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Quitting must be encouraged in all smokers, and passive smoking should be avoided as much as possible. Very brief advice may be advantageous when time is limited (Table 9). A major impetus for cessation occurs at the time of diagnosis or treatment of CVD. Prompting a person to try to quit, brief reiteration of CV and other benefits of quitting, and agreeing on a specific plan with a follow-up arrangement are evidence-based interventions. Smokers who quit may expect an average weight gain of 5 kg, but the health benefits of tobacco cessation outweigh risks from weight gain.495 Persistent or reuptake of smoking is common in patients with CHD, in particular in those with severe depression and environmental exposures.498 Mood-management therapies may improve outcomes in patients with current or past depression.499

4.5.2. Evidence-based drug interventions Drug support for stopping smoking should be considered in all smokers who are ready to undertake this action. Evidence-based drug interventions include nicotine-replacement therapy (NRT), bupropion, varenicline, and cytisine (not widely available).489491 All forms of NRT (chewing gum, transdermal nicotine patches, nasal spray, inhaler, sublingual tablets) are effective. Combination vs. single-form NRT and 4 mg vs. 2 mg gum can increase success.492 NRT shows no adverse effects in patients with ASCVD,493 but evidence of efficacy in this group is inconclusive.494 In patients with ASCVD, varenicline (RR 2.6), bupropion (RR 1.4), telephone therapy (RR 1.5), and individual counselling (RR 1.6) all increase success rates.494 The antidepressant, bupropion, aids longterm smoking cessation with similar efficacy to NRT.490 Varenicline 1 mg b.i.d. (twice a day) increases quitting rates more than two-fold compared with placebo.491 The RR for abstinence vs. NRT was 1.25 and vs. bupropion, 1.4. Lower or variable doses are also effective and reduce side-effects. Varenicline beyond the 12week standard regimen is well tolerated. Varenicline initiated in hospital following ACS is efficacious and safe.500 The main side-effect of varenicline is nausea, but this usually subsides. A causal link between varenicline and neuropsychiatric adverse events is unlikely.501 Varenicline, bupropion, and NRT do not increase serious CV adverse event risks during or after treatment.502 Cytisine is effective for smoking cessation, but evidence to date is limited.491

4.5.2.1 Electronic cigarettes Electronic cigarettes (e-cigarettes) simulate combustible cigarettes by heating nicotine and other chemicals into a vapour. E-cigarettes deliver nicotine without most of the tobacco chemicals, and are probably less harmful than tobacco.

Recent evidence suggests that e-cigarettes are probably more effective than NRT in terms of smoking cessation.503505 The longterm effects of e-cigarettes on CV and pulmonary health, however, require more research.506 Dual use with cigarettes should be avoided. Furthermore, as e-cigarettes are addictive, their use should be subject to similar marketing controls as standard cigarettes, especially the flavoured varieties that appeal to children.507 Despite being lower in toxicants than regular cigarettes, ‘heat-not-burn’ cigarettes do contain tobacco and should be discouraged.

4.6 Lipids

This section covers recommendations for the diagnosis and treatment of unfavourable blood lipid levels. More detail and guidance for complex cases/tertiary care, including genetic lipid disorders, are available in the 2019 ESC/European Atherosclerosis Society (EAS) Guidelines for the management of dyslipidaemias.3 Recent evidence has confirmed that the key initiating event in atherogenesis is the retention of LDL and other cholesterol-rich lipoproteins within the arterial wall. The causal role of LDL-C, and other apo- B-containing lipoproteins, in the development of ASCVD is demonstrated beyond any doubt by genetic, observational, and interventional studies.20 Meta-analysis of clinical trials has indicated that the relative reduction in CVD risk is proportional to the absolute reduction of LDL-C, irrespective of the drug(s) used to achieve such change, with no evidence of a lower limit for LDL-C values or ‘J-curve’ effect.21 The absolute benefit of lowering LDL-C depends on the absolute risk of ASCVD and the absolute reduction in LDL-C, so even a small absolute reduction in LDL-C may translate to significant absolute risk reduction in a high- or very-high-risk patient.22 A recent LDL-C target-driven RCT in patients after ischaemic stroke or transient ischaemic attack (TIA) demonstrated a target LDL-C level of <1.8 mmol/L (70 mg/dL) with the use of statin and, if required, ezetimibe, was associated with a lower CVD risk than those who had a target range of 2.32.8 mmol/L (90110 mg/dL).508 Studies on the clinical safety of (very) low achieved LDL-C values have not caused particular concerns, although monitoring for longer periods is required.

4.6.1. Measurement of lipids and lipoproteins 4.6.1.1 Fasting vs. non-fasting measurements Non-fasting sampling of lipid parameters is recommended for general risk screening, since it has the same prognostic value as fasting samples.509,510 In patients with metabolic syndrome, DM, or hypertriglyceridaemia, calculated LDL-C from non-fasting samples should be interpreted with care.

Table 10 Corresponding non-high-density lipoprotein cholesterol and apolipoprotein B levels for commonly used low-density lipoprotein cholesterol goals

LDL-C Non-HDL-C Apolipoprotein B

2.6 mmol/L (100 mg/dL) 3.4 mmol/L (131 mg/dL) 100 mg/dL

1.8 mmol/L (70 mg/dL) 2.6 mmol/L (100 mg/dL) 80 mg/dL 1.4 mmol/L (55 mg/dL) 2.2 mmol/L (85 mg/dL) 65 mg/dL HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol. ESC 2021

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Table 9 ‘Very brief advice’ for smoking cessation

‘Very brief advice’ on smoking is a proven 30-second clinical intervention, developed in the UK, which identifies smokers, advises them on the best method of quitting, and supports subsequent quit attempts. There are three elements to very brief advice: • ASK - establishing and recording smoking status • ADVISE - advising on the best ways of stopping • ACT - offering help

UK = United Kingdom. ESC 2021

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