ARTHRITIS & RHEUMATISM
Vol. 43, No. 1, January 2000, pp 103–108
© 2000, American College of Rheumatology
THE EFFECT OF MINI-DOSE ASPIRIN ON RENAL FUNCTION AND
URIC ACID HANDLING IN ELDERLY PATIENTS
D. CASPI, E. LUBART, E. GRAFF, B. HABOT, M. YARON, and R. SEGAL
Objective. Aspirin is known to have a bimodal
effect on the renal handling of uric acid (UA). High
dosages (>3 gm/day) are uricosuric, while low dosages
(1–2 gm/day) cause UA retention. Although very-low-
dose (mini-dose) aspirin is used increasingly as a plate-
let aggregation inhibitor, no studies have been pub-
lished on whether aspirin’s renal effects occur at
dosages of <0.5 gm/day. The aim of the present study
was to evaluate the effects of commonly used mini-
dosages of aspirin on renal function and UA handling in
elderly patients.
Methods. The study included 49 elderly inpa-
tients (age 61–94). Patients were excluded if they had
renal failure, hyperuricemia, gout, or a history of
bleeding, or if they were receiving anticoagulants,
aspirin, or nonsteroidal antiinflammatory drugs. Pre-
vious medications and diet were kept unchanged.
Aspirin was administered as follows: 75 mg/day (week
1), 150 mg/day (week 2), 325 mg/day (week 3), and 0
mg/day (week 4). Baseline and weekly samples of
blood and urine were evaluated for UA, creatinine,
blood urea nitrogen, creatinine clearance, UA excre-
tion, UA clearance, and plasma levels of aspirin.
Results. At the lowest dosage, aspirin caused a
15% decrease in the rate of UA excretion (P 5 0.045 by
t-test), which was associated with a slight but significant
increase in serum levels of UA (P 5 0.009). These effects
on UA levels were gradually reduced with increasing
dosages of aspirin (multivariate analysis of variance
with repeated measures showed no statistically signifi-
cant difference in the rate of UA excretion between
weeks 1–3 and week 0 [baseline], but the difference in
serum UA levels for the same comparison was statisti-
D. Caspi, MD, E. Graff, PhD, M. Yaron, MD: Tel Aviv
University, Tel Aviv, Israel; E. Lubart, MD, B. Habot, MD, R. Segal,
MD: Shmuel Harofeh Geriatric Medical Center, Beer Yaacov, Israel.
Address reprint requests to D. Caspi, MD, Rheumatology
Day Care Unit, Tel Aviv (Sourasky) Medical Center, 6 Weizmann
Street, Tel Aviv 64239, Israel.
Submitted for publication December 2, 1998; accepted in
revised form August 17, 1999.
103
cally significant [P 5 0.038]). Generally, creatinine and
UA clearance rates paralleled each other during aspirin
treatment. However, 1 week after aspirin was discontin-
ued, creatinine clearance remained decreased while UA
clearance returned to baseline. Plasma aspirin concen-
trations were low and variable. However, patients with
above-median aspirin levels had significantly greater
changes in serum creatinine levels, urinary UA excre-
tion rates, and UA clearance rates following the first
week of aspirin treatment. Hypoalbuminemia and con-
comitant treatment with diuretics enhanced the effects
of aspirin on renal function and UA retention.
Conclusion. Mini-dose aspirin, even at a dosage
of 75 mg/day, caused significant changes in renal func-
tion and UA handling within 1 week in a group of elderly
inpatients, mainly in those with preexisting hypoalbu-
minemia. Given the widespread (and often unmoni-
tored) use of mini-dose aspirin, especially among the
elderly, these findings call for clinician alertness as well
as for further studies to clarify the mechanisms under-
lying these phenomena.
