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Management Of Dyslipidemia - Dr Vivek Baliga Presentation

For more articles on health, visit http://baligadiagnostics.com/author/drbvb/<br><br>Dyslipidemia management is not just important in the management of heart disease but also in diabetes. Take a look at how to manage high lipids in the setting of diabetes and heart disease.

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Management Of Dyslipidemia - Dr Vivek Baliga Presentation

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  1. Dyslipidemia Management: An Evidence Based Approach Dr Vivek Baliga Consultant Internal Medicine Director, HeartSenseTM

  2. Types of Plasma Lipids

  3. 2013 ACC/AHA Guidelines: Statins without any lipid “goals” • Clinical ASCVD* • LDL-C ≥190 mg/dL, Age ≥21 years • Primary prevention – Diabetes: Age 40-75 years, LDL-C 70-189 mg/dL • Primary prevention - No Diabetes†: ≥7.5%‡ 10-year ASCVD risk, Age 40-75 years, LDL-C 70-189 mg/dL *Atherosclerotic cardiovascular disease †Requires risk discussion between clinician and patient before statin initiation ‡Statin therapy may be considered if risk decision is uncertain after use of ASCVD risk calculator Circulation. 2014;129[suppl 2]:S1-S45 Circulation 2014; 129: S1-S45

  4. LAI 2016 Statement: Both LDL-C/Non-HDL-C goals are important in Indian context Journal of The Association of Physicians of India March 2016 supplement

  5. Clinical Conditions where Lipid Lowering therapy required • Patients with ASCVD • Patients undergoing PCI • Primary prevention of CVD for DM • Patients with low HDL-C • For patients with CKD • For patients with very high LDL-C (> 190 mg/dl) • Patients with IGT and High CV risk • Patients with statin intolerance • Residual risk with statin therapy: a. Atherogenic(Mixed) Dyslipidemia with T2DM b. Atherogenic(Mixed) Dyslipidemia without T2DM

  6. Statin For Secondary Prevention • Current guidelines recommend moderate to high dose of statins for secondary prevention. • Atorvastatin has multiple landmark trials for secondary prevention Amongst all statins, Atorvastatin has robust evidence for secondary prevention of ASCVD Higher dose atorvastatin has shown incremental benefits over and above those expected with lower dose statins

  7. TNT: High Vs Low Dose statin in Stable CAD 22% risk reduction by 80 mg Vs 10 mg atorvastatin p<0.001 High dose statin is more effective for CV protection in stable IHD patients Primary Endpoint: Major cardiovascular event defined as coronary heart death (CHD), nonfatal MI, resuscitated cardiac arrest, and fatal or nonfatal stroke Waters DD et al. N Engl J Med 2005;352:1425-35

  8. CV events in PROVE IT study Death/MI/Urg. Revascu. Death/MACE ↓33% ↓16% Intensive statin Rx provides more benefits than moderate statin Rx PROVE IT trial randomly assigned 4,162 patients who had been hospitalized within the previous 10 days for ACS to receive pravastatin 40 mg vs intensive regimen of 80 mg atorvastatin. Cannon et al. NEJM 2004 Ray et al. Am J Cardiol 2006

  9. Pitavastatin in Secondary Prevention : Ongoing Study

  10. Clinical Conditions where Lipid Lowering therapy required • Patients with ASCVD • Patients undergoing PCI • Primary prevention of CVD for DM • Patients with low HDL-C • For patients with CKD • For patients with very high LDL-C (> 190 mg/dl) • Patients with IGT and High CV risk • Patients with statin intolerance • Residual risk with statin therapy: a. Atherogenic (Mixed) Dyslipidemia with T2DM b. Atherogenic (Mixed) Dyslipidemia without T2DM

  11. Loading High dose statin before PCI in ACS reduces CV events: ARMYDA-ACS % 17 P=0.01 5 Among patients with ACS undergoing PCI, pretreatment with atorvastatin 80 mg improves clinical outcomes, driven mainly by reduction in periprocedural MI 171 NSTEACS patients randomized to atorvastatin (80 mg 12 h before PCI, with a further 40-mg pre-PCI or placebo. All patients received long-term atorvastatin thereafter (40 mg/day). Primary end point : 30-day incidence of MACE(death, myocardial infarction, or unplanned revascularization) JACC 2007:49:1272-78

