High density lipoprotein or HDL, often known as the
'good cholesterol', is known to protect the heart against diseases. On the
other hand, LDL or low density lipoprotein is the 'bad cholesterol' associated
with heart diseases. A higher level of HDL and a lower level of LDL are thus
associated with a healthy heart.
Taking the above into consideration, newer drugs are
now being developed that could increase the levels of HDL, and thereby improve
cardiovascular health. These drugs belong to a group that is referred to as the
cholesteryl ester transfer protein (CETP) inhibitors. The first among these
called torcetrapib was found to increase HDL cholesterol by more than 70% and
decrease LDL cholesterol by 25%. Unfortunately, it was associated with deaths
and morbidity due to a concomitant increase in the levels of the hormone
aldosterone and blood pressure.
Another CETP inhibitor drug dalcetrapib has been
found to increase HDL level by 30%, without similar side effects in a small
study. Therefore, researchers conducted a bigger study to evaluate the effects
of this drug in patients with a recent acute coronary syndrome (conditions
affecting the blood supply to the heart). These included people who showed the
presence of increase in markers of cardiac disease, symptoms of angina or heart
attack, new changes in the ECG, or damage to the heart muscle as seen on
imaging studies. In addition, patients with a recent heart attack who had
undergone angioplasty were also included in the study.
The study enrolled 15,871 patients from 27
countries. The patients included in the study received either dalcetrapib 600
mg daily or a matching placebo. The study was terminated before the stipulated
time at 31 months when the futility of continuing the trial was agreed upon.
dalcetrapib increased the HDL cholesterol levels from 31 to 40% with minimal
effect on LDL cholesterol level
this increase in HDL levels was not associated with a decrease in deaths or
incidence of coronary heart disease or unanticipated coronary revascularization
procedures (like angioplasty)
fact, the group that received dalcetrapib showed a significant increase in
C-reactive protein level, which reflects the proinflammatory effect of the drug
and ability to cause increased cardiovascular events.
systolic blood pressure was significantly higher in the group that received
dalcetrapib as compared to the group that received placebo
. Diarrhea was also more
common in the dalcetrapib group, thus contributing to its discontinuation. In
addition, patients also complained of insomnia.
Some suggestions have been made by the researchers
to explain the lack of effect of dalcetrapib treatment in patients with acute
coronary disease despite the increase in HDL levels. These are:
It is possible that HDL levels are not protective in
patients who were receiving other treatments like statins, antiplatelet
therapy, beta-blockers, ACE inhibitors or ARBs, and coronary revascularization
It is also possible that HDL is protective in
healthy individuals but not in those who are already suffering from cardiovascular
It is also not known if dalcetrapib affected the
function of HDL.
The favorable effects of dalcetrapib may also have
been offset by the side effects of treatment like a rise in systolic blood
pressure and an increase in C-reactive protein level.
Thus, though dalcetrapib increased HDL levels, it
did not result in a significant decrease in cardiovascular events in patients
with coronary artery disease. The utility of such drugs thus remains
1. Effects of Dalcetrapib in Patients with a Recent Acute Coronary
Syndrome; Gregory Schwartz et al; N Engl J Med 2012; 367:2089-2099