 |
|
Association of Nonsteroidal Anti-inflammatory Drugs With First Occurrence of Heart Failure and With Relapsing Heart Failure
The Rotterdam Study
Johan Feenstra, MD, PhD;
Eibert R. Heerdink, PharmD, PhD;
Diederick E. Grobbee, MD, PhD;
Bruno H. Ch. Stricker, MB, PhD
Arch Intern Med. 2002;162:265-270.
ABSTRACT
| |
Background Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with
first hospitalization for congestive heart failure (CHF). It is likely, however,
that NSAIDs precipitate a relapse but are less likely to induce a first occurrence
of (incident) heart failure.
Methods A total of 7277 participants in the Rotterdam Study were followed up
from the interview date until the first of the following events: a diagnosis
of incident heart failure, death, removal, or end of the follow-up period.
Excluded from the study population were all participants with prevalent heart
failure at baseline. Exposure to NSAIDs and other medication was calculated
on the basis of automated data on filled drug prescriptions in the pharmacies
within the study area. In a second analysis, we followed up all participants
with incident heart failure until the first relapse or the end of follow-up.
Results Incident heart failure was encountered in 345 participants during follow-up.
Current use of NSAIDs was associated with a relative risk of incident heart
failure of 1.1 (95% confidence interval [CI], 0.7-1.7), after adjustment for
age, sex, and concomitant medication. In patients with prevalent heart failure
who filled at least 1 NSAID prescription since diagnosis of heart failure,
the univariate and adjusted relative risks of a relapse were 3.8 (95% CI,
1.1-12.7) and 9.9 (95% CI, 1.7-57.0), respectively.
Conclusions The use of NSAIDs is not associated with an increased risk of incident
heart failure. In patients with prevalent heart failure, current use of NSAIDs
is associated with a substantially increased risk of a relapse.
INTRODUCTION
HEART FAILURE is a syndrome that results from complex circulatory and
neurohormonal responses to cardiac dysfunction.1-2
The main causes of heart failure are ischemic heart disease and arterial hypertension.3-4 According to recent guidelines of the
European Society of Cardiology, objective evidence of cardiac dysfunction
has to be present in addition to symptoms, such as shortness of breath or
fatigue at rest or during exercise and ankle swelling, to establish the presence
of heart failure.5
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with
the occurrence of heart failure in several case reports.6-9
Inhibition of the enzyme cyclo-oxygenase may result in a decrease in prostaglandin
synthesis. Prostaglandins have an important role in renal physiology, and
inhibition of their synthesis may give rise to fluid retention.10
Fluid retention caused by NSAIDs may adversely affect cardiovascular homeostasis,
and patients with a propensity for congestive heart failure seem to be particularly
susceptible to the cardiovascular effects of NSAIDs. Moreover, NSAIDs may
interfere with the cardiovascular effects of angiotensin-converting enzyme
inhibitors and diuretics.10
Previous studies demonstrated that NSAIDs may precipitate a first hospitalization
for heart failure,11-12 which
suggests that NSAIDs may not only induce a relapse of preexisting heart failure
but also be a cause of a first occurrence of (incident) heart failure. In
view of the pathophysiology of NSAID-induced heart failure, however, there
can be doubt whether NSAIDs may induce heart failure in patients without preexisting
left ventricular impairment. We tested the hypothesis that NSAIDs do not cause
a first occurrence of heart failure but may induce a relapse in patients with
prevalent heart failure. We first studied the association between NSAIDs and
a first occurrence of (incident) heart failure in a population of elderly
patients. Subsequently, we studied the association between NSAIDs and the
first relapse in these same patients to investigate a potential different
effect of NSAIDs on incident and prevalent heart failure.
