Statinsshould be in the water supply. Lipid Drug Therapy: Use in Special Populations. Objectives. TSHP 2014 Annual Seminar 1

Transcription

1 Lipid Drug Therapy: Use in Special Populations Mark C. Granberry, Pharm.D. Professor Texas A&M Rangel College of Pharmacy Objectives Discuss background for recommendations from the recent AHA/ACC Lipid Guidelines Develop treatment plans for lipid therapy for patients with ESRD on HD, heart failure, mixed dyslipidemia Statinsshould be in the water supply. TSHP 2014 Annual Seminar 1

2 Patient Case 66 year-old man with stable symptoms PMH: CAD, ESRD on HD (MWF) x 1 year, hypertension PSH: AV fistula for HD FH: NC SH: No tobacco, EtOHor DoA Meds: ASA 81 mg daily, amlodipine10 mg daily, lisinopril 20 mg daily VS: AF, P 84, BP 138/88, RR 18, Wt 82 kg Labs: CBC WBC 8, Hb9, HCT 31, PLT 221 Chem7 Na 136, K 4.3, Cl101, HCO3 22, BUN 34, Cr 2 Fasting Lipids TC 198, Trig 180, HDL-C 38, LCL-C 124 Assessment/Plan: Inclusion/Exclusion of Major Statin Trials Trial Year Heart Failure ESRD on HD 4S 1994 Excluded Excluded WOSCOPS 1995?? CARE 1996 Excluded EF < 25%? LIPID 1998 Excluded Excluded AFCAPS-TexCAPS 1998 No No HPS 2002 Excluded Severe HF Excluded PROSPER 2002 Excluded NYHA III-IV Excluded ALLHAT-LLA 2002 Excluded Excluded ASCOT-LLA 2003 Excluded Excluded (?) PROVE-IT 2004 No Excluded CARDS 2004 Excluded NYHA III-IV Excluded JUPITER 2008 Excluded Excluded TSHP 2014 Annual Seminar 2

3 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults The Expert Panel makes no recommendations regarding the initiation or discontinuation of statins in patients with NYHA class II IV ischemic systolic heart failure or in patients on maintenance hemodialysis. Stone NJ, Robinson J, Lichtenstein AH, Bairey MerzCN, Lloyd-Jones DM, Blum CB, McBride P, EckelRH, Schwartz JS, Goldberg AC, Shero ST, Gordon D, Smith JrSC, Levy D, Watson K, Wilson PWF ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc Current Guidelines No recommendation for or against ( There is insufficient evidence or evidence is unclear or conflicting. ) Net benefit is unclear. Balance of benefits and harms cannot be determined because of no evidence, insufficient evidence, unclear evidence, or conflicting evidence, and the Work Group thought no recommendation should be made. Further research is recommended in this area ACCF/AHA Guideline for the Management of Heart Failure Statins: Recommendation Class III: No Benefit 1. Statinsare not beneficial as adjunctive therapy when prescribed solely for the diagnosis of HF in the absence of other indications for their use. (Level of Evidence: A) YancyCW, Jessup M, BozkurtB, Masoudi FA, Butler J, McBride PE, Casey Jr DE, McMurray JJV, DraznerMH, Mitchell JE, Fonarow GC, Peterson PN, GeraciSA, HorwichT, JanuzziJL, Johnson MR, Kasper EK, Levy WC, RiegelB, Sam F, Stevenson LW, Tang WHW, Tsai EJ, Wilkoff BL, 2013 ACCF/AHA Guideline for the Management of Heart Failure, Journal of the American College of Cardiology (2013), doi: /j.jacc TSHP 2014 Annual Seminar 3

4 CORONA Trial Inclusion Criteria: Ischemic CM, EF < 40%, NYHA II-IV, investigators thought they had no clear indication for lipid drug therapy Exclusion Criteria: Competing risks, recent MI, USA, stroke, PCI Design: R, DB, rosuvastatin10 mg daily vs placebo Baseline Characteristics Major Results TSHP 2014 Annual Seminar 4

5 GISSI HF Trial Inclusion Criteria: NYHA II-IV Heart failure regardless of ejection fraction, Tx: ESC guidelines Exclusion Criteria: Competing risks: cancer, ACS Study Design: R, DB, PC; Primary Endpoint -Time to death Results: Baseline Characteristics Major Results TSHP 2014 Annual Seminar 5

6 ESRD on Hemodialysis NKF KDOQI GUIDELINES 1. For adults with Stage 5 CKD and LDL >100 mg/dl(>2.59 mmol/l), treatment should be considered to reduce LDL to <100 mg/dl(<2.59 mmol/l). (B) 2. Few patients with chronic kidney disease have been included in clinical trials with hard cardiovascular endpoints. 4D Trial Inclusion Criteria: Type 2 DM on hemodialysis for < 2 years Exclusion Criteria: LDL-C < 80 mg/dlor > 190 mg/dl Study Design: R, DB, AtorvastatinvsPlacebo; Primary End point CV death, NF stroke, NF MI Results: Baseline Characteristics TSHP 2014 Annual Seminar 6

