Cardiovascular Therapeutics - Applications of Biotechnology in Cardiovascular Therapeutics - page 18

Cardiac arrhythmias . There is a peak frequency of ventricular tachycardia or
fibrillation between 6 a.m. and noon. Arrhythmias are usually suppressed during
sleep.
A major objective of chronotherapy is to deliver the drug in the highest concen-
tration during the time of greatest need, for example, early morning hours.
Chronotherapeutic agents for hypertension and angina pectoris have been marketed
to match drug delivery to the circadian BP and myocardial ischemic rhythms in a
novel delivery form. COER-24 contains verapamil as the active drug in a controlled
onset, extended release formulation which has a delay in release followed by
extended release for approximately 18 h. When taken at bed time, the delivery
system provides optimal drug concentration between 4-5 a.m. and noon.
An international study, Controlled ONset Verapamil INvestigation of
Cardiovascular End-point (CONVINCE) trial showed that chronopharmacotherapy
can reduce the incidence of myocardial infarction and stroke that closely follow
fluctuations in BP. Chronotherapy has not yet been recommended as a therapy of
choice by various health organizations such as the WHO or the US Joint National
Committee V or VI. Comparative trials are still needed to evaluate the effects of
chronotherapeutic versus conventional antihypertensive or anti-ischemic therapies.
Cardioprotection
Apart from the common and the best known cause of myocardial damage due to
ischemic heart disease and ischemic/reperfusion injury, several other factors can
cause damage to the heart, indicating the need of strategies for cardioprotection.
These include cardiac surgery, viral diseases, cardiotoxic chemotherapeutics, ath-
erosclerosis of smaller coronary artery branches, environmental toxins such as
carbon monoxide, hypoxia, and aging.
Strategies for cardioprotection are an important part of preventive cardiology
and include pharmaceutical as well as non-pharmaceutical measures as shown in
Table 1.2 . Those relevant to biotechnology are described in this topic. Details of
other measures for cardioprotection are beyond the scope of this topic.
The first strategy in cadioprotection is to remove the causes of ischemic heart
disease; the second is to attenuate ongoing ischemic and reperfusion injury; the
third is to prevent the progression of cardiac remodeling and chronic heart failure
following ischemic injury. For prevention of acute myocardial infarction, it is
widely accepted to treat high-risk patients with aspirin and/or statins. On the other
hand, several medications such as angiotensin-converting enzyme inhibitors, aldos-
terone receptor antagonists, and beta blockers have been used for the prevention of
postinfarction heart failure in patients who have suffered from an acute myocardial
infarction. However, there is adjunctive drug therapy to reduce infarct size in the
acute phase in patients with myocardial infarction. The J-WIND trials suggested
that an infusion of human atrial natriuretic peptide in the acute phase and oral
administration of nicorandil in the chronic phase of infarction result in a better
outcome in patients with a myocardial infarction (Asakura and Kitakaze 2010 ).