Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney, Australia.
Clinical Committee, National Heart Foundation of Australia.
Eur Heart J. 2021 Apr 14;42(15):1464-1475. doi: 10.1093/eurheartj/ehab068.
Whilst we continue to wrestle with the immense challenge of implementing equitable access to established evidence-based treatments, substantial gaps remain in our pharmacotherapy armament for common forms of cardiovascular disease including coronary and peripheral arterial disease, heart failure, hypertension, and arrhythmia. We need to continue to invest in the development of new approaches for the discovery, rigorous assessment, and implementation of new therapies. Currently, the time and cost to progress from lead compound/product identification to the clinic, and the success rate in getting there reduces the incentive for industry to invest, despite the enormous burden of disease and potential size of market. There are tremendous opportunities with improved phenotyping of patients currently batched together in syndromic 'buckets'. Use of advanced imaging and molecular markers may allow stratification of patients in a manner more aligned to biological mechanisms that can, in turn, be targeted by specific approaches developed using high-throughput molecular technologies. Unbiased 'omic' approaches enhance the possibility of discovering completely new mechanisms in such groups. Furthermore, advances in drug discovery platforms, and models to study efficacy and toxicity more relevant to the human disease, are valuable. Re-imagining the relationships among discovery, translation, evaluation, and implementation will help reverse the trend away from investment in the cardiovascular space, establishing innovative platforms and approaches across the full spectrum of therapeutic development.
虽然我们继续努力应对公平获得既定循证治疗方法的巨大挑战,但在我们的心血管疾病(包括冠状动脉和外周动脉疾病、心力衰竭、高血压和心律失常)的药物治疗武器库中仍存在实质性差距。我们需要继续投资于新方法的开发,以发现、严格评估和实施新疗法。目前,从先导化合物/产品鉴定到临床应用的时间和成本,以及成功的几率都降低了行业投资的积极性,尽管疾病负担巨大,市场潜力巨大。在目前按综合征“桶”分组的患者中进行更精确的表型分析,有巨大的机会。使用先进的成像和分子标志物可以以更符合生物学机制的方式对患者进行分层,从而可以通过使用高通量分子技术开发的特定方法来靶向这些机制。无偏“组学”方法增加了在这些群体中发现全新机制的可能性。此外,药物发现平台的进步和更能反映人类疾病的疗效和毒性的模型也是有价值的。重新构想发现、转化、评估和实施之间的关系将有助于扭转远离心血管领域投资的趋势,在整个治疗开发的全光谱中建立创新的平台和方法。