PATIENTS AND METHODS
SETTING
The study was a part of the Rotterdam Study, a population-based prospective
cohort study on the prevalence, incidence, and determinants of cardiovascular,
neurologic, ophthalmologic, and locomotor diseases in the elderly.13 The first cross-sectional survey started in June
1990 and was completed in June 1993. All inhabitants of Ommoord, a suburb
of the city of Rotterdam, the Netherlands, who were 55 years or older were
invited to participate in the Rotterdam Study. Of the 10 275 eligible
subjects, 7983 (78%) agreed to participate and signed informed consent. Since
the start of the Rotterdam Study, cross-sectional surveys have been carried
out periodically by means of home interviews and periodic visits of participants
to the research center. In addition, all neurologic, ophthalmologic, cardiovascular,
and locomotor diseases that occurred since the start of follow-up in participants
of the Rotterdam Study have systematically been gathered.
STUDY POPULATION
From the cohort of 7983 participants in the Rotterdam Study, we excluded
participants who were not registered at the pharmacy or who had an unknown
date of death (n = 48). Participants with prevalent heart failure at study
entrance were excluded from the analyses (n = 453). In addition, baseline
echocardiographic data were available for 2246 participants. We excluded from
the analyses 205 participants with a fractional shortening less than 30%,
defined as [(left ventricular internal dimension at end diastole - left
ventricular internal dimension at end systole)/left ventricular internal dimension
at end diastole] x 100%.
A total of 7277 participants were included in the study population for
the present study. The study period ran from July 1, 1991, through December
31, 1998. The cohort was followed up from the date of entry in the study until
the end point of the follow-up, which was the first of one of the following
events: a diagnosis of incident heart failure, death, removal from the study
area or institutionalization, and end of the follow-up period. In a second
analysis, we followed up all participants with incident heart failure until
the first relapse or the end of follow-up as defined.
EXPOSURE DEFINITION
Computerized pharmacy records were available for all participants of
the Rotterdam Study as of January 1, 1991. All prescriptions dispensed to
participants of the Rotterdam Study by the 3 automated pharmacies in the study
area were routinely stored in a database. Drugs were coded according to the
Anatomical Therapeutic Chemical Classification.14
Every prescription included a filling date, the product name, daily dosage,
the number of filled tablets or capsules, and the prescribed daily number.
For each member of the study population, exposure to NSAIDs and concomitant
cardiovascular and pulmonary medication was assessed during follow-up. The
drug-exposure window was defined as the legend duration (prescription length),
which was calculated on the basis of the total number of filled tablets divided
by the prescribed daily number, plus a carryover period of 7 days. If the
drug-exposure windows of consecutive prescriptions of the same drug overlapped,
this was considered to be a single period of drug exposure. Hence, the follow-up
period for each member of the cohort was divided into periods of exposure
and nonexposure to the drugs of interest. Patients were considered to be current
users of each drug for which the exposure window overlapped the date of diagnosis
of incident heart failure.
OUTCOME DEFINITION
The outcome of the first analysis was considered to be a diagnosis of
incident heart failure, defined as the first occurrence of heart failure.
Heart failure is one of the areas of special interest in the Rotterdam Study.
The continuous follow-up of all participants of the Rotterdam Study, in close
cooperation with the participating general practitioners, is aimed at identifying
all events of interest, including heart failure. It is part of the routine
follow-up procedure that all available data on the events of interest, such
as hospital discharge letters and notes from general practitioners, are copied
from the records of the general practitioner. Two research physicians independently
evaluate all information on cases of heart failure that have occurred during
follow-up of the Rotterdam Study. Certainty of diagnosis is rated as possible,
probable, or definite, on the basis of the availability of additional information.
A definite diagnosis of heart failure is assumed if a medical specialist has
diagnosed heart failure on the basis of typical symptoms such as fatigue,
ankle edema, orthopnea, nocturnal dyspnea, pulmonary edema on radiography,
and a decreased ejection fraction or ventricular hypertrophy on echocardiography.
If the 2 research physicians disagree on the certainty of diagnosis, they
reevaluate these events during a consensus meeting. When disagreement on the
certainty of diagnosis remains, a cardiologist makes a final decision. In
addition, a cardiologist reevaluates all potential cases of heart failure
on which the 2 research physicians agree during the first evaluation. In the
present study, participants were regarded as patients with incident heart
failure only if there was a first diagnosis of definite heart failure as defined
above.
