Discontinuation of low-dose acetylsalicylic acid therapy in UK primary care: incidence and predictors in patients with cardiovascular disease

Figures & data

Table 1 Patient characteristics, ASA indication, and reason for termination of follow-up

Characteristic	Total (n = 35,639) n (%)
Age at start date (years)
50–64	13,092 (36.7)
65–74	12,606 (35.4)
75–84	9941 (27.9)
Sex
Male	19,962 (56.0)
Female	15,677 (44.0)
ASA indication
Myocardial infarction	8372 (23.5)
Unstable angina	680 (1.9)
Chronic ischemic heart disease	15,013 (42.1)
Cerebrovascular disease	11,574 (32.5)
Cardiovascular risk factors
Hypertensionb	18,443 (51.7)
Hyperlipidemiab	7714 (21.6)
Current smoker	6861 (19.3)
Former smoker	11,834 (33.2)
Reasons for termination of follow-up
ASA discontinuation	11,729 (32.9)
Met exclusion criteriaa	1989 (5.6)
Reached 85 years of age	1912 (5.4)
Death	2050 (5.8)
End of study period	17,959 (50.4)

Notes:

a Alcohol abuse, alcohol-related disease or cancer diagnosis;

b diagnosed prior to the start date.

Abbreviation: ASA, acetylsalicylic acid.

Figure 1 Kaplan–Meier survival curves illustrating acetylsalicylic acid discontinuation over the study period, in the whole cohort (A) and according to ASA indication (B).

Abbreviations: ASA, acetylsalicylic acid; CeVD, cerebrovascular disease; IHD, ischemic heart disease; MI, myocardial infarction; UA, unstable angina.

Table 2 Association between patient characteristics and ASA discontinuation risk

	ASA discontinuers (n = 11,729) n (%)	ASA non-discontinuers (n = 23,910) n (%)	Adjusted ORa (95% CI)
Age at index date (years)
50–64	4288 (36.6)	6920 (28.9)	1.00 (–)
65–74	3836 (32.7)	8498 (35.5)	0.79 (0.75–0.84)
75–84	3605 (30.7)	8492 (35.5)	0.73 (0.69–0.78)
Sex
Men	6318 (53.9)	13,644 (57.1)	1.00 (–)
Women	5411 (46.1)	10,266 (42.9)	1.18 (1.12–1.24)
BMI (kg/m^2)b
13–19	304 (2.6)	637 (2.7)	0.90 (0.78–1.05)
20–24	2881 (24.6)	5707 (23.9)	1.00 (–)
25–29	4165 (35.5)	8666 (36.2)	0.97 (0.91–1.03)
≥30	2479 (21.1)	5183 (21.7)	0.95 (0.89–1.02)
Unknown	1900 (16.2)	3717 (15.6)	1.03 (0.95–1.12)
Smoking statusb
Non-smoker	4951 (42.2)	9981 (41.7)	1.00 (–)
Current	2448 (20.9)	4413 (18.5)	1.13 (1.06–1.20)
Former	3648 (31.1)	8186 (34.2)	0.92 (0.87–0.98)
Unknown	682 (5.8)	1330 (5.6)	1.12 (1.00–1.25)
Alcohol use (units/week)b
0–1	5613 (47.9)	11,437 (47.8)	1.00 (–)
2–15	3478 (29.7)	7045 (29.5)	0.99 (0.94–1.05)
16–42	983 (8.4)	1987 (8.3)	0.98 (0.90–1.08)
≥43	8 (0.1)	27 (0.1)	0.62 (0.27–1.40)
Unknown	1647 (14.0)	3414 (14.3)	0.92 (0.84–1.00)
Number of PCP visitsc
0–5	3664 (31.2)	6951 (29.1)	1.00 (–)
6–10	3440 (29.3)	7019 (29.4)	0.95 (0.89–1.09)
≥11	4625 (39.4)	9940 (41.6)	0.94 (0.89–1.00)
Referral and hospitalizationc
No	9958 (84.9)	18,839 (78.8)	1.00 (–)
Yes	1771 (15.1)	5071 (21.2)	0.69 (0.65–0.73)
Number of concomitant medicationsd
0–2	4662 (39.8)	6443 (27.0)	1.00 (–)
3–5	3862 (32.9)	9605 (40.2)	0.61 (0.57–0.64)
6–10	2586 (22.1)	6494 (27.2)	0.64 (0.60–0.68)
≥11	619 (5.3)	1368 (5.7)	0.74 (0.66–0.83)
ASA indication
Myocardial infarction	2007 (17.1)	6365 (26.6)	1.00 (–)
Unstable angina	233 (2.0)	447 (1.9)	1.71 (1.44–2.03)
Chronic IHD	5687 (48.5)	9326 (39.0)	1.86 (1.74–1.98)
Cerebrovascular disease	3802 (32.4)	7772 (32.5)	1.40 (1.31–1.50)