7 Results AURORA Trial Inclusion Criteria: ESRD on HD > 3 months Exclusion Criteria: No statinx 6 months, competing risks Study Design: R, DB, rosuvastatinvsplacebo; Primary endpoint CVD death, NF stroke, NF MI Results: Baseline Characteristics TSHP 2014 Annual Seminar 7

8 Major Results Subgroup Analysis SHARP Trial Inclusion Criteria: Serum Creatinine 1.7 men and 1.5 women Exclusion Criteria: Study Design: R, DB, PC. First year Simvavs simva+ ezetimibevsplacebo then Simva+ ezetimibevsplacebo; Primary endpoint cardiac death, stroke, NFMI or revascularization TSHP 2014 Annual Seminar 8

9 Baseline Characteristics 107 mg/dl 43 mg/dl Major Results Subgroup Analysis TSHP 2014 Annual Seminar 9

10 Combinations with Statins LDL-C still high on maximum dose statin Triglycerides high on statin HDL-C low on statin MACE while on statin 2013 ACC/AHA Cholesterol Guidelines Combination Statin Therapy Clinicians treating high-risk patients who have a less-than-anticipated response to statins, who are unable to tolerate a less-than-recommended intensity of a statin, or who are completely statin intolerant may consider the addition of a nonstatin cholesterol-lowering therapy. High-risk individuals include those with ASCVD, those with LDL C 190 mg/dl and individuals with diabetes ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults TSHP 2014 Annual Seminar 10

11 Combination Therapy Statins plus Niacin ER Statins plus Fenofibrate Statins plus PUFA Statins plus New Drugs Combination Therapy Study Year Patients Intervention Primary Outcome AIM-HIGH 2011 N= 3414 CAD, LDL <180 HDL < 40/50 HPS THRIVE ACCORD LIPID Statin Plus ER Niacin Simva40 +/- Niaspan 2014 N = Simva+/- Niacin ER + laropriprant 2010 N = 5518 DM2 highrisk LDL HDL < 55/50 Statin Plus Fenofibrate Simva +/- Fenofibrate CV death, NF MI, Stroke, ACS, Revasc CV death, NF MI, Stroke, Revasc CV death, NF MI, NF stroke Result HR 1.02 (95%CI ) RR 0.96 (95% CI ) HR 0.92 (95% CI ) P ACCORD LIPID Subgroup Analysis TSHP 2014 Annual Seminar 11

12 Combination Therapy Study Year Patients Intervention Primary Outcome ILLUMINATE 2007 N = CAD or DM2 Atorva +/- torcetrapib 60 mg MACE: CHD death, NF MI, Stroke, USA Result HR 1.25 (95% CI ) P JELIS 2007 N = /- CAD LDL > 250 JELIS Subgroup JELIS Subgroup N =3664 CAD N=14981 No CAD Statin +/- EPA 1800 mg MACE: CHD death, MI, Revasc HR 0.81 (95% CI ) HR 0.81 (95% CI ) HR 0.81 (95% CI ) Case 66 year-old man with stable symptoms PMH: CAD, ESRD on HD (MWF) x 1 year, hypertension PSH: AV fistula for HD FH: NC SH: No tobacco, EtOHor DoA Meds: ASA 81 mg daily, amlodipine10 mg daily, lisinopril 20 mg daily VS: AF, P 84, BP 138/88, RR 18, Wt 82 kg Labs: CBC WBC 8, Hb9, HCT 31, PLT 221 Chem7 Na 136, K 4.3, Cl101, HCO3 22, BUN 34, Cr 2 Fasting Lipids TC 198, Trig 180, HDL-C 38, LCL-C 124 Assessment/Plan: TSHP 2014 Annual Seminar 12

13 References Stone NJ, et al ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, Journal of the American College of Cardiology (2013), doi: /j.jacc Scandinavian SimvastatinSurvival Study Investigators. Lancet 1994;344: Shepherd J for West of Scotland Study Group. N Engl J Med 1995; 333: LIPID Study Group. N Engl J Med. 1998;339: Downs JR for AFCAPS-TexCAPSStudy Group. JAMA 1998;279: Heart Protection Study Collaborative Group. Lancet 2002;360:7-22. Shepherd J for PROSPER Study Group. Lancet 2002;360: ALLHAT Collaborative Research Group. JAMA; 288: ASCOT Investigators. Lancet 2003; 361: Cannon CP for the PROVE-IT TIMI22 Investigators. NEngJMed2004;350: CARDS Investigators. Lancet 2004;364: CARE Investigators. N Engl J Med 1996;335: FellströmBC for AURORA Study Group. N Engl J Med 2009;360: Wanner C for the German Diabetes Dialysis Study Investigators. N EnglJ Med 2005;353: SHARP Investigators. Lancet 2011;377: Kjekshus J for the CORONA Study Group. N Engl J Med 2007;357:2248:61. GISSI-HF Investigators. Lancet 2008; 372: AIM-HIGH Inverstigators. N EnglJ Med 2011;365: ACCORD Investigators. N EnglJ Med 2010; 326: JELIS Investigatoers. Lancet 2007; 369: ILLUMINATE Study Investigators. N EnglJ Med 2007;357: TSHP 2014 Annual Seminar 13