Am J Cardiovasc Drugs DOI 10.1007/s40256-014-0079-y

ORIGINAL RESEARCH ARTICLE

Represcription of Low-Dose Acetylsalicylic Acid After Discontinuation in Patients Receiving Treatment for Secondary Cardiovascular Disease Prevention in the UK Elisa Martı´n-Merino • Saga Johansson • Pe´ter Nagy • Luis A. Garcı´a Rodrı´guez

Ó Springer International Publishing Switzerland 2014

Abstract In this retrospective database study, carried out using The Health Improvement Network, a UK primary care database, we followed up patients who were prescribed low-dose acetylsalicylic acid (ASA) (75–300 mg/ day) for the secondary prevention of cardiovascular disease in 2000–2007, and who discontinued therapy for a period of at least 90 days during that time (n = 11,565). We assessed the incidence of, and factors associated with, ASA represcription. Patients were followed up from the first day after their initial 90-day period of discontinuation (start date) until ASA represcription, death, or the end of the study period (31 December 2010). Hazard ratios for factors associated with represcription were calculated using Cox regression models. The cumulative incidence of ASA represcription was 85.2 % over the entire follow-up period, and 63.5 % of all represcriptions were received in the first 6 months after patients’ start dates. Factors significantly associated with a reduced likelihood of ASA represcription included being aged 75–84 years, cardiovascular and gastrointestinal comorbidities (in particular, atrial fibrillation and high overall gastrointestinal risk), adverse drug reactions experienced during therapy, and use of gastroprotective or cardiovascular medications (most notably warfarin). Factors significantly associated with an increased likelihood of ASA represcription included obesity, diabetes mellitus, stable angina, depression, and use of non-steroidal anti-inflammatory drugs. In

conclusion, approximately 85 % of patients who discontinued low-dose ASA therapy were subsequently represcribed ASA during the study period. Comorbidities and comedication use affected represcription rates.

Key Points In this retrospective database study, we assessed rates of represcription of low-dose acetylsalicylic acid (ASA) for secondary prevention of cardiovascular disease among patients who discontinued therapy between 2000 and 2007. The cumulative incidence of ASA represcription was 85.2 % over the entire follow-up period (up to 31 December 2010). Factors significantly associated with a reduced likelihood of ASA represcription included older age, cardiovascular and gastrointestinal comorbidities, adverse drug reactions, and use of gastroprotective or cardiovascular medications (most notably warfarin).

1 Introduction E. Martı´n-Merino  L. A. G. Rodrı´guez (&) Spanish Centre for Pharmacoepidemiologic Research (CEIFE), Almirante 28-2, 28004 Madrid, Spain e-mail: [email protected] S. Johansson  P. Nagy AstraZeneca R&D, Mo¨lndal, Sweden

Low-dose acetylsalicylic acid (ASA) is recommended for the secondary prevention of cardiovascular disease in all patients with no contraindications [1]. However, low-dose ASA use is associated with adverse events, including peptic ulcer development and gastrointestinal bleeding [2, 3]. Adverse events may lead to discontinuation of

E. Martı´n-Merino et al.

2 Materials and Methods

for the selection of patients included in the original study have been described in detail elsewhere [11]. Briefly, patients were identified who were aged 50–84 years and received at least two consecutive prescriptions for low-dose ASA (75–300 mg/day) for the secondary prevention of cardiovascular or cerebrovascular disease during the study period (1 January 2000 to 31 December 2007). Patients were required to have been enrolled with their PCP for at least 2 years, and to have a computerized prescription history of at least 1 year before their first ASA prescription during the study period. Patients were excluded if they had received a low-dose ASA prescription before 1 January 2000, or if they had a history of alcohol abuse, had been diagnosed with alcohol-related disease, or had a recorded diagnosis of cancer (with the exception of basal cell carcinoma). More than 80 % of all patients prescribed low-dose ASA during the study period received a dose of 75 mg/day. Patients were identified as having discontinued therapy if they were found to have a period of 90 days during the study period after a prescribed course of ASA had been completed in which no repeat prescription was issued. Overall, 11,729 patients out of a total of 35,639 low-dose ASA users were found to have discontinued therapy in a median follow-up period of 1.9 years (overall rate of discontinuation 13.1 per 100 person-years). Of these, 11,565 individuals were included in this follow-up study (164 patients were lost to follow-up).

