Consumption of NSAIDS in the Development of Congestive Heart Failure

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Consumption of NSAIDs in the development of Congestive Heart Failure

JoAnn Guest

Mar 07, 2004 12:56 PST

 

Arch Intern Med. 2000 Mar 27;160(6):777-84.

Related Articles, Links

Comment in: Arch Intern Med. 2000 Oct 23;160(19):3004-5.

 

Consumption of NSAIDs and the development of congestive heart

failure in elderly patients:

an underrecognized public health problem.

 

Page J, Henry D.

 

Centre for Clinical Epidemiology and Biostatistics, Faculty of Medicine

and Health Sciences, The University of Newcastle, Australia.

 

BACKGROUND: Experimental studies have shown that administration of

nonsteroidal anti-inflammatory drugs (NSAIDs) to susceptible individuals

can lead to the development of congestive heart failure (CHF). There

have been few epidemiological investigations of the importance of this

adverse effect.

 

OBJECTIVE: To estimate the relative risk of first admission to a

hospital with CHF in recent users of NSAIDs, compared with nonusers, and

to determine whether the estimated relative risk was increased in those

with a history of heart disease and the extent to which the level of

risk varied with the dose and half-life of the drugs consumed.

 

METHODS: We conducted a matched case-control study of the relationship

between recent use of NSAIDs and hospitalization with CHF. Cases (n =

365) were patients admitted to hospitals with a primary diagnosis of

CHF. Controls (n = 658) were patients without CHF who were admitted to

the same hospitals as case patients.

 

Structured interviews were used to obtain information on several study

factors, including recent use of aspirin and other NSAIDs. RESULTS: Use

of NSAIDs in the previous week was associated with a doubling of the

odds of a hospital admission with CHF (adjusted odds ratio, 2.1; 95%

confidence interval, 1.2-3.3).

 

Use of NSAIDs by patients with a history of heart disease was associated

with an odds ratio of 10.5 (95% confidence interval, 2.5-44.9) for first

admission with heart failure, compared with 1.6 (95% confidence

interval, 0.7-3.7) in those without such a history.

 

The odds of a first admission to a hospital with CHF was positively

related to the dose of NSAID consumed in the previous week, and was

increased to a greater extent with long half-life than with short

half-life drugs. Assuming these relationships are causal, NSAIDs were

responsible for approximately 19% of hospital admissions with CHF.

CONCLUSIONS: The burden of illness resulting from NSAID-related CHF may

exceed that resulting from gastrointestinal tract damage. NSAIDs should

be used with caution in patients with a history of cardiovascular

disease.

 

PMID: 10737277 [PubMed - indexed for MEDLINE]

 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

0737277 & dopt=Abstract

 

_________________

Posted: Sun Mar 07, 2004 12:41 pm

Post subject: Aspirin, like all other drugs, is a poison

 

---Editorials

 

 

Aspirin, like all other drugs, is a poison

Papers p 1183

 

 

Aspirin is an old drug. Some 2000 years ago the Greeks used the bark and

leaves of the willow tree (which contains salicylic acid) to relieve

pain and fever.

 

At the end of the 19th century acetyl salicylic acid started being

produced on an industrial scale and aspirin soon became a widely used

painkiller. In the late 1960s it was found that a single dose of aspirin

irreversibly inhibits the normal aggregation of platelets by suppressing

the cycloxygenase mediated synthesis of thromboxane A2.

 

The effect of aspirin persists until newly formed platelets have been

released; their biological lifespan is about nine days.

 

Sometimes, adverse drug reactions can be turned to advantage, and the

antithrombotic effects of aspirin have been widely exploited. Aspirin

has been given successfully both to healthy people and to patients with

coronary artery disease to prevent myocardial infarction, to patients

with acute myocardial infarction to reduce vascular mortality, to

patients with atrial fibrillation to prevent stroke and systemic

embolism, and to patients with a history of stroke or transient

ischaemic attack to prevent further ischaemic events.

 

It has been suggested that aspirin should be given to all men aged 50

years or older and to all women after the menopause.

 

There are, however, two related reasons why this enthusiasm needs to be

dampened.

 

Firstly, aspirin, through its ability to block the synthesis of

prostaglandins, may damage the gastrointestinal mucosa.

 

Erosions may be trivial, but they may progress to ulcers, which in turn

may bleed or perforate, and may even kill. This happens more often than

many doctors like to believe.

 

Secondly, reduced thrombus formation results in a greater tendency to

bleed. Thus, in a patient who is taking aspirin any ulcer that may arise

may bleed even more extensively.

 

It seems, therefore, a logical aim to use the minimum dose of aspirin

that inhibits thrombus formation and also minimises the risk of any

gastrointestinal complications.

Thus, physicians have been treating their patients with low dose

aspirin on the understanding that they did more good than harm to them.

 

There is now strong evidence in this issue of the BMJ from yet another

systematic review of randomised trials that this may not necessarily be

so (p 1183).

 

These authors tested the risk of gastrointestinal haemorrhage from long

term (average duration 28 months) treatment with subanalgesic doses of

aspirin used for preventing ischaemic events. There were two main

results.

 

Firstly, gastrointestinal haemorrhage occurred on average in 2.5% of

patients exposed to aspirin compared with 1.4% who were not; this

difference was statistically significant.

 

Secondly, there was no evidence of dose responsiveness over a wide

range of doses (50 to 1500 mg/day).

 

How do these numbers compare with others, and what are the

implications?