Notes:

a Relative to the indicated category (1.00 [–]). Adjusted for age at the index date, sex, BMI at the start date, time between the start and index dates, smoking history at the start date, number of PCP visits from 15 days to 1 year prior to the start date, referral or hospitalization (yes or no) from 15 days to 1 year prior to the start date, ASA indication and number of co-medications taken in the 60 days prior to the index date;

b at the start date;

c from 15 days to 1 year prior to the start date;

d within 60 days prior to the index date.

Abbreviations: ASA, acetylsalicylic acid; CI, confidence interval; BMI, body mass index; IHD, ischemic heart disease; OR, odds ratio; PCP, primary care physician.

Table 3 Association between comorbiditiesa and ASA discontinuation risk

	ASA discontinuers (n = 11,729) n (%)	ASA non-discontinuers (n = 23,910) n (%)	Adjusted ORb (95% CI)
Upper gastrointestinal comorbidities or symptoms
Peptic ulcer disease	202 (1.7)	115 (0.5)	5.45 (4.29–6.91)
Esophageal ulcer	32 (0.3)	61 (0.3)	1.77 (1.14–2.74)
GERD	415 (3.5)	959 (4.0)	1.30 (1.15–1.47)
Epigastric pain	217 (1.9)	346 (1.5)	1.90 (1.59–2.27)
Dyspepsia/gastritis	930 (7.9)	1730 (7.2)	1.69 (1.54–1.84)
Nausea	247 (2.1)	515 (2.2)	1.43 (1.22–1.68)
Bloating	128 (1.1)	286 (1.2)	1.40 (1.12–1.73)
Any of the above	1482 (12.6)	2770 (11.6)	1.74 (1.61–1.88)
Other comorbidities
Hypertension	2064 (17.6)	5889 (24.6)	0.91 (0.85–0.97)
Hyperlipidemia	962 (8.2)	2421 (10.1)	1.05 (0.97–1.15)
Anemia	328 (2.8)	541 (2.3)	1.91 (1.65–2.20)
Rheumatoid arthritis	67 (0.6)	129 (0.5)	1.58 (1.16–2.15)
Heart failure	313 (2.7)	679 (2.8)	1.47 (1.27–1.69)
Osteoarthritis	777 (6.6)	1886 (7.9)	1.30 (1.18–1.43)
Asthma	569 (4.9)	1418 (5.9)	1.21 (1.09–1.35)
COPD	383 (3.3)	995 (4.2)	1.13 (1.00–1.29)
Diabetes	1143 (9.8)	3038 (12.7)	1.02 (0.94–1.10)

Notes:

a Diagnosed at any point during the study period;

b relative to patients who never received a diagnosis for these conditions. Adjusted for age at the index date, sex, body mass index at the start date, time between the start and index dates, smoking history at the start date, number of primary care physician visits from 15 days to 1 year prior to the start date, referral or hospitalization (yes or no) from 15 days to 1 year prior to the start date, ASA indication and number of co-medications taken in the 60 days prior to the index date.

Abbreviations: ASA, acetylsalicylic acid; COPD, chronic obstructive pulmonary disease; CI, confidence interval; GERD, gastroesophageal reflux disease; OR, odds ratio.