2.1 Data Source

2.3 Data Collection and Analysis

Data were collected from The Health Improvement Network (THIN), a computerized medical research database containing systematically recorded, anonymized data on over 3 million individuals currently registered with participating primary care practices in the UK [12]. Patients included in the database are representative of the general UK population with respect to age, sex, and geographical region [13]. Information contained in THIN includes patient demographics and details of consultations with primary care physicians (PCPs), and data on consultant referrals, hospitalizations, laboratory test results, diagnoses, and prescriptions. THIN has been used in recent studies of ASA safety [3, 14], and its validity for use in pharmacoepidemiological research has been demonstrated [15]. This study was approved by a multicenter research ethics committee (08/H0305/49).

An outline of the patient selection process and data collection timeline is shown in Fig. 1. Participants were followed up from the first day after their 90-day discontinuation period had ended (start date) until one of the following endpoints: a new prescription for low-dose ASA; death; or the end of the study period (31 December 2010). The following information was collected for each patient: demographic and lifestyle characteristics at the start date; initial low-dose ASA indication (MI, cerebrovascular disease, ischemic heart disease, or unstable angina); comedications used and any adverse drug reactions recorded between their first low-dose ASA prescription and the start date; use of healthcare services in the year before the start date; and comorbidities recorded at any point before the start date. For comedications, current use was defined as having an active drug prescription at the start date or ending in the week before the start date, past use (not reported in the results) was defined as having received a prescription after the date of the first low-dose ASA prescription and ending more than 1 week before the start date, and non-use was defined as having received no prescription at any point between the date of the first lowdose ASA prescription and the start date.

treatment, leaving patients at risk of having a secondary myocardial infarction (MI), stroke, or other cardiovascular event [4–9]. In addition, therapy is often discontinued perioperatively in patients undergoing surgery, in order to reduce bleeding risk [10]. We have previously shown in an observational, primary care cohort study that the rate of low-dose ASA discontinuation among 35,639 patients who received treatment for secondary cardiovascular or cerebrovascular disease prevention in the UK in 2000–2007 was 13.1 per 100 person-years, and was higher in the first year of treatment (26.7 per 100 person-years) than in subsequent years (6.8 per 100 person-years for all subsequent years) [11]. In that study, patients who developed gastrointestinal symptoms during therapy were significantly more likely to discontinue treatment than those who did not. As a follow-up to the original study, we analyzed rates of represcription of low-dose ASA in patients who discontinued treatment and assessed factors positively and negatively associated with represcription. Patients who are not represcribed low-dose ASA or an alternative antithrombotic medication are left at an elevated risk of recurrent cardiovascular events, including MI and stroke [4, 5].

2.2 Study Population The patient population used for the current study consisted of those who were identified in the previous study as having discontinued low-dose ASA therapy prescribed for secondary cardiovascular disease prevention [11]. The criteria

Represcription of Low-Dose Acetylsalicylic Acid After Discontinuation Fig. 1 Cohort follow-up and data collection schedule. ASA acetylsalicylic acid

90-day period of discontinuation (n = 11,729)

Date of first low-dose ASA prescription (n = 35,639)

• Low-dose ASA represcription • Death • End of study period (31 December 2010)

Start of follow-up (start date; n = 11,565)