Apart from the follow-up procedure of the Rotterdam Study, we used hospital
discharge diagnoses concerning the study population as gathered from all hospitals
in the Rotterdam area. We considered hospital admissions for heart failure
after January 1, 1993, as incident heart failure if these patients had not
been admitted to the hospital for heart failure in the period from January
1, 1991, through January 1, 1993. If participants were identified in both
the follow-up procedure and the hospital discharge database, we took the first
date as the date of incident heart failure. For the second analysis, we defined
a relapse of CHF as a hospital admission because of heart failure in the patients
who had been followed up since the occurrence of incident heart failure. As
of that date, these individuals were considered patients with prevalent heart
failure.
COFACTORS
Apart from age and sex, we assessed the following independent risk factors
for heart failure. Hypertension was defined as systolic blood pressure greater
than 160 mm Hg and/or diastolic blood pressure greater than 95 mm Hg, or use
of antihypertensive medication for the indication hypertension. If the latter
was unsure, the variable was classified as uncertain. History of myocardial
infarction was assessed by questionnaire with confirmation on electrocardiography.
If patients mentioned myocardial infarction in their history but an electrocardiogram
was negative, the history was classified as uncertain. Atrial fibrillation
was diagnosed on the basis of a baseline electrocardiogram. Furthermore, a
serum creatinine level greater than 1.1 mg/dL (100 µmol/L) was considered
a potential risk factor for heart failure.
STATISTICAL ANALYSIS
The statistical analysis was carried out with a Cox regression model
with time-dependent covariates. Drug exposure was entered in the model as
segmented time-dependent covariates, with different values at different times.
The value of the time-dependent covariates could be calculated for each individual
member of the cohort on each day during follow-up by splitting up the follow-up
time into periods of exposure and nonexposure to the drugs of interest, based
on the start date of filled drug prescriptions and the end date plus 7 days.
First, we performed univariate analyses with the potential risk factors defined
above, NSAIDs, and cardiovascular and pulmonary medication. In the multivariate
analyses, we included all risk factors that were univariately associated with
heart failure. All tests were 2 sided, with a rejection of the null hypothesis
at P<.05. All risks were expressed as relative
risks (RRs) with 95% confidence intervals (CIs).
RESULTS
General characteristics of the study population (n = 7277) are presented
in Table 1. Mean age of the study
participants at study entrance was 70 years. Of the study population, 62%
were female. Mean follow-up was 6.0 years. Serum creatinine had been assessed
in 4882 persons, of whom 563 had a value of 1.1 mg/dL (100 µmol/L) or
more. A total of 2356 participants had hypertension, 749 participants had
a certain history of myocardial infarction, and 164 patients definitely had
atrial fibrillation at study entrance. A diagnosis of incident heart failure
during follow-up was made in 345 participants. Age, sex, hypertension, history
of myocardial infarction, atrial fibrillation, and a serum creatinine level
of 1.1 mg/dL (100 µmol/L) or more were independently associated with
incident heart failure.
|
|
|
|
Table 1. General Characteristics of the Study Population*
|
|
|
Table 2 shows that several
classes of drugs were associated with the occurrence of incident heart failure.