Table 4 Association between concomitant medicationsa and ASA discontinuation risk

	ASA discontinuers (n = 11,729) n (%)	ASA non-discontinuers (n = 23,910) n (%)	Adjusted ORb (95% CI)
Anti-inflammatory/analgesic drugs
Oral steroids	436 (3.7)	752 (3.2)	1.43 (1.25–1.62)
NSAIDs (overall)	1312 (11.2)	2335 (9.8)	1.27 (1.18–1.37)
Cyclo-oxygenase-2 inhibitors	285 (2.4)	347 (1.5)	1.80 (1.53–2.13)
Traditional NSAIDs	1058 (9.0)	2026 (8.5)	1.15 (1.06–1.25)
Paracetamol	2444 (20.8)	5716 (23.9)	1.03 (0.96–1.09)
Cardiovascular medications
Oral anticoagulants (warfarin)	911 (7.8)	394 (1.7)	7.10 (6.26–8.05)
Other antiplatelet drugsc	1293 (11.0)	3493 (14.6)	0.79 (0.74–0.86)
Antihypertensive drugs	8690 (74.1)	20,509 (85.8)	0.63 (0.59–0.67)
Statins	6543 (55.8)	17,411 (72.8)	0.55 (0.52–0.58)
Nitrates	2174 (18.5)	4919 (20.6)	0.88 (0.83–0.94)
Digoxin	523 (4.5)	653 (2.7)	1.99 (1.76–2.25)
Gastroprotective medications
Proton pump inhibitors	2385 (20.3)	5629 (23.5)	1.01 (0.95–1.07)
Histamine type 2 receptor antagonists	469 (4.0)	802 (3.4)	1.23 (1.09–1.39)
Hormone replacement therapyd	288 (5.3)	310 (3.0)	1.51 (1.27–1.80)
Anti-infective drugs	1406 (12.0)	3042 (12.7)	1.14 (1.05–1.22)
Antidiabetic drugs	1163 (9.9)	2735 (11.4)	1.04 (0.96–1.13)

Notes:

a Within the 30 days prior to the index date;

b relative to non-use in the year prior to the index date. Adjusted for age at the index date, sex, body mass index at the start date, time between the start and index dates, smoking history at the start date, number of primary care physician visits from 15 days to 1 year prior to the start date, referral or hospitalization (yes or no) from 15 days to 1 year prior to the start date, ASA indication, and number of co-medications taken in the 60 days prior to the index date.

c clopidogrel, dipyridamole, ticlopidine, cilostazol, anagrelide, abciximab, eptifibatide, tirofiban. The most common antiplatelet drug was clopidogrel (80.6% among discontinuers, 71.7% among non-discontinuers);

d percentages calculated from female patients only (ASA discontinuers, n = 5411; ASA non-discontinuers, n = 10,266).

Abbreviations: ASA, acetylsalicylic acid; CI, confidence interval; NSAIDs, non-steroidal anti-inflammatory drugs; OR, odds ratio.

Table 5 Association between use of gastroprotective medication since the start of ASA therapya and discontinuation risk

	ASA discontinuers (n = 11,729) n (%)	ASA non-discontinuers (n = 23,910) n (%)	Adjusted ORb (95% CI)
Proton pump inhibitors
Overall	1585 (13.5)	4338 (18.1)	0.80 (0.75–0.86)
Ongoing usec	1246 (10.6)	3040 (12.7)	0.89 (0.83–0.96)
New used	339 (2.9)	1298 (5.4)	0.59 (0.52–0.67)
Histamine type 2 receptor antagonists
Overall	324 (2.8)	578 (2.4)	1.20 (1.04–1.39)
Ongoing use	278 (2.4)	486 (2.0)	1.22 (1.04–1.42)
New use	46 (0.4)	92 (0.4)	1.12 (0.77–1.61)

Notes:

a Use within both the first and last 30 days of ASA therapy;

b relative to non-use in the year prior to the index date. Adjusted for age at the index date, sex, body mass index at the start date, time between the start and index dates, smoking history at the start date, number of primary care physician visits from 15 days to 1 year prior to the start date, referral or hospitalization (yes or no) from 15 days to 1 year prior to the start date, ASA indication, and number of co-medications taken in the 60 days prior to the index date;

c at least one proton pump inhibitor prescription within the 6 months prior to the first low-dose ASA prescription;

d no proton pump inhibitor prescription within the 6 months prior to the first low-dose ASA prescription.

Abbreviations: ASA, acetylsalicylic acid; CI, confidence interval; OR, odds ratio.