Comedication and adverse drug reaction information collected

End of follow-up

Follow-up period Demographic and lifestyle characteristics information collected

Comorbidity information collected

Patients were defined as being at high overall gastrointestinal risk if they had a history of complicated or uncomplicated peptic ulcer disease, had received a concomitant non-steroidal anti-inflammatory drug (NSAID), anticoagulant, or antiplatelet therapy prescription in the 30 days after their first low-dose ASA prescription, had been diagnosed at any point as having a Helicobacter pylori infection without receiving eradication therapy, had begun H. pylori eradication therapy in the 6 months before or at any time after their first low-dose ASA prescription, or had two or more of the following risk factors: aged over 60 years at the time of their first low-dose ASA prescription, concomitant corticosteroid therapy (one or more prescriptions in the 30 days after their first low-dose ASA prescription), and gastroesophageal reflux disease or dyspepsia symptoms recorded in the year before their first lowdose ASA prescription [2]. 2.4 Statistical Methods A Kaplan–Meier curve and life table were computed to show the cumulative incidence of ASA represcription after patients’ start dates. Hazard ratios (HRs) assessing the associations of demographic or lifestyle characteristics, comorbidities, and comedications with low-dose ASA represcription were calculated using Cox regression models. The duration of follow-up (as described in Sect. 2.3) was included as a time variable (e.g., time to reach the event of interest—in this case represcription), and patients without a new prescription were censored at the end of the study period or death. HRs were adjusted, unless stated otherwise, according to age at the start date, sex, initial

low-dose ASA indication, the number of PCP visits in the year before the start date, whether patients had received a specialist referral or had been hospitalized in the year before the start date, and the number of drugs prescribed in the month before the start date. Data analysis was carried out using Stata/SE (version 11.2; StataCorp, College Station, TX, USA).

3 Results 3.1 Patient Demographics and Rates of Represcription The 11,565 patients included in the study were followed up for a median of 5.7 months. Over half of patients were men, and the mean age at the start date was 68.5 years. The most common initial indication for low-dose ASA was ischemic heart disease (48.5 %), followed by cerebrovascular disease (32.4 %), MI (17.1 %), and unstable angina (2.0 %). The mean body mass index (BMI) of patients was 27.5 kg/m2, 42.6 % of all participants had never smoked, and 50.8 % consumed no more than 1 unit of alcohol per week. In total, 8,960 patients were represcribed low-dose ASA during the entire follow-up period (maximum 11 years), giving a cumulative incidence of represcription of 85.2 % (Fig. 2). The rate of represcription was greatest during the first 6 months after patients’ initial 90-day period of discontinuation, with 63.5 % of new prescriptions occurring during this period (n = 5,687, cumulative incidence of represcription 49.6 %). Among patients who were represcribed low-dose ASA, 96.4 % were prescribed the same

E. Martı´n-Merino et al.

Low-dose ASA represcription, proportion of patients (%)

100

75

50

25

0 0

0.5

1

2

3

4

5

6

7

8

9

10

11

Duration of follow-up (years) Time, years

0–0.5 0.5–1

1–2

2–3

3–4

4–5

5–6

6–7

7–8

8–9

9–10

10–11

Patients at risk at start of period

11,565 5,671

4,363

3,209

2,561

1,775

1,228

789

449

235

101

19

New low-dose ASA prescriptions during period

5,687 1,215

965

460

310

161

82

46

21

11

2

0

Cumulative incidence of represcription (%)

49.6

69.4

74.0

77.4

79.7

81.3

82.6

83.7

84.7

85.2

85.2

60.5

Fig. 2 Kaplan–Meier plot and life table of the proportion of patients represcribed low-dose ASA after discontinuation. ASA acetylsalicylic acid

dose as they had received before discontinuation, 2.1 % received a reduced dose, and 1.5 % received a higher dose (data not shown). 3.2 Predictors of Low-Dose ASA Represcription After adjustment for confounding variables, patients with a BMI of 30 kg/m2 or over had a slightly increased likelihood of represcription relative to those with a BMI of 20–24 kg/m2 (Table 1). Older age (75–84 years relative to 50–64 years) was associated with a reduced likelihood of being represcribed low-dose ASA, as was having more frequent PCP visits in the year before the start date (C12 relative to \6), and having had either specialist referral or hospitalization in the year before the start date. There were no differences between men and women, or among patients with different initial low-dose ASA indications, smoking statuses, or alcohol intakes. Patients with atrial fibrillation, heart failure, or anemia, and those with a history of hemorrhagic stroke at the start date were all significantly less likely to be represcribed low-dose ASA during follow-up than those without these comorbidities, as were those at high overall gastrointestinal risk, and those with a history of peptic ulcer disease, gastroesophageal reflux disease, or dyspepsia/gastritis (Table 2). Conversely, patients with diabetes mellitus or stable angina were more likely than those without to be represcribed low-dose ASA. The effects of atrial fibrillation and heart failure were also analyzed in a separate model adjusted for the use of