Though high-dose aspirin, once the king of anti-
inflammatory drugs, has lost its monarchy to modern
nonsteroidal antiinflammatory drugs (NSAIDs), the use
of low-dose and very-low-dose (mini-dose) aspirin for
the prevention of thrombosis has been greatly expanded
during the last decade. Current consumption of aspirin
in the US is estimated to be 10,000–20,000 tons per year
(1), and in Israel, with a population of ;6 million, 5 tons
of the 100-mg enteric coated preparation alone were
distributed during 1997. The drug is taken, often as an
over-the-counter remedy, by many patients and by
healthy subjects as well. Data on the influence of aspirin
on uric acid (UA) kinetics are based on the classical
studies by Yu and Gutman from 1959 (2) and by Yu et
al from 1963 (3), involving dosages of $1 gm/day. Those
investigators found that while aspirin dosages of .3
gm/day tend to promote uricosuria, lower dosages (1–2
gm/day) may cause UA retention. The effects of mini-
104
Table 1. The effects of mini-dose aspirin on uric acid*
Week Serum Urine UA,
(dosage, mg/day) UA, mg/dl P mg/24 hours
0 (0) 4.38 6 1.6 315 6 184
1 (75) 4.65 6 1.6 0.009† 269 6 133
2 (150) 4.59 6 1.5 284 6 127
3 (325) 4.42 6 1.5 0.038‡ 291 6 137
4 (0) 4.46 6 1.4 0.05§ 330 6 153
* Values are the mean 6 SD. UA 5 uric acid; NS 5 not significant.
† By t-test, for week 1 versus week 0 (baseline).
‡ By multivariate analysis of variance with repeated measures, for simple contrast of weeks 1–3 with week 0.
§ By t-test, for week 4 versus week 1.
¶ By t-test, for week 4 versus week 0.
dose aspirin (,0.5 gm/day) on this bimodal phenome-
non have not been studied, nor have its effects on basal
renal function. Elderly subjects may be at higher risk for
NSAID- and aspirin-induced adverse effects in general
and for renal side effects in particular (4,5). This popu-
lation is also more likely to use low-dose aspirin for
primary or secondary prevention of cardiovascular dis-
ease (6–8).
The aim of the present study was to assess
prospectively the possible effects of the more common
mini-dose aspirin regimens (75–325 mg/day) on renal
function and UA handling in a group of elderly inpa-
tients without known renal disease, hyperuricemia,
or gout.
PATIENTS AND METHODS
Patients. Forty-nine elderly inpatients (26 women and
23 men; mean 6 SD age 82.5 6 7.6 years, range 61–94) in
long-term geriatric care for a variety of chronic medical
conditions were included in the study after they or their
guardians provided informed consent. The study was approved
by the Helsinki Committee of our hospital. All patients were
clinically stable during the study period, although some were
classified as frail. Excluded were subjects with a history of
peptic disease, gastrointestinal or genitourinary bleeding,
chronic liver disease, gout, hyperuricemia, or alcohol consump-
tion, or the recent use of aspirin, NSAIDs, or anticoagulants.
Patients with known renal failure or serum creatinine levels of
.1.6 mg/dl were excluded. (The range of basal creatinine
clearance rates was later found to be 14–130 ml/minute.) The
patients were maintained on a controlled diet of 50–80 gm/day
of protein and 200–300 mg/day of purine starting 1 week
before the 4-week study and continuing throughout the study.
Their various medications (9 patients were taking diuretics)
were kept unchanged during the same period of time.
Aspirin administration and laboratory tests. With
compliance surveillance performed by a nurse, aspirin was
administered orally as a single dose immediately after break-
fast, in increasing dosages as follows: 75 mg/day during the first
CASPI ET AL
UA Urine UA:
clearance, creatinine
P ml/minute P clearance P
5.91 6 4.3 7.4 6 2.6
0.045† 4.56 6 3.0 0.009† 8.1 6 4.4 NS†
5.06 6 3.5 8.0 6 3.4
NS‡ 5.26 6 3.3 0.096‡ 8.4 6 5.2 NS‡
NS§ 5.71 6 3.0 0.006§ 9.3 6 5.1 0.01¶
0.054§
week, 150 mg/day during the second week, 325 mg/day during
the third week, and none during the fourth week. Blood and
24-hour urine samples were collected weekly as follows: im-
mediately before the first dose of aspirin, at the end of each
dosage week (before aspirin dosage was changed), and 1 week
after aspirin was discontinued. Collection from incontinent or
mentally incompetent patients was done with either indwelling
catheters or a Penrose device, as indicated by the patients’
medical conditions. Special nursing attention was provided to
ensure a complete urinary collection during the day of 24-hour
urinary collection for the rest of the patients. Plasma for
determining salicylate concentrations was obtained weekly 4
hours following aspirin administration, then separated and
stored at 220°C until processed. Morning-urine pH was deter-
mined twice: once before the first dose of aspirin and once at
the highest dosage (third week).