Among the classes with the strongest association were digoxin, antiarrhythmics,
vasodilators (mainly nitrates), loop diuretics, and potassium-sparing diuretics. Table 3 presents the results of the Cox
regression model analysis with time-dependent variables. Current use of NSAIDs
was univariately associated with a 50% increased risk of incident heart failure
(RR, 1.5; 95% CI, 1.0-2.3). In patients with a serum creatinine level less
than 1.1 mg/dL (100 µmol/L), the univariate RR of the association between
NSAIDs and heart failure was 1.4 (95% CI, 0.8-2.4). In patients with a serum
creatinine level of 1.1 mg/dL (100 µmol/L) or more, the RR was 2.0 (95%
CI, 1.9-5.5). After adjustment for age, sex, hypertension, history of myocardial
infarction, atrial fibrillation, renal function at baseline, and concomitant
medication, the RR of the association between current NSAID use and the occurrence
of incident heart failure declined to 1.1 (95% CI, 0.7-1.7). Among participants
who filled at least 1 NSAID prescription, these RRs were univariately 1.4
(95% CI, 0.9-2.1) and, after adjustment, 1.2 (95% CI, 0.8-1.8). In the second
analyses in patients who had been followed up since the occurrence of incident
heart failure, the crude and adjusted RRs of a relapse of heart failure were
1.4 (95% CI, 0.5-3.8) in both the univariate and the adjusted analyses. As
the relapses occurred in those who had had incident heart failure shortly
before, baseline hypertension, history of myocardial infarction, a serum creatinine
level of 1.1 mg/dL (100 µmol/L) or more, and atrial fibrillation were
not associated with a relapse and therefore not adjusted for. Among patients
with prevalent heart failure who filled at least 1 NSAID prescription during
follow-up, the crude RR of a first relapse of CHF was 3.8 (95% CI, 1.1-12.7).
Adjusted for age, sex, and concomitant medication, the RR was 9.9 (95% CI,
1.7-57.0).
|
|
|
|
Table 2. Association Between Use of Cardiovascular and Pulmonary Medication
and Occurrence of Incident Heart Failure*
|
|
|
|
|
|
|
Table 3. Association Between Incident Heart Failure and Use of NSAIDs*
|
|
|
COMMENT
This study indicates that current use of NSAIDs is not associated with
an increased risk of a first occurrence of heart failure. However, in the
analysis of patients who had been followed up since their diagnosis of incident
heart failure and who had filled at least 1 NSAID prescription at any time
during follow-up, the use of NSAIDs was associated with a substantially increased
risk of a relapse of heart failure.
To study the association between NSAIDs and incident heart failure appropriately,
one must exclude all patients who might already have had heart failure before
the first diagnosis. This may be difficult because a substantial number of
the patients with left ventricular impairment appear to be asymptomatic or
are undiagnosed despite signs and symptoms of heart failure.15
Our study population included 345 patients with a certain diagnosis of incident
heart failure. We excluded all patients from the study population who might
have had a possible or probable diagnosis of heart failure. This could be
achieved by means of the intensive follow-up procedure of all participants
in Rotterdam Study, which provided the information by which we were able to
decide whether participants truly represented incident cases of heart failure.
Moreover, we excluded from the analysis 205 patients with a baseline fractional
shortening less than 30%, which is regarded as the lower limit of normality.16-17 Hence, the study population consisted
only of patients with a certain diagnosis of truly incident heart failure
and patients without heart failure. In this study population, no association
between current use of NSAIDs and incident heart failure was present.
Adverse effects of NSAIDs on cardiovascular homeostasis are well established.10 Particularly in the clinical setting of reduced renal
perfusion that can be seen in patients with various disorders such as dehydration,
cardiovascular disease, and renal dysfunction, NSAIDs may impair the adequacy
of renal prostaglandin production. In patients with reduced left ventricular
function, renal prostaglandin production has a crucial role in compensatory
renal hemodynamics.18 Inhibition of cyclo-oxygenase
enzyme activity by NSAIDs will have a substantial inhibitory effect on prostaglandin
synthesis that may deteriorate cardiovascular homeostasis in these susceptible
patients. Although not statistically significant, the stratified analysis
of baseline serum creatinine level also indicated that impaired renal function,
defined as serum creatinine level of 1.1 mg/dL (100 µmol/L) or more,
seems to be associated with an increased risk of NSAID-associated heart failure.
A number of case reports have been published in which the onset of heart
failure was attributed to the use of NSAIDs.6-9
In most of these reports, patients did have preexisting cardiovascular disease
that may have predisposed to the onset of heart failure. An earlier published
record-linkage study has shown a 2-fold increased risk of a first hospitalization
for heart failure during concomitant use of NSAIDs and diuretics as compared
with use of diuretics alone in patients older than 55 years.11
As this record-linkage study was carried out within a cohort of users of diuretics,
it is likely that a number of these patients did have symptomatic left ventricular
dysfunction in the period preceding the first hospitalization for heart failure.