warfarin, in order to reduce the effect of confounding by anticoagulant therapy use. In this model, the negative association between atrial fibrillation and low-dose ASA represcription was considerably reduced [HR 0.85, 95 % confidence interval (CI) 0.77–0.93], and no significant association was seen between heart failure and low-dose ASA represcription (HR 1.01, 95 % CI 0.92–1.11). Patients with depression were more likely than those without to be represcribed low-dose ASA, while those who experienced any adverse drug reaction during therapy were less likely to be represcribed low-dose ASA than those who did not (Table 2). As would be expected, this association was particularly strong for those whose adverse drug reaction was specific to ASA or other salicylates. Among comedications, the use of warfarin, clopidogrel, digoxin, other anti-atrial fibrillation drugs, or antihypertensives at the start date was associated with a reduced likelihood of low-dose ASA represcription, as was the use of proton pump inhibitors and histamine type-2 receptor antagonists. The use of NSAIDs was associated with an increased likelihood of being represcribed low-dose ASA. As with atrial fibrillation and heart failure, the associations between the use of digoxin, anti-atrial fibrillation drugs, and antihypertensives and low-dose ASA represcription were analyzed in a model adjusted for the use of warfarin. For digoxin and antihypertensives, the association remained significant but was reduced in magnitude (HR 0.85, 95 % CI 0.73–0.98 for digoxin; HR 0.92, 95 % CI, 0.87–0.98 for antihypertensives), while for anti-atrial

Represcription of Low-Dose Acetylsalicylic Acid After Discontinuation Table 1 Patient characteristics and associations with low-dose ASA represcription Total (n = 11,565) [n (%)]

No represcription (n = 2,605) [n (%)]

Represcription (n = 8,960) [n (%)]

HR (95 % CI)a

Male

6,228 (53.9)

1,317 (50.6)

4,911 (54.8)

1 (–)

Female

5,337 (46.1)

1,288 (49.4)

4,049 (45.2)

0.97 (0.93–1.01)

50–64

4,185 (36.2)

704 (27.0)

3,481 (38.9)

1 (–)

65–74

3,767 (32.6)

865 (33.2)

2,902 (32.4)

0.97 (0.92–1.02)

3,613 (31.2)

1,036 (39.8)

2,577 (28.8)

0.92 (0.87–0.97)

Sex

Age at start of follow-up, years

75–84 Initial low-dose ASA indication Cerebrovascular disease

3,751 (32.4)

942 (36.2)

2,809 (31.4)

0.96 (0.90–1.02)

Ischemic heart disease

5,605 (48.5)

1,157 (44.4)

4,448 (49.6)

1.01 (0.95–1.07) 0.91 (0.78–1.07)

Unstable angina

231 (2.0)

56 (2.2)

175 (2.0)

1,978 (17.1)

450 (17.3)

1,528 (17.1)

13–19

354 (3.1)

101 (3.9)

253 (2.8)

20–24

2,949 (25.5)

719 (27.6)

2,230 (24.9)

1 (–)

25–29

4,300 (37.2)

949 (36.4)

3,351 (37.4)

1.01 (0.96–1.07)

C30

2,689 (23.3)

563 (21.6)

2,126 (23.7)

1.09 (1.03–1.16)

Unknown

1,273 (11.0)

101 (3.9)

253 (2.8)

1.03 (0.90–1.17)

Current

2,093 (18.1)

1,111 (42.6)

3,814 (42.6)

1 (–)

Former

4,169 (36.0)

363 (13.9)

