Heart Failure Factors in Patients on Etoricoxib or Diclofenac
Heart Failure Factors in Patients on Etoricoxib or Diclofenac
Aims: Non-steroidal anti-inflammatory drugs have been associated with increased risk of congestive heart failure (CHF). We aimed to assess the impact of treatment with etoricoxib or diclofenac on risk of CHF relative to baseline risk factors.
Methods and Results: We performed a multivariate analysis of 34 701 patients with arthritis receiving etoricoxib 60 or 90 mg, or diclofenac 150 mg, daily for a mean of 18 months, to assess the incidence of confirmed, adjudicated CHF events resulting in emergency room visit or hospitalization. Analyses were performed using a Cox proportional hazard model to evaluate the hazard ratio (HR) between the levels of each risk marker for the incidence of CHF. Significant risk markers included history of CHF (HR: 6.69, 95% CI 3.59–12.47; P <0.0001), age ≥65 years (2.56, 1.65–3.98; P <0.0001), and history of hypertension (1.83, 1.16–2.89; P = 0.0094) or diabetes (1.83, 1.15–2.94; P = 0.0116). Etoricoxib vs. diclofenac was a significant risk factor only when pooling the etoricoxib 90 mg cohorts (1.88; 1.13–3.10; P = 0.0143). Etoricoxib 60 mg did not significantly increase risk vs. diclofenac.
Conclusion: History of CHF was highly associated with risk for CHF hospitalization. Hypertension, diabetes, and older age also increased risk modestly. There appeared to be a dose-related increase in CHF with etoricoxib compared with diclofenac, which reached statistical significance when the etoricoxib 90 mg groups (osteoarthritis and rheumatoid arthritis) were pooled.
Traditional, non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) and cyclo-oxygenase-2 (COX-2) selective inhibitors are widely used to control symptoms in osteoarthritis (OA) and rheumatoid arthritis (RA). There has been considerable controversy and interest regarding the cardiovascular (CV) safety of COX-2 inhibitors and NSAIDs in general after studies demonstrated increased thrombotic CV events with both COX-2 selective inhibitors and nsNSAIDs. However, relatively less attention has been paid to the effects of these drugs on exacerbation of the syndrome of congestive heart failure (CHF).
The effects of NSAIDs on renal physiology have been well documented, where an increase in fluid retention is the predominant effect, and several large epidemiological studies or meta-analyses have demonstrated increased rates of CHF with nsNSAIDs and COX-2 selective inhibitors. These studies were primarily observational, without adjudication of CHF as an endpoint. In some of these studies, a significant increase in CHF events was only observed in patients with a history of CHF, whereas the rate of incident CHF was not significantly increased. Others showed that CHF incidence was only significantly increased in those with concurrent oedema or increased blood pressure, but not for the overall study population. In addition, many studies showed that the risk of CHF was further increased in patients with one or more CHF risk factors, suggesting that patient characteristics and comorbid disease may play a central role in the effect of NSAIDs on CHF risk.
We performed a multivariate analysis of risk factors for CHF using data from the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) program, a large, prospective CV outcomes study, to assess the relative impact of the baseline factors on the incidence of confirmed adjudicated hospitalizations or emergency room (ER) visits for CHF, while accounting for treatment with a COX-2 selective inhibitor or nsNSAID.
Abstract and Introduction
Abstract
Aims: Non-steroidal anti-inflammatory drugs have been associated with increased risk of congestive heart failure (CHF). We aimed to assess the impact of treatment with etoricoxib or diclofenac on risk of CHF relative to baseline risk factors.
Methods and Results: We performed a multivariate analysis of 34 701 patients with arthritis receiving etoricoxib 60 or 90 mg, or diclofenac 150 mg, daily for a mean of 18 months, to assess the incidence of confirmed, adjudicated CHF events resulting in emergency room visit or hospitalization. Analyses were performed using a Cox proportional hazard model to evaluate the hazard ratio (HR) between the levels of each risk marker for the incidence of CHF. Significant risk markers included history of CHF (HR: 6.69, 95% CI 3.59–12.47; P <0.0001), age ≥65 years (2.56, 1.65–3.98; P <0.0001), and history of hypertension (1.83, 1.16–2.89; P = 0.0094) or diabetes (1.83, 1.15–2.94; P = 0.0116). Etoricoxib vs. diclofenac was a significant risk factor only when pooling the etoricoxib 90 mg cohorts (1.88; 1.13–3.10; P = 0.0143). Etoricoxib 60 mg did not significantly increase risk vs. diclofenac.
Conclusion: History of CHF was highly associated with risk for CHF hospitalization. Hypertension, diabetes, and older age also increased risk modestly. There appeared to be a dose-related increase in CHF with etoricoxib compared with diclofenac, which reached statistical significance when the etoricoxib 90 mg groups (osteoarthritis and rheumatoid arthritis) were pooled.
Introduction
Traditional, non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) and cyclo-oxygenase-2 (COX-2) selective inhibitors are widely used to control symptoms in osteoarthritis (OA) and rheumatoid arthritis (RA). There has been considerable controversy and interest regarding the cardiovascular (CV) safety of COX-2 inhibitors and NSAIDs in general after studies demonstrated increased thrombotic CV events with both COX-2 selective inhibitors and nsNSAIDs. However, relatively less attention has been paid to the effects of these drugs on exacerbation of the syndrome of congestive heart failure (CHF).
The effects of NSAIDs on renal physiology have been well documented, where an increase in fluid retention is the predominant effect, and several large epidemiological studies or meta-analyses have demonstrated increased rates of CHF with nsNSAIDs and COX-2 selective inhibitors. These studies were primarily observational, without adjudication of CHF as an endpoint. In some of these studies, a significant increase in CHF events was only observed in patients with a history of CHF, whereas the rate of incident CHF was not significantly increased. Others showed that CHF incidence was only significantly increased in those with concurrent oedema or increased blood pressure, but not for the overall study population. In addition, many studies showed that the risk of CHF was further increased in patients with one or more CHF risk factors, suggesting that patient characteristics and comorbid disease may play a central role in the effect of NSAIDs on CHF risk.
We performed a multivariate analysis of risk factors for CHF using data from the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) program, a large, prospective CV outcomes study, to assess the relative impact of the baseline factors on the incidence of confirmed adjudicated hospitalizations or emergency room (ER) visits for CHF, while accounting for treatment with a COX-2 selective inhibitor or nsNSAID.
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