DEVELOPMENT AND INNOVATION IN CARDIOVASCULAR MEDICINE - Innovation in the Biopharmaceutical Industry - page 39

successful treatments for coronary disease is an excellent example of the value of
ongoing research and innovation to make better use of existing drugs. In relation
to thrombolytic therapy, the key developments that allowed their widespread and
rapid use were (1) the introduction highly successful large (mega) clinical trails, (2)
evidence that their efficacy did not require intra-coronary delivery, and (3) recog-
nition that optimal effectiveness was critically dependent on their use as soon as
possible after the onset of the symptoms of myocardial infarction.
Lipid lowering drugs
It has been known for several decades that plasma cholesterol level is a major risk
factor for coronary heart disease. For most of that period, this knowledge was cou-
pled with uncertainty as to whether lowering cholesterol levels would confer any
benefit in preventing complications of coronary heart disease. Treatments had been
available to lower plasma lipids, and had been shown to reduce the complications
of coronary heart disease but not overall mortality (Co-operative trial in the primary
prevention of ischaemic heart disease using clofibrate, 1978). The key development
which advanced lipid-lowering therapy was understanding lipid transport (Brown
and Goldstein, 1976), which in turn, led to the breakthrough introduction of statins,
which block cholesterol synthesis in the liver by inhibiting the enzyme 3-hydroxy-
3-methylglutaryl coenzyme-A reductase. In a landmark study, the “4-S” trial clearly
demonstrated a reduction in overall mortality in patients who had a previous history
of angina or myocardial infarction and who were given statin therapy for 5 years
(Scandinavian Simvastatin Survival Study Group, 1994). This led to the widespread
introduction of statins for the prevention of complications in patients with coronary
heart disease. Important questions remained as to the use of statins in other patient
groups — for example, in patients with cerebral vascular disease, peripheral vascu-
lar disease, and diabetes. These have now been the subject of major clinical trials.
The Heart Protection Study Collaborative Group (2002), which investigated over
25,000 patients with peripheral vascular disease, clearly showed survival benefit in
patients with peripheral vascular disease and cerebral vascular disease, including
a reduction in stroke and overall mortality. A large sub-study of the ASCOT trial
(Sever et al. , 2003) subsequently demonstrated that patients who are being treated
for hypertension derive additional benefit when given statin therapy. More recently,
the CARDS trial (Colhoun et al. , 2004) has demonstrated that patients with type
II diabetes have significantly improved survival when given statin therapy. These
clinical trials exemplify the concept that a drug is only as good as our understand-
ing of how to use it effectively to benefit patients. It is essential to recognise the
innovative importance and value of studies that extend our understanding of how to
use drugs more effectively.