Ischaemic cardiovascular risk and prescription of non-steroidal anti-inflammatory drugs for musculoskeletal complaints

Figures & data

Table I. Baseline characteristics in the study population.

		Per CV risk group
	Total (n = 474 201) n (%)	Low CV risk (n = 365 534) n (%)	Moderate CV risk (n = 67 184) n (%)	High CV risk (n = 41 483) n (%)
Age (mean ± SD)	46.6 ± 17.4	42.2 ± 15.5	58.9 ± 14.7	65.3 ± 14.5
Age category:
18–35 years 36–50 years 51–65 years > 65 years	144 797 (30.5) 147 497 (31.1) 108 132 (22.8) 73 775 (15.6)	138 809 (38.0) 127 403 (34.9) 69 526 (19.0) 29 796 (8.2)	4 532 (6.7) 14 773 (22.0) 25 735 (38.3) 22 144 (33.0)	1 456 (3.5) 5 321 (12.8) 12 871 (31.0) 21 835 (52.6)
Female	256 015 (54.0)	196 550 (53.8)	38 906 (57.9)	20 559 (49.6)
NSAID prescription in six months prior to diagnosis	37 637 (7.9)	26 472 (7.2)	6 831 (10.2)	4 334 (10.4)
MSK complaint episode: Symptomatic diagnosis
Back/neck Upper extremity Lower extremity Generalized/other	108 213 (22.8) 82 026 (17.3) 66 107 (13.9) 59 986 (12.6)	86 957 (24.1) 63 366 (17.3) 49 802 (13.6) 46 572 (12.7)	12 641 (18.8) 11 810 (17.6)^NS1 10 003 (14.9) 8 035 (12.0)	7 615 (18.4) 6 850 (16.5) 6 302 (15.2) 5 379 (13.0)^NS2
Arthritis	21 529 (4.5)	11 548 (3.2)	5 739 (8.5)	4 242 (10.2)
Inflammatory arthritis Osteoarthritis Gout	4 676 (1.0) 11 211 (2.4) 5 642 (1.2)	2 874 (0.8) 5 944 (1.6) 2 730 (0.7)	1 045 (1.6) 3 056 (4.5) 1 638 (2.4)	757 (1.8) 2 211 (5.3) 1 274 (3.1)
Radiculopathy Trauma Other	25 409 (5.4) 55 211 (11.6) 55 720 (11.8)	19 180 (5.2) 45 586 (12.5) 41 523 (11.4)	3 822 (5.7) 6 064 (9.0) 9 070 (13.5)	2 407 (5.8) 3 561 (8.6) 5 127 (12.4)
Individual CV risk factors:^3
Diabetes Hypertension Hyperlipidaemia MI/AP Stroke/TIA PAD	28 597 (6.0) 63 841 (13.5) 30 600 (6.5) 27 118 (5.7) 14 118 (3.0) 5 715 (1.2)	– – – – – –	20 847 (31.0) 46 077 (68.6) 18 129 (27.0) – – –	7 750 (18.7) 17 764 (42.8) 12 471 (30.1) 27 118 (65.4) 14 118 (34.0) 5 715 (13.8)
UGI risk group:
Low UGI risk Moderate UGI risk High UGI risk	335 556 (70.8) 63 843 (13.5) 74 802 (15.8)	305 168 (83.5) 34 692 (9.5) 25 674 (7.0)	22 003 (32.8) 21 058 (31.3) 24 123 (35.9)	8 385 (20.2) 8 093 (19.5) 25 005 (60.3)
Renal insufficiency	285 (0.1)	27 (0.01)	118 (0.2)	140 (0.3)

Notes: CV: cardiovascular; NSAID: non-steroidal anti-inflammatory drug; NS: non-significant; MSK: musculoskeletal; MI: myocardial infarction; AP: angina pectoris; TIA:transient ischaemic attack; PAD: peripheral arterial disease; UGI: upper gastrointestinal. Comparisons were made for the moderate versus the low CV risk group and for the high versus the low CV risk group. All comparisons between moderate or high CV risk patients and low CV risk patients were statistically significant (p-value < 0.05), unless otherwise stated with the letters ‘NS’: non-significant. ¹Comparison with low CV risk patients not statistically significant, p-value 0.13. ²Comparison with low CV risk patients not statistically significant, p-value 0.19. ³Risk factors used to define low, moderate, and high CV risk groups.

Table II. Predictors of prescription of nsNSAIDs and coxibs.

