Do NSAIDs and ASA Cause More Upper Gastrointestinal Bleeding in Elderly than Adults?

Purpose. NSAIDs and ASA may cause upper gastrointestinal bleeding (UGIB) both in adults and in elderly. There is no study that compares this increased bleeding risk between adult and elderly subjects. Methods. A total of 524 patients with UGIB were included in this study. The data of patients were, respectively, analyzed. Results. NSAIDs and ASA-associated UGIB rates were similar between <65 years (345 patients) (group 1) and ≥65 years (179 patients) (group 2) (28.4% versus 23.5%, p = 0.225 and 13% versus 19%, p = 0.071, resp.). Warfarin-associated UGIB was found significantly higher in group 2 than group 1. Elderly patients with NSAID-associated UGIB had significantly higher length of stay (LoS) and CoH than adult patients with NSAID-associated UGIB (p = 0.002 and 0.001, resp.). Elderly patients with ASA-associated UGIB had significantly higher CoH than adult patients with NSAID-associated UGIB. Conclusions. Using NSAIDs without gastroprotective drugs or using ASA with gastroprotective drugs in elderly patients is as safe as in adult patients. Not only should adding gastroprotective drugs to ASA or NSAID be based on their risk of UGIB, but the cost of hospitalization of ASA or NSAID-associated UGIB should be considered.


Introduction
The older population is growing faster than the total population in all regions of the world and more than 1% of elderly people are hospitalized each year because of upper gastrointestinal bleeding (UGIB) [1,2]. Advanced age has been consistently identified as a risk factor for mortality among patients with UGIB, presumably because of a higher prevalence of comorbid illnesses in the elderly [3,4]. The incidence and outcome of gastrointestinal bleeding in elderly people can also be influenced by the use of aspirin, other nonsteroidal anti-inflammatory drugs, and other antiplatelet and anticoagulant agents [5,6].
Previous studies have shown that almost 30% of the elderly people have been taking NSAIDs (including ASA) [7,8]. NSAIDs and ASA have widespread usage in various diseases and their relationship with UGIB is well known.
In all ages, including elderly, people using NSAIDs or ASA tended to have higher UGIB risk than those who do not use [9][10][11][12].
Several studies showed that NSAIDs and ASA are risk factors for UGIB both in adults and in elderly patients, but whether NSAIDs and ASA cause more UGIB events in elderly than adults, or vice versa, is debatable. So, in this study, we have tried to answer the question of "do NSAIDs and ASA cause more UGIB events in elderly than adults?"

Materials and Methods
A total of 524 patients' data who consecutively admitted to our hospital with the diagnosis of UGIB over the last three years were obtained from the hospital records and from patients or their relatives as well. The diagnosis of UGIB in all
The mean CoH for patients with UGIB was $413.98 ± 374.5 (US Dollar). Also there was a positive correlation between patients' age and CoH ( = 0.293; = 0.001). We also compared the LoS (day) and CoH (in US Dollar [exchange currency; 2 Turkish Liras = 1 US Dollar]) according to whether taking warfarin, ASA, or NSAID and patients' age (Table 3). LoS and CoH were significantly higher in patients (both adult and elderly) with warfarin than those without warfarin ( was 0.002 and 0.001, resp.). When we compared patients with and without ASA, only CoH, but not LoS, was significantly different ( = 0.024). Elderly patients with ASA had significantly higher CoH than adult patients with ASA and all patients without ASA ( was 0.007 and 0.013, resp.). Adult patients with NSAID had significantly lower LoS and CoH than elderly patients with NSAID and all patients without NSAID (see Table 3 for values).

Discussion
In our study, female and male percentages of patients younger than 65 years and patients aged 65 years or older were found similar with previous studies [13,14]. Viviane et al. determined the mean LoS for UGIB as 4.4 ± 2.7 days. In our study, it was 6.35 ± 4.94 days. Also mean LoS of patients younger than 65 years (7.8 ± 6.23 days) was found significantly higher than patients younger than 65 years (5.59 ± 3.89 days). As we know that having comorbid illness increases the LoS [15,16], the difference between elderly and adult patients' hospital stay duration could be explained by having more comorbidities in elderly patients.
Previous studies have shown that peptic ulcer (includes gastric ulcer, duodenal ulcer, and peptic ulcer not otherwise specified) is the most common cause of bleeding in elderly patients [6]. In our study, the most common cause of bleeding was bulbar (duodenal) ulcer in both groups; but the second common cause was gastric malignant ulcer/mass in the elderly group whereas gastric ulcer was the second cause in adult patients.
According to our study, warfarin-user elderly patients had more UGIB than adult patients. In a study by Chen et al. which is consistent with our finding, age >65 years old has been found an independent risk factor for warfarinassociated gastrointestinal bleeding [17]. Pilotto et al. have stated in their study that elderly users of acute NSAIDs and regular-dose ASA have increased risk of UGIB [10], but in their study they did not compare these risks with adult subjects. We showed that UGIB risk of NSAIDs (if not cotreated with gastroprotective drugs) is not different in both groups (adult patients and elderly). Similarly UGIB risk of ASA (if cotreated with gastroprotective drugs) is not different in both groups (adult patients and elderly). In this study, we have also determined that there were no differences in ASAassociated UGIB-related mortality and NSAIDs-associated UGIB-related mortality rates between two groups. As we do not have enough number of patients who were treated with ASA but not with gastroprotective drugs, we cannot state any particular comment on this situation.
The mean CoH for patients with UGIB was $413.98 ± 374.5. Also there was a positive correlation between patients' age and CoH. Cryer et al. [18] have investigated the economics of UGIB in US and they have determined the mean CoH for patients with UGIB as $13,059. Also 12-month cost of a patient with UGIB, including total healthcare, medical, and pharmacy costs, was determined as $20,405. And they have shown that patients with UGIB experienced significantly higher 12-month health-resource utilization and costs than patients without UGIB. The other important point is that According to our study, patients with warfarin-associated UGIB had higher CoH than all patients with UGIB without warfarin. Also, elderly patients with ASA-associated UGIB had higher CoH than adult patients with ASA-associated UGIB and all patients with UGIB without ASA. Interestingly, adult patients with NSAID-associated UGIB had lower LoS and CoH than elderly patients with NSAID-associated UGIB and all patients with UGIB without NSAID.

Conclusion
A positive correlation was determined between patients' age and cost of hospitalization.
Even though elderly patients are more prone to have warfarin-associated UGIB, physicians should be more careful when prescribing warfarin in not only elderly patients but also adult patients as those patients with warfarin-associated UGIB had higher CoH than patients with UGIB without warfarin.
When we consider only UGIB risk, using NSAIDs without gastroprotective drugs in elderly patients is as safe as in adult patients. But, even though there was no difference in the risk of NSAID-associated UGIB in between elderly and adult patients without gastroprotective drugs, elderly patients with NSAID-associated UGIB had significantly higher LoS and CoH than adult patients with NSAID-associated UGIB.
Similarly when ASA is prescribed with gastroprotective drugs in elderly, it can be used in elderly patients as safely as in adult patients. But, even though there was no difference in the risk of ASA-associated UGIB in between elderly and adult patients with gastroprotective drugs, elderly patients with ASA-associated UGIB had significantly higher CoH than adult patients with NSAID-associated UGIB.
Not only should adding gastroprotective drugs to ASA or NSAID be based on their risk of UGIB, but the cost of hospitalization of their-associated UGIB should be considered.