  12. ARMYDA-RECAPTURE: loading 80 mg atorvastatin pre-PCI in those on statin already also reduces CV events Reloading with high-dose atorvastatin resulted in 50% reduced risk of MACE at 30 days versus placebo 9.1 P=0.045 MACE (%) 3.4 Atorvastatin Placebo These findings support strategy of routine reload with high-dose atorvastatin early before intervention even in the background of chronic therapy. 383 patients with stable angina (53%) or NSTMI(47%) and chronic statin therapy undergoing PCI were randomized to atorvastatin reload (80 mg 12 h before PCI , + 40-mg pre-PCI) or placebo. All patients received long-term atorvastatin thereafter (40 mg/day). Primary end point : 30-day MACE (cardiac death, myocardial infarction, or unplanned revascularization) JACC 2009:54:558-65

  13. Clinical Conditions where Lipid Lowering therapy required • Patients with ASCVD • Patients undergoing PCI • Primary prevention of CVD for DM • Patients with low HDL-C • For patients with CKD • For patients with very high LDL-C (> 190 mg/dl) • Patients with IGT and High CV risk • Patients with statin intolerance • Residual risk with statin therapy: a. Atherogenic(Mixed) Dyslipidemia with T2DM b. Atherogenic(Mixed) Dyslipidemia without T2DM

  14. Major Statin Primary Prevention Trials * sub-analysis

  15. CARDS: Statin For Primary Prevention In T2DM (2838 patients) Atorvastatin 10 mg (LDL 119) (n=1428) Placebo (LDL 118) (n=1410) 127 events median follow-up 3.9 years Atorvastatin 10 mg daily is safe and efficacious in reducing risk of first cardiovascular disease events, including stroke, in patients with T2DM without high LDL-C. The level of LDL should not dictate statin use. Cumulative incidence of events (% of patients) 83 events RRR=37% p=0.001 Time (years) Collaborative Atorvastatin Diabetes Study – Performed in patients without CVD Colhoun HM et al. Lancet. 2004;364:685-696. *Acute CHD event, coronary revascularization, stroke. RRR: Relative risk reduction

  16. EFFECT ON BLOOD GLUCOSE LEVELS • 28th Feb 2012: • FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs • Increases in HbA1c and fasting serum glucose levels have been reported with statin use A 2016 analysis estimated that high-dose statin therapy (eg, atorvastatin 40 mg daily) would lead to 50 to 100 new cases of diabetes in 10,000 treated individuals. www.fda.gov

  17. Effect on Blood Sugar Levels • Statins could have effects on glucose metabolism that might influence the development of diabetes mellitus in non-diabetics or affect glycemic control in patients with existing diabetes. • A 2011 meta-analysis of five randomized trials (N = 32,752) also found an increased risk of incident diabetes with intensive statin therapy compared with moderate statin therapy • Consider risk Vs benefit

  18. Pitavastatin in T2DM:No glycemic disturbances T2DM patients were treated by Atorvastatin 10 mg (n=99), pravastatin 10 mg (n=85) and pitavastatin 2 mg (n=95) for 3 months. Pitavastatin does not increase FPG and HbA1c in T2DM patients unlike Atorvastatin J Atheroscler Thromb. 2008;15(5):269–275

  19. LIVES study: 2 years of Pitavastatin in T2DM Pitavastatin does not increase FPG and HbA1c in T2DM patients even in long term therapy (upto 2 years) Pitavastatin is a good option for long term treatment in T2DM patients Expert Opin Pharmacother. 2010;11(5):817–828.

  20. Clinical Conditions where Lipid Lowering therapy required • Patients with ASCVD • Patients undergoing PCI • Primary prevention of CVD for DM • Patients with low HDL-C • For patients with CKD • For patients with very high LDL-C (> 190 mg/dl) • Patients with IGT and High CV risk • Patients with statin intolerance • Residual risk with statin therapy: a. Atherogenic(Mixed) Dyslipidemia with T2DM b. Atherogenic(Mixed) Dyslipidemia without T2DM

  21. B. Effect on HDL-C LIVES : Pitavastatin increases HDL-C upto 32.4%^ Pitavastatin's ability to significantly and continually increase HDL-C levels over time suggests a particular benefit for patients with low baseline levels of HDL-C and/or those that fail to increase their HDL-C levels using alternative statins. Effects of pitavastatin on HDL-cholesterol in the LIVES study according to the previous use of statins. *p < 0.05; **p < 0.01; ***p < 0.001 (vs baseline, one-sample t-test). ^ in patients with low HDL-C Expert Opin. Pharmacother. 2012;13(6): 859–865

  22. Shifting from other statins to Pitavastatin further increases HDL-C 129 dyslipidemia patients (already on statin for 3 months were crossed over to other statins for 3 months ↑ 7.7% (p< 0.05) ↓5.5% (p< 0.05) ↓2.9.% ↑ 7.5% (p< 0.05)