				OR (95% CI)
	No NSAID prescribed (n = 352 032) n (%^1)	nsNSAID prescribed (n = 115 713) n (%^1)	Coxib prescribed (n = 6 456) n (%^1)	nsNSAID vs. no NSAID	coxib vs. no NSAID
Age category:
18–35 years 36–50 years 51–65 years > 65 years	114 077 (78.8) 105 154 (71.3) 76 359 (70.6) 56 442 (76.5)	29 948 (20.7) 40 815 (27.7) 29 688 (27.5) 15 262 (20.7)	772 (0.5) 1 528 (1.0) 2 085 (1.9) 2 071 (2.8)	1 (ref.) 1.5 (1.5–1.5) 1.5 (1.5–1.5) 1.0 (1.0–1.1)	1 (ref.) 2.2 (2.0–2.3) 4.0 (3.7–4.4) 5.4 (5.0–5.9)
Gender:
Male Female	159 766 (73.2) 192 266 (75.1)	55 909 (25.6) 59 804 (23.4)	2 511 (1.2) 3 945 (1.5)	1 (ref.) 0.9 (0.9–0.9)	1 (ref.) 1.3 (1.2–1.4)
NSAID prescription in six months prior	24 860 (66.1)	11 688 (31.1)	1 089 (2.9)	1.5 (1.4–1.5)	2.7 (2.5–2.9)
MSK complaint:
Trauma Symptomatic diagnosis	49 345 (89.4)	5 605 (10.2)	261 (0.5)	1 (ref.)	1 (ref.)
Back/neck Upper extremity Lower extremity Generalized/other	70 464 (65.1) 56 150 (68.5) 54 211 (82.0) 46 926 (78.2)	36 477 (33.7) 24 558 (29.9) 11 109 (16.8) 12 308 (20.5)	1 272 (1.2) 1 318 (1.6) 787 (1.2) 752 (1.3)	4.6 (4.4–4.7) 3.9 (3.7–4.0) 1.8 (1.7–1.9) 2.3 (2.2–2.4)	3.4 (3.0–3.9) 4.4 (3.9–5.1) 2.8 (2.4–3.2) 3.0 (2.6–3.5)
Arthritis	13 943 (64.8)	6 545 (30.4)	1 041 (4.8)	4.1 (4.0–4.3)	14.1 (12.3–16.2)
Inflammatory arthritis Osteoarthritis Gout	3 027 (64.7) 8 239 (73.5) 2 677 (47.4)	1 386 (29.6) 2 349 (21.0) 2 810 (49.8)	263 (5.6) 623 (5.6) 155 (2.7)	4.0 (3.8–4.3) 2.5 (2.4–2.6) 9.2 (8.7–9.8)	16.4 (13.8–19.6) 14.3 (12.3–16.6) 10.9 (8.9–13.4)
Radiculopathy Other	16 699 (65.7) 44 294 (79.5)	8 269 (32.5) 10 842 (19.5)	441 (1.7) 584 (1.0)	4.4 (4.2–4.5) 2.2 (2.1–2.2)	5.0 (4.3–5.8) 2.5 (2.2–2.9)
Individual CV risk factors:
No CV risk factors Diabetes Hypertension Hyperlipidaemia MI/AP Stroke/TIA PAD	270 758 (74.1) 21 113 (73.8) 48 168 (75.6) 23 118 (75.5) 21 113 (77.9) 11 209 (79.4) 4 484 (78.5)	90 615 (24.8) 6 864 (24.0) 14 261 (22.4) 6 853 (22.4) 5 356 (19.8) 2 626 (18.6) 1 117 (19.5)	4 161 (1.1) 620 (2.2) 1 312 (2.0) 629 (2.1) 649 (2.4) 283 (2.0) 114 (2.0)	1 (ref.) 1.0 (1.0–1.0) 0.9 (0.9–0.9) 0.9 (0.9–0.9) 0.8 (0.7–0.8) 0.7 (0.7–0.7) 0.7 (0.7–0.8)	1 (ref.) 1.9 (1.8–2.1) 1.8 (1.7–1.9) 1.8 (1.6–1.9) 2.0 (1.8–2.2) 1.6 (1.5–1.9) 1.7 (1.4–2.0)
CV risk group:
Low CV risk Moderate CV risk High CV risk	270 758 (74.1) 48 970 (72.9) 32 304 (77.9)	90 615 (24.8) 16 852 (25.1) 8 246 (19.9)	4 161 (1.1) 1 362 (2.0) 933 (2.2)	1 (ref.) 1.0 (1.0–1.1) 0.8 (0.7–0.8)	1 (ref.) 1.8 (1.7–1.9) 1.9 (1.8–2.0)
UGI risk group:
Low UGI risk Moderate UGI risk High UGI risk	248 705 (74.1) 45 724 (71.6) 57 603 (77.0)	83 753 (25.0) 16 792 (26.3) 15 168 (20.3)	3 098 (0.9) 1 327 (2.1) 2 031 (2.7)	1 (ref.) 1.1 (1.1–1.1) 0.8 (0.8–0.8)	1 (ref.) 2.3 (2.2–2.5) 2.8 (2.7–3.0)
Renal insufficiency:
No renal insufficiency Renal insufficiency	351 801 (74.2) 231 (81.1)	115 666 (24.4) 47 (16.5)	6 449 (1.4) 7 (2.5)	1 (ref.) 0.6 (0.5–0.8)	1 (ref.) 1.7 (0.8–3.5)

Notes: nsNSAID: non-selective non-steroidal anti-inflammatory drug; NSAID: non-steroidal anti-inflammatory drug; MSK: musculoskeletal; CV: cardiovascular; MI: myocardial infarction; AP: angina pectoris; TIA: transient ischaemic attack; PAD: peripheral arterial disease; UGI: upper gastrointestinal. ¹Row percentage.

