Drug discovery articles within Nature Reviews Cardiology

Featured

  • Review Article |

    In this Review, the authors discuss the clinical and experimental data on immunomodulatory effects of evidence-based treatments for heart failure and their primary mechanisms of action, and highlight potential therapeutic targets and opportunities for the development and application of novel immunomodulatory treatments for heart failure.

    • George Markousis-Mavrogenis
    • , Lukas Baumhove
    •  & Peter van der Meer
  • Review Article |

    In this Review, Gawaz and colleagues discuss the pathophysiological role of platelets in acute myocardial ischaemia, vascular inflammation and atherosclerotic progression, summarize the current clinical concepts in antiplatelet therapy and describe novel therapeutic targets for antiplatelet drugs that are currently in development.

    • Meinrad Gawaz
    • , Tobias Geisler
    •  & Oliver Borst
  • Review Article |

    Alternative splicing determines which exons are included in mature RNA and accounts for the majority of transcriptomic diversity. In this Review, Gotthardt and colleagues discuss how alternative splicing is regulated in the heart and how it differs in cardiac development, physiological adaptation and pathological remodelling. They also summarize technological advances in the field and potential applications of splicing data in cardiovascular medicine.

    • Michael Gotthardt
    • , Victor Badillo-Lisakowski
    •  & Leslie Leinwand
  • Review Article |

    Drugs can be repurposed for new therapeutic indications. In this Review, Mercola and colleagues summarize the latest techniques for systematic drug repurposing and re-engineering, which could increase the pace, efficiency and cost-effectiveness of drug discovery for the treatment of cardiovascular disease.

    • Mena Abdelsayed
    • , Eric J. Kort
    •  & Mark Mercola
  • Review Article |

    Novel peroxisome proliferator-activated receptor (PPAR) agonists are providing new opportunities in the management of metabolic and cardiovascular diseases. In this Review, Staels and colleagues discuss the physiological regulation and actions of the PPAR family and their modulation of the atherogenic lipid profile, atherosclerosis and cardiac remodelling.

    • David Montaigne
    • , Laura Butruille
    •  & Bart Staels
  • Review Article |

    In this Review, Holmes and colleagues compare and contrast the use of Mendelian randomization to evaluate potential drug targets versus quantitative traits and explain how genetic epidemiological studies can be used to assess the aetiological roles of biomarkers in disease and to prioritize drug targets, including designing their evaluation in clinical trials.

    • Michael V. Holmes
    • , Tom G. Richardson
    •  & George Davey Smith
  • Comment |

    The advent of ‘big data’ and modern analytics mandates a change of scale in every aspect of the biomedical enterprise. These forces are realigning academic medicine and traditional industrial partners, and also creating the context for an emerging new ecosystem for discovery, translation, care and implementation that promises to transform and integrate all these areas of endeavour.

    • Calum A. MacRae
  • Review Article |

    This Review discusses the latest findings and current theories on the pathogenesis of abdominal aortic aneurysm (AAA) and highlights potential medical therapies for AAA, summarizing previous, ongoing, and potential clinical trials of medical interventions for small AAAs. This expanding volume of research is expected to result in a range of novel medical therapies for AAA within the next decade.

    • Jonathan Golledge
  • Comment |

    Despite substantial advances, bona fide regeneration of the damaged human heart is still an unmet ambition. By extracting our current knowledge from developmental biology, animal models of heart regeneration, and clinical observations, we propose five hallmarks of cardiac regeneration and suggest a holistic approach to reconstituting human heart function.

    • Alessandro Bertero
    •  & Charles E. Murry
  • Review Article |

    This Review discusses the advances in therapeutic approaches for cardiac repair and regeneration, including cell-based therapies as well as the use of secretory factors, such as microRNAs and exosomes, direct reprogramming strategies, and gene editing to control cardiac remodelling and redirect the adult heart to a regenerative state, and highlights the future prospects of preclinical and clinical trials of heart regeneration.

    • Hisayuki Hashimoto
    • , Eric N. Olson
    •  & Rhonda Bassel-Duby
  • Review Article |

    The conflicting results of cell therapy clinical trials for heart regeneration have led to some confusion over the efficacy of this approach. This Review summarizes the main outcomes of these studies and gives perspectives for future cell-based regenerative trials largely based on the primary therapeutic target: regeneration of lost myocardium by exogenous cells or promotion of intrinsic repair though paracrine signalling.

