Novel and Emerging LDL-C Lowering Strategies: A New Era of Dyslipidemia Management.

Atherosclerotic cardiovascular disease (ASCVD) represents a major global health challenge, significantly contributing to mortality rates. This chronic inflammatory condition affecting blood vessels is intricately linked to hypercholesterolemia, with elevated levels of low-density lipoprotein cholesterol (LDL-C) recognized as a central and modifiable risk factor. The effectiveness of lipid-lowering therapy (LLT) in mitigating ASCVD risk is well established, with studies revealing a substantial reduction in major ischemic events correlating with LDL-C reduction. While statins, often combined with ezetimibe, remain fundamental in dyslipidemia management, a significant proportion of patients on statin therapy continue to experience cardiovascular events. Recent pharmacological advancements, driven by a deeper understanding of atherogenesis, have unveiled novel therapeutic targets and potent drugs. Notably, agents like bempedoic acid and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (evolocumab, alirocumab, inclisiran) have emerged as effective options to intensify LLT and achieve LDL-C goals, addressing limitations associated with statins, such as myopathy. Molecular insights into alternative pathways have spurred the investigation of emerging agents, offering promising perspectives for novel medications with efficacy comparable to established treatments, associated with advantages in cost and administration. This review provides a comprehensive overview of the evolving landscape of lipid-lowering strategies, highlighting the progress made in addressing ASCVD risk and the potential of upcoming therapies to further optimize cardiovascular prevention.

Short Duration of DAPT Versus De-Escalation After Percutaneous Coronary Intervention for Acute Coronary Syndromes.

OBJECTIVES: The aim of this study was to compare short dual antiplatelet therapy (DAPT) and de-escalation in a network meta-analysis using standard DAPT as common comparator. BACKGROUND: In patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), shortening DAPT and de-escalating to a lower potency regimen mitigate bleeding risk. These strategies have never been randomly compared. METHODS: Randomized trials of DAPT modulation strategies in patients with ACS undergoing PCI were identified. All-cause death was the primary outcome. Secondary outcomes included net adverse cardiovascular events (NACE), major adverse cardiovascular events, and their components. Frequentist and Bayesian network meta-analyses were conducted. Treatments were ranked on the basis of posterior probability. Sensitivity analyses were performed to explore sources of heterogeneity. RESULTS: Twenty-nine studies encompassing 50,602 patients were included. The transitivity assumption was fulfilled. In the frequentist indirect comparison, the risk ratio (RR) for all-cause death was 0.98 (95% CI: 0.68-1.43). De-escalation reduced the risk for NACE (RR: 0.87; 95% CI: 0.70-0.94) and increased major bleeding (RR: 1.54; 95% CI: 1.07-2.21). These results were consistent in the Bayesian meta-analysis. De-escalation displayed a >95% probability to rank first for NACE, myocardial infarction, stroke, stent thrombosis, and minor bleeding, while short DAPT ranked first for major bleeding. These findings were consistent in node-split and multiple sensitivity analyses. CONCLUSIONS: In patients with ACS undergoing PCI, there was no difference in all-cause death between short DAPT and de-escalation. De-escalation reduced the risk for NACE, while short DAPT decreased major bleeding. These data characterize 2 contemporary strategies to personalize DAPT on the basis of treatment objectives and risk profile.

Efficacy and Safety of Aspirin for Primary Cardiovascular Risk Prevention in Younger and Older Age: An Updated Systematic Review and Meta-analysis of 173,810 Subjects from 21 Randomized Studies.

AIMS: The efficacy and safety of aspirin for primary cardiovascular disease (CVD) prevention is controversial. The aim of this study was to investigate the efficacy and safety of aspirin in subjects with no overt CVD, with a focus on age as a treatment modifier. METHODS AND RESULTS: Randomized trials comparing aspirin use versus no aspirin use or placebo were included. The primary efficacy outcome was all-cause death. The primary safety outcome was major bleeding. Secondary ischemic and bleeding outcomes were explored. Subgroup analyses were conducted to investigate the consistency of the effect sizes in studies including younger and older individuals, using a cut-off of 65 years. A total of 21 randomized trials including 173,810 individuals at a mean follow-up of 5.3 years were included. Compared with control, aspirin did not reduce significantly the risk of all-cause death (risk ratio: 0.96; 95% confidence interval: 0.92-1.00, p = 0.057). Major adverse cardiovascular events were significantly reduced by 11%, paralleled by significant reductions in myocardial infarction and transient ischemic attack. Major bleeding, intracranial hemorrhage, and gastrointestinal bleeding were significantly increased by aspirin. There was a significant age interaction for death (p for interaction = 0.007), with aspirin showing a statistically significant 7% relative benefit on all-cause death in studies including younger patients. CONCLUSION: The use of aspirin in subjects with no overt CVD was associated with a neutral effect on all-cause death and a modest lower risk of major cardiovascular events at the price of an increased risk in major bleeding. The benefit of aspirin might be more pronounced in younger individuals.

