Smoking cessation is of utmost importance as it is associated with an increased risk of recurrent coronary events. Patients who continue to smoke have a 51% higher risk of recurrent coronary events than non-smokers. Nonetheless, patients who quit smoking after AMI have a 17% higher risk of recurrent events than non-smokers, but their risk declines quickly and approaches that of non-smokers within three years after cessation [17].

Electronic cigarettes (e-cigarettes) have emerged over the last few years and have been advertised as a “healthy alternative” to classical tobacco cigarettes. However, some studies have reported an increased risk of MI in persons using e-cigarettes (odds ratio (OR) 1.79) compared to non-smokers, whereas conventional cigarette smoking has an OR 2.72 [18]. Data on e-cigarette use in patients after AMI is lacking. Some small studies indicate that e-cigarettes are harmful due to their effect on the cardiovascular system. Vaping leads to an acute increase in both heart rate and blood pressure [19, 20] and shifts the heart rate variability towards a sympathetic predominance [21].

Some authors have recommended the use of e-cigarettes as a smoking cessation tool. Due to insufficient data, the use of e-cigarettes for smoking cessation is advised by neither the US Preventive Services Task Force (USPSTF) [22] nor the European Association of Preventive Cardiology (EAPC) [23]. The latter recommends considering e-cigarettes to aid tobacco cessation only alongside a formal tobacco cessation programme [23].

Exercise training in patients with coronary artery disease (post-MI, with angiographically documented coronary artery disease or after coronary intervention) can decrease total mortality by 20% and cardiovascular mortality by 26% [24]. Exercise leads to increased coronary blood flow and higher myocardial oxygen delivery; repeated increases in blood flow improve endothelial and coronary smooth muscle function, leading to improved coronary vasodilatation [25]. Furthermore, exercise has beneficial effects on cardiovascular risk factors [26]. Exercise does not add much to low-density lipoprotein cholesterol (LDL-C) lowering in patients already on statin therapy but changes the LDL-C particles’ structures, increases high-density lipoprotein cholesterol (HDL-C) levels, and lowers triglyceride levels [27, 28]. Aerobic and resistance exercise decreases the averaged systolic blood pressure (SBP) by 2–4 mmHg and diastolic blood pressure (DBP) by three mmHg [29].

Determining the exact impact of dietary changes on the prognosis of AMI patients is complicated. The general principles of heart-healthy diets also apply to post-acute coronary syndrome (ACS) patients [30]. The Lyon Diet Heart Study has shown that a Mediterranean-type diet reduces the recurrence rate after the first myocardial infarction, and this protective effect lasted for four years [31]. A recent AHA statement on dietary guidance shifts the focus more on dietary patterns, such as the Mediterranean style, the Dietary Approaches to Stop Hypertension (DASH) style, the Healthy US-Style, and healthy vegetarian diets. All these diets improve cardiovascular health [32].

The dietary approach (calory restriction) is also necessary for bodyweight reduction [33]. Overweight and obese patients with an AMI are younger than those with normal body weight and have a higher risk of developing heart failure. However, the overall in-hospital mortality is not increased [34]. Metabolic syndrome is associated with an increased three-years cardiovascular mortality and reinfarction in patients with NSTEMI [35]. Nevertheless, studies directed at bodyweight reduction in post-ACS patients are lacking. There are also no studies focusing on bariatric surgery after ACS, but some evidence suggests that bariatric surgery could help in improving the prognosis. In one study, bariatric surgery prior to the cardiac event had a protective effect on survival after an AMI [36]. In a prospective SOS (Swedish Obese Subjects) study in a non-randomised design, a reduction of cardiovascular death in the bariatric surgery group was observed compared with the control group. Unfortunately, one of the exclusion criteria was MI during the previous six months, and in the whole cohort, only 1.4% of the patients had previous MI [37].

Psychosocial risk factors (PSRFs) influence the cardiovascular system through changes in the immune, neuroendocrine, and behavioural pathways [38], while at the same time, CVD leads to patients’ distress [39, 40]. As depression increases the risk of fatal and nonfatal cardiovascular events in post-ACS patients, the American Heart Association (AHA) recommends considering depression as a risk factor for adverse medical outcomes in ACS patients [41]. The screening and treatment of PSRFs are among the core components of cardiac rehabilitation/secondary prevention (CR/SP) programmes [42]. The depression treatment decreases symptoms in coronary patients and improves the heart-related quality of life (HRQoL), but without any proven effect on mortality [43].

Intriguingly, the prevalence of depression remains the same during the first year after an acute coronary event, but the fluctuation of depressive symptoms is considerable in individual subjects. Thus, depressive symptoms disappear without treatment in some patients, whereas in others without depressive symptoms, these appear during the consequent months [44]. Therefore, screening for depressive symptoms is advised during the acute event and during at least the consequent year.

