Risk of cardiac events in patients with asthma and long-QT syndrome treated with Beta(2) agonists
ABSTRACT The clinical course and risk factors associated with beta(2)-agonist therapy for asthma have not been investigated previously in patients with the long-QT syndrome (LQTS). The risk of a first LQTS-related cardiac event due to beta(2)-agonist therapy was examined in 3,287 patients enrolled in the International LQTS Registry with QTc > or = 450 ms. The Cox proportional hazards model was used to assess the independent contribution of clinical factors for first cardiac events (syncope, aborted cardiac arrest, or sudden death) from birth through age 40. Time-dependent beta(2)-agonist therapy for asthma was associated with an increased risk for cardiac events (hazard ratio [HR] = 2.00, 95% confidence interval 1.26 to 3.15, p = 0.003) after adjustment for relevant covariates including time-dependent beta-blocker use, gender, QTc, and history of asthma. This risk was augmented within the first year after the initiation of beta(2)-agonist therapy (HR = 3.53, p = 0.006). The combined use of beta(2)-agonist therapy and anti-inflammatory steroids was associated with an elevated risk for cardiac events (HR = 3.66, p <0.01); beta-blocker therapy was associated with a reduction in cardiac events in those using beta(2) agonists (HR = 0.14, p = 0.05). In conclusion, beta(2)-agonist therapy was associated with an increased risk for cardiac events in patients with asthma with LQTS, and this risk was diminished in patients receiving beta blockers.
- SourceAvailable from: Claudia R Morris
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- "Also, concerning with regards to β2-agonists is the increased incidence of prolonged QTc interval documented in patients with SCD . Independent of sickle cell disease, the use of β2-agonists in patients with prolonged QTc has been associated with an increased risk for life-threatening cardiac events . This combination of observations suggests that it may be prudent to perform a baseline ECG in patients with SCD prior to initiating therapy with β2-agonists. "
ABSTRACT: Asthma is a common comorbid factor in sickle cell disease (SCD). However, the incidence of asthma in SCD is much higher than expected compared to rates in the general population. Whether "asthma" in SCD is purely related to genetic and environmental factors or rather is the consequence of the underlying hemolytic and inflammatory state is a topic of recent debate. Regardless of the etiology, hypoxemia induced by bronchoconstriction and inflammation associated with asthma exacerbations will contribute to a cycle of sickling and subsequent complications of SCD. Recent studies confirm that asthma predisposes to complications of SCD such as pain crises, acute chest syndrome, and stroke and is associated with increased mortality. Early recognition and aggressive standard of care management of asthma may prevent serious pulmonary complications and reduce mortality. However, data regarding the management of asthma in SCD is very limited. Clinical trials are needed to evaluate the effectiveness of current asthma therapy in patients with SCD and coincident asthma, while mechanistic studies are needed to delineate the underlying pathophysiology.11/2013; 2013:604140. DOI:10.1155/2013/604140
- Circulation 02/2009; 119(2):204-6. DOI:10.1161/CIRCULATIONAHA.108.826198 · 14.95 Impact Factor
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ABSTRACT: Asthma is a common comorbidity in sickle cell disease (SCD) with a reported prevalence of 30-70%. The high frequency of asthma in this population cannot be attributed to genetic predisposition alone, and likely reflects in part, the contribution of overlapping mechanisms shared between these otherwise distinct disorders. There is accumulating evidence that dysregulated arginine metabolism and in particular, elevated arginase activity contributes to pulmonary complications in SCD. Derangements of arginine metabolism are also emerging as newly appreciated mechanism in both asthma and pulmonary hypertension independent of SCD. Patients with SCD may potentially be at risk for an asthma-like condition triggered or worsened by hemolysis-driven release of erythrocyte arginase and low nitric oxide bioavailability, in addition to classic familial asthma. Mechanisms that contributed to asthma are complex and multifactorial, influenced by genetic polymorphisms as well as environmental and infectious triggers. Given the association of asthma with inflammation, oxidative stress and hypoxemia, factors known to contribute to a vasculopathy in SCD, and the consequences of these factors on sickle erythrocytes, comorbid asthma would likely contribute to a vicious cycle of sickling and subsequent complications of SCD. Indeed a growing body of evidence documents what should come as no surprise: Asthma in SCD is associated with acute chest syndrome, stroke, pulmonary hypertension, and early mortality, and should therefore be aggressively managed based on established National Institutes of Health Guidelines for asthma management. Barriers to appropriate asthma management in SCD are discussed as well as strategies to overcome these obstacles in order to provide optimal care.American Journal of Hematology 04/2009; 84(4):234-41. DOI:10.1002/ajh.21359 · 3.48 Impact Factor