Ultrasound imaging techniques for the evaluation of cardiovascular therapies.
Cardiovascular disease remains a substantial cause of morbidity and mortality in the developed world, and is becoming an increasingly important cause of death in developing countries too. While current cardiovascular treatments can help to reduce this disease burden, a substantial number of patients still retain a high risk of experiencing a life-threatening cardiovascular event. Thus, the development of new therapies capable of reducing this residual risk remains an important healthcare objective. The time taken to bring new therapies to the patient in need is lengthened by the unavoidable requirement to demonstrate a statistically significant benefit in terms of clinical events beyond that achievable with current treatments. However, clinical trials utilizing surrogate endpoints-biomarkers of disease progression that manifest before potentially fatal cardiovascular events occur-have the potential to enhance the process of drug development by enabling a statistically sound assessment of the efficacy of new therapies several years in advance of the availability of data from clinical endpoint trials. Two vascular ultrasound imaging techniques, measurement of carotid intima-media thickness (CIMT) and intravascular ultrasound (IVUS) of the coronary arteries, are increasingly being used to assess novel cardiovascular therapies in surrogate endpoint trials forming integral components of larger trial programmes utilizing both surrogate and clinical endpoints. The rationale for the use of CIMT- and IVUS-based surrogates, with supporting evidence from historical and recent trials, is presented in this review article.
Kastelein
John J P
JJ
Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. j.j.kastelein@amc.uva.nl
de Groot
Eric
E
D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000628:therapy; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging* / Q000628:therapy; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging*; D002986:Clinical Trials as Topic; D017023:Coronary Angiography / Q000379:methods; D018450:Disease Progression; D023381:Endpoint Determination; D006801:Humans; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography