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Acute Pain | Chronic Pain | General

NSAIDs and Heart Failure

 

Clinical bottom line

NSAIDs increase the risk of developing heart failure in patients with a history of hypertension, diabetes or renal failure, particularly during the first month of treatment.


Reference


LA Garcia Rodriguez, S Hernandez-Diaz. Non-steroidal anti-inflammatory drugs as a trigger of clinical heart failure. Epidemiology 2003, 14: 240-246.


Background

Epidemiological studies suggest a two-fold increase in the incidence of hospitalisation for congestive heart failure in users of NSAIDs, and individuals with pre-existing cardiovascular diseases are at greatest risk. The widespread use of this class of drugs has prompted further investigation of the relationship between the use of NSAIDs and new cases of heart failure

Study

This was a nested case-control study using the UK General Practice Research Database (GPRD), involving all individuals aged 40 to 84 years at 1st January 1996, who were not pregnant and had no diagnosis of heart failure or cancer (n = 689,467). Participants were followed for one year (to 31st December 1996), or until they had a first time diagnosis of heart failure or cancer (index date).

Details were recorded for age, sex, smoking status, body mass index, alcohol consumption, comorbidity, and drug use. Exposure to non-aspirin NSAIDs was defined as current (last prescription ended 0 to 30 days before index date), intermediate (31 to 90 days), recent (91 to 365 days), or past (more than 365 days).

New cases of heart failure were diagnosed mainly in older individuals (70% over 69 years), and overweight, smoking and a medical history of heart or respiratory disease were risk factors. The most common indication for NSAID use was osteoarthritis (77%), followed by non-vascular pain and rheumatoid arthritis; use in vascular pain was 1% or less.

Results

Overall 9% (465/5000) of controls were current users of NSAIDs, compared to 15% (126/857) of cases with heart failure, giving a relative risk (RR) of 1.8 (95% CI 1.5 to 2.3). Adjusting for known confounding variables slightly reduced the RR to 1.6 (1.2 to 2.1). There was an increased risk for current use across all NHYA grades. The risk was increased by simultaneous use of more than one NSAID (adjusted RR 3.6; 1.4 to 9.5). It was highest during the first month of NSAID use, and fell rapidly if treatment was stopped (Table 1). Mortality following the diagnosis was 12% (103 cases) in the first month.

Table 1: Risk of CHF with NSAID use


 
Controls
(n = 5000)
Cases
(n = 857)
Relative Risk*
(95% CI)
NSAID use
None
2342
345
1.0
Current
465
126
1.59
(1.23 to 2.05)
Intermediate
158
29
1.08
(0.69 to 1.70
Recent
473
92
1.13
(0.85 to 1.49)
Past
1562
265
0.96
(0.79 to 1.16)
NSAID duration
1 to 30 days
110
31
2.13
(1.36 to 3.33)
31 to 365 days
148
38
1.32
(0.87 to 2.00)
365+ days
207
57
1.54
(1.08 to 2.18)
* Relative risk adjusted for known potential confounders

The risk of developing heart failure with NSAIDs was higher if the underlying etiology was hypertension, or if there was a history of hypertension, diabetes or renal failure. There was no significant difference between users and non-users if there was no history of hypertension, diabetes or renal failure (Table 2).

Table 2: Risk of CHF and undelying medical problems


Medical History
Relative Risk*
(95% CI)
With diabetes, renal failure, or hypertension
1.9
(1.3 to 2.8)
Without diabetes, renal failure, or hypertension
1.3
(0.9 to 1.9)
With hypertension and renal failure or diabetes
5.9
(1.8 to 19.0)
With hypertension but no renal failure or diabetes
1.7
(1.1 to 2.7)
* relative risk adjusted for known potential confounders
Non-users without diabetes, renal failure, hypertension
1.00 (ref)
Non-users with diabetes, renal failure, hypertension
1.6
(1.2 to 2.0)
Users without diabetes, renal failure, hypertension
1.3
(0.9 to 2.0)
Users with diabetes, renal failure, hypertension
2.9
(2.0 to 4.1)
* relative risk adjusted for known potential confounders

Comment

NSAIDs increase the risk of developing heart failure in patients with a history of hypertension, diabetes or renal failure, particularly during the first month of treatment. They should be used with care in patients with impaired vascular haemostasis or renal function.