Table III. Prescription of coxibs and nsNSAIDs versus no NSAID in moderate and high CV risk patients versus low CV risk patients per UGI risk group.

						OR (95% CI)		Adj. OR (95% CI)^2
UGI risk group	CV risk group	Number of patients	No NSAID n (%^1)	nsNSAID n (%^1)	Coxib n (%^1)	nsNSAID vs. no NSAID	coxib vs. no NSAID	nsNSAID vs. no NSAID	coxib vs. no NSAID
Low	Low	305 168	226 617 (74.3)	75 915 (24.9)	2 636 (0.9)	1 (ref.)	1 (ref.)	1 (ref.)	1 (ref.)
	Moderate	22 003	15 842 (72.0)	5 836 (26.5)	325 (1.5)	1.1 (1.1–1.1)	1.7 (1.5–1.9)	0.9 (0.9–0.9)	1.1 (1.0–1.2)
	High	8 385	6 246 (74.5)	2 002 (23.9)	137 (1.6)	1.0 (0.9–1.0)	1.9 (1.6–2.3)	0.8 (0.8–0.8)	1.3 (1.1–1.5)
Moderate	Low	34 692	24 776 (71.4)	9 164 (26.4)	752 (2.2)	1 (ref.)	1 (ref.)	1 (ref.)	1 (ref.)
	Moderate	21 058	14 945 (71.0)	5 708 (27.1)	405 (1.9)	1.0 (1.0–1.1)	0.9 (0.8–1.0)	1.0 (1.0–1.1)	0.9 (0.8–1.2)
	High	8 093	6 003 (74.2)	1 920 (23.7)	170 (2.1)	0.9 (0.8–0.9)	1.0 (0.8–1.1)	0.8 (0.8–0.9)	1.0 (0.8–1.2)
High	Low	25 674	19 365 (75.4)	5 536 (21.6)	773 (3.0)	1 (ref.)	1 (ref.)	1 (ref.)	1 (ref.)
	Moderate	24 123	18 183 (75.4)	5 308 (22.0)	632 (2.6)	1.0 (1.0–1.1)	0.9 (0.8–1.0)	1.0 (1.0–1.1)	0.9 (0.8–1.0)
	High	25 005	20 055 (80.2)	4 324 (17.3)	626 (2.5)	0.8 (0.7–0.8)	0.8 (0.7–0.9)	0.8 (0.7–0.8)	0.8 (0.7–0.9)

Notes: nsNSAID: non-selective non-steroidal anti-inflammatory drug; NSAID: non-steroidal anti-inflammatory drug; CV: cardiovascular; UGI: upper gastrointestinal. ¹Row percentage. ²Adjusted for age, gender, prescription of NSAIDs in six months prior, type of MSK complaint, and presence of renal insufficiency.

Figure 1. Percentage of patients with a high CV risk and with a low CV risk prescribed an nsNSAID or a coxib per year.

Table IV. Prescription of coxibs and nsNSAIDs versus no NSAID in moderate and high CV risk patients versus low CV risk patients per time period.

						Adj. OR (95% CI)^2
Time period	CV risk group	Number of patients	No NSAID n (%^1)	nsNSAID n (%^1)	Coxib n (%^1)	nsNSAID vs. no NSAID	coxib vs. no NSAID
2000–2004	Low	181 443	127 912 (70.5)	50 670 (27.9)	2 861 (1.6)	1 (ref.)	1 (ref.)
	Moderate	27 421	18 939 (69.1)	7 703 (28.1)	779 (2.8)	1.0 (1.0–1.1)	1.9 (1.7–2.1)
	High	18 574	13 619 (73.3)	4 349 (23.4)	606 (3.3)	0.8 (0.8–0.8)	2.0 (1.8–2.2)
2005–2010	Low	184 091	142 846 (77.6)	39 945 (21.7)	1 300 (0.7)	1 (ref.)	1 (ref.)
	Moderate	39 763	30 031 (75.5)	9 149 (23.0)	583 (1.5)	1.1 (1.1–1.1)	2.3 (1.9–2.4)
	High	22 909	18 685 (81.6)	3 897 (17.0)	327 (1.4)	0.8 (0.7–0.8)	1.9 (1.7–2.2)

Notes: CV: cardiovascular; NSAID: non-steroidal anti-inflammatory drug; nsNSAID: non-selective non-steroidal anti-inflammatory

drug. ¹Row percentage. ²Adjusted for year of MSK complaint episode within the time period.