Many elderly patients are treated by their general practitioner because of
mild to moderate signs and symptoms of heart failure before hospital admission
is indicated. This may explain the finding in the above-mentioned record-linkage
study that the strongest increase in hospitalization risk was seen in patients
who were likely to have preexisting heart failure. Hence, a first hospitalization
for heart failure is not by definition the same as truly incident heart failure.
In our study, we included not only first hospital admissions but also all
patients with diagnoses of incident heart failure, irrespective of whether
they were admitted to the hospital or not, and excluded all patients with
an uncertain diagnosis of incident heart failure.
In a recent matched case-control study,12
use of NSAIDs in the preceding week was associated with a doubling of the
odds ratio of a hospital admission for heart failure. In patients with a first
diagnosis of heart failure, a 3-fold increased odds ratio was calculated.
A much stronger association was shown in patients with a history of heart
disease. In view of the pathophysiology of NSAID-induced heart failure,18 it seems likely that a substantial part of the cases
in this study did have preexisting left ventricular impairment before hospitalization.
In addition, the remarkably high consumption of NSAIDs of nearly 30% in the
week before hospitalization among the cases may imply either recall bias or
significant comorbidity.
The univariate association between various cardiovascular drugs and
the onset of heart failure reflects the presence of preexisting cardiovascular
disorders such as hypertension, atrial fibrillation, and ischemic heart disease,
which predispose to the development of heart failure. Although we excluded
from the analysis all patients who may have had prevalent heart failure, we
cannot exclude the possibility that some patients in the study population
did use these drugs because of heart failure. However, the presence in the
study population of some patients with prevalent heart failure is likely to
overestimate the relative risk. Hence, it seems plausible that the risk estimate
of the association between incident heart failure and NSAID use might be even
lower if we were able to exclude these patients.
The second analysis in our study in patients who were followed up since
diagnosis of heart failure (n = 292) demonstrates the different effects of
NSAIDs in patients with incident and prevalent heart failure. In patients
with prevalent heart failure who filled at least 1 NSAID prescription, current
use of NSAIDs was associated with a substantially increased risk of a relapse.
From a pathophysiologic point of view, the different effects of NSAIDs with
respect to incident and prevalent heart failure seem to be plausible, as cardiovascular
homeostasis is much more likely to be prostaglandin dependent in patients
with prevalent heart failure than in patients with unimpaired left ventricular
function.
A cohort study lacks some of the intrinsic limitations of case-control
studies. The availability of prospectively stored drug exposure data from
the automated pharmacies in the study area prevents potential differential
misclassification of exposure that may occur in case-control studies. Intensive
follow-up procedures of participants in the Rotterdam Study provided the possibility
of including only patients with definite incident heart failure and excluding
from the study population those with an uncertain diagnosis. However, we cannot
exclude the possibility that some patients with asymptomatic left ventricular
dysfunction were included in our study population.
Several cardiovascular drugs were associated with increased risk of
incident heart failure (Table 3).
Patients who develop incident heart failure are likely to have potential risk
factors such as hypertension or coronary artery disease. The findings in our
analysis on the association between NSAIDs and incident heart failure indicate
that NSAIDs do not have a substantial additional contribution to the risk
but that this is largely caused by cardiovascular comorbidity, as reflected
by cardiovascular comedication.
An important source of bias in cohort studies may arise from the degree
of accuracy with which participants have been classified regarding their exposure
and disease status. In this present study, a diagnosis of incident heart failure
could be made only on the basis of information from a medical specialist.
Two research physicians independently reviewed all available information before
rating the event as definite heart failure. In addition, this decision of
the 2 research physicians had to be confirmed by a specialist in cardiovascular
medicine. Therefore, substantial misclassification of the diagnosis of definite
heart failure seems unlikely, especially as the physicians were unaware of
the study hypothesis.
