The Impact of Smoking on Cardiovascular Outcomes and Comorbidities in Statin-treated Patients with Coronary Artery Disease: A Post hoc Analysis of the GREACE Study

Vasilios   G.   Athyros; Konstantinos      Tziomalos; Niki      Katsiki; Thomas   D.   Gossios; Olga      Giouleme; Panagiotis      Anagnostis; Efstathios   D.   Pagourelias; Eleni      Theocharidou; Asterios      Karagiannis; Dimitri   P.   Mikhailidis; for the GREACE Study Collaborative Group

Abstract

Background: Smoking adversely affects cardiovascular disease (CVD) morbidity and mortality; however the effect of long-term statin treatment in high risk smokers is not entirely clear.

The primary endpoint of this post hoc analysis of the GREek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study (n=1,600 patients with established coronary heart disease, mean follow-up 3-years) was the incidence of major CVD events, a composite of death, myocardial infarction, revascularization, unstable angina, heart failure, and stroke in statin-treated patients (n=880) who continued to smoke (n=129) compared with ex-smokers (n=309) and never smokers (n=442) as well as on patients not treated with a statin (n=720) of all smoking categories. Secondary endpoints were the effect of smoking on chronic kidney disease (CKD) and on non-alcoholic fatty liver disease (NAFLD), two major and common independent CVD risk factors.

Results: Among statin treated patients the hazard ratio (HR) for current smokers compared with never smokers was 1.86 [95% confidence interval-(CI) 1.19-2.10); similar was the HR for current smokers compared with ex-smokers. Absolute (16.3%) and relative (45.6%) CVD risk reduction was great in current smokers on statins compared with those not on a statin; however they still had the highest absolute CVD event incidence (19.4%). Low high density lipoprotein cholesterol and higher triglycerides may account, at least in part, for this. The highest risk of CVD events in any of the 6 groups was in the smokers not on a statin (35.7%). CKD and NAFLD were not negatively affected by smoking and they do not appear to be implicated in the adverse effect of smoking on CVD event rate in patients on a statin.

Conclusions: Statins reduce CVD morbidity and mortality in current smokers with CVD, but these remain high in terms of absolute incidence compared with ex- and never smokers. CKD and NAFLD are not affected by smoking and do not seem to contribute to this high CVD event incidence. These make smoking cessation imperative in high risk patients even if they are on statins.

Keywords: Cardiovascular disease, smoking, statin, morbidity, mortality, chronic kidney disease, non-alcoholic fatty liver disease.

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