Levels of serum creatinine, blood urea nitrogen
(BUN), UA, and albumin were determined by standard meth-
ods. Levels of urine creatinine and UA were determined at
24-hour collections (6 AM to 6 AM). The pH of fresh urine was
promptly read with a pH meter. Plasma salicylate level was
determined by the colorimetric method (Sigma Diagnostics, St.
Louis, MO) using a Beckman Instruments Synchron CX-5
analyzer (Beckman Instruments, Palo Alto, CA) calibrated and
quality-controlled for low dynamic range.
Statistical analysis. Statistical analysis was performed
by Student’s t-test (paired or unpaired as appropriate), multi-
variate analysis of variance (MANOVA) with repeated mea-
sures and simple contrast with time 0 (baseline) reference
category, chi-square test (with Yates’ correction), and Pear-
son’s product-moment correlation coefficient.
RESULTS
Forty-nine elderly inpatients treated with increas-
ing dosages of oral daily mini-dose aspirin for 3 weeks
(75 mg/day, 150 mg/day, and 325 mg/day for weeks 1–3,
respectively) and none for the fourth week were moni-
tored for the influence of the drug on their serum and
urine creatinine and UA concentrations. The drug was
well tolerated, and no adverse effects such as allergy,
MINI-DOSE ASPIRIN, RENAL FUNCTION, AND UA HANDLING
Figure 1. The effects of mini-dose aspirin on serum concentrations of
uric acid (UA) and UA clearance rates in 49 patients during 3 weeks
of increasing dosage and 1 week after discontinuing the drug. Note the
gradual normalization after week 1 (mean 6 SD and P values are also
reported in Table 1). p 5 statistically significant change from baseline.
gastrointestinal symptoms, bleeding, renal failure, in-
creased arterial hypertension, or gout were recorded.
The effect of mini-dose aspirin on uric acid.
Table 1 shows the mean 6 SD levels of serum UA
(mg/dl), urine UA (mg/24 hours), and UA clearance
(ml/minute), as well as the ratio of 24-hour urine UA:
creatinine clearance before and after various dosages of
aspirin. A 6.2% increase in the mean serum UA level
(P 5 0.009 by t-test) in parallel with a 22.8% decrease in
the mean UA clearance rate (P 5 0.009) was already
observed at the first week of mini-dose aspirin treatment
(75 mg/day). During the following 2 weeks, although the
dosage of aspirin was doubled twice, serum UA concen-
trations and UA clearance rates gradually returned to
near-baseline levels, and by the third week (325 mg/day)
the differences from baseline were not statistically sig-
nificant (Figure 1). The effects of mini-dose aspirin on
serum UA levels during weeks 1–3 were significant in
comparison with week 0 (P 5 0.038 by MANOVA)
Table 2. The effects of mini-dose aspirin on renal function*
Week
(dosage, mg/day) BUN, mg/dl P mg/dl
0 (0) 21.4 6 10.2
1 (75) 24.1 6 11.1 0.001†
2 (150) 23.0 6 11.9
3 (325) 22.7 6 11.5
4 (0) 24.4 6 10.4 0.071‡
0.016§
* Values are the mean 6 SD. BUN 5 blood urea nitrogen.
† By t-test, for week 1 versus week 0 (baseline).
‡ By multivariate analysis of variance with repeated measures, for simple contrast of weeks 1–4 with week 0.
§ By t-test, for week 4 versus week 0.
105
(Table 1). Importantly, although these changes were
statistically significant, levels still remained within nor-
mal limits.
The effect of mini-dose aspirin on renal function.
Mini-dose aspirin administration caused mild, though
significant, impairment of renal function. Although pa-
tients with known renal failure or serum creatinine levels
of .1.6 mg/dl were excluded, baseline creatinine clear-
ance was found to be 47 6 28 ml/minute (range 14–130).
As shown in Table 2, levels of BUN and serum creati-
nine increased from baseline by 12.6% (P 5 0.001) and
4.8% (P 5 0.015), respectively, after 7 days of aspirin (75
mg/day), while creatinine clearance decreased by 13.8%
(P 5 0.03 by t-test). These changes were more or less
stable across aspirin dosages, including that of 0 mg/day
during week 4 (P 5 0.071, P 5 0.05, and P 5 0.073 by
MANOVA for comparison with week 0 for BUN level,
serum creatinine level, and creatinine clearance, respec-
tively).