Exposure to NSAIDs was based on the information on filled drug prescriptions
in the 3 automated pharmacies in the study area. Information on over-the-counter
use of NSAIDs was not available. In the Netherlands, however, since 1995 only
a small proportion of total NSAID consumption consists of over-the-counter
drugs. Moreover, misclassification of exposure is likely to be nondifferential,
as signs and symptoms of heart failure do not prompt the use of NSAIDs.
The NSAIDs are drugs that may have several beneficial effects, particularly
for musculoskeletal disease that occurs frequently in the elderly. Despite
their potential adverse effects, many patients take advantage of the potent
analgesic and anti-inflammatory properties of these drugs. In view of the
risk-benefit profile of drugs, our finding that NSAIDs were not associated
with an increased risk of incident heart failure in a cohort of patients without
preexisting signs or symptoms of heart failure is of clinical significance.
This implies that, regarding the risk of heart failure, these drugs can safely
be prescribed to elderly patients with uncompromised left ventricular function.
In conclusion, NSAIDs were not associated with incident heart failure
in our study population. In patients with prevalent heart failure, however,
a substantially increased risk with NSAIDs was demonstrated, implying that
NSAIDs should be prescribed with caution to patients with prevalent heart
failure.
AUTHOR INFORMATION
Accepted for publication June 7, 2001.
Corresponding author and reprints: Bruno H. Ch. Stricker, MB, PhD,
Department of Epidemiology & Biostatistics, Erasmus Medical Center Rotterdam,
PO Box 1738, 3000 DR Rotterdam, the Netherlands.
From the Pharmacoepidemiology Unit, Departments of Epidemiology &
Biostatistics and Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam
(Drs Feenstra and Stricker); Drug Safety Unit, Inspectorate for Health Care,
the Hague (Drs Feenstra and Stricker); Department of Pharmacoepidemiology
and Pharmacotherapy, University of Utrecht, Utrecht (Dr Heerdink); and Julius
Center for Patient Oriented Research, Academic Hospital Utrecht, Utrecht (Dr
Grobbee), the Netherlands.
REFERENCES
| |
1. Packer M. Pathophysiology of chronic heart failure. Lancet. 1992;340:88-92.
FULL TEXT
|
ISI
| PUBMED
2. Packer M. The neurohormonal hypothesis: a theory to explain the mechanism of
disease progression in heart failure. J Am Coll Cardiol. 1992;20:248-254.
ABSTRACT
3. Cowie MR, Wood DA, Coats AJ, et al. Incidence and aetiology of heart failure: a population-based study. Eur Heart J. 1999;20:421-428.
FREE FULL TEXT
4. Cowie MR, Mosterd A, Wood DA, et al. The epidemiology of heart failure. Eur Heart J. 1997;18:208-225.
5. Task Force of the Working Group on Heart Failure of the European Society
of Cardiology. The treatment of heart failure. Eur Heart J. 1997;18:736-753.
FREE FULL TEXT
6. Schooley RT, Wagley PF, Lietman PS. Edema associated with ibuprofen therapy. JAMA. 1977;237:1716-1717.
FREE FULL TEXT
7. Tashima CK, Rose M. Pulmonary edema and salicylates. Ann Intern Med. 1974;81:274-275.
8. Nevins M, Berque S, Corwin N, Lyon L. Phenylbutazone and pulmonary oedema. Lancet. 1969;2:1358.
9. Van den Ouweland FA, Gribnau FW, Meyboom RH. Congestive heart failure due to nonsteroidal anti-inflammatory drugs
in the elderly. Age Ageing. 1988;17:8-16.
FREE FULL TEXT
10. Feenstra J, Grobbee DE, Mosterd A, Stricker BH. Adverse cardiovascular effects of NSAIDs in patients with congestive
heart failure. Drug Saf. 1997;17:166-180.
ISI
| PUBMED
11. Heerdink ER, Leufkens HG, Herings RM, Ottervanger JP, Stricker BH, Bakker A. NSAIDs associated with increased risk of congestive heart failure in
elderly patients taking diuretics. Arch Intern Med. 1998;158:1108-1112.
FREE FULL TEXT
12. Page J, Henry D. Consumption of NSAIDs and the development of congestive heart failure
in elderly patients: an underrecognized public health problem. Arch Intern Med. 2000;160:777-784.