Platelet activation plays a central role in atherothrombosis development, and therefore antiplatelet therapy is an integral part of cardiovascular disease prevention and treatment [45]. The duration and type of antiplatelet therapy depends on an individualized assessment of the ischemic and bleeding risks. After an ACS event, dual antiplatelet therapy (DAPT) is indicated for 12 months unless contraindicated [15]. Acetylsalicylic acid (ASA) (at doses of 75–100 mg s.i.d.) remains the mainstay of DAPT, and a potent P2Y${}_{12}$ receptor inhibitor is added (prasugrel 10 mg s.i.d., ticagrelor 90 mg b.i.d. or clopidogrel 75 mg s.i.d.). In most patients, ticagrelor or prasugresl are preferred, and clopidogrel should be used when modern P2Y${}_{12}$ inhibitors are unavailable or contraindicated. The duration of DAPT can be shortened or extended depending on the balance between the bleeding and thrombotic/ischemic risks. In patients with high and very high bleeding risk, the shortening of DAPT to six months can be considered, and antiplatelet treatment with only ASA, (eventually clopidogrel) continued. In patients with low bleeding risk and high ischemic risk who have tolerated 12 months of DAPT, prolongation of DAPT, e.g., ASA with ticagrelor 60 mg b.i.d. for more than one year (up to three years), may be considered. A combination of ASA and low-dose rivaroxaban (2.5 mg b.i.d.) may also be considered in these patients, especially in the presence of diabetes), chronic kidney disease or peripheral arterial disease [46]. The concomitant use of anticoagulation therapy also influences the duration and type of antiplatelet therapy. The proper timing and extent of antithrombotic therapy are out of the scope of the current review; more information can be found in the guidelines and position papers of the ESC [15, 46].

The first publication of the Framingham Study already noted that high blood pressure and high cholesterol levels were associated with increased incidence of IHD and AMI [5]. After which, evidence has emerged about the beneficial prognostic effect of lipid-lowering therapy. After ACS, both the magnitude and speed of achieving recommended cholesterol levels are essential. Data from the SWEDEHEART registry show that more significant early low-density lipoprotein cholesterol (LDL-C) reductions are associated with a reduced hazard ratio (HR) of all-cause mortality (HR 0.71) and CV mortality (HR 0.68). Moreover, patients benefited most from high-intensity statin therapy [47]. In the ALPS-AMI study, rapid LDL-C reduction to target levels within four weeks after the acute event was associated with better outcomes in patients after AMI [48].

Nevertheless, statin therapy does not eliminate cardiovascular risk [49], and some patients on maximal statin therapy do not meet the guideline-recommended levels of LDL-C (1.4 mmol/L in post-ACS patients) [50]. In such cases, the addition of other lipid-lowering agents is indicated. The first choice is ezetimibe, especially in patients with LDL-C levels near the target levels. Adding ezetimibe to statin therapy can lead to a mean LDL-C decrease of 16.7 mg/dL (0.43 mmol/L), i.e., a further 24 % LDL-C level lowering [51].

When the LDL-C is high despite high dose statin therapy, the addition of PCSK-9 inhibitors is an option. In ODYSSEY OUTCOMES, the addition of alirocumab in post-ACS patients resulted in a mean LDL-C of 1.2 mmol/L in the treatment group compared to 2.5 mmol/L in the placebo group. This difference was accompanied by a lower risk of recurrent ischemic cardiovascular events (HR 0.85) [52]. Furthermore, better results with PCSK-9 inhibitor (evolocumab) were observed in the sub-analysis of the post-ACS patients of the FOURIER study when the PCSK-9 inhibitor was started early after the index event compared to beginning the therapy after more than 12 months post-ACS [53]. The first results of the HUYGENS study presented at the ESC annual congress in 2021 showed that the addition of evolocumab to high dose statin therapy leads to increased fibrous cap thickness and fewer lipids in the core of the atherosclerotic plaque, forming a more stable atherosclerotic plaque [54].

Novel lipid lowering therapies are under investigation, e.g., inclisiran [55], anacetrapib [56, 57], evinacumab (ANGPTL3 inhibitor) [58], bempedoic acid [59], pelacarsen [60] but none of them have available data in patients after ACS yet.

Familial hypercholesterolaemia (FH) deserves special attention. Patients with FH have higher levels of LDL-C and higher all-cause and cardiovascular mortality [61]. The prevalence of genetically confirmed FH in patients with ACS below the age of 65 and LDL-C $>$160 mg/dL (4.14 mmol/L) was 9%. Nevertheless, when using the Dutch Lipid Clinic (DLC) criteria, the prevalence of probable to definite FH increased to 27.2% [62]. Thus, it is essential not to forget to screen for patients with FH in the post-ACS population.