    • Philippe Menasché
  • Review Article |

    Therapeutic decision-making requires integration of complex information on patient-specific and therapy-specific factors. Physicians and prescribers face the daunting task of assessing the efficacy and safety of medications relative to each patient. In this Review, Drs Woosley and Romero discuss the challenges of safe medication prescribing to prevent drug-induced adverse events, and the efforts made to improve clinical decision support systems, using examples from several new evidence-based, online resources.

    • Raymond L. Woosley
    •  & Klaus Romero
  • News & Views |

    Trials in patients with dyslipidaemia or cardiovascular disease have shown no beneficial effects on 'hard' clinical end points, and increased rates of adverse effects, when niacin is added to statin therapy. These findings lead us to question whether niacin has a role in modern lipid-lowering strategies.

    • Anthony S. Wierzbicki
  • Review Article |

    Gliptins are a novel class of oral antihyperglycaemic agent that inhibit dipeptidyl peptidase 4. Professor Scheen describes the pleiotropic beneficial effects of these drugs, beyond basic glycaemic control in patients with type 2 diabetes mellitus, to emerging data and ongoing trials on cardiovascular protection in patients with ischaemic heart disease or congestive heart failure.

    • André J. Scheen
  • News & Views |

    Adding C-reactive protein (CRP) level to conventional cardiovascular risk models has been suggested to improve risk prediction for cardiovascular events. However, evaluation of the potential impact of CRP measurement in cardiovascular risk management will require studies designed to quantify the effect of additional CRP assessment on medical decision-making, patient outcomes, and cost-effectiveness.

    • Sanne A. E. Peters
    • , Frank L. J. Visseren
    •  & Diederick E. Grobbee
  • News & Views |

    A 3-h algorithm using high-sensitivity assays for cardiac troponin to rule out myocardial infarction (MI) is recommended in current ESC guidelines. Whether faster rule-out algorithms can discriminate between MI and other conditions that elevate the troponin level, or be safely implemented across the whole spectrum of patient risk, is unclear.

    • Evangelos Giannitsis
    •  & Hugo A. Katus
  • News & Views |

    A new, observational study suggests that aspirin only marginally increases the bleeding risk in patients with diabetes mellitus, perhaps reflecting impaired platelet inhibition. Inconclusive evidence from small, randomized trials and mechanistic studies reinforces the need for larger trials to determine the relative cardioprotective benefits and bleeding risks of aspirin in these patients.

    • Carlo Patrono
  • Review Article |

    Direct inhibitors of thrombin are a novel class of anticoagulant. The authors critically review the data from clinical trials on the use of the parenteral and oral forms of these drugs for primary or secondary prevention or treatment in patients with acute coronary syndrome, atrial fibrillation, or venous thromboembolism, or those undergoing percutaneous coronary intervention or orthopedic surgery.

    • Kyle A. Arsenault
    • , Jack Hirsh
    •  & John W. Eikelboom
  • Review Article |

    Dr. Moss and colleagues review data from randomized clinical trials which suggest that important sex-specific differences in the epidemiology and clinical characteristics of patients with heart failure can affect their response to both medical and device therapies.

    • Alon Barsheshet
    • , Andrew Brenyo
    •  & Arthur J. Moss
  • News & Views |

    Inflammation has a pivotal role in cardiac remodeling, and circulating biomarkers of inflammation are independently associated with risk of developing heart failure and with prognosis after onset of the condition. Pentraxin 3 has been suggested as a novel biomarker of left ventricular diastolic dysfunction and heart failure with normal ejection fraction.

    • Bernhard M. Kaess
    •  & Ramachandran S. Vasan
  • News & Views |

    A network meta-analysis by Trelle and colleagues has confirmed that the routine use of all nonsteroidal anti-inflammatory drugs, both nonselective and selective, is associated with an increased risk of cardiovascular events. Although a rigorous method was used in this analysis, comparative safety research in which data from randomized clinical trials is used has some important strengths and weaknesses to consider.

    • Seo Young Kim
    •  & Daniel H. Solomon
  • News & Views |

    Worsening renal function is common among patients hospitalized with acute heart failure and is associated with poor outcomes. Although preliminary studies suggested that adenosine receptor antagonists could preserve renal function and improve diuretic responsiveness, the A1-receptor antagonist rolofylline did not provide benefit in patients with acute heart failure in PROTECT.

    • Frank Ruschitzka
    •  & William T. Abraham
  • News & Views |

    Whether thiazolidinediones should be used to treat patients with type 2 diabetes mellitus is controversial, as studies on the cardiovascular effects of these drugs have produced conflicting results. A trial in which rosiglitazone and glipizide were compared supports earlier findings that rosiglitazone does not have an adverse effect on the progression of coronary atherosclerosis.

    • Michael E. Farkouh
    •  & Valentin Fuster