1. Step 3 P-treatment: Drug Class Selection

2. Pharmacological and Non- Pharmacological Management Dyslipidemia drug therapyLifestyle modification Smoking cessation Weight management Regular physical exercise Adequate blood pressure monitoring and control Dietary management: low fat, low cholesterol

3. Drug Classes Statins Nicotinic Acid Fibric Acid Derivatives Bile-Acid Binding Resins Ezetimibe

4. Statins MOA – HMG-CoA reductase inhibitor : reduces hepatic cholesterol synthesis Efficacy (++++) – Significant reduction of LDL (up to 35%) – Increase in HDL (5-10 %) – Decreased triglyceride levels – Level of evidence: meta analysis

5. Statins - Continued Safety: (+++) – Risk of myositis if taken in combination with fibrates or niacin – Not recommended in those with hepatic derangements Suitability (+++) – Primary concern is LDL lowering – Ease of administration: oral preparation, once a day. Cost: (++++) – Afordel: Php 203.25/ month at 10 mg/day

6. Nicotinic Acid MOA – Reduces production of VLDL: secondary reduction in LDL and increase in HDL Efficacy (+++) – Significant increase in HDL (~30%) – Decrease in LDL (~20%) – Significant decrease in Triglycerides – Long experience: reduction in coronary events and mortality

7. Safety (++) – Intolerance is common with full doses – “hot flashes” and pruritus – Precaution if used with statins Suitability (++) – Suboptimal LDL lowering if not at full dose Cost (+++) – Niaspan: Php 555 pesos / month at 500 mg/day Nicotinic Acid- Continued

8. Fibric Acid Derivatives MOA – PPAR-alpha agonist – Reduced Apolipoprotein C-III synthesis: increased lipoprotein lipase activity: increased VLDL clearance Efficacy (++) – Significantly reduces triglycerides (~40%) – Increase HDL (~20%) – Reduce LDL (~15%) – Reduced CHD rates among hypercholesterolemics

9. Safety (++) – Risk of developing cholelithiasis, hepatitis, and myositis Suitability (++) – Most benefit is seen among those with hypertriglyceridemia and low HDL cholesterol – Taken twice a day Cost (++) – Nubrex: Php 1072 / month at 200 mg/day Fibric Acid Derivatives- Continued

10. Bile Acid Binding Resins MOA – Reduces enterohepatic circulation of bile acids – Increases hepatic production of bile acids, consuming hepatic cholesterol Efficacy (+++) – Reducton in LDL (~20%) – Increase in triglycerides – No effect to HDL – Reduced incidence of coronary events in studies

11. Safety (+++) – Interferes with absorption of fat-soluble vitamins – Caution with warfarin Suitability (++) – Primary effect targets LDL – Monotherapy may be insufficient – Doses need to be divided Cost N/A – Cost abroad is greater than that of statins BAB Resins- Continued

12. Ezetimibe MOA – Inhibits a cholesterol transporter in the intestine, reducing enteric absorption Efficacy (+++) – Reduces LDL (~20%) – No significant effect on HDL and Triglycerides

13. Safety (++) – Can be used in combination with statins Suitability (++) – Specific for LDL reduction – Monotherapy may be insufficient – Once a day dosing Cost (+) – Ezetrol: Php 3000/month at 10 mg/day Ezetimibe- Continued

14. Summary Drug ClassEfficacySafetySuitabilityCost Statins+++++++ ++++ Nicotinic Acid+++++ +++ Fibrates++ Resins+++++ N/A Ezetimibe+++ +++ Therefore, considering the efficacy, safety and suitability and the cost of the available treatment options, STATINS is the most preferred drug class of choice. Statins are composed of several kinds, and thus we discuss this further.

15. STATINS Drug class of most benefit

16. Locally Available Statins Simvastatin Atorvastatin Rosuvastatin Fluvastatin

17. Quick Info for the Different Statins StatinBrand NameManufacturer SimvastatinZocorMerck and Co. AtorvastatinLipitorPfizer RosuvastatinCrestorAstra Zeneca FluvastatinLescolZuellig All are 100% synthetic. ** Lovastatin, example of a fungus-derived stain. Not available in the Philippines.

18. Quick Info for the Different Statins StatinBrand Name ManufacturerClaim of Percent Lipid Lowering Effect* Nature of Source** SimvastatinZocorMerck and Co.26-47%100% Synthetic AtorvastatinLipitorPfizer26-60%100% Synthetic RosuvastatinCrestorAstra Zeneca45-63%100% Synthetic FluvastatinLescolZuellig22-36%100% Synthetic *At prescribed optimum doses. Low validity study. ** Lovastatin, example of a fungus-derived stain. Not available in the Philippines.

19. Simvastatin Brand name: Zocor, manufactured by Merck and Co. (Zeullig) Contains: starch, talc, cellulose, lactose, magnesium stearate, iron oxides or titanium dioxide as inactive ingredients in the drug.

20. Atorvastatin Brand name: Lipitor, manufactured by Pfizer. Pfizer claims that Lipitor is the most researched statin on the market. 100% synthetic, compared to other statins which are derived from fungus.

21. Rosuvastatin Brand name: Crestor, manufactured by AstraZeneca Claims to lower cholesterol by

22. Fluvastatin Brand name: Lescol, manufactured by Zuellig Also 100% synthetic

23. Summary Drug ClassEfficacySafetySuitabilityCost Simvastatin (Afordel, 40mg) +++++++++++ +++ (P 17.33/day) Atorvastatin (Lipitor, 10mg) +++++++++++ ++ (P 34.45/day) Rosuvastin (Crestor, 10mg) +++++++++++ ++ (P 57.66/day) Fluvastatin (Lescol, 40mg) +++++++++++ ++ (P52.61/day) Therefore, SIMVASTATIN is the best option among the statins option.

24. STEP 4 Prescription Writing

25. A.Dionisia 62Female Simvastatin, 40 mg tablet 30 Inomin 1x tuwing gabi. Dr. Manny Kalayaan 123456 Date: November 17, 2010

26. Manny Kalayaan, MD, FPCP, FPMID Philippine General Hospital Mon-Friday 9am to 4pm 0917-12345678 Patient: ADDate: November 17, 2010 Address: ManilaAge/Sex: 62/F R/ Simvastatin 40 mg tablet#30 Sig: Inomin 1 tablet sa gabi Dr. Manny Kalayaan Lic. No.123456