  23. Clinical Conditions where Lipid Lowering therapy required • Patients with ASCVD • Patients undergoing PCI • Primary prevention of CVD for DM • Patients with low HDL-C • For patients with CKD • For patients with very high LDL-C (> 190 mg/dl) • Patients with IGT and High CV risk • Patients with statin intolerance • Residual risk with statin therapy: a. Atherogenic(Mixed) Dyslipidemia with T2DM b. Atherogenic(Mixed) Dyslipidemia without T2DM

  24. Dose of statins in patients with CKD • Atorvastatin: No dose adjustment required • Rosuvastatin: In patients severe CKD with creatinine clearance < 30 ml/min (not on hemodialysis), Maximum dose: 10 mg/day • Pitavastatin: In patients with moderate/severe CKD (GFR: 15-59 ml/min) Maximum dose: 2 mg/day GFR: Glomerular Filtration Rate

  25. Atorvastatin Vs Rosuvastatin For Proteinuria: A Meta-analysis • A meta-analysis of 5 clinical trials head to head comparing atorvastatin vs rosuvastatin Atorvastatin is better than rosuvastatin for reduction in proteinuria Circ J 2012;76:1259-66

  26. Effect of pitavastatin on eGFR in CKD patients (eGFR<60 ml/min/1.73m2) Pitavastatin 2 mg provides nephroprotective effects in CKD patients (eGFR 15-59 ml/min) J Atheroscler Thromb 2010;17:601-609

  27. Effect of Pitavastatin on proteinuria 20 T2DM patients were treated with pitavastatin or placebo for 12 months * P <0.01 Vs Control Diabetes Care 2005;28:2728–2732

  28. Even at 1 mg/day dosage, pitavastatin reduces proteinuria in CKD patients 12-16 week treatment with pitavastatin (n=65) or control (n=40) ** p< 0.01 Am J Cardiol 2011;107:1644 –1649

  29. Clinical Conditions where Lipid Lowering therapy required • Patients with ASCVD • Patients undergoing PCI • Primary prevention of CVD for DM • Patients with low HDL-C • For patients with CKD • For patients with very high LDL-C (> 190 mg/dl) • Patients with IGT and High CV risk • Patients with statin intolerance • Residual risk with statin therapy: a. Atherogenic(Mixed) Dyslipidemia with T2DM b. Atherogenic(Mixed) Dyslipidemia without T2DM

  30. For patients with very high LDL-C (> 190 mg/dl)WOSCOPS 31% Risk Reduction Statin therapy can reduce CV events in those without CVD and LDL-C > 190 mg/dl P=0.0001 Shepherd J, et al, N Engl J Med 1995;333:1301-7

  31. Lipid Lowering with Various statins : VOYAGER Meta analysis-37 trials, > 32,000 patients Rosuvastatin showed higher reduction in LDL-C & Non-HDL-C compared to other statins Am J Cardiol 2010;105:69 –76

  32. Clinical Conditions where Lipid Lowering therapy required • Patients with ASCVD • Patients undergoing PCI • Primary prevention of CVD for DM • Patients with low HDL-C • For patients with CKD • For patients with very high LDL-C (> 190 mg/dl) • Patients with IGT and High CV risk • Patients with statin intolerance • Residual risk with statin therapy: a. Atherogenic(Mixed) Dyslipidemia with T2DM b. Atherogenic(Mixed) Dyslipidemia without T2DM

  33. 13 statins trials included, 91140 participants. • Statins therapy is associated with 9% increase in the risk of new diabetes (usually in patients predisposed to developing T2DM). • Conclusion: Statin therapy is associated with a slightly increased risk of development of diabetes Lancet 2010;375:735-42

  34. J PREDICT: Effect of Pitavastatin on NOD in IGT patients Only large scale prospective study done to evaluate effect of statin therapy on new onset DM in IGT (impaired glucose tolerance) patients 1,269 IGT patients were randomized to lifestyle changes + pitavastatin or control (lifestyle changes only) Patients are followed upto > 5 years Primary End Point: % patients developing New onset DM

  35. J PREDICT: Effect of Pitavastatin on NOD in IGT patients 18% Pitavastatin significantly reduces the new onset of DM by 18%in IGT patients ADA 2013, Late breaking abstract No. 61-LB

  36. J-PREDICT Sub-analysis based on BMI: ADA 2015 Pitavastatin significantly reduces the new onset of DM by 39%in IGT patients with BMI < 23.4 kg/m2 Abstract No: 1199-P, June 7, 2015

  37. Clinical Conditions where Lipid Lowering therapy required • Patients with ASCVD • Patients undergoing PCI • Primary prevention of CVD for DM • Patients with low HDL-C • For patients with CKD • For patients with very high LDL-C (> 190 mg/dl) • Patients with IGT and High CV risk • Patients with statin intolerance • Residual risk with statin therapy: a. Atherogenic(Mixed) Dyslipidemia with T2DM b. Atherogenic(Mixed) Dyslipidemia without T2DM

