By Seema Gupta, MD, MSPH
Primary Care Physician,
Dr. Gupta reports no financial relationships relevant to this field of study.
Synopsis: In a study of patients with atrial fibrillation, there was a higher risk of severe bleeding in smokers, mainly in those treated with vitamin K antagonists.
Source: Angoulvant D, et al. Effect of active smoking on comparative efficacy of antithrombotic therapy in patients with atrial fibrillation: The Loire Valley Atrial Fibrillation Project. Chest 2015 Mar 26. doi: 10.1378/chest.14-3006. [Epub ahead of print].
Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice, affecting an estimated 2.7 million individuals in the United States.1 The proportion of strokes attributable to AF increases strikingly from 1.5% at 50-59 years of age to 23.5% at 80-89 years of age.2 Approximately 15-20% of all strokes are due to AF. To predict the thromboembolic risk in the individual patient, risk models used most frequently are CHA2DS2-VASc and CHADS2 scores. The CHA2DS2-VASc score may be the better option since both the 2014 American Heart Association, American College of Cardiology, Heart Rhythm Society AF guidelines, and the 2012 European Society of Cardiology AF guidelines prefer it when evaluating the individual thromboembolic risk associated with AF and to determine the risk:benefit ratio of antithrombotic therapy.3
Anticoagulation has been shown to substantially reduce the risk of ischemic stroke by up to 60%. However, this is at the expense of an increase in risk of bleeding, including intracranial hemorrhage, which may be disabling or fatal. To assess the risk for anticoagulation-induced bleeding, risk models for patients with AF include the HEMORR2HAGES risk index and the HAS-BLED risk score.4 Each includes a number of risk factors, including age, renal or hepatic dysfunction, hypertension, bleeding tendency, and stroke.
Interestingly, active smoking is a frequent cardiovascular risk factor that is usually associated with a higher risk of thrombotic events. Smoking has been shown to independently influence poor INR control in patients with AF (SAMe-TT2R2 score) initiated on vitamin K antagonists (VKA).5 Therefore, active smoking could influence the risks of stroke and bleeding in AF patients treated with VKA or with antiplatelet therapy (APT).
In their study, Angoulvant and colleagues compared the clinical outcomes of 7809 consecutive patients with a diagnosis of AF seen at a French hospital from 2000 to 2010 with relation to their smoking status. Of those, 62% were male, with mean age of 71 ± 15 years. Smokers tended to be younger, more males than females, and have more comorbidities compared to non-smokers. Overall, 1034 (13%) participants were actively smoking. APT was prescribed for 2761 patients (35%) and VKA in 4534 (57%).
Smokers were found to have higher HAS-BLED and SAMe-TT2R2 scores, while the CHA2DS2-VASc score was similar in the smokers and non-smokers. After a follow-up of 929 ± 1082 days (median = 463 days), researchers found that smoking was not independently associated with a higher risk of stroke or thromboembolism in AF patients (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.78-1.22; P = 0.66). However, on conducting the multivariate analysis, smoking was independently associated with a worse prognosis for the risk of severe bleeding (HR, 1.23; 95% CI, 1.01-1.49; P = 0.04) and for the risk of major bleeding (HR, 1.40; 95% CI, 1.02-1.90; P= 0.03). In comparing the use of VKA with APT, smoking was independently associated with a higher risk of bleeding in patients treated with VKA (HR, 1.32; 95% CI, 1.04-1.67; P = 0.02), while the risk was statistically non-significant in patients treated with APT (HR, 1.28; 95% CI, 0.94-1.74; P = 0.11).
In this study, researchers found that while actively smoking AF patients did not have a higher risk of thromboembolic events, they did exhibit a significantly higher risk of severe bleeding risk, particularly in patients treated with VKA such as warfarin. This is an especially interesting finding since the risk of bleeding in AF patients with anticoagulation therapy increases with age and the active smoking status AF patients in the study were significantly younger. Previous studies in this field have demonstrated a variety of effects of smoking on VKA use. A meta-analysis suggested that smoking may potentially cause significant interactions with warfarin by enhancing its clearance, leading to reduced warfarin effects.6
Other studies have demonstrated that smoking cessation is associated with increased INR values. Perhaps, based on current and previous findings, it would be fair to draw the conclusion that smoking induces INR instability, which may lead to increased bleeding risk and, therefore, would require closer monitoring of the INR in such an AF patient being treated with VKA. This study did not include the newer non-vitamin K oral anticoagulants. Regardless of the choice of agent for use, this is yet another reason to recommend smoking cessation in our patients.
- Go AS, et al. Prevalence of diagnosed atrial fibrillation in adults: National implications for rhythm management and stroke prevention — the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370-2375.
- Wolf PA, et al. Atrial fibrillation as an independent risk factor for stroke: The Framingham Study. Stroke 1991;22:983-988.
- American College of Cardiology Foundation, American Heart Association, European Society of Cardiology, Heart Rhythm Society, Wann LS, Curtis AB, Ellenbogen KA, et al. Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS recommendations): A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Circulation 2013;127:1916-1926.
- Thomas IC, Sorrentino MJ. Bleeding risk prediction models in atrial fibrillation. Curr Cardiol Rep 2014;16:432.
- Apostolakis S, et al. Factors affecting quality of anticoagulation control among patients with atrial fibrillation on warfarin: The SAMe-TT2R2 score. Chest 2013;144:1555-1563.
- Nathisuwan S, et al. Assessing evidence of interaction between smoking and warfarin: A systematic review and meta-analysis. Chest 2011;139:1130-1139.
- Colucci VJ, Knapp JF. Increase in international normalized ratio associated with smoking cessation. Ann Pharmacother 2001;35:385.