Epidemiological and randomized studies have demonstrated that the incidence of cardiovascular morbidity and mortality rises when the concentration of low-density lipoprotein cholesterol increases . Conversely, reducing the concentration of serum cholesterol helps to lower the risk of cardiovascular morbidity . Specifically, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, also known as statins, reduce morbidity and mortality rates among female and male patients, those at high and low vascular risk, diabetics, non-diabetics, hypertensive and non-hypertensive patients and those without a history of cardiovascular disease, as well as in younger and older patients . However, Sattar et al. reported a 9% risk of developing diabetes in non-diabetic patients, and questioned the safety of long-term statin use. Adverse events, such as muscle damage and musculoskeletal pain, are common in statin users compared with non-users, potentially preventing the cardiovascular benefit of regular exercise, and therefore reducing quality of life in young and/or active patients .

Besides low-density lipoprotein, smoking is an undisputable strong modifiable risk factor for cardiovascular disease, and is associated with a poor survival prognosis . Smokers had a two-fold increased risk of a limited prognosis in the study by Séguro et al. , and smoking has been shown to reduce life expectancy by an average of 5.5 years . Mons et al. showed that smoking cessation, even at an older age, reduces cardiovascular mortality. Thus, smoking cessation should be a major goal in patient management. Nevertheless, the EUROASPIRE investigators reported unsatisfactory achievement of secondary prevention strategies, with limited smoking cessation, weight loss and physical activity, and an increase in the prevalence of diabetes.

Surprisingly, the benefit of statin therapy in active smokers versus non- or ex-smokers has not been investigated separately to establish a risk-benefit ratio in this particular subgroup. The JUPITER trial reported no differences in primary outcome (defined as first cardiovascular incident) between subgroups including smokers. Although this is a valuable information, data regarding smokers’ habits and whether participants stopped smoking during the study were not reported. Meta-analyses have included smokers in their data analysis, and adjusted for risk factors such as smoking, but the smokers’ status during the studies was not detailed, which limits interpretation of the findings in this subgroup .

To conclude, recent studies – especially large meta-analyses – have made us think carefully about the use of statins and their true benefits. Randomization of active smokers to statins or placebo would definitely help to identify whether statin use in patients with modifiable risk factors, such as smoking, is really of benefit and cost-effective, as the literature does not provide data to support the notion that statin treatment is truly beneficial in current smokers. Many harmful side-effects are linked with statin use, thus adverse events should be considered and treatment should be tailored to every patient.