The impact of preadmission oral bisphosphonate use on 30-day mortality following stroke: a population-based cohort study of 100,043 patients

Figures & data

Table 1 Characteristics of 100,043 first-time stroke patients, by preadmission use of oral bisphosphonate, Denmark, July 2004–December 2012

	AIS			ICH			SAH			Unspecified
	Current use	Recent use	No use	Current use	Recent use	No use	Current use	Recent use	No use	Current use	Recent use	No use
	N (%)	N (%)	N (%)	N (%)	N (%)	N (%)	N (%)	N (%)	N (%)	N (%)	N (%)	N (%)
Total	1,730 (100)	322 (100)	49,930 (100)	444 (100)	72 (100)	11,263 (100)	112 (100)	22 (100)	4,394 (100)	1,141 (100)	236 (100)	30,377 (100)
Female	1,460 (84.4)	269 (83.5)	22,964 (46)	384 (86.5)	61 (84.7)	5,231 (46.4)	94 (83.9)	18 (81.8)	2,503 (57.0)	960 (84.1)	201 (85.2)	14,885 (49.0)
Age, years
<60	46 (2.7)	10 (3.1)	10,354 (20.7)	23 (5.2)	4 (5.6)	2,834 (25.2)	9 (8.0)	3 (13.6)	2,422 (55.1)	28 (2.5)	5 (2.1)	5,146 (16.9)
60–69	205 (11.8)	40 (12.4)	11,487 (23.0)	61 (13.7)	10 (13.9)	2,381 (21.1)	31 (27.7)	5 (22.7)	921 (21.0)	141 (12.4)	25 (10.6)	6,096 (20.1)
70–79	591 (34.2)	88 (27.3)	13,277 (26.6)	150 (33.8)	27 (37.5)	2,878 (25.6)	40 (35.7)	5 (22.7)	583 (13.3)	353 (30.9)	78 (33.1)	8,306 (27.3)
≥80	888 (51.3)	184 (57.1)	14,812 (29.7)	210 (47.3)	31 (43.1)	3,170 (28.1)	32 (28.6)	9 (40.9)	468 (10.7)	619 (54.3)	128 (54.29)	10,829 (35.6)
Recent osteoporotic fracturea	102 (5.9)	19 (5.9)	661 (1.3)	27 (6.1)	5 (6.9)	168 (1.5)	7 (6.3)	1 (4.5)	39 (0.9)	86 (7.5)	18 (7.6)	488 (1.6)
Nonrecent osteoporotic fractureb	686 (39.7)	125 (38.8)	4,505 (9.0)	192 (43.2)	35 (48.6)	1,131 (10.0)	37 (33.0)	7 (31.8)	252 (5.7)	483 (42.3)	98 (41.5)	3,172 (10.4)
Simple osteoporosisc	363 (21.0)	69 (21.4)	654 (1.3)	91 (20.5)	11 (15.3)	147 (1.3)	30 (26.8)	5 (22.7)	45 (1.0)	197 (17.3)	49 (20.8)	431 (1.4)
Myocardial infarction	152 (8.8)	24 (7.5)	4,152 (8.3)	26 (5.9)	4 (5.6)	693 (6.2)	6 (5.4)	2 (9.1)	138 (3.1)	92 (8.1)	32 (13.6)	2,977 (9.8)
