Despite the emergence of effective therapies for lowering the risk of erosive disease and PUD, these remain the most common etiologies of UGH in our cohort of patients. In a dramatic change from historically reported patterns, erosive disease was more common than PUD. In prior studies, PUD accounted for almost 2/3 of all UGH. 2
While some of the newer therapeutics such as PPIs and COX-2s, reduce the risk for acid related bleeding of all types, H. pylori
eradication is effective primarily for PUD. Therefore, it may be that widespread testing and treatment of H. pylori
have dramatically decreased rates of PUD. Unfortunately, this study does not allow us to directly evaluate the effect of H. pylori
treatment on the changing epidemiology of UGH as that would require a population based study.
While decreasing rates of PUD could explain a portion of the change in the distribution of etiologies, increasing rates of erosive disease could also be playing a role. Prior studies have suggested that African Americans and the elderly are more susceptible to erosive disease, particularly in the setting of NSAIDs and/or aspirin and less susceptible to cirrhosis. 13,16,17, 20-23
Our finding of a higher rate of erosive disease and lower rates of cirrhosis in center 1 with a higher proportion of African Americans and greater aspirin use is consistent with these prior findings. However, in multivariate analyses, neither race nor pre-admission medication use patterns explained the differences in etiologies seen. This suggests that some other factors must play a role in the differences between the two centers studied. These results emphasize the importance of local site characteristics in the interpretation and implementation of national guidelines and recommendations. This finding may be particularly important in diseases and clinical presentations that rely on protocol driven pathways, such as UGH. Current recommendations on implementing clinical pathways derived from national guidelines emphasize the fact that national development and local implementation optimization is probably the best approach for effective pathway utilization.24
It is important to understand why erosive disease and PUD, for which we now have effective pharmacologic therapies, continue to account for such a large percentage of the burden of UGH. In this study, we found that a majority of subjects were known to have significant risk factors for UGH (aspirin use, NSAID use, COX-2s, or prior UGH) and only 31% of the subjects could not have been identified as at-risk prior to admission. PPIs or COX-2s should neither be used universally as preventive therapy nor are they completely effective at preventing UGH in at-risk patients. In this study, 2/3 of patients with risk factors were not on preventive therapy, but almost 1/3 of patients with risk factors had bleeding despite being on preventive therapy. A better understanding of why these treatment failures (bleeding despite preventive therapy) occur may be helpful in our future ability to prevent UGH. This study was not designed to determine if the 2/3 of patients not taking preventive therapy were being treated consistent with established guidelines. However, current guidelines have significant variation in recommendations about which patients are at high enough risk to warrant preventive therapy.13-15
and there is no consensus about which patients are at high enough risk to warrant preventive therapy. Our data suggest that additional studies will be required to determine the optimal recommendations for preventive therapy among at-risk patients.
There are several limitations to this study. First, it only included two academic institutions. However, these institutions represented very different patient populations. Secondly, the study design is not a population-based study. This limitation prevents us from addressing questions such as the effectiveness or cost-effectiveness of interventions to prevent admission for UGH. Although we analyzed pre-admission PPI or COX-2 use in at-risk patients as preventive therapy, we are unable to determine the actual intent of the physician in prescribing these drugs. Finally, although the mechanisms by which PPIs and COX-2 affect the risk of UGH are fundamentally different and should not be considered equivalent choices, we chose to analyze either option as representing a preventive strategy in order to provide the most conservative estimate possible of preventive therapy utilization rates. However, our assumptions would generally overestimate the use of preventive therapy (as opposed to PPI use for symptom control) as we assumed all potentially preventive therapy was intended as such.
This study highlights several unanswered questions that may be important in the management of UGH. First, identifying factors that affect local patters of UGH may better inform local implementation of nationally developed guidelines. Second, a more complete understanding of the impact positive and negative risk factors for UGH have on specific patient populations may allow for a more consistent targeted approach to using preventive therapy in at risk patients.
Finally, and perhaps most importantly, is to determine if the change in distribution of etiologies is in fact related to a decline in bleeding related to PUD. In addition to this being a marker of the success of the H. pylori story, it may have important implications on our understanding of the acute management of UGH. If PUD is of a different severity than other common causes of UGH, such as erosive disease, current risk stratification prediction models may need to be re-validated. For example, if UGH secondary to PUD results in greater morbidity and mortality than UGH secondary to ED, our current models identifying who requires ICU admission, urgent endoscopy, and other therapeutic interventions may result in over utilization of these resource intensive interventions. However if larger studies do not confirm this decline in PUD it suggests the need for additional studies to identify why PUD remains so prevalent despite the major advances in treatment and prevention of PUD through H.pylori identification and eradication.