  38. Upto 29% of patients on statin develops muscle related symptoms LAI estimate – 10 – 15%. 75% of cases in first 3 months, 90% in first 6 months

  39. Re-challenge with different statin is important if symptoms disappear

  40. Pitavastatin For Statin Intolerant Patients: Study 1 • In Florida, USA, 152 patients intolerant to > 2 previous statins due to myopathy (average 2.7 statins) were placed on pitavastatin therapy. • Percentage (%) of patients tolerating pitavastatin and achieving NCEP ATP-III LDL-C goal non-HDL-C goal were measured • 104 patients (76%) patients tolerated pitavastatin therapy and continued it for > 6 months • 87% of patients with intermediate CV risk achieved their NCEP-ATP III LDL-C goals with pitavastatin therapy Pitavastatin is a good option for those who cannot tolerate other statins Journal of Clinical Lipidology 2012: 6(3) : 274

  41. Pitavastatin For Statin Intolerant Patients: Study 2 In a study, 148 patients who had history of > 2 statin intolerance were prescribed pitavastatin. 104 patients who tolerated pitavastatin > 6 weeks were followed up for 1 year to detect long term tolerance of pitavastatin Results: 80.1% of the patients were still tolerating pitavastatin after 1 year use. 79% of patients who tolerated pitavastatin reached NCEP LDL goal Conclusions Pitavastatin is well tolerated by majority of statin intolerant patients Journal of Clinical Lipidology 2013;7(3):264

  42. Pitavastatin For Statin Intolerant Patients: Study 3 • A study presented in ACC 2013 conference • 40 patients (USA) who were intolerant to other statins were treated with pitavastatin 2 mg • 27 (68%) patients could tolerate pitavastatin for > 3 months • LDL-C was reduced by 34% (from 147 mg/dl to 93 mg/dl) • Conclusion: Low dose pitavastatin is an acceptable alternative to abandoning statin among 2/3rd of patients documented to be intolerant to other statins, providing an average LDL-C reduction of 34%. JACC 2013;61(10):E1465

  43. Minimum rise in CK enzymes with Pitavastatin Incidence of adverse effects (%) Pitavastatin-lesser incidence of CK elevation: Better tolerance? Drug Design, Development and Therapy 2011:5 283–297

  44. Atorvastatin Pitavastatin -7.7% * -26.1% Pitavastatin: Less change in CoQ10 levels • An open, randomized, four-phased crossover study using 4 mg of pitavastatin or 20 mg of atorvastatin was performed to compare their efficacy and safety, especially regarding plasma levels of coenzyme Q10 (CoQ10). • Results: Change in plasma CoQ10 from baseline (%) Pitavastatin-lesser Change in Co-enzyme-Q10 : Better tolerance * P = 0.0007 vs. baseline Clin Pharmacol Ther. 2008 May;83(5):731-9

  45. Clinical Conditions where Lipid Lowering therapy required • Patients with ASCVD • Patients undergoing PCI • Primary prevention of CVD for DM • Patients with low HDL-C • For patients with CKD • For patients with very high LDL-C (> 190 mg/dl) • Patients with IGT and High CV risk • Patients with statin intolerance • Residual risk with statin therapy: a. Atherogenic(Mixed) Dyslipidemia with T2DM b. Atherogenic(Mixed) Dyslipidemia without T2DM

  46. Residual CV risk: after using High dose statin TNT study RRR=22% P=0.001 78% residual risk N Engl J Med 2005;352:1425-35

  47. Drug therapy for Non-HDL-C As mentioned, in a patient on optimal statin therapy, TG lowering therapy is preferred for non-HDL-C reduction • Saroglitazar (Dual PPAR agonist)- For T2DM • Fibrates

  48. Saroglitazar – Mechanism of actionPPAR α action – reduces TG and non HDLPPAR γ action – improves insulin sensitivity Diabetes. 2005 Aug;54(8):2460-70

  49. Efficacy and Safety of Saroglitazar in Indian diabetics - 2 year data (ADA-2016) • Design: Observational, post-marketing surveillance study (phase 4 study). • Eligibility: As per the approved indication and prescribing information of saroglitazar • Medication: Saroglitazar 4mg OD • Background Tx : Antidiabeticsand statin therapy • Outcome: Safety(adverse event monitoring) and effectiveness(lipid and glycemic parameters) at baseline and 2 years follow up • Statistics: Significant differences in the means from baseline to post baseline were assessed by paired t-tests. • P<0.05 was considered significant

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