Newer Beta Blockers Offered for Use in Atherosclerosis Prevention

Introduction

Beta-blockers are not typically used specifically for atheroprevention, i.e., the prevention of atherosclerosis or ASCVD. The early generation of BBs showed undesirable effects on lipoprotein levels and glucose and insulin metabolism in many studies. However, newer BBs often do not affect these factors in the pathophysiology of ASCVD or may even act favorably in this regard.

Guidelines Speech

According to current guidelines for the management of arterial hypertension, BBs are particularly suitable in specific situations, such as symptomatic angina pectoris, tachycardia, post-myocardial infarction (MI) state, heart failure with reduced ejection fraction (HFrEF), and as an alternative to angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) in hypertensive women planning pregnancy.

Among the most common BB users are patients with recent MI (with or without hypertension). Even in these cases, where BBs are given to patients with existing ASCVD, it is not primarily for atheroprevention but rather to address impaired systolic function, reduce adverse cardiac remodeling, and alleviate congestive heart failure.

Not All Beta Blockers Are the Same

As a drug group, BBs encompass a number of substances that widely differ in pharmacological properties and physiological effects. Differences include selectivity for beta-adrenergic receptors and their subtypes, hydro- or lipophilicity, effects on blood pressure and heart rate, influence on lipoprotein and glucose metabolism, and direct effect on the arterial wall.

Relatively recent publications have clarified the diversity of BBs with regards to undesirable, neutral, or favorable effects on lipoproteins, particularly triglycerides (TG) and low-density lipoprotein particles (LDL), and glucose and insulin metabolism. Especially for newer BBs (bisoprolol, carvedilol ER, metoprolol ER, and nebivolol), a metabolic benefit has been documented. 

New Data Debunk Outdated Concepts

Current data debunk the traditional view of beta-blockers as universally metabolically harmful substances that must be used sparingly, if at all, in atheroprevention. Some BBs can reduce platelet adhesion and improve the function of major cell types in the arterial wall, including endothelium, macrophages, and smooth muscle cells (for instance, enhancing endothelial function by improving arterial vasodilation and suppressing monocyte adhesion and transmigration), reducing the number and activity of inflammatory cells, including the proliferation of smooth muscle cells and their transformation into inflammatory cells.

For distinguishing metabolically suitable BBs, their likely overall effects on the arteries (whether they accelerate the development of atherosclerosis or prevent it) appear crucial. It seems newer BBs may be useful components in combination regimens not only for treating arterial hypertension, heart failure, and arrhythmias but potentially also for preventing atherosclerosis and ASCVD.

Conclusion

Further research is needed to help clarify the use of potential benefits of the most promising BBs when combined with other, better-established atheropreventive substances. Especially prospective randomized studies focused on cardiovascular outcomes (CVOT) in high-risk patients are necessary, specifically in cases such as adding BBs to baseline LDL-lowering therapy (statins and others) or TG-lowering therapy (particularly ethyl icosapent, which reduces ASCVD in patients with high TG levels, albeit not necessarily by reducing TG levels) and/or to antidiabetic drugs (sodium-glucose cotransporter 2 inhibitors /SGLT2i/, i.e., gliflozins, and glucagon-like peptide 1 receptor agonists /GLP-1RA/), based on the indications for the given population.

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Source: Vrablík M., Corsini A., Tůmová E. Beta-blockers for atherosclerosis prevention: a missed opportunity? Curr Atheroscler Rep 2022 Mar; 24 (3): 161–169, doi: 10.1007/s11883-022-00983-2.