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).
- Cases: Of 3,123 identified cases of newly diagnosed heart failure, 1,200 were randomly selected for validation by GP questionnaire and manual review of computerised records, and 857 were both confirmed and had complete data on severity (NYHA) and underlying cause.
- Contols: A random sample of 5,000 controls, frequency-matched by age and sex, was taken from the remaining cohort who did not have a diagnosis of heart failure or cancer.
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
(n = 5000) |
(n = 857) |
(95% CI) |
|
| NSAID use |
|||
| None | |||
| Current | (1.23 to 2.05) |
||
| Intermediate | (0.69 to 1.70 |
||
| Recent | (0.85 to 1.49) |
||
| Past | (0.79 to 1.16) |
||
| NSAID duration
|
|||
| 1 to 30 days |
|
|
(1.36 to 3.33) |
| 31 to 365 days |
|
|
(0.87 to 2.00) |
| 365+ days |
|
|
(1.08 to 2.18) |
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
(95% CI) |
|
| With diabetes, renal failure, or hypertension | (1.3 to 2.8) |
| Without diabetes, renal failure, or hypertension | (0.9 to 1.9) |
| With hypertension and renal failure or diabetes | (1.8 to 19.0) |
| With hypertension but no renal failure or diabetes | (1.1 to 2.7) |
| Non-users without diabetes, renal failure, hypertension | |
| Non-users with diabetes, renal failure, hypertension | (1.2 to 2.0) |
| Users without diabetes, renal failure, hypertension | (0.9 to 2.0) |
| Users with diabetes, renal failure, hypertension | (2.0 to 4.1) |
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.