Combinatorial approaches for novel cardiovascular drug discovery: a review of the literature

ABSTRACT

Introduction

In this article, authors report an inclusive discussion about the combinatorial approach for the treatment of cardiovascular diseases (CVDs) and for counteracting the cardiovascular risk factors. The mentioned strategy was demonstrated to be useful for improving the efficacy of pharmacological treatments and in CVDs showed superior efficacy with respect to the classical monotherapeutic approach.

Areas covered

According to this topic, authors analyzed the combinatorial treatments that are available on the market, highlighting clinical studies that demonstrated the efficacy of combinatorial drug strategies to cure CVDs and related risk factors. Furthermore, the review gives an outlook on the future perspective of this therapeutic option, highlighting novel drug targets and disease models that could help the future cardiovascular drug discovery

Expert opinion

The use of specifically designed and increasingly rational and effective drug combination therapies can therefore be considered the evolution of polypharmacy in cardiometabolic and CVDs. This approach can allow to intervene on multiple etiopathogenetic mechanisms of the disease or to act simultaneously on different pathologies/risk factors, using the combinations most suitable from a pharmacodynamic, pharmacokinetic, and toxicological perspective, thus finding the most appropriate therapeutic option.

KEYWORDS:

• Cardiovascular diseases (CVDs)
• combinatorial drug discovery
• fixed-dose combination (FDC)
• cardiovascular risk factors

Article highlights

• Combinatorial drug discovery in cardiovascular diseases (CVDs) and related risk factors represent an effective approach with improved therapeutic efficacy over the conventional single-agent therapies presenting numerous advantages with respect to the classical drug treatment.

• Available therapeutic options in the market to treat CVDs based on a single pill enclosing combined drugs demonstrated several benefits including lowering toxicity and individual administered doses as well as the insurgence of drug resistance, due to the synergistic or additive effects.

• The use of specifically designed and increasingly rational and effective FDCs and FrDCs can therefore be considered the evolution of polypharmacy in cardiometabolic and CVDs. This approach can in fact allow to intervene on multiple etiopathogenetic mechanisms of the disease or to act simultaneously on different pathologies/risk factors, using the combinations most suitable from a pharmacodynamic, pharmacokinetic, and toxicological point of view.

• Emerging drug targets to be modulated in the next generation of combined drug treatments for CVDs can represent novel frontiers for achieving effective therapies for treating cardiac-related disorders as well as attractive targets for preventing cardiovascular risk factors.

• Innovative disease models in the cardiovascular field will be usable for efficiently screening potential drug combinations for treating CVDs.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosure

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.