1,730 (19.3)

1.06 (1.00–1.13)

Never Unknown

4,925 (42.6) 378 (3.3)

1,058 (40.6) 73 (2.8)

3,111 (34.7) 305 (3.4)

1.00 (0.95–1.05) 0.97 (0.86–1.09)

0–1

5,880 (50.8)

1,388 (53.3)

4,492 (50.1)

1 (–)

2–21

4,057 (35.1)

879 (33.7)

3,178 (35.5)

0.99 (0.95–1.04)

C22

498 (4.3)

88 (3.4)

410 (4.6)

1.01 (0.91–1.12)

1,130 (9.8)

250 (9.6)

880 (9.8)

0.96 (0.89–1.03)

Myocardial infarction

1 (–)

Body mass index, kg/m2 1.03 (0.90–1.17)

Smoking status

Alcohol intake per week, units

Unknown

Number of PCP visits in the year before the start date \6

1,304 (11.3)

140 (5.4)

1,164 (13.0)

1 (–)

6–11

3,264 (28.2)

491 (18.9)

2,773 (31.0)

0.98 (0.92–1.05)

C12

6,997 (60.5)

1,974 (75.8)

5,023 (56.1)

0.76 (0.71–0.82)

Specialist referral in the year before the start date No

2,870 (24.8)

407 (15.6)

2,463 (27.5)

1 (–)

Yes

8,695 (75.2)

2,198 (84.4)

6,497 (72.5)

0.90 (0.86–0.95)

Hospitalization in the year before the start date No

8,582 (74.2)

1,632 (62.6)

6,950 (77.6)

1 (–)

Yes

2,983 (25.8)

973 (37.4)

2,010 (22.4)

0.80 (0.76–0.85)

ASA acetylsalicylic acid, CI confidence interval, HR hazard ratio, PCP primary care physician a

Adjusted according to age at the start date, sex, initial low-dose ASA indication, the number of PCP visits in the year before the start date, whether patients had received a specialist referral or had been hospitalized in the year before the start date, and the number of drugs prescribed in the month before the start date

fibrillation drugs the significant association was lost (HR 1.02, 95 % CI, 0.94–1.10). No other factors were found to be associated significantly with low-dose ASA represcription.

4 Discussion In this study, we have shown that, for 11,565 patients who were prescribed low-dose ASA therapy for secondary

E. Martı´n-Merino et al. Table 2 Comorbidities and comedications significantly associated with low-dose ASA represcription (non-significant factors are not listed) Total (n = 11,565) [n (%)]

No represcription (n = 2,605) [n (%)]

Represcription (n = 8,960) [n (%)]

HR (95 % CI)a

Cardiovascular comorbiditiesb Atrial fibrillation Heart failure Anemia Hemorrhagic stroke Diabetes mellitus Stable angina Gastrointestinal comorbiditiesb Overall high gastrointestinal riskc Peptic ulcer disease

1,269 (11.0)

641 (24.6)

628 (7.0)

804 (7.0)

300 (11.5)

504 (5.6)

0.81 (0.73–0.88)

1,049 (9.1)

325 (12.5)

724 (8.1)

0.90 (0.83–0.97)

97 (1.1)

0.45 (0.42–0.49)

151 (1.3)

54 (2.1)

1,670 (14.4)

379 (14.5)

1,291 (14.4)

1.22 (1.14–1.29)

0.74 (0.61–0.91)

4,641 (40.1)

877 (33.7)

3,764 (42.0)

1.18 (1.13–1.25)

4,076 (35.2)

1,095 (42.0)

2,981 (33.3)

0.90 (0.86–0.94)

814 (7.0)

268 (10.3)

546 (6.1)

0.77 (0.70–0.84)

GERD

2,094 (18.1)

573 (22.0)

1,521 (17.0)

0.92 (0.87–0.97)

Dyspepsia or gastritis

3,012 (26.0)

779 (29.9)

2,233 (24.9)

0.94 (0.89–0.98)

2,719 (23.5)

620 (23.8)

2,099 (23.4)

