By Harold L. Karpman, MD, FACC, FACP
Clinical Professor of Medicine, UCLA School of Medicine
Dr. Karpman reports no financial relationships relevant to this field of study.
SYNOPSIS: Use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an increased risk of incident atrial fibrillation, especially among new users of NSAIDs.
A trial fibrillation (AF) is the most common rhythm disorder observed in clinical practice. It is associated with an increase in mortality and morbidity1 and a three-fold to four-fold increased risk of thromboembolic stroke.2 Although the precise mechanisms of AF are not fully understood, inflammation may be involved in many cases of AF,3 and, if so, nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) may confer protection against AF; however, the epidemiologic literature regarding the effects of NSAID use and the frequency of AF is mixed.4-7 Because NSAIDs are used so extensively in daily practice to treat inflammatory conditions, Liu and his associates attempted to quantify the association between the use of nonaspirin NSAIDs and AF by performing a meta-analysis of all pertinent existing studies in an attempt to discern which patients are at greater risk of developing AF due to NSAID use.8
Liu and colleagues identified five studies that met the inclusion criteria regarding the reported risk of AF associated with nonaspirin NSAID use. Overall, NSAID use was associated with a 12% increased risk for the development of AF; however, the association was found to be greater for new NSAID users with a 53% increase in risk. The risk of the association was increased in patients who were afflicted with chronic heart failure and/or renal disease. Liu and colleagues concluded that the findings overall suggest that AF needs to be added to the list of cardiovascular risks when prescribing NSAIDs.
Although systemic inflammation has been associated with longer duration of AF and influences the success rates of cardioversion and catheter ablation,9-11 the results of the Liu study revealed that new use of NSAIDs was associated with a significant 53% increase in the risk of AF despite the anti-inflammatory effects of the drugs, suggesting that the precipitation of AF was due to factors other than inflammation (i.e., renal, cardiovascular-related such as congestive heart failure).
It can be hypothesized that the increased risk of developing AF among new NSAID users may be attributable to the short-term adverse renal effects that can be produced by NSAIDs. The studies analyzed in this meta-analysis were controlled for the most influential known confounders such as age and gender and for other known and suspected risk factors of AF (i.e., cigarette smoking, alcohol consumption, body mass index, and comorbidities such as diabetes, hypertension, and ischemic heart disease).
The strengths of the present study include the large size and population-based nature of the nationwide cohort and case-control studies analyzed; however, it should be noted that there was only limited information available on study participant characteristics and on which specific anti-inflammatory agents and dosages had been used. Additional well-designed and well-conducted epidemiologic studies may be necessary to further our understanding of the relationship between specific anti-inflammatory drugs, the dosages utilized, and the development of AF by investigating the relative effects of specific agents and doses in various populations of patients.
In summary, clinicians should be aware that when prescribing NSAIDs in clinical practice, an increased risk of developing AF is definitely present, especially in patients with renal disease and cardiac conditions such as congestive heart failure.
- Miyasaka Y, et al. Mortality trends in patients diagnosed with first atrial fibrillation: A 21-year community-based study. J Am Coll Cardiol 2007;49:986-992.
- Wolf PA, et al. Atrial fibrillation as an independent risk factor for stroke: The Framingham Study. Stroke 1991;22:993-998.
- Issac TT, et al. Role of inflammation in initiation and perpetuation of atrial fibrillation. J Am Coll Cardiol 2007;50:2021-2028.
- DeCaterina R, et al. Long-term use of anti-inflammatory drugs and risk of atrial fibrillation. Arch Int Med 2010;170:1450-1455.
- Schmidt M, et al. Nonsteroidal anti-inflammatory drug use and risk of atrial fibrillation or flutter: A population-based care case-control study. BMJ 2011;343.
- Chao TF, et al. The association between the use of nonsteroidal anti-inflammatory drugs and atrial fibrillation: A nationwide case-control study. Int J Cardiol 2013;168:312-316.
- Krijthe BP, et al. Nonsteroidal anti-inflammatory drugs and the risk of atrial fibrillation: A population-based follow-up study. BMJ Open 2014;4:e004059.
- Liu G, et al. Meta-analysis of nonsteroidal anti-inflammatory drug use and risk of atrial fibrillation. Am J Cardiol 2014;114:1521-1529.
- Liu T, et al. Association between C-reactive protein and recurrence of atrial fibrillation after successful electrical cardioversion: A meta-analysis. J Am Coll Card 2007;49:1642-1648.
- Chung MK, et al. C-reactive protein elevation in patients with atrial arrhythmia: Inflammatory mechanisms and persistence of atrial fibrillation. Circulation 2001;104:2886-2891.
- Lin YJ, et al. Prognostic implications of the high-sensitive C-reactive protein in the catheter ablation of atrial fibrillation. Am J Cardiol 2010; 105:495-501.