Tobacco use is one of the major public health concerns and it is the most preventable cause of morbidity and mortality worldwide. Smoking cessation reduces subsequent cardiovascular events and mortality. Smoking is a real chronic disorder characterized by the development of an addiction status mainly due to nicotine. This condition makes the smokers generally unable to quit smoking without help. Different strategies are available to treat smoking dependence that include both non-pharmacological (behavioral counselling) and pharmacological therapies. Currently, it is well accepted that smoking cessation drugs are effective and safe in real-world settings. Nicotine replacement therapy (NRT), varenicline, bupropion and cytisine are the main pharmacological strategies available for smoking cessation. Their efficacy and safety have been proved even in patients with chronic cardiovascular disease. Each of these drugs has peculiar characteristics and the clinician should customize the smoking cessation strategy based on currently available scientific evidence and patient's preference, paying particular attention to those patients having specific cardiovascular and psychiatric comorbidities. The present document aims to summarize the current viable pharmacological strategies for smoking cessation, also discussing the controversial issue regarding the use of alternative tobacco products, in order to provide useful practical indications to all physicians, mainly to those involved in cardiovascular prevention.

A worsening renal function is prevalent among patients with cardiovascular disease, especially heart failure (HF). Sacubitril/valsartan appears to prevent worsening of renal function and progression of chronic kidney disease (CKD) as compared with renin-angiotensin system (RAS) inhibitors alone in HF patients. It is unclear whether these advantages are present in HF patients only, or can be extended to other categories of patients, in which this drug was studied. We performed a systematic review and meta-analysis to assess the consistency of effect size regarding renal outcome across randomized controlled trials (RCTs) that compared sacubitril/valsartan with RAS inhibitors in patients with or without HF. We searched Medline (PubMed), Scopus, and Thomson Reuters Web of Science databases until June 2020. We took into account RCTs that compared sacubitril/valsartan with a RAS inhibitor and reported data regarding renal function. We used random-effects models to obtain summary odds ratio (OR) with 95% confidence interval (CI). We extracted hazard ratios for renal outcomes, glomerular filtration rate slopes or rates of renal adverse events. Sensitivity analyses were performed by moderator analysis and random-effects meta-regression. The search revealed 10 RCTs (published between 2012 and 2019) on 16 456 subjects. Sacubitril/valsartan resulted in a lower risk of renal dysfunction as compared with RAS inhibitors alone [k ¼ 10; pooled OR ¼ 0.70 (95% CI 0.57-0.85); P < 0.001], with a moderate inconsistency between studies [Q(9) ¼ 15.18; P ¼ 0.086; I 2 ¼ 40.73%]. A stronger association was found in studies including older patients (k ¼ 10; β ¼ À0.047730; P ¼ 0.020) or HF patients with preserved ejection fraction [pooled OR ¼ 0.53 (0.41-0.68) vs. 0.76 (0.57-1.01) for studies on HF patients with reduced ejection fraction; P for comparison ¼ 0.065]. The effect size did not change with different comparators (angiotensin-converting enzyme inhibitors vs. angiotensin II type 1 receptor blockers, P ¼ 0.279). No significant association was found when the analysis was restricted to studies on non-HF patients [k ¼ 3; pooled OR ¼ 0.86 (0.61-1.22); P ¼ 0.403] and studies with high risk of bias [k ¼ 3; pooled OR ¼ 0.34 (0.08-1.44); P ¼ 0.143]. Our findings support the role of sacubitril/valsartan on preservation of renal function, especially in older patients and HF patients with preserved ejection fraction. However, evidence is currently limited to HF patients, while the renal outcome of sacubitril/valsartan therapy outside the HF setting needs to be further investigated.