Angina pectoris	325 (18.8)	41 (12.7)	7,376 (14.8)	56 (12.6)	14 (19.4)	1,332 (11.8)	18 (16.1)	5 (22.7)	306 (7.0)	223 (19.5)	47 (19.9)	5,087 (16.7)
Atrial fibrillation or flutter	321 (18.6)	57 (17.7)	6,404 (12.8)	72 (16.2)	18 (25.0)	1,468 (13.0)	11 (9.8)	3 (13.6)	229 (5.2)	226 (19.8)	50 (21.2)	4,355 (14.3)
Heart valve disease	112 (6.5)	23 (7.1)	2,115 (4.2)	16 (3.6)	9 (12.5)	458 (4.1)	6 (5.4)	–	82 (1.9)	84 (7.4)	16 (6.8)	1,422 (4.7)
Claudication, intermittent	67 (3.9)	4 (12)	1,556 (3.1)	6 (1.4)	1 (1.4)	205 (1.8)	5 (4.5)	–	49 (1.1)	38 (3.3)	12 (5.1)	901 (3.0)
Venous tromboembolism	74 (4.3)	13 (4.0)	1,724 (3.5)	16 (3.6)	5 (6.9)	398 (3.5)	4 (3.6)	–	89 (2.0)	63 (5.5)	12 (5.1)	1,237 (4.1)
Obesity	42 (2.4)	7 (2.2)	1,966 (3.9)	10 (2.3)	1 (1.4)	367 (3.3)	5 (4.5)	1 (4.5)	134 (3.0)	31 (2.7)	9 (3.8)	1,262 (4.2)
Diabetes mellitus	169 (9.8)	34 (10.6)	6,360 (12.7)	32 (7.2)	12 (16.7)	1,096 (9.7)	4 (3.6)	2 (9.1)	252 (5.7)	103 (9.0)	23 (9.7)	4,533 (14.9)
Chronic kidney disease	41 (2.4)	4 (1.2)	1,173 (2.3)	6 (1.4)	2 (2.8)	316 (2.8)	3 (2.7)	–	67 (1.5)	19 (1.7)	11 (4.7)	954 (3.1)
Hypertension	568 (32.8)	94 (29.2)	12,222 (24.5)	140 (31.5)	26 (36.1)	2,583 (22.9)	29 (25.9)	5 (22.7)	617 (14.0)	359 (31.5)	92 (39.0)	7,954 (26.2)
Chronic pulmonary disease	552 (31.9)	102 (31.7)	9,848 (19.7)	147 (33.1)	21 (29.2)	2,058 (18.3)	39 (34.8)	11 (50.0)	767 (17.5)	383 (33.6)	93 (39.4)	6,429 (21.2)
Alcoholism-related disease	74 (4.3)	14 (4.3)	3,157 (6.3)	25 (5.6)	4 (5.6)	922 (8.2)	9 (8.0)	–	32 (7.4)	53 (4.6)	7 (3.0)	2,124 (7.0)
Dementia	99 (5.7)	10 (3.1)	1,389 (2.8)	32 (7.2)	2 (2.8)	430 (3.8)	5 (4.5)	1 (4.5)	54 (1.2)	67 (5.9)	9 (3.8)	1,218 (4.0)
Cancer	332 (19.2)	69 (21.4)	6,724 (13.5)	86 (19.4)	16 (22.2)	1,732 (15.4)	12 (10.7)	5 (22.7)	381 (8.7)	224 (19.6)	52 (22.0)	4,737 (15.6)
HRT	159 (9.2)	30 (9.3)	2,131 (4.3)	34 (7.7)	6 (8.3)	400 (3.6)	12 (10.7)	–	204 (4.6)	94 (8.2)	14 (5.9)	1,238 (4.1)
