The prevalence of prescription aspirin use was 4.6% in the GPRD and 3.4% in BIFAP. Over 95% of the aspirin use recorded in the GPRD and 59% of the use in BIFAP was for cardioprotection. In both data sources the prevalence of aspirin use increased substantially with age (Figure ).
Figure 1 Prevalence of aspirin use for cardioprotection in the UK (General Practice Research Database; GPRD) and Spain (Base de Datos para la Investigación Farmacoepidemiológica en Atención Primaria; BIFAP) by age for females and males. (more ...)
The distribution of gastrointestinal risk factors among cardioprotection aspirin users is presented in Figure . Overall, the proportion of aspirin users above 60 years of age was 88% in the GPRD and 79% in BIFAP. The proportion of males was 52% in the GPRD and 54% in BIFAP. The proportion of aspirin users with a recorded history of gastrointestinal ulcer was 3.8% in the GPRD and 5.9% in BIFAP. The proportion of aspirin users with a recorded past episode of UGIC was 1.2% in the GPRD and 1.9% in BIFAP. The proportion of aspirin users concomitantly using NSAIDs was 14.8% in the GPRD and 13.2% in BIFAP. NSAID use was not included in the figure to simplify the presentation.
Figure 2 Distribution of risk factors for upper gastrointestinal tract complications (UGIC) among cardioprotective aspirin users in the UK (General Practice Research Database; GPRD) and Spain (Base de Datos para la Investigación Farmacoepidemiológica (more ...)
Figure depicts how the estimated incidence rate of UGIC increases with age and with past history of ulcer both for males and females. These rates would be around four times higher among NSAID users and would double with aspirin use. Taking into account the distribution of baseline gastrointestinal risk factors among aspirin users in each population, the estimated average incidence rate of UGIC among aspirin users was 12 cases per 1,000 person-years in the GPRD and 10 in the BIFAP. However, this rate can be more than 20 cases per 1,000 person-years in certain high-risk groups. For example, considering, age, sex, ulcer history and use of NSAIDs as stratifying factors, the expected UGIC incidence rate would be above 20 per 1,000 person-years in 14% and 11% of aspirin users, based on GPRD and BIFAP, respectively. Moreover, in a smaller fraction of the population, for example males 70 and older with a recent history of peptic ulcer and who take aspirin and NSAIDs concomitantly, the risk might exceed 100 cases per 1,000 person-years.
Figure 3 Estimated incidence rate of upper gastrointestinal tract complications (UGIC) per 1,000 person-years and estimated excess number of cases per 1,000 cardioprotection aspirin users per year attributable to aspirin within levels of gastrointestinal risk (more ...)
The number of cases that could be attributable to aspirin among aspirin users according to age, sex, and ulcer history is also presented in Figure . For cardioprotection aspirin users overall, the estimated excess risk of UGIC was 6 and 5 cases per 1,000 users per year in the GPRD and BIFAP, respectively. These figures would be larger in high-risk groups. For example, patients with baseline incidence rates over 20 per 1,000 person-years, such as males 70 years and older with a past history of uncomplicated peptic ulcer, would develop over 40 cases per 1,000 person-years if they were treated with low-dose aspirin; thus, more than 20 cases per 1,000 aspirin users with these risk factors per year could be attributable to their use of aspirin.
The number of extra cases attributable to aspirin depends on the assumptions regarding incidence rates, distribution of risk factors, and relative risks used throughout the analyses. Estimates were particularly sensitive to the value used for the relative risk of UGIC associated with aspirin use. Figure presents the number of extra cases potentially attributable to aspirin according to age, sex, and ulcer history for a plausible range of relative risks associated with low-dose aspirin (i.e., from 1.5 to 3).
Figure 4 Sensitivity analysis. Estimated excess number of upper gastrointestinal tract complications (UGIC) cases attributable to aspirin (measured as the incidence rate difference between users and non-users) stratified by prior ulcer history and age for male (more ...)
Based on our estimates, the expected incidence of UGIC in the control groups of the Vioxx Gastrointestinal Outcomes Research (VIGOR) trial [21
], the Celecoxib Long-term Arthritis Safety Study (CLASS) [22
], and the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) [23
] would have been 7, 9.5 and 8.1 cases per 1,000 person-years, respectively; the actual reported annualized rates were 8.6, 14.5, and 9.1 per 1,000 person-years, respectively (Table ).
Table 1 Application of upper gastrointestinal tract complications (UGIC) risk estimations to the populations of patients included in the control groups (exposed to traditional non-steroidal anti-inflammatory drugs) for the Vioxx Gastrointestinal Outcomes Research (more ...)