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32 Cardio Diabetes Medicine 2017

this data is that sub-group analysis of ACCORD trial reduction of CV events by 20-25% approximately ir-
in patients with raised TG>204 mg/dL and low HDL-C respective of baseline LDL-C. This means that statins
<34 mg/dL did show a benefit but sub-group analysis are powered to decrease 50 % of dyslipidemia related
are only hypothesis generating and the finding needs atherogenic risk.
to be confirmed in large randomized trial which is We have already witnessed the revolutionary era
non-existent at the present state of time. Likewise of statins for last 30 years and indeed statins have
in the meta-analysis of fibrate trials , fibrates were emerged as uncontested king for lipid management.
6
not used on top of statins in all trials. It is important We have voluminous data on statins and they are
to realize that it is apoB particles which enters the class IA recommendation for primary as well as sec-
vessel wall and not TG per se. The risk of atheroscle- ondary prevention of coronary artery disease. They
rosis is related to the number of atherogenic particles are highly effective drugs and have minimal side
and each atherogenic lipoprotein particle contains a effects. 2015 came with breaking news when two
single molecule of apoB. Therefore the concentration PCSK9 inhibitors, evolocumab and alirocumab were
of apoB provides a direct measure of the number of approved for clinical use by EMA and ACC/AHA.
circulating atherogenic lipoprotein. In most hypertrigl- With this a new revolutionary era of PCSK9 has
ceridemic (HyperTG) patients including diabetics, LDL erupted and this kicked off the second revolution in
particles make up 85-90% of total apoB particles and dyslipidemia after the Statins. PCSK9 inhibitors de-
the contribution of VLDL is only 10-15%. Fibrates only crease LDL-C by another 1 mmol and this is expected
lower LDL particle by only about 10% and therefore to decrease CVE by another 20-25%. Therefore with
fibrates at most may only play a minor role. The Que- combination of both drugs the dyslipidemia related
bec cardiovascular study also showed that if there atherogenecity can be minimized to a great extent.
is HyperTG with normal apoB levels, there is no in- The effect of reduction in LDL-C on cardiovascular
crease in Odds ration of IHD but if there is HyperTG events is shown in Table 4.
with increased apoB levels, the Odds ratio of IHD are
significantly increased. Atherogenic Risk Reduction Drug Decrease
Non Lipid Lipid in Utilized in CV
What are the drugs for dyslipidemia related related LDL-C events
The drugs utilized for modulating dyslipidemia are High
outlined in 1 mmol intensity 25%
statins
LDL-C Non- TG HDL 50% 50% Statins +
HDL-C
2 mmol PCSK9 45%
Statins Intensify Fibrate No drug inhibitors
Ezetimibe statin OM3 fatty recom- Table 4: Effect of LDL-C reduction on atherogenic cardio-
PCSK9 inhibitors Fibrates acid mended vascular events
a. Evolocumab OM3 fatty Saroglita-
#
b. Aliorocumab acid zar Non Statin drugs:
Colesevelam In selected high-risk patients, such as those with
Lomipatide (For existing ASCVD or LDL-C ≥190 mg/dl, use of non-
FH*) statins may be considered if maximally tolerated
Mipomersen (For statin therapy has not achieved >50% reduction in
FH*) LDL-C from baseline.
siRNA Inclisiran +
Ezetimibe is the first non-statin medication that
Table 3: Drugs for treatment of dyslipidemia should be considered in most of the patient scenar-
ios, given its safety and tolerability, though modest
*Familial Hypercholesterolemia ,
#Available only in India, no approved by FDA., efficacy, when added to moderate-dose statin in the
7.
+Under evaluation. IMPROVE IT Trial
Statins are the first line agents for targeting dyslip- Bile acid sequestrants (BAS) may be considered as
idemia. CTT meta-analysis Collaboration (Figure 7) second-line therapy for patients in whom ezetimibe is
has shown that high intensity statins on an average not tolerated, but they should be avoided in patients
decrease LDL-C by 1 mmol and this reduction is seen with triglycerides >300 mg/dl.
across the range of LDL-C and this translates into

GCDC 2017