Therapeutic strategies for atherosclerosis and atherothrombosis: Past, present and future

Abstract

SummaryEven two centuries after they were first described, atherosclerosis and atherothrombosis remain among the leading causes of death worldwide. Over the last decades it has become clear that atherosclerosis is not only a lipid-driven disease but also a multifactorial process largely driven by inflammatory mediators, an insight that has instigated additional research and drug development focussing on anti-inflammatory therapies. In this review, we will provide a brief historical overview, followed by a more general synopsis of the range of currently available state-of-the-art therapies for atherosclerosis and atherothrombosis. Finally, we will highlight some of the promising therapeutic strategies that are currently under intense investigation. We believe that the next years will witness highly interesting developments and clinical trials investigating yet more novel therapies, and at the same time looking into potential combinations of all available therapies. This prospect closes in on the ultimate goal, which is to reduce the residual risk that still persists despite present therapeutic options.

Untitled

“…24 Integrating gender specificities in scientific statements, medical investigations, and practical guidelines will be determinant in improving women's health care. 25,26…”

Platelet lipidome: Dismantling the “Trojan horse” in the bloodstream

“…In acute coronary syndrome (ACS) patients oxLDL binding to platelets correlates with activation status . Intraplatelet oxLDL levels are elevated in coronary artery disease (CAD) patients, particularly in ACS patients diagnosed with intracoronary thrombi, suggesting that platelet‐lipid associations may enhance thrombotic risk …”

Can modulators of apolipoproteinB biogenesis serve as an alternate target for cholesterol-lowering drugs?

“…Most likely, new cholesterol lowering drugs would also initially be used for individuals with these severe diseases as well. Finally, these drugs are cost prohibitive and may increase health care costs by 38% over the next 5 years [135, 146]. …”

“…Prior to its approval in 2013, phase 3 clinical trials indicated a reduction in LDL-associated circulating cholesterol by 25–40% [152, 153]. However, Mipomersen is similarly only approved for those suffering from homozygous familial hypercholesteremia and has not been approved for use in Europe due to concerns with liver toxicity and other side effects [135, 137, 148, 154]. Further investigation is undoubtedly required to understand the long-term effects of this drug in humans.…”

“…Lomitapide treatment lowered triglyceride levels by 65% and LDL levels by 50% [155]. However, Lomitapide may cause liver damage and steatosis, and users must still maintain a low lipid diet [135, 156]. …”