Even after achieving the CV risk factor goals, patients remain at increased cardiovascular risk. One of the possible factors is higher levels of plasmatic triglycerides [63]. Some novel triglyceride-lowering drugs have been shown to decrease triglycerides and atherogenic lipoproteins in those patients with moderate hypertriglyceridemia who are at high risk for or with established cardiovascular disease [64]. Unfortunately, cardiovascular outcome data in post-ACS is lacking.

In patients with left ventricular (LV) dysfunction, angiotensin-converting enzyme (ACE) inhibitors can lower mortality, AMI and stroke rates [65]. ACE inhibitors (or ARBs – angiotensin receptor blockers when ACE inhibitors are not tolerated) are indicated in post-ACS patients with concomitant LV ejection fraction $\le$40%, hypertension, diabetes or renal impairment [15]. The American guidelines recommend an ACE inhibitor for patients with anterior location or heart failure [66].

Historically beta-blocker use decreased cardiovascular deaths and any subsequent AMI by 30% [67]. In the reperfusion era, beta-blocker therapy reduces the short-term recurrence of AMI and angina but not mortality [68]. Long term beta-blocker usage in patients after ACS without heart failure in the reperfusion era remains controversial [69, 70]. At least two randomised trials testing the efficacy of beta-blocker therapy after myocardial infarction without reduced left ventricular systolic function are ongoing, with results expected by the end of 2022 and 2023 [71, 72].

Even in patients admitted for ACS without known diabetes, the prevalence of disturbances in glucose metabolism is high [73]. An abnormal oral glucose tolerance test upon discharge is a strong risk factor for future cardiovascular events [74]. Nowadays, we have glucose-lowering agents with proven cardioprotective data. In the last guidelines on cardiovascular prevention, using a GLP-1RA or SGLT2 inhibitor with proven outcome benefits is recommended in those with type 2 diabetes mellitus and atherosclerotic cardiovascular disease (ASCVD) to reduce cardiovascular and/or cardiorenal outcomes [50]. Thus screening for diabetes is mandatory in all post-ACS patients.

It has been observed that the incidence of AMI increases during seasonal influenza epidemics [75]. In a meta-analysis, influenza vaccination leads to a 36% reduction of major adverse cardiovascular events in high-risk patients [76]. The administration of an influenza vaccine within 72 hours of a coronary angiography for AMI resulted in a reduction of all-cause mortality (HR 0.59), cardiovascular death (HR 0.59) and myocardial infarction (HR 0.86). The effect of an influenza vaccine administration was observed early after the index event [77]. The protective effect of influenza vaccination is essential in both primary and secondary prevention, and Habib et al. [78] called on cardiologists to “promote influenza vaccination and actively advice their patients to get the seasonal influenza vaccination”.

By the end of 2019, the world was unsettled by the COVID-19 pandemic. Patients with underlying cardiovascular diseases have five times higher mortality when encountering the SARS-CoV2 virus [79]. Thus, patients with cardiovascular diseases were among the first to be vaccinated against COVID-19. The ESC advocates the administration of SARS-CoV-2 vaccines to patients with prior cardiovascular diseases [80].

Although the role of inflammation in the initiation and progression of atherosclerosis has been known for a long time [3, 4], only recently have we had studies which prove the beneficial effect of anti-inflammatory therapies on cardiovascular outcomes [81]. A recent meta-analysis showed that the addition of low-dose colchicine to the guideline-recommended treatments in patients with recent AMI or chronic coronary disease reduced the risk of major adverse cardiac events by 25% (RR 0.75) and the risk of myocardial infarction by 22% (RR 0.78), with no effect on all-cause mortality (RR 1.08) but a decreased risk of cardiovascular death (RR 0.82) [82]. Still, the use of colchicine remains reserved for a highly selected population of post-ACS patients, mostly those with recurrent events.

Hyperuricaemia is a well-established risk factor for gout and gout kidney disease. The association between higher uric acid (UA) levels and cardiovascular events is known from the Framingham study. In recent years some studies have shown the potential benefits of UA lowering therapies on cardiovascular outcomes [83]. Currently, we are awaiting the results of the ALL-HEART study which randomized patients with established ischemic heart disease (including post myocardial infarction patients) to a treatment of allopurinol or placebo [83]. At time of publication, the treatment of hyperuricaemia is indicated only as the prevention and treatment of gout.

While patients after STEMI with identifiable standard modifiable cardiovascular risk factors (SMuRFs) are at increased risk of early all-cause mortality, patients without SMuRFs are at risk too, which is even higher than in those with SMuRF [84]. The risk disappeared when taking into account the guideline-recommended secondary prevention pharmacotherapy, underlining the need to treat all STEMI patients with guideline-recommended treatments irrespective of any identified risk factors [84].