 

A previous systematic review reported a considerably lower incidence of

gastrointestinal bleeds with non-steroidal anti-inflammatory drugs

including aspirin, and there was evidence of dose-responsiveness for

bleeds that were related to aspirin.

 

The difference between the two meta-analyses is probably due to

different definitions of adverse events. For instance, in the

physician's health study,1 a large randomised trial included in both

meta-analyses, 8 9 of 11 037 patients given aspirin 325 mg every other

day for 60 months, as many as 3.6% had symptoms of haematemesis or

melaena.

This was the level of harm that Derry and Loke were extracting for the

purpose of their systematic review.

 

There was evidence of dose responsiveness8: the incidence of serious

bleeds (and perforations) was 0.3% with 325 mg aspirin every other day

for 60 months,1 0.6% with 1 g/day for 36 months,10 and 0.9% with 2.5-5.2

g/day for two months.

Indeed, the most important message in Derry and Loke's paper is that

there is no gain without pain.

And as with many systematic reviews, their's leaves more questions open

than it answers. Thus, the research agenda is set:

Who should be given what dose of aspirin, and for how long? In patients

with a history of stroke or transient ischaemic attack, the minimal

effective dose of aspirin to prevent further vascular accidents remains

unknown. In elderly patients with atrial fibrillation the benefit of

prophylactic aspirin to prevent strokes is unproved.

 

Also the risk of both gastrointestinal complications and perhaps

congestive heart failure with non-steroidal anti-inflammatory drugs may

increase with increasing age.

 

Finally, there is a methodological message. Derry and Loke analysed data

from almost 66 000 patients chronically exposed to a wide range of

different doses of aspirin. It is unlikely that the same body of data

would ever be tested in a single randomised controlled trial.

 

Innovative models are needed to estimate rare events with confidence,

and systematic reviews currently provide the best solution.

 

 

In the light of Derry and Loke's analyses, it may be more appropriate

for some people to eat an apple

rather than an aspirin a day.

 

Martin R Tramèr, staff anaesthetist.

 

Division of Anaesthesiology, Geneva University Hospitals, CH-1211 Geneva

14, Switzerland (martin.-)

 

--

 

 

1. Steering Committee of the Physician's Health Study Research Group.

Final report on the aspirin component of the ongoing physicians' health

study. N Engl J Med 1989; 321: 129-135[Abstract].

2. 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 1991; 336: 827-830.

3. ISIS-2 (Second International Study of Infarct Survival) Collaborative

Group. Randomised trial of intravenous streptokinase, oral aspirin,

both, or neither among 17 187 cases of suspected acute myocardial

infarction: ISIS-2. Lancet 1988; 336: 349-360.

4. Preliminary report of the stoke prevention in atrial fibrillation

study. N Engl J Med 1990; 322: 863-868[Abstract].

5. Chen ZM, Sandercock P, Pan HC, Counsell C, Collins R, Liu LS, et al.

Indications for early aspirin use in acute ischemic stroke. A combined

analysis of 40,000 randomized patients from the Chinese Acute Stroke

Trial and the International Stroke Trial. Stroke 2000; 31:

1240-1249[Abstract/Free Full Text].

6. Dalen JE. An apple a day or an aspirin a day? Arch Int Med 1991; 151:

1066-1068[CrossRef][Medline].

7. Henry D, Lim LLY, Rodriquez LAG, Gutthann SP, Carson JL, Griffin M,

et al. Variability in risk of gastrointestinal complications with

individual non-steroidal anti-inflammatory drugs: results of a

collaborative meta-analysis. BMJ 1996; 312: 1563-1566[Abstract/Free Full

Text].

8. Tramèr MR, Moore RA, Reynolds DJ, McQuay HJ. Quantitative estimation

of rare adverse events which follow a biological progression: a new

model applied to chronic NSAID use. Pain 2000; 85:

169-182[CrossRef][Medline].

9. Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long-term

use of aspirin: meta-analysis. BMJ 2000; 321: 1183-1187[Abstract/Free

Full Text].

10. Kurata JH, Abbey DE. The effect of chronic aspirin use on duodenal

and gastric ulcer hospitalizations. J Clin Gastroenterol 1990; 12:

260-266[Medline].

11. Roth S, Agrawal N, Mahowald M, Montoya H, Robbins D, Miller S, et

al. Misoprostol heals gastroduodenal injury in patients with rheumatoid

arthritis receiving aspirin. Arch Intern Med 1989; 149:

775-779[Abstract].

12. Roderick PJ, Wilkes HC, Meade TW. The gastrointestinal toxicity of

aspirin: an overview of randomised controlled trials. Br J Clin Pharmaco

1993; 35: 219-226[Medline].

13. Johnson ES, Lanes SF, Wentworth III CE, Satterfield MH, Abebe BL,

Dicker LW. A Metaregression analysis of the dose-response effect of

aspirin on stroke. Arch Int Med 1999; 159: 1248-1253[Abstract/Free Full

Text].

14. Hawkey CJ. Non-steroidal anti-inflammatory drugs and peptic ulcers.

Facts and figures multiply, but do they add up? BMJ 1990; 300:

278-284[Medline].

15. Page J, Henry D. Consumption of NSAIDs and the development of

congestive heart failure in elderly patients. Arch Int Med 2000; 160:

777-784[Abstract/Free Full Text].

 

http://bmj.bmjjournals.com/cgi/content/full/321/7270/1170

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JoAnn Guest

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