1.06 (1.01–1.12)

To any drug

637 (5.5)

240 (9.2)

397 (4.4)

0.75 (0.68–0.83)

To ASA or other salicylates

118 (1.0)

81 (3.1)

37 (0.4)

0.26 (0.19–0.36)

To drugs other than ASA or other salicylates

178 (1.5)

64 (2.5)

114 (1.3)

0.78 (0.65–0.94)

Other comorbiditiesb Depression Adverse drug reactionsb

Comedicationsd Warfarin

1,026 (8.9)

645 (24.8)

381 (4.3)

0.28 (0.25–0.31)

Clopidogrel

950 (8.2)

488 (18.7)

462 (5.2)

0.40 (0.36–0.44)

Digoxin Other drugs used for atrial fibrillatione

470 (4.1) 965 (8.3)

256 (9.8) 273 (10.5)

214 (2.4) 692 (7.7)

0.43 (0.38–0.50) 0.90 (0.83–0.98)

Antihypertensives

7,285 (63.0)

1,846 (70.9)

5,439 (60.7)

0.85 (0.80–0.90)

PPIs

1,868 (16.2)

720 (27.6)

1,148 (12.8)

0.65 (0.61–0.69)

H2RAs

306 (2.6)

82 (3.1)

224 (2.5)

0.83 (0.72–0.94)

NSAIDs

798 (6.9)

130 (5.0)

668 (7.5)

1.15 (1.06–1.24)

ASA acetylsalicylic acid, CI confidence interval, GERD gastroesophageal reflux disease, HR hazard ratio, H2RA histamine type-2 receptor antagonist, NSAID non-steroidal anti-inflammatory drug, PCP primary care physician, PPI proton pump inhibitor a

Adjusted according to age at the start date, sex, initial low-dose ASA indication, the number of PCP visits in the year before the start date, whether patients had received a specialist referral or had been hospitalized in the year before the start date, and the number of drugs prescribed in the month before the start date

b

Relative to not having the indicated comorbidity or adverse drug reaction

c

As described in ‘‘Materials and Methods’’

d

Current use, relative to non-use

e

Verapamil, diltiazem, disopyramide, propafenone, amiodarone, quinidine, procainamide, and flecainide

cardiovascular and cerebrovascular disease prevention in 2000–2007, and who were found to discontinue therapy for at least 90 days during this period, the cumulative incidence of represcription during a median follow-up period after the initial 90-day period of discontinuation of 5.7 months was 85.2 %. In total, 14.8 % of patients were therefore not represcribed low-dose ASA during the entire follow-up period. Represcription of therapy was most common within 6 months of patients’ initial 90-day period of discontinuation.

Patients with a BMI of 30 kg/m2 or above were more likely to be represcribed low-dose ASA than those with a BMI of 20–24 kg/m2, possibly reflecting the increased cardiovascular risk in these patients, while older age (75–84 years relative to 50–64 years) and frequent use of healthcare services reduced the likelihood of represcription. The reduced likelihood of represcription in elderly individuals may reflect a less positive risk–benefit balance for treatment in these patients. However, it should also be noted that elderly individuals are more likely than younger

