Mortality With Upper Gastrointestinal Bleeding and Perforation: Effects of Time and NSAID Use

Sebastian Straube; Martin R Tramèr; R. Andrew Moore; Sheena Derry; Henry J. McQuay


BMC Gastroenterol 

In This Article


Searches, and references from the previous systematic review,[1] provided 65 studies with 244,329 patients in total, of whom 61,067 experienced an upper gastrointestinal bleed or perforation, and of whom 5,001 died (we provide all the references not included in[1] in Additional file 1). Data from after 1997 made up 81% of the cases and 74% of the deaths.

There were six randomised trials (292 cases of bleed or perforation, 5 deaths), six cohort studies (12,024 bleeds or perforations, 1404 deaths), eight case-control studies (4,487 bleeds or perforations, 258 deaths), 39 case series (39,908 bleeds or perforations, 2674 deaths), three case reports (226 bleeds or perforations, 9 deaths), one yellow card report (3,443 bleeds or perforations, 576 deaths), one audit (524 bleeds or perforations, 52 deaths), and one cross sectional study (163 bleeds or perforations, 23 deaths). In total, 77 data sets from these studies contributed data on 61,067 patients who had suffered a gastrointestinal bleed or perforation.

Figure 1 shows the mortality rate (as 95% CI) according to study type and number of deaths. There were substantial differences in mortality rates between different study architectures. The causal relationship between death and gastrointestinal complication was rarely examined, nor was it possible to distinguish between bleed and perforation as cause of death. Characteristics of patients who died were again rarely reported separately from the population as a whole.

Figure 1.

Mortality by study type. Mean and 95% CI of percentage mortality. Numbers in parenthesis indicate the number of deaths.

Mortality was reported in different ways; as a simple report of death, 30-day mortality, death in hospital or at home, upper-gastrointestinal-related death, and others. Studies rarely stratified mortality according to a specific diagnosis, and it was not possible to perform analyses based on diagnosis. There were also inconsistencies regarding reporting of NSAID use. Few studies differentiated between use and non-use of NSAID (or aspirin). Where such a distinction was made, NSAID use was usually inferred using prescription analysis, with prescriptions for NSAID or aspirin filled within a defined period before the bleed or perforation, usually 30 days. Adherence to and details of NSAID therapy (dose, drug, frequency) were rarely specified. Because of these limitations it was feasible only to compare definite NSAID use with all patient data, whether NSAIDs or aspirin were used or not.

Table 1 shows mortality rates in all cases and in the 5,526 cases (9% of all cases) using NSAID or aspirin. Overall average mortality was 8.2% (95% CI 8.0 to 8.4%). In studies published before 1997 it was 11.6% (11.0 to 12.2%), and in studies published from 1997 onwards, it had fallen to 7.4% (7.2 to 7.6%). These later studies contained 81% of total cases and 74% of deaths. The mean reduction in mortality was by 4.2% (3.6 to 4.8%), a statistically significant reduction (p < 0.00001, t-test and Fisher's exact test). There was considerable variation between individual studies, particularly where the number of cases was smaller (Figure 2).

Figure 2.

Mortality rates in cases of upper GI (gastrointestinal) bleed or perforation, for all patients and those taking NSAID. Size of symbol is proportional to number of deaths in each study (inset scale). Vertical line shows overall average mortality rate.

For cases identified as taking an NSAID or aspirin, mortality in studies published before 1997 was 14.7% (13.6 to 15.8%), rising to 20.9% (18.8 to 22.9%) in studies published from 1997 onwards. These later studies contained 27% of total NSAID cases and 34% of deaths. The mean increase in mortality was by 6.2% (3.8 to 8.5%), a statistically significant increase (p < 0.00001, t-test and Fisher's exact test).

Mortality for cases taking an NSAID was higher than for all cases, both in older and newer data sets, but excess mortality for NSAID and aspirin users was greater in more recent studies. Before 1997 mortality for NSAID and aspirin users was an average of 3.1% higher (1.9 to 4.3; p < 0.00001). Between 1997 and 2008 mortality for NSAID users was an average of 13.5% higher (11.4 to 15.6; p < 0.00001).

Most of the data (95% of cases and deaths) was in the 39 datasets with at least 200 cases, and studies with fewer than 100 cases contributed little (Table 1). Effects of study size were inconsistent. For all cases experiencing a bleed or perforation there was no consistent trend; small studies contributed 2,862 bleeds or perforations and 246 deaths. For patients on NSAIDs in these small studies, there were only 617 cases with a bleed or perforation and only 31 deaths. Here the estimated mortality rate of 5.0% was less than a third that found in larger studies (Table 1).


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