Secondary Cardiovascular Prevention after Acute Coronary Syndrome: Emerging Risk Factors and Novel Therapeutic Targets

Abstract

The control of cardiovascular risk factors, the promotion of a healthy lifestyle, and antithrombotic therapy are the cornerstones of secondary prevention after acute coronary syndrome (ACS). However, many patients have recurrent ischemic events despite the optimal control of traditional modifiable risk factors and the use of tailored pharmacological therapy, including new-generation antiplatelet and lipid-lowering agents. This evidence emphasizes the importance of identifying novel risk factors and targets to optimize secondary preventive strategies. Lipoprotein(a) (Lp(a)) has emerged as an independent predictor of adverse events after ACS. New molecules such as anti-PCSK9 monoclonal antibodies, small interfering RNAs, and antisense oligonucleotides can reduce plasma Lp(a) levels and are associated with a long-term outcome benefit after the index event. The inflammatory stimulus and the inflammasome, pivotal elements in the development and progression of atherosclerosis, have been widely investigated in patients with coronary artery disease. More recently, randomized clinical trials including post-ACS patients treated with colchicine and monoclonal antibodies targeting cytokines yielded promising results in the reduction in major cardiovascular events after an ACS. Gut dysbiosis has also raised great interest for its potential pathophysiological role in cardiovascular disease. This evidence, albeit preliminary and needing confirmation by larger population-based studies, suggests the possibility of targeting the gut microbiome in particularly high-risk populations. The risk of recurrent ischemic events after ACS is related to the complex interaction between intrinsic predisposing factors and environmental triggers. The identification of novel risk factors and targets is fundamental to customizing patient clinical management with a precision medicine perspective.

The Benefits of a Comprehensive Cardiac Rehabilitation Program for Patients with Acute Coronary Syndrome: A Follow-Up Study

“…This improvement remained unchanged until the end of the 12th month after ACS [29]. Recently, numerous other drug attempts to reduce cardiac outcomes after ACS have been carried out [30][31][32][33][34][35], but not all of them have proven their effectiveness, which proves the recommendation of the guidelines in secondary prevention all the more.…”

“…MAP (mmHg) 104. 35 All patients analyzed (n = 480) at baseline were characterized by an increased cardiovascular risk profile at the time of ACS: 85% had hypertension; 86% had elevated total cholesterol values; 69% were characterized by metabolic syndrome; 43% were obese; 31% were active smokers; 29% had type 2 diabetes mellitus.…”

The effectiveness of a web-based information-knowledge-attitude-practice continuous intervention on the psychological status, medical compliance, and quality of life of patients after coronary artery bypass grafting surgery: a parallel randomized clinical trial

“…Thus, compared to these commonly risky indexes, we hypothesized that the WIKAP intervention alone might be insufficient to demonstrate significant effects on the occurrence of MACCE in CAD patients who underwent CABG surgery. Other clinically innovative therapeutic strategies should also be considered for the prevention of MACCE [ 32 , 33 ].…”

Methotrexate and cardiovascular prevention: an appraisal of the current evidence

“…A significant number of patients with previous atherosclerotic cardiovascular events, for example, acute coronary syndrome and ischaemic stroke, suffer from further events despite maximal treatment with statins, beta-blockers, antiplatelet agents, anticoagulants, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers. 39 , 40 This observation suggests the presence of a significant ‘residual cardiovascular risk’, that is, the component of an individual patient’s cardiovascular risk that is not influenced by existing treatments. 41 – 43 The increasing recognition of the critical role played by excess inflammation and dysregulated immunity in driving this residual risk has led several experts to rename this phenomenon ‘residual inflammatory risk’.…”