michael s
(Michael S)
#1
11 What drugs should I choose to treat
dyslipidaemia, and how should I monitor
treatment?
John Betteridge
SSttaattiinnssinhibit the conversion of HMG-CoA to mevalonate (the
rate-determining step in cholesterol synthesis). Hepatic LDL
receptors (recognising both apoproteins E and B) are upregulated,
and uptake of LDL cholesterol and remnant particles (IDL) is
increased. Hepatic VLDL output is also modestly decreased.
Plasma LDL-cholesterol levels thus fall by 30–60% with the bulk
of the decrease with the starting dose. A further 7% LDL reduction
is obtained for each doubling of the dose. HDL cholesterol levels
are modestly reduced (8%), and if plasma triglyceride levels are
above 2.5mmol/l, these are lowered by a similar fraction as LDL.
Statins are the first choice for patients requiring LDL reduction,
and for treatment of mixed lipaemia if triglycerides are below
5mmol/l. Action on hepatic VLDL output probably underlies the
modest reduction in cholesterol levels in patients homozygous for
receptor negative familial hypercholesterolaemia (FH). There is
little information on the use of statins in children, and they
should be stopped in women at least 6 weeks prior to conception.
AAnniioonn--eexxcchhaannggee rreessiinnssinterrupt the enterohepatic circulation
of bile and cholesterol, causing body levels to fall. Hepatic LDL
activity is upregulated to obtain cholesterol for new bile acid
formation. LDL reductions of up to 30% can be achieved. They
may increase triglyceride levels to a modest and often transient
degree. Their poor tolerability generally reserves them for use in
children heterozygous for FH, the treatment (in combination with
statins) of severe adult FH, in FH women contemplating preg-
nancy (when some physicians use them in preference to statins)
and in patients intolerant of statins. The resins have been used
with positive outcome in several angiographic trials and in an
early positive end point trial (the Lipid Research Clinics trial).
FFiibbrraatteessare ligands for the nuclear hormone receptors, perox-
isome proliferation activator receptors (PPARs). They decrease
apoprotein C-III synthesis (an inhibitor of lipoprotein lipase) and
therefore increase lipoprotein lipase activity. Triglyceride levels
thus fall by 40–60%. They also upregulate apoprotein A-1
synthesis (the major protein of HDL). HDL cholesterol levels rise