Unlike serum UA, renal function did not recover
either during treatment or 1 week after discontinuation
of aspirin (see below). At week 4, creatinine clearance
remained 13.2% below its baseline rate (P 5 0.04), while
BUN and serum creatinine levels remained 14% and
8.3% higher, respectively (P 5 0.016 and P 5 0.004,
respectively, by t-test) (Table 2). To determine whether
patients with low basal renal function were at higher
risk, changes in creatinine clearance were plotted against
basal creatinine clearance. A negative correlation was
found (r ranging from 20.66 to 20.80, P , 0.001),
implying that high basal creatinine clearance did not
prevent mini-dose aspirin from decreasing creatinine
clearance, and that low basal creatinine clearance was
not a prerequisite for this effect.
The effect of urinary pH. The urinary pH, which
can influence UA excretion, was determined before
Creatinine
Creatinine, clearance,
P ml/minute P
0.84 6 0.26 47 6 28.0
0.88 6 0.27 0.015† 40.5 6 21.8 0.03†
0.89 6 0.29 38.8 6 18.3
0.88 6 0.29 40.7 6 18.8
0.91 6 0.27 0.05‡ 40.8 6 18.3 0.073‡
0.004§ 0.04§
106 CASPI ET AL

aspirin administration and at the maximum aspirin dos-

age. Most patients (46 of 49) maintained a constant
urinary pH. When we compared the effects of aspirin on
renal and UA parameters in patients with persistently
more alkaline urine (pH .6.0, n 5 26) versus those in
patients with persistently acid urine (pH ,6.0, n 5 20),
we found these parameters to be affected almost iden-
tically for the 2 groups (data not shown).
The relationship of renal function to UA han-
dling. Generally, renal function and UA excretion and
clearance appeared to operate in parallel. Indeed, we
found a significant correlation (P , 0.0001) between
changes in UA clearance and creatinine clearance after
the first week of aspirin administration and during the
following weeks. Accordingly, the ratio of daily UA
excretion:creatinine clearance remained approximately
unchanged during the 3-week treatment schedule (P 5
0.496 by MANOVA), due to a proportional decrease of
both rates. Following cessation of aspirin at week 4,
Figure 2. Changes from baseline in creatinine clearance rate (A) and
however, this ratio increased significantly (P 5 0.01 and
daily uric acid excretion (B) in patients with hypoalbuminemia (mean
P 5 0.054 for comparisons with week 0 [baseline] and 6 SD albumin level 2.48 6 0.3 gm/dl, n 5 27) versus patients with
week 1, respectively) due to the complete normalization normal albumin levels (mean 6 SD 3.34 gm/dl, n5 22).* 5 statistically
of UA excretion (Table 1) without simultaneous recov- significant difference between patients with hypoalbuminemia and
ery of creatinine clearance (Table 2). those with normal albumin levels.
The effect of serum albumin. Since serum albu-
min is known to play an important role in salicylate
pharmacokinetics, the impact of low albumin levels was group (P 5 0.009) following the first week of aspirin
studied. Patients with serum albumin levels of ,3 gm/dl treatment (Figure 2B). The group with hypoalbumine-
(mean 6 SD 2.48 6 0.3 gm/dl, n 5 27) were compared mia tended to be slightly older than the group with
with those whose serum albumin levels were .3 gm/dl normal albumin levels (mean age 83 years versus 81
(mean 6 SD 3.34 6 0.4 gm/dl, n 5 22). years). However, this difference was not statistically
It was found that aspirin-induced decreases in significant.
