ABSTRACT
BACKGROUND: Varenicline is an effective smoking cessation medication. Some concern has been raised that its use may precipitate adverse cardiovascular events although no patho-physiological mechanism potentially underlying such an effect has been reported. The aim of this study was to test the hypothesis that varenicline impacts on sympatho-vagal balance during smoking withdrawal. METHODS: In this randomised, placebo-controlled trial, muscle sympathetic nerve activity (MSNA), baroreflex sensitivity (BRS), heart rate, and blood pressure were assessed in 17 smokers four weeks before a quit attempt (baseline) and again on the third day of that quit attempt (acute smoking withdrawal). RESULTS: Regarding the primary endpoint of our study, we did not find a significant effect of varenicline compared to placebo on changes in MSNA burst incidence between baseline and acute smoking withdrawal (-3.0 ± 3.3 vs.-3.9 ± 5.0 bursts/100 heart beats; p = 0.308). However, heart rate and systolic blood pressure significantly decreased in the placebo group only, while no significant changes in these parameters were observed in the varenicline group. Exposure to smoking cues during acute withdrawal lead to a significant increase of heart rate in the placebo group, while heart rate decreased in the varenicline group, and the difference in these changes was significant between groups (+2.7 ± 1.0 vs.-1.8 ± 0.5 1/min; p = 0.002). In all 17 participants combined, a significant increase in heart rate during smoking cue exposure was detected in subjects who relapsed in the course of six weeks after the quit date compared to those who stayed abstinent (+2.5 ± 1.2 vs.-1.1 ± 0.7; p = 0.018). Six-week abstinence rates were higher in the varenicline group compared to placebo (88 vs. 22 % p = 0.015). CONCLUSION: We did not find evidence of adverse effects of varenicline on sympatho-vagal balance. Varenicline probably blunts the heart rate response to smoking cues, which may be linked to improved cessation outcome.
ABSTRACT
BACKGROUND: Neurohumoral activation is present in COPD and might provide a link between pulmonary and systemic effects, especially cardiovascular disease. Because long acting inhaled ß-agonists reduce hyperinflation, they could reduce sympathoexcitation by improving the inflation reflex. We aimed to evaluate if inhaled therapy with salmeterol reduces muscle sympathetic nerve activity (MSNA) evaluated by microneurography. METHODS: MSNA, heart rate, blood pressure, and respiration were continually measured. After baseline recording of 20 minutes, placebo was administered; after further 45 minutes salmeterol (50 µg) was administered which was followed by a further 45 minutes of data recording. Additionally, lung function, plasma catecholamine levels, arterial pulse wave velocity, heart rate variability, and baroreflex sensitivity were evaluated. Following 4 weeks of treatment with salmeterol 50 µg twice daily, measurements were repeated without placebo administration. RESULTS: A total of 32 COPD patients were included. Valid MSNA signals were obtained from 18 patients. Change in MSNA (bursts/100 heart beats) following acute administration of salmeterol did not differ significantly from the change following placebo (-1.96 ± 9.81 vs. -0.65 ± 9.07; p = 0.51) although hyperinflation was significantly reduced. Likewise, no changes in MSNA or catecholamines were observed after 4 weeks. Heart rate increased significantly by 3.8 ± 4.2 (p < 0.01) acutely and 3.9 ± 4.3 bpm (p < 0.01) after 4 weeks. Salmeterol treatment was safe and well tolerated. CONCLUSIONS: By using microneurography as a gold standard to evaluate sympathetic activity we found no change in MSNA following salmeterol inhalation. Thus, despite an attenuation of hyperinflation, the long acting ß-agonist salmeterol does not appear to reduce nor incite sympathoexcitation. TRIAL REGISTRATION: This study was registered with the European Clinical Trials Database (EudraCT No. 2011-001581-18) and ClinicalTrials.gov ( NCT01536587 ).