ACE-I or ARB	511 (29.5)	75 (23.3)	13,010 (26.1)	115 (25.9)	22 (30.6)	2,266 (20.1)	29 (25.9)	5 (22.7)	637 (14.5)	299 (26.2)	48 (20.3)	7,865 (25.9)
Beta-blockers	425 (24.6)	62 (19.3)	10,064 (20.2)	86 (19.4)	19 (26.4)	1,808 (16.1)	16 (14.3)	3 (13.6)	394 (9.0)	259 (22.7)	61 (25.8)	6,318 (20.8)
Calcium channel blockers	317 (18.3)	59 (18.3)	7,723 (15.5)	48 (10.8)	9 (12.5)	1,106 (9.8)	19 (17.0)	4 (18.2)	342 (7.8)	207 (18.1)	40 (16.9)	4,824 (15.9)
Diuretics	645 (37.3)	106 (32.9)	12,637 (25.3)	138 (31.1)	21 (29.2)	2,359 (20.9)	33 (29.5)	6 (27.3)	550 (12.5)	475 (41.6)	94 (39.8)	9,286 (30.6)
Nitrates	48 (2.8)	9 (2.8)	831 (1.7)	7 (1.6)	–	140 (1.2)	2 (1.8)	–	26 (0.6)	43 (3.8)	10 (4.2)	665 (2.2)
Statins	344 (19.9)	47 (14.6)	8,079 (16.2)	71 (16.0)	12 (16.7)	1,566 (13.9)	19 (17.0)	4 (18.2)	436 (9.9)	199 (17.4)	44 (18.6)	4,876 (16.1)
Acetylsalicylic acid	578 (33.4)	75 (23.3)	11,351 (22.7)	136 (30.6)	21 (29.2)	2,309 (20.5)	28 (25.0)	3 (13.6)	427 (9.7)	370 (32.4)	69 (29.2)	7,832 (25.8)
Clopidogrel	49 (2.8)	5 (1.6)	928 (1.9)	4 (0.9)	2 (2.8)	174 (1.5)	3 (2.7)	1 (4.5)	40 (0.9)	27 (2.4)	12 (5.1)	597 (2.0)
Vitamin K antagonists	83 (4.8)	20 (6.2)	2,123 (4.3)	52 (11.7)	11 (15.3)	1,128 (10.0)	7 (6.3)	1 (4.5)	150 (3.4)	93 (8.2)	19 (8.1)	1,640 (5.4)
Systemic glucocorticoids	277 (16.0)	43 (13.4)	2,002 (4.0)	59 (13.3)	4 (5.6)	402 (3.6)	12 (10.7)	4 (18.2)	110 (2.5)	195 (17.1)	40 (16.9)	1,497 (4.9)
SSRIs	238 (13.8)	44 (13.7)	3,973 (8.0)	66 (14.9)	18 (25.0)	1,052 (9.3)	12 (10.7)	2 (9.1)	306 (7.0)	195 (17.1)	29 (12.3)	3,033 (10.0)
NSAIDs	240 (13.9)	41 (12.7)	5,101 (10.2)	64 (14.4)	7 (9.7)	1,142 (10.1)	22 (19.6)	6 (27.3)	461 (10.5)	173 (15.2)	34 (14.4)	3,544 (11.7)
CT scan	1,558 (90.1)	292 (90.7)	44,238 (88.6)	400 (90.1)	62 (86.1)	10,076 (89.5)	106 (94.6)	18 (81.8)	3,990 (90.8)	880 (77.1)	166 (70.3)	24,118 (79.4)
MR scan	151 (8.7)	35 (10.9)	7,861 (15.7)	19 (4.3)	5 (6.9)	879 (7.8)	3 (2.7)	2 (9.1)	268 (6.1)	47 (4.1)	4 (1.7)	1,970 (6.5)

