n (%)	619 (1)	111 (0)	< 0.001
Stroke/TCI^b, n (%)	4,206 (8)	1,546 (2)	< 0.001
Arterial thromboembolism, n (%)	430 (1)	173 (0)	< 0.001
Deep vein thrombosis, n (%)	1,746 (4)	1,537 (2)	< 0.001
Pulmonary embolism, n (%)	909 (2)	494 (1)	< 0.001
Fracture type, n (%)
Femoral neck	30,027 (59)	60,880 (59)
Pertrochanteric	17,512 (35)	35,378 (34)
Subtrochanteric	3,086 (6)	7,164 (7)	< 0.001
30-day mortality, n (%)	6,545 (13)	8,785 (9)	< 0.001

a Mann-Whitney U-test.

b TCI: transient cerebral ischemia.

Figure 1. Proportion of hip fracture patients who used antithrombotics, 1996 to 2012. Panel A shows the overall results, whereas panels B and C show the results for the individual anticoagulants and antiplatelet drugs, respectively. w/o ASA: without patients who used only acetylsalicylic acid.

* p-value for trend <0.001.

Table 2. Temporal trends in the use of antithrombotics, 1996 to 2012

Drug n, %	1996 (11,399)	1997 (10059)	1998 (9681)	1999 (9697)	2000 (9426)	2001 (9464)	2002 (9253)	2003 (8901)	2004 (8976)	2005 (8949)	2006 (8598)	2007 (8612)	2008 (8607)	2009 (8208)	2010 (8479)	2011 (8079)	2012 (7659)	P for trend
Any antithrom.	2,140	2,166	2,226	2,478	2,553	2,676	2,852	3,024	3,127	3,273	3,366	3,470	3,600	3,405	3,546	3,417	3,306
50,625, 32.9%	18.8%	21.5%	23.0%	25.6%	27.1%	28.3%	30.8%	34.0%	34.8%	36.6%	39.2%	40.3%	41.8%	41.5%	41.8%	42.3%	43.2%	< 0.001
Any anticoag.	134	142	180	199	210	234	280	294	326	410	441	490	501	478	521	563	616
6,020, 3.9%	1.2%	1.4%	1.9%	2.1%	2.2%	2.5%	3.0%	3.3%	3.6%	4.6%	5.1%	5.7%	5.8%	5.8%	6.1%	7.0%	8.1%	< 0.001
Vit. K ant.	134	142	180	199	210	234	280	294	326	410	441	490	501	478	520	558	567
5,964, 3.9%	1.2%	1.4%	1.9%	2.1%	2.2%	2.5%	3.0%	3.3%	3.6%	4.6%	5.1%	5.7%	5.8%	5.8%	6.1%	6.9%	7.4%	< 0.001
NOAC	–	–	–	–	–	–	–	–	–	–	–	–	0	0	1	6	68
75, 0.1%															0.0%	0.1%	0.9%	< 0.001
Any antiplat.	2,022	2,037	2,070	2,301	2,376	2,472	2,623	2,792	2,890	2,987	3,049	3,124	3,273	3,093	3,191	3,072	2,860
46,240, 30.0%	17.7%	20.3%	21.4%	23.7%	25.2%	26.1%	28.4%	31.4%	32.2%	33.4%	35.5%	36.3%	38.0%	37.7%	37.7%	38.0%	37.3%	< 0.001
ASA	2,021	2,030	2,061	2,258	2,311	2,379	2,529	2,663	2,715	2,748	2,807	2,860	2,995	2,809	2,855	2,740	2,471
43,259, 28.1%	17.7%	20.2%	21.3%	23.3%	24.5%	25.2%	27.3%	29.9%	30.3%	30.7%	32.7%	33.2%	34.8%	34.2%	33.7%	33.9%	32.3%	< 0.001
Clopidogrel	–	–	0	1	5	21	33	67	98	129	113	128	190	189	221	308	396
1,899, 1.2%				0.0%	0.1%	0.2%	0.4%	0.8%	1.1%	1.4%	1.3%	1.5%	2.2%	2.3%	2.6%	3.8%	5.2%	< 0.001
Dipyridamole	4	15	34	132	215	297	371	411	420	450	444	473	492	480	502	474	429
5,645, 3.7%	0.0%	0.2%	0.4%	1.4%	2.3%	3.1%	4.0%	4.6%	4.7%	5.0%	5.2%	5.5%	5.7%	5.9%	5.9%	5.9%	5.6%	< 0.001
Combination	–	–	–	–	–	–	0	25	86	164	169	207	213	182	200	148	123
1,518, 1.0%								0.3%	1.0%	1.8%	2.0%	2.4%	2.5%	2.2%	2.4%	1.8%	1.6%	< 0.001

The total number of hip fracture patients is shown under each year.

Antithrom: antithrombotics; Anticoag: anticoagulant; Vit. K. ant.: vitamin K antagonist; NOAC: new oral anticoagulants; antiplat.: antiplatelet; ASA: acetylsalicylic acid; Combination: combination antiplatelets; -: drug not marketed.

Figure 2. Proportion of hip fracture patients who used more than 1 antithrombotic from 1996 to 2012. * p-value for trend <0.001.

Table 3. Multivariable analysis – factors associated with the use of antithrombotics

	Any antithrombotic		Any anticoagulant		Any antiplatelet
	RR (95% CI)	p-value	RR (95% CI)	p-value	RR (95% CI)	p-value
Year (per year)^a	1.03 (1.03–1.04)	< 0.001	1.09 (1.09–1.10)	< 0.001	1.03 (1.02–1.04)	< 0.001
Gender (men)	1.13 (1.11–1.14)	< 0.001	1.40 (1.34–1.46)	< 0.001	1.11 (1.09–1.12)	< 0.001
Age (per 10 years)	1.34 (1.33–1.35)	< 0.001	1.14 (1.07–1.21)	< 0.001	1.37 (1.35–1.38)	< 0.001
CCI (per unit)	1.15 (1.14–1.16)	< 0.001	1.18 (1.16–1.20)	< 0.001	1.15 (1.15–1.16)	< 0.001

The Poisson regression model included all 4 variables shown in the table.

a Calender year was included as a variable ranging from 0 to 16 (1996 = 0).

Table 4. Use of antithrombotics in the general Danish population in 1999 and 2012

	Age ≥18 years			Age ≥60 years
	1999^a	2012		1999^a	2012
	(n = 4,180,601)	(n = 4,378,227)	p-value	(n = 1,045,579)	(n = 1,318,937)	p-value
Vit. K ant.	1.0% (41,091)	2.1% (92,348)	< 0.001	2.8% (29,373)	5.8% (75,889)	< 0.001
NOAC	0.0% (248)	0.5% (20,177)	< 0.001	0.0% (2)	0.2% (2,969)	< 0.001
ASA	5.6% (232,128)	9.3% (408,286)	< 0.001	18.6% (194,409)	25.4% (335,366)	< 0.001
Clopidogrel	0.0% (1,615)	1.5% (64,549)	< 0.001	0.1% (902)	3.9% (51,438)	< 0.001
Dipyridamole	0.4% (15,607)	0.9% (39,495)	< 0.001	1.2% (12,232)	2.6% (33,638)	< 0.001
Combination	0.0% (323)	0.3% (13,018)	< 0.001	0.0% (224)	0.8% (10,836)	< 0.001

a For NOAC the first year the drug was marketed was 2008, and for the combination antiplatelets it was 2002; the numbers indicated are from these years.

ASA: acetylsalicylic acid; Vit. K ant.: vitamin K antagonist; NOAC: new oral anticoagulants; Combination: combination antiplatelet drugs.