Represcription of Low-Dose Acetylsalicylic Acid After Discontinuation

patients to be prescribed warfarin, which may confound the result. Patients requiring frequent PCP visits, hospitalization or specialist consultations may be prescribed alternative antithrombotic treatments. The co-prescription of lowdose ASA with warfarin is not recommended for most patients [16, 17]. Several cardiovascular comorbidities, particularly atrial fibrillation, reduced patients’ likelihood of being represcribed low-dose ASA therapy. This is also likely to be due to the use of warfarin in these patients, who are at high cardiovascular risk. Having diabetes mellitus or stable angina increased the likelihood of ASA represcription, in line with these patients’ increased cardiovascular risk. Patients at high overall gastrointestinal risk and those with specific gastrointestinal comorbidities, most notably peptic ulcer disease, were significantly less likely to be represcribed low-dose ASA therapy during the study period than those without these comorbidities. This reflects an increased risk of adverse gastrointestinal events in these patients, and is in agreement with our previous finding that gastrointestinal symptoms and comorbidities increase the likelihood of individuals discontinuing low-dose ASA therapy [11]. Perhaps counterintuitively, however, patients receiving gastroprotective medication were less likely than those not receiving such therapy to be represcribed lowdose ASA, despite the fact that gastroprotective medications reduce the risk of complications associated with lowdose ASA use [2]. A potential explanation for this is confounding by indication; the use of gastroprotective medication may indicate higher baseline gastrointestinal risk or ongoing gastrointestinal symptoms or complications in patients, factors that are likely to discourage low-dose ASA represcription. The use of gastroprotective medications should be considered in patients in whom gastrointestinal complications are a concern, as adherence to these drugs may be often poor [18]. Patients who are not represcribed therapy may be left at high risk of secondary cardiovascular events if they are not treated with an alternative antithrombotic medication [4– 9]. The increased risk of cardiovascular events in patients who stop taking low-dose ASA is highest soon after discontinuation; we have previously shown a 43 % increase in the risk of cardiovascular death or non-fatal MI and a 40 % increase in the risk of ischemic stroke or transient ischemic attack within 6 months of the end date of the last low-dose ASA prescription [4, 5]. It is notable, therefore, that in the present study, more than half of all patients were not represcribed ASA therapy in the 6 months after their initial period of discontinuation, resulting in a period of at least 9 months without low-dose ASA. These patients represent approximately 20 % of all new users of low-dose ASA (total 35,639) for secondary cardiovascular disease prevention in the THIN database, 2000–2007 [11].

Although a number of studies have examined adherence to low-dose ASA therapy and the reasons for its discontinuation [19], to our knowledge, this is the first study of the rate of represcription of low-dose ASA after discontinuation among patients receiving therapy for secondary cardiovascular disease prevention. The study has the strength of using a large primary care database that has been validated for use in epidemiological studies, containing information on a representative selection of the UK general population [15]. Limitations include potential confounding and the fact that the use of over-the-counter medications cannot be monitored. Patients aged over 60 years in the UK receive free prescriptions, reducing the likelihood of over-the-counter medication use. Despite this, some studies have suggested that as many as 20–40 % of patients receiving low-dose ASA obtain it over the counter [20, 21]. Furthermore, because follow-up was stopped after one new prescription for low-dose ASA, it is unknown how long patients who were represcribed therapy continued to receive the medication.

5 Conclusion We have shown that, of 11,565 patients prescribed lowdose ASA therapy for secondary cardiovascular disease prevention in 2000–2007 and who discontinued treatment, 60.5 % were represcribed low-dose ASA within 1 year, and 85.2 % overall received a new prescription during the maximum follow-up period of 11 years. Patients who do not receive a new low-dose ASA prescription may remain at high risk of secondary cardiovascular events if they do not receive another antithrombotic drug [4, 5]. Acknowledgments The study was funded in part with financial research support from AstraZeneca R&D, Mo¨lndal, Sweden. AstraZeneca reviewed the manuscript, but had no role in the analysis of the data. Medical writing support was provided by Stephen Sweet of TM Oxford PharmaGenesis Ltd, and was funded by AstraZeneca R&D, Mo¨lndal, Sweden. All authors have had full access to the data and have contributed to drafting of the paper. Conflict of interest Luis A. Garcı´a Rodrı´guez and Elisa Martı´nMerino work for CEIFE, which has received research funding from AstraZeneca R&D, Mo¨lndal, Sweden. Luis A. Garcı´a Rodrı´guez has also received honoraria for serving on scientific advisory boards for AstraZeneca. Saga Johansson and Pe´ter Nagy are employees of AstraZeneca R&D, Mo¨lndal, Sweden.

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Represcription of low-dose acetylsalicylic acid after discontinuation in patients receiving treatment for secondary cardiovascular disease prevention in the UK.

In this retrospective database study, carried out using The Health Improvement Network, a UK primary care database, we followed up patients who were p...
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