UA excretion, UA clearance, and creatinine clearance The effect of concomitant diuretics. Nine patients
were almost confined to the low-albumin group (by both receiving long-term treatment with a diuretic (furo-
chi-square and t-tests [data not shown]). The mean 6 semide, 20–40 mg/day) were compared with patients not
SD change in creatinine clearance following 1 week of receiving diuretics. While the baseline creatinine clear-
aspirin (75 mg/day) was 212 6 24 ml/minute from ance of the furosemide group was similar to that of the
baseline (225.5%) for patients with low serum albumin entire group (P . 0.9), and their mean serum albumin
levels compared with 10.2 6 22 ml/minute (10.4%) for level was higher than that of the entire group, their
patients with normal levels (P 5 0.038). Similarly, it was responses to 75 mg/day of aspirin were generally more
noted that the impaired creatinine clearance persisted prominent, as shown by increases in levels of BUN
for 1 week after discontinuation of aspirin (213.7 6 29 (31.5% versus 13.7%, respectively) and serum UA
ml/minute from baseline [229%]) for the low-albumin (12.6% versus 6.8%, respectively). The differences were
group, while this late effect of mini-dose aspirin was not not statistically significant (P 5 0.08 and P 5 0.055,
seen for patients with normal albumin levels (10.37 6 respectively), however, probably due to the small num-
23 ml/minute [10.78%]) (P 5 0.039) (Figure 2A). ber of patients (data not shown).
Reduction of UA excretion in response to mini-dose Salicylate levels. Plasma salicylate levels in 41
aspirin was also associated with low serum albumin patients were determined 4 hours after ingestion of
levels. The urate excretion of the low-albumin group aspirin. A relatively large array of concentrations was
decreased by 105 6 199 mg/day, compared with an found (range 0.1–6.5 mg/dl). Patients were grouped by
increase of 23 6 167 mg/day for the normal-albumin salicylate levels above (n 5 22) or below (n 5 19) the
MINI-DOSE ASPIRIN, RENAL FUNCTION, AND UA HANDLING
median value and compared by t-test. The higher-level
group had significantly greater changes in serum creat-
inine levels, urinary UA excretion rates, and UA clear-
ance rates compared with the lower-level group (P 5
0.025, 0.04, and 0.004, respectively) following the first
week of aspirin treatment (data not shown).
Age. The age of the patients did not appear to
influence their renal and UA responses to low-dose
aspirin. No correlation was found between age and
changes in any of the parameters studied, or between
age and serum albumin levels. Similarly, t-tests compar-
ing patients older (n 5 24) with those younger (n 5 25)
than the median age did not show statistically significant
differences for these parameters.
DISCUSSION
Although high- and low-dose aspirin are known
to influence UA balance and renal function (1–3,9), no
data have been published about very low dosages.
Aspirin in the dosage range of 75–325 mg/day is cur-
rently used as a platelet aggregation inhibitor by many
patients and healthy subjects (10,11). A considerable
fraction of low-dose aspirin consumers are elderly peo-
ple (6–8). The present prospective study is the first to
demonstrate that even mini-dose aspirin has the poten-
tial to cause (within 1 week) significant changes in renal
function and UA handling in elderly patients hospital-
ized for a variety of other acute and chronic conditions.
The impairment of creatinine clearance persisted for $1
week after discontinuation of the drug, while UA excre-
tion gradually returned to near-baseline levels after
dosages were increased to 150 mg/day and 325 mg/day.
Although these adverse effects did not reach alarming
proportions, they were found to be significantly more
prominent in patients with lower serum albumin and,
independently, in patients taking diuretics concomi-
tantly.
We must emphasize that patients with a history
of renal impairment, serum creatinine levels of .1.6
mg/dl, or hyperuricemia were excluded from our study.
(Nevertheless, the range of creatinine clearance rates
included data from patients with low basal creatinine
clearance rates [mean 6 SD 47 6 28 ml/minute, range
14–130 ml/minute].) Surprisingly, when we plotted
aspirin-induced creatinine clearance changes versus
basal creatinine clearance, we found that high–basal
creatinine clearance patients had an even greater de-
crease in creatinine clearance than did patients with low
basal creatinine clearance.
107
Aspirin is a nonselective cyclooxygenase inhibitor
(9,11–13) and therefore exerts antiinflammatory activity
by globally inhibiting production of inflammatory pros-
taglandins (PG). At the same time, it inhibits other
constitutive cyclooxygenase products, including gastric
PGE1, thromboxane A2, and vascular prostacyclins,
which accounts for some of its adverse effects (9,14).
