Management of Hypertension and cholesterol

1. MANAGEMENT
• LDL-C is the primary target for therapy.
• The target LDL-C level will depend on the individual’s global risk:
1

2. TYPE OF
MANAGEMENT
THERAPEUTIC
LIFESTYLE CHANGES
1) Dietary
modification
2) Weight reduction
3) Regular physical
activity
4) Cessation of
smoking
5) Alcohol
restriction
DRUG THERAPY
Lipid lowering
drugs:
a) Statin
b) Fibrates
c) Resins
d) Niasin
e) Cholesterol
Absorption
Inhibitors
f) PCSK 9 inhibitors
LDL-C APHERESIS

3. STATINS
HMG CoA reductase inhibitor (rate limiting enzyme in hepatic cholesterol synthesis)
Treatment of choice in reducing LDL-C
Suitable first-line agents in familial hypercholesterolemia, for primary prevention of CVD,
secondary prevention of CVD and CHD equivalents
Starting dose with the evening meal or at bed time (except for long-acting statins that can be
taken at any time)
Serum lipids and alanine aminotransferase(ALT) should be measured at 6-8 weeks
Contraindicated in pregnancy and lactation
Adverse effects
 Liver function (elevation of ALT)
 Muscle symptoms (myalgia, myositis, rhabdomyolisis)
 Diabetes( new onset)
 Kidney problem (proteinuria)
 Neurocognitive function ( memory loss and confusion)
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5. Fibrates (Fibric acid derivatives)
Peroxisome Proliferator Activated Receptor (PPAR) –α agonist which in
turn stimulates synthesis of fatty acid oxidation
Reduce TG levels and increase HDL-C levels effectively
Useful in individuals with combined (mixed) dyslipidaemia and
hypertriglyceridaemia
Alternatives for mild to moderate hypercholesterolaemia that has
Statin intolerance
Doses adjusted in patients with CKD
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7. Resins
Bile acid sequestrants bind to bile acids to promote their secretion into
the intestines -- effective in lowering LDL-C
May increase TG and HDL-C slightly
Other medications should be taken 1 hour before and/or 4 hours after
resins
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8. Niacin (Nicotinic acid)
Decrease mobilization of free fatty acids from adipose tissues
Very effective in increasing HDL-C and lower both TC and TG levels
Its side effects (particularly flushing and gastrointestinal side effects) tend
to limit compliance
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9. Cholesterol Absorption Inhibitors
Selectively block intestinal absorption of both dietary and biliary
cholesterols and other phytosterols -- reduction in hepatic cholesterol
delivery
Indicated as monotherapy for primary hypercholesterolemia patients
who cannot tolerate statin or fibrate
Used also in combination with statins to further lower LDL-C
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10. PCSK9 inhibitors
This is a new class of lipid-lowering drug that target the proprotein convertase subtilisin
kexin type 9 (PCSK9).
MOA by inhibiting the binding of PCSK9 to the LDL-receptors. Hence, it decreases the
degradation of the LDL-receptors
resulting in higher LDL-receptors causing an increased clearance with resulting
decrease in LDL-C levels.
Indication:
individuals with high CV risk who have persistently elevated LDL-C despite optimum lipid-
modifying therapy
those with familial hypercholesterolemia – heterozygous FH and to a lesser extent those with
homozygous FH
Very High Risk and High-Risk patients with true statin intolerance and persistently high
levels of LDL-C may also be candidates for PCSK9 inhibitors
Recommended Dose:
• Dose of evolocumab: 140 mg SC every two weeks or 420 mg SC monthly
• Dose of alirocumab: 75-150 mg SC every two weeks

11. Summary of anti-lipid drugs

12. RECOMMENDED DRUG TREATMENT
• If target lipid goals have not been achieved after 8-12 weeks of optimal
monotherapy, combination therapy is suggested
• Statin + Cholesterol absorption inhibitors ~ reduce CV events and renal
outcomes in patients with CKD
• Fibrates + Statins ~ potentially adverse effects especially myositis
(incidence : 0.5-2.5%)

13. MONITORING AND THERAPY DURATION
• After starting drug therapy, LDL-C level should be measured at 6-8 weeks
• Drug doses titrated if necessary
• Once target lipid levels are achieved, a 4-6 monthly follow up is
recommended

14. Monitoring of ALT is necessary if statins and fibrates are used for
treatment
• Liver function tests should be carried out before and within 1-3
months of starting treatment
• Statin is discontinued if ALT levels rise to at 3x upper limit of normal
• If the levels are elevated between 2 to 3 times upper limit of normal,
the trend should be monitored at monthly intervals
• If myositis is suspected, then creatinine kinase levels should be
measured. If the level is more than 10 times the upper limit of
normal, then the drug should be discontinued

15. Pharmacoeconomics of Lipid Lowering
Therapy
LDL-C apheresis
• indicated in patients with homozygous familial hypercholesterolemia
(FH) who do not respond satisfactorily to maximum multiple drug
therapy (high intensity statin at maximal dose with ezetimibe/PCSK9)