FREE FULL TEXT
13. Hofman A, Grobbee DE, de Jong PT, van den Ouweland FA. Determinants of disease and disability in the elderly: the Rotterdam
Elderly Study. Eur J Epidemiol. 1991;7:403-422.
FULL TEXT
|
ISI
| PUBMED
14. Anatomical Therapeutic Chemical Classification Index. Oslo, Norway: World Health Organization Collaborating Centre for
Drug Statistics Methodology; 1993.
15. Mosterd A, Hoes AW, de Bruyne MC, et al. Prevalence of heart failure and left ventricular dysfunction in the
general population: the Rotterdam Study. Eur Heart J. 1999;20:447-455.
FREE FULL TEXT
16. Gutgesell HP, Paquet M, Duff DF, McNamara DG. Evaluation of left ventricular size and function by echocardiography:
results in normal children. Circulation. 1977;56:457-462.
FREE FULL TEXT
17. Quinones MA, Pickering E, Alexander JK. Percentage of shortening of the echocardiographic left ventricular
dimension: its use in determining ejection fraction and stroke volume. Chest. 1978;74:59-65.
FREE FULL TEXT
18. Dzau VJ, Packer M, Lilly LS, Swartz SL, Hollenberg NK, Williams GH. Prostaglandins in severe congestive heart failure: relation to activation
of the renin-angiotensin system and hyponatremia. N Engl J Med. 1984;310:347-352.
ABSTRACT
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED ARTICLE
Archives of Internal Medicine Reader's Choice: Continuing Medical Education
Arch Intern Med. 2002;162(3):367-368.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Baseline factors associated with congestive heart failure in patients receiving etoricoxib or diclofenac: multivariate analysis of the MEDAL program
Krum et al.
Eur J Heart Fail 2009;11:542-550.
ABSTRACT
| FULL TEXT
Non-steroidal anti-inflammatory drugs and cardiac failure: meta-analyses of observational studies and randomised controlled trials
Scott et al.
Eur J Heart Fail 2008;10:1102-1107.
ABSTRACT
| FULL TEXT
Review: Adverse cardiovascular effects of NSAIDs: driven by blood pressure, or edema?
Aneja and Farkouh
Ther Adv Cardiovasc Dis 2008;2:53-66.
ABSTRACT
Coxibs and Heart Disease: What We Have Learned and What Else We Need to Know
Zarraga and Schwarz
J Am Coll Cardiol 2007;49:1-14.
ABSTRACT
| FULL TEXT
Non-steroidal anti-inflammatory drugs and risk of first hospital admission for heart failure in the general population
Huerta et al.
Heart 2006;92:1610-1615.
ABSTRACT
| FULL TEXT
NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland
Helin-Salmivaara et al.
Eur Heart J 2006;27:1657-1663.
ABSTRACT
| FULL TEXT
Novel anti-inflammatory drugs in hypertension
Hermann and Ruschitzka
Nephrol Dial Transplant 2006;21:859-864.
FULL TEXT
Differences in outcomes of patients with congestive heart failure prescribed celecoxib, rofecoxib, or non-steroidal anti-inflammatory drugs: population based study
Hudson et al.
BMJ 2005;330:1370.
ABSTRACT
| FULL TEXT
Chronic non-malignant musculoskeletal pain in older adults: clinical issues and opioid intervention
Podichetty et al.
Postgrad. Med. J. 2003;79:627-633.
ABSTRACT
| FULL TEXT
Pharmacotherapy for Heart Failure in Patients with Renal Insufficiency
Shlipak
ANN INTERN MED 2003;138:917-924.
ABSTRACT
| FULL TEXT
Analysis of a Large Cohort of Health Maintenance Organization Patients With Congestive Heart Failure
Gladowski et al.
American Journal of Medical Quality 2003;18:73-81.
ABSTRACT
NSAIDs May Increase Risk for Worsening Heart Failure
Journal Watch Cardiology 2002;2002:3-3.
FULL TEXT
|