The different pharmacologic targets can be reached by
different dosages. The antiinflammatory effects of aspi-
rin take place at high dosages (usually $3 gm/day). Its
analgesic and antipyretic effects are produced at dosages
of 0.3–1 gm, while its anti–platelet aggregation effects
are achieved at lower dosages (there are many
thrombosis-prevention regimens of only 75–325 mg/day)
(15–17).
Renal UA handling in response to aspirin is
similarly dose dependent. Aspirin at high and low doses
has been shown to exert a peculiar bimodal influence on
UA kinetics. Higher dosages (.3 gm/day) increase renal
excretion, probably by inhibiting tubular reabsorption of
UA. At dosages of 1–2 gm/day, aspirin causes UA
retention, probably by inhibiting tubular secretion sites
(2) and possibly by decreasing glomerular filtration rate
(18,19) (although it has been suggested that very low
dosages [30–50 mg/day] improve renal function of pa-
tients with chronic glomerular disease [20]). Competi-
tion of salicylate (a weak organic acid) or its metabolites
with UA at tubular secretion/reabsorption sites may also
play a role (3).
The various modern mini-dose aspirin protocols
have been extensively studied for their efficacy (6–8,15–
17,21,22) and also, to some extent, for their gastrointes-
tinal side effects (4,23,24), but not for their possible
influence on renal function and urate handling. Renal
function of patients receiving mini-dose aspirin is not
routinely monitored, nor is this recommended by text-
books (1,9,11).
Our study shows that mini-dose aspirin signifi-
cantly changes renal function and UA handling, at least
for inpatients aged 61–94 years and having a variety of
chronic medical conditions, although age distribution
did not seem to modify the effects of aspirin within this
group. Although the decrease in UA excretion paral-
leled the decrease of creatinine clearance, it seems these
phenomena are not necessarily united. Indeed, while
UA excretion and clearance gradually returned to base-
line levels after we increased the aspirin dosage (Table 1
and Figure 1), serum creatinine levels continued to be
elevated and creatinine clearance significantly impaired
during the 3-week aspirin treatment. Moreover, these
changes persisted 7 days after aspirin was discontinued
108
(Table 2). Unsurprisingly, patients receiving diuretics
concomitant with aspirin tended to have further impair-
ment of renal function induced by mini-dose aspirin.
The influence of hypoalbuminemia in the same direction
may be explained by the known role of albumin in
binding salicylate (1), and thus by the higher serum
levels of the drug in hypoalbuminemic patients.
In conclusion, aspirin at dosages of 75–325 mg/
day was found to impair renal function and UA handling
in elderly inpatients. These effects were already noted at
the week-1 dosage of 75 mg/day. Concomitant diuretic
treatment and especially low serum albumin seem to
increase the susceptibility to these side effects. The
mechanisms underlying urate retention and renal im-
pairment appear to be at least partially independent.
Although further studies of clinical and biochemical
mechanisms are needed, we suggest that clinicians be
alert to possible mini-dose aspirin treatment phenomena
for elderly patients.
ACKNOWLEDGMENTS
We thank the nursing and laboratory staff of Shmuel
Harofeh Medical Center for their patient patients’ care, Dr. J.
Atzmon for his helpful advice, Mr. Elon Neumann, MSc, for
his friendly guidance in statistics, and the anonymous reviewer
no. 1 for Arthritis & Rheumatism for helpful comments.
REFERENCES
1. Insel PA. The salicylates. In: Hardman JG, Limbird LE, Molinoff
PB, Ruddon RW, Goodman Gilman A, editors. Goodman and
Gilman’s the pharmacological basis of therapeutics. 9th ed. New
York: McGraw-Hill; 1996. p. 625–31.
2. Yu TF, Gutman AB. Study of the paradoxical effects of salicylate
in low, intermediate and high dosage on the renal mechanisms of
excretion of urate in man. J Clin Invest 1959;38:1298–313.
3. Yu TF, Dayton PG, Gutman AB. Mutual suppression of the
uricosuric effects of sulfinpyrazone and salicylate: a study in
interactions between drugs. J Clin Invest 1963;42:1330–9.
4. Silagy CA, McNeil JJ, Donnan GA, Tonkin AM, Worsam B,
Campion K. Adverse effects of low dose aspirin in a healthy elderly
population. Clin Pharmacol Ther 1993;54:84–9.