Notes:

a Fracture ≤6 months prior to the stroke;

b fracture >6 months prior to the stroke;

c hospital-diagnosed osteoporosis without fracture, – indicates that no event has occured.

Abbreviations: AIS, acute ischemic stroke; ICH, intracerebral hemorrhage; SAH, subarachnoidal hemorrhage; HRT, hormone replacement therapy; ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; SSRIs, selective serotonin reuptake inhibitors; NSAIDs, nonsteroidal anti-inflammatory drugs; CT, computed tomography; MR, magnetic resonance.

Table 2 Preadmission bisphosphonate use and 30-day mortality risk and mortality rate ratios following stroke

	Mortality risk % (95% CI)	MRRs (95% CI) unadjusted	MRRs (95% CI) adjusteda	PS-matched (95% CI)
Stroke overall
No useb	13.9 (13.7; 14.2)	1 (reference)	1 (reference)	1 (reference)
Current usec	19.2 (17.9; 20.5)	1.42 (1.31; 1.53)	0.97 (0.89; 1.05)	0.94 (0.85; 1.05)
Recent used	20.2 (17.3; 23.5)	1.49 (1.26; 1.77)	0.99 (0.83; 1.18)	1.12 (0.87; 1.43)
New usee	20.8 (18.0; 23.9)	1.55 (1.32; 1.83)	1.06 (0.90; 1.25)	1.11 (0.88; 1.40)
Long-term usef	18.7 (17.3; 20.3)	1.38 (1.26; 1.51)	0.94 (0.85; 1.03)	0.98 (0.86; 1.10)
AIS
No use	8.5 (8.2; 8.7)	1 (reference)	1(reference)	1 (reference)
Current use	11.9 (10.4; 13.5)	1.43 (1.24; 1.64)	0.87 (0.75; 1.01)	0.90 (0.74; 1.08)
Recent use	14.7 (11.2; 19.0)	1.80 (1.35; 2.40)	1.12 (0.84; 1.50)	1.25 (0.82; 1.91)
New use	11.5 (8.6; 15.4)	1.39 (1.02; 1.89)	0.80 (0.58; 1.10)	0.97 (0.63; 1.50)
Long-term use	12.0 (10.4; 13.8)	1.44 (1.23; 1.68)	0.88 (0.75; 1.04)	1.06 (0.85; 1.33)
ICH
No use	34.5 (33.7; 35.4)	1 (reference)	1(reference)	1 (reference)
Current use	43.2 (38.8; 48.0)	1.37 (1.19; 1.58)	1.05 (0.90; 1.23)	1.02 (0.83; 1.24)
Recent use	43.4 (32.8; 55.6)	1.37 (0.96; 1.95)	1.03 (0.72; 1.47)	0.98 (0.60; 1.61)
New use	44.3 (35.1; 54.8)	1.42 (1.05; 1.92)	1.07 (0.79; 1.46)	1.29 (0.83; 2.00)
Long-term use	42.9 (37.9; 48.3)	1.36 (1.15; 1.60)	1.04 (0.88; 1.24)	0.99 (0.79; 1.24)
SAH
No use	23.2 (22.0; 24.5)	1 (reference)	1 (reference)	1 (reference)
Current use	40.3 (31.9; 50.0)	1.82 (1.35; 2.45)	1.15 (0.83; 1.61)	1.44 (0.92; 2.26)
Recent use	31.8 (16.6; 55.4)	1.51 (0.72; 3.17)	0.97 (0.46; 2.08)	1.49 (0.48; 4.61)
New use	50.0 (32.2; 70.9)	2.38 (1.35; 4.20)	1.52 (0.85; 2.74)	1.64 (0.68; 3.97)
Long-term use	37.6 (28.4; 48.7)	1.67 (1.18; 2.37)	1.05 (0.71; 1.54)	1.27 (0.76; 2.13)
Unspecified stroke
No use	14.0 (13.6; 14.4)	1 (reference)	1(reference)	1 (reference)
Current use	18.8 (16.6; 21.2)	1.39 (1.21; 1.59)	0.94 (0.81; 1.09)	0.88 (0.73; 1.06)
Recent use	19.5 (15.0; 25.2)	1.42 (1.06; 1.90)	0.91 (0.68; 1.22)	1.04 (0.69; 1.58)
New use	21.7 (17.1; 27.4)	1.63 (1.25; 2.13)	1.22 (0.93; 1.59)	1.09 (0.75; 1.60)
Long-term use	17.9 (15.6; 20.6)	1.32 (1.12; 1.54)	0.86 (0.73; 1.02)	0.86 (0.70; 1.07)

Notes:

a Adjusted for sex, age groups, recent osteoporotic fracture (≤6 months), nonrecent osteoporotic fracture (>6 months), simple osteoporosis (no fracture), myocardial infarction, angina pectoris, atrial fibrillation or flutter, heart valve disease, intermittent arterial claudication, venous thromboembolism, obesity, diabetes, chronic kidney disease, hypertension, chronic obstructive pulmonary disease (includes inhalation medications for chronic pulmonary obstructive disease), alcoholism-related diseases, dementia, cancer, and use of cardiovascular drugs (angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, beta-blockers, calcium channel blockers, diuretics, nitrates, statins, acetylsalicylic acid, clopidogrel, and vitamin K antagonists), hormone replacement therapy, systemic glucocorticoids, nonsteroidal anti-inflammatory drugs, and selective serotonin receptor inhibitors;

b no prescription redemption within 0–180 days before admission date;

c prescription redemption within 90 days before admission date;

d prescription redemption within 90–180 days before admission date;

e prescription redemption within 90 days before admission day and no additional prescriptions;

f prescription redemption within 90 days before admission date and at least one additional prescription 90–180 days prior to admission and eventually additional prescriptions before this period.

Abbreviations: MRRs, mortality rate ratios; CI, confidence interval; PS-matched, propensity-score-matched; AIS, acute ischemic stroke; ICH, intracerebral hemorrhage; SAH, subarachnoid hemorrhage.