Obstacles to the development of novel thrombolytic agents for acute myocardial infarction therapy

Is the good the enemy of the best?

R. Fears, George Poste

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

During the past decade, it became well established that the timely use of thrombolytic agents in the treatment of acute myocardial infarction patients decreases coronary mortality and morbidity. However, an increasing focus on mortality as the only meaningful endpoint in clinical trials has created major logistical and economic obstacles to the search for potentially even better plasminogen activators and their adjunct therapies. The pace of new drug development has slowed. Alternative approaches to measuring efficacy, whether in terms of surrogate endpoints (patency, left ventricular function), or composite clinical indices, or by innovative clinical protocols (e.g. factorial design) have not yet achieved consensus. Results from the recent study, Global Utilisation of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) provide a new impetus to the employment of early patency data as an appropriate surrogate endpoint. Nonetheless, despite the creativity of molecular genetics, current efforts to develop novel plasminogen activators with improved pharmacological attributes still appear relatively diffident and key questions on augmenting the efficacy of thrombolytic regimens remain unanswered. If we are to capitalise on the healthcare gains generated over the past few years, to treat increasing numbers of eligible patients, we need to combine the sustained progress in drug discovery creativity with a plurality of innovative approaches to clinical study design.

Original languageEnglish (US)
Pages (from-to)203-213
Number of pages11
JournalFibrinolysis and Proteolysis
Volume8
Issue number4
DOIs
StatePublished - 1994
Externally publishedYes

Fingerprint

Fibrinolytic Agents
Creativity
Plasminogen Activators
Biomarkers
Myocardial Infarction
Streptokinase
Mortality
Drug Discovery
Clinical Protocols
Left Ventricular Function
Molecular Biology
Coronary Vessels
Consensus
Economics
Clinical Trials
Pharmacology
Morbidity
Delivery of Health Care
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "Obstacles to the development of novel thrombolytic agents for acute myocardial infarction therapy: Is the good the enemy of the best?",
abstract = "During the past decade, it became well established that the timely use of thrombolytic agents in the treatment of acute myocardial infarction patients decreases coronary mortality and morbidity. However, an increasing focus on mortality as the only meaningful endpoint in clinical trials has created major logistical and economic obstacles to the search for potentially even better plasminogen activators and their adjunct therapies. The pace of new drug development has slowed. Alternative approaches to measuring efficacy, whether in terms of surrogate endpoints (patency, left ventricular function), or composite clinical indices, or by innovative clinical protocols (e.g. factorial design) have not yet achieved consensus. Results from the recent study, Global Utilisation of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) provide a new impetus to the employment of early patency data as an appropriate surrogate endpoint. Nonetheless, despite the creativity of molecular genetics, current efforts to develop novel plasminogen activators with improved pharmacological attributes still appear relatively diffident and key questions on augmenting the efficacy of thrombolytic regimens remain unanswered. If we are to capitalise on the healthcare gains generated over the past few years, to treat increasing numbers of eligible patients, we need to combine the sustained progress in drug discovery creativity with a plurality of innovative approaches to clinical study design.",
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