5. Carson JL, Strom BL. Nonsteroidal antiinflammatory drugs. In:
Hazzard WR, Bierman EL, Blass JP, Ettinger WH, Halter JB,
editors. Principals of geriatric medicine and gerontology. 3rd ed.
New York: McGraw-Hill; 1994. p. 947–53.
6. Krumholtz HM, Radford MJ, Ellerbeck EF, Hennen J, Meehan
TP, Petrillo MP, et al. Aspirin in the treatment of acute myocardial
infarction in elderly Medicare beneficiaries. Circulation 1995;92:
2841–7.
CASPI ET AL
7. Krumholtz HM, Radford MJ, Ellerbeck EF, Hennen J, Meehan
TP, Petrillo MP, et al. Aspirin in the treatment of acute myocardial
infarction in elderly: prescribed use and outcomes. Ann Intern
Med 1966;124:292–8.
8. Gurwitz JH, Gore JM, Goldberg RJ, Rubison M, Chandra N,
Rogers WJ. Recent age related trends in the use of thrombolytic
therapy in patients who have had acute myocardial infarction. Ann
Intern Med 1996;124:283–91.
9. Aspirin. In: Renolds JEF, editor. Martindale the extrapharmaco-
poeia. 31st ed. London: The Royal Pharmacological Society; 1996.
p. 17–22.
10. UK TIA study group. United Kingdom transient ischaemic attack
aspirin trial interim results. BMJ 1988;296:316–20.
11. Handin RI. Anticoagulant, fibrinolytic and antiplatelet therapy.
In: Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB,
Kasper DL, et al, editors. Harrison’s principles of internal medi-
cine. 14th ed. New York: McGraw-Hill; 1998. p. 746–7.
12. Roth GJ, Stanford N, Majerus PW. Acetylation of prostaglandin
synthetase by aspirin. Proc Natl Acad Sci U S A 1975;72:3073–6.
13. Smith MJH, Ford-Hutchinson AW, Elliot PNC. Prostaglandins
and the anti-inflammatory activities of aspirin and sodium salicy-
late. J Pharm Pharmacol 1975;27:473–8.
14. Pederson AK, Fitzgerald GA. Dose related kinetics of aspirin:
presystemic acetylation of platelet cyclooxygenase. N Engl J Med
1984;311:1206–11.
15. Antiplatelet Trialists’ Collaboration. Collaborative overview of
randomised trials of antiplatelet therapy. I. Prevention of death,
myocardial infarction and stroke by prolonged antiplatelet therapy
in various categories of patients. BMJ 1994;308:81–106.
16. Antiplatelet Trialists’ Collaboration. Collaborative overview of
randomised trials of antiplatelet therapy. II. Maintenance of
vascular graft or arterial patency by antiplatelet therapy. BMJ
1994;308:159–68.
17. Antiplatelet Trialists’ Collaboration. Collaborative overview of
randomised trials of antiplatelet therapy. III. Reduction in venous
thrombosis and pulmonary embolism by antiplatelet prophylaxis
among surgical and medical patients. BMJ 1994;308:235–46.
18. Beeley L, Kendall MJ. Effect of aspirin on renal clearance of
125
I-diatrizoate. BMJ 1971;1:707–8.
19. Kimberly RP, Plotz PH. Aspirin induced depression of renal
function. N Engl J Med 1977;296:418–24.
20. Patrono C, Pierucci A. Renal effects of nonsteroidal anti-
inflammatory drugs in chronic glomerular disease. Am J Med
1986;81 Suppl 2B:71–83.
21. The RISC Group. Risk of myocardial infarction and death
during treatment with low dose aspirin and intravenous heparin
in men with unstable coronary artery disease. Lancet 1990;2:
349–60.
22. The SALT Collaborative Group. Swedish aspirin low dose trial
(SALT) of 75 mg aspirin as secondary prophylaxis after cerebro-
vascular ischaemic events. Lancet 1991;338:1345–9.
23. Weil J, Colin-Jones D, Langman M, Lawson D, Logan R, Murphy
M, et al. Prophylactic aspirin and the risk of peptic ulcer bleeding.
BMJ 1995;310:827–30.
24. Stalinkowicz-Darvasi R. Gastrointestinal bleeding during low dose
aspirin administration for prevention of arterial occlusive events: a
critical analysis. J Clin Gastroenterol 1995;21:13–6.