Appraising the contemporary role of aspirin for primary and secondary prevention of atherosclerotic cardiovascular events.

INTRODUCTION: Although the role of aspirin for primary prevention of atherosclerotic cardiovascular disease (ASCVD) has been disputed, its use in secondary ASCVD prevention is well established. Recent trials of primary prevention do not suggest a significant net benefit with aspirin, whereas accruing evidence supports adopting aspirin-free strategies in the context of potent P2Y12 inhibition for the secondary prevention of selected patients undergoing percutaneous coronary intervention. AREAS COVERED: This updated review aims at summarizing and appraising the pharmacological characteristics and the contemporary role of aspirin for the primary and secondary prevention of ASCVD. EXPERT OPINION: Recent trials and metanalyses in the context of primary prevention highlighted a modest reduction in ischemic events with aspirin use, counterbalanced by a significant increase in bleeding events. However, ongoing studies on cancer prevention could modify the current paradigm of the unfavorable benefit-risk ratio of aspirin in patients with no overt ASCVD. Conversely, aspirin use is crucial for secondary ASCVD prevention, both in chronic and acute coronary syndromes. Nevertheless, after a brief period of dual antiplatelet therapy, patients at high bleeding risk may benefit from discontinuation of aspirin if a P2Y12 inhibitor is used, hence reducing the bleeding risk with no rebound in thrombotic events.

Mechanisms of ST-segment elevation myocardial infarction in patients with atrial fibrillation, prior stenting and long-standing chronic coronary syndrome.

BACKGROUND: The optimal antithrombotic regimen for patients with atrial fibrillation (AF) and chronic coronary syndromes beyond 1 year after percutaneous coronary intervention (PCI) is a matter of debate. For these patients, guidelines recommend oral anticoagulation (OAC) alone, but the risk of thrombotic complications remains a concern. The aim of this study was to characterize the incidence, presentation and use of antithrombotic therapy in patients with AF, prior stenting > 12 months and new ST-segment elevation myocardial infarction (STEMI). METHODS: Consecutive patients were selected from an institutional registry over a 3-year period if they matched the following criteria: 1) STEMI undergoing primary PCI; 2) AF; 3) chronic coronary syndrome with prior stenting > 12 months. RESULTS: Among 852 consecutive STEMI patients undergoing primary PCI, the prevalence of AF was 4.1%, and 6 (0.9%) patients met all the inclusion criteria. Substantial heterogeneity in antithrombotic treatment for these patients was noted (e.g., OAC alone, OAC plus a single antiplatelet agent, no antithrombotic therapy). In 50% of patients, the STEMI episode was linked to a previously stented lesion or documented plaque. CONCLUSIONS: This case review illustrates the wide heterogeneity in antithrombotic pharmacotherapy among AF patients presenting with STEMI > 12 months after PCI. The underlying reason for STEMI is only partly related to disease progression or stent-related events. This finding suggests that multiple mechanisms of recurrence may be advocated, and are not only limited to antithrombotic therapy but may be explained by the natural history of coronary artery disease in remote vessels.

Aspirin for the primary prevention of cardiovascular disease: latest evidence.

Introduction: While the clinical merits of aspirin in secondary cardiovascular disease (CVD) prevention remain undisputed, its role in primary prevention is controversial. Recently, three trials of primary prevention reported neutral net benefit results or evidence of harm for aspirin in patients with no overt CVD. Areas covered: This article aims to inform clinical practitioners by appraising the current body of evidence on the use of aspirin for primary CVD prevention, ranging from general pharmacology to clinical outcomes and future directions. Expert opinion: Based on meta-analyses incorporating latest trials in the field of primary prevention, the modest reduction in ischemic events with aspirin, if any, is offset by a modest increase in nonfatal bleeding. Improved control of CVD risk factors and broader use of statins may have reduced the thrombotic complications of atherosclerosis, thus limiting the opportunity for aspirin to prevent clinical CVD events in the contemporary era. As such, decision-making about aspirin for primary prevention is challenging even when selected patients are considered and involves careful weighing of risks and benefits. Ongoing investigations conducted in patients with cancer could rapidly modify the current perception of the unfavorable benefit-risk ratio of aspirin in patients with no overt CVD.