Updates in Cardiovascular Recommendations for Diabetic Patients

Transcription

1 Updates in Cardiovascular Recommendations for Diabetic Patients Chris Tawwater, Pharm.D., BCPS Clinical Pharmacist, Abilene Regional Medical Center Assistant Professor, Adult Medicine Division Pharmacotherapy (PGY1/PGY2) Residency Program Director

2 2 Disclosures I have no actual or potential conflicts of interest in relation to this presentation.

3 3 Learning Objectives Summarize the current treatment recommendations for hypertension in diabetes. Review the current treatment recommendations for dyslipidemia in diabetes.

4 4 JNC 7 (2003) vs JNC 8 (2014) JNC 7 Incremental evolution of prior guidelines Non-systematic review of clinical trials Variable quality of data Provides: Definition of HTN Stages of HTN Goal BPs JNC 8 Started from scratch Only randomized, control trials of reasonable quality Provides: 9 Recommendations Goal BPs

5 5 An Abundance of Recommendations JNC 8 (2014) ADA (2014) KDIGO (2012) (-) proteinuria KDIGO (2012) (+) proteinuriaii

6 6 UKPDS 38: Strict vs Lenient BP Randomized, controlled: 1,148 DM subjects: Strict: < 150/85 Lenient: < 180/105 First-line ACEi or BB Baseline characteristics: Age: 56 years A1c: 6.9% BP: 160/94 Proteinuria: 21% BMJ. 1998;317(7160): % 40% 30% 20% 10% 0% On-Treatment Blood Pressure Total Death Strict BP p<0.05 DM Death Lenient BP

7 7 ACCORD BP: Systolic 120 vs 140 Randomized, controlled: 4,733 DM subjects Systolic BP < 120 Systolic BP < 140 Baseline characteristics: Age: 62 years A1c: 8.3% 5.0% 4.5% 4.0% 3.5% 3.0% 2.5% 2.0% 1.5% 1.0% 0.5% BP: 139/76 0.0% On-Treatment Blood Pressure MI Stroke CV Death SBP < 120 SBP < p< Cushman WC, et al. N Engl J Med Apr 29;362(17):

8 8 So Which BP Target(s) Now? Diabetes 140/90 (JNC8) No useful randomized trials for old recommendation of 130/80 If already controlled at SBP , may continue (or taper Rx if symptomatic) DBP < CV events DBP < 60 End-stage CKD Diabetes w/ CKD Extrapolate from standard DM trials regardless of CKD 140/90 per JNC8 Extrapolate from CKD trials w/o DM 130/80 per KDIGO (not diabetes specific)

9 9 Attaining Goal Blood Pressure in Diabetes Non-Pharmacological Methods

10 10 Lifestyle Changes and BP Effects Lifestyle Modification Target Parameters SBP Reduction Weight Reduction BMI < mmhg / 1 kg loss Physical Activity 50 minutes 3-4 times/week 4-10 mmhg DASH Diet CPAP for OSA More: fruit, vegetables, dairy Less: saturated fat, total fat CPAP for clinically significant obstructive sleep apnea (OSA) 8-14 mmhg 5-10 mmhg Sodium restriction Less than 2.4 grams/day 2-8 mmhg Moderate EtOH Males 2/day; Females 1/day 2-4 mmhg

11 Diastolic BP Systolic BP 11 Guided Exercise: 60 minutes 3x/week Body Mass Index Exercise Control Baseline 36 months Exercise Control p<0.05 p<0.05 Yavari A, et al. J Sports Med Phys Fitness Jun 19.

12 Diastolic BP Systolic BP 12 Treatment of Sleep Apnea in T2DM Retrospective cohort: 221 DM subjects New diagnosis of OSA Treated w/ CPAP or APAP Baseline characteristics: Age: 63 years Sex: 100% male (veterans) BMI: 34.7 A1c: 7.1% BP: 139 / p<0.05 p<0.05 CPAP APAP Prasad B, et al. J Clin Sleep Med. 2012;8(5):481-7.

13 13 Attaining Goal Blood Pressure in Diabetes Pharmacological Methods

14 14 First-line Antihypertensives Thiazide Diuretic Calcium Channel Blocker ACE-i or ARB

15 15 Anti-Hypertensive Selection DM only DM + CKD DM+ CVD ACE-i or ARB African American CCB or Thiazide 1: ACE-i or ARB 2: DHP-CCB 1: ACE-i or ARB 2: Selective BB

16 16 Diabetes & Hypertension = ACE-i or ARB First-Line (ADA/AHA) Similar to other classes for CVD outcomes Reduced development and progression of nephropathy Metabolically neutral Less effective in African Americans than CCB and thiazides ACE-i vs ARB In general, ACE-i and ARB are interchangeable ACE-i may reduce CVD compared to ARB ACE-i and ARB similar in renal outcomes ARB if ACE-i intolerant Both classes have options that are generics

17 17 After the ACE-i or ARB? Calcium Channel Blocker Reduces CKD progression May reduce CVD compared to thiazide Metabolically neutral 14.0% 12.0% 10.0% 8.0% 6.0% ACCOMPLISH Major CVD Events p < % Take at bedtime to reduce edema / enhance dipping 2.0% 0.0% Benazepril + Amlodipine Benazepril + HCTZ Jamerson KA, et al. Hypertension. 2011;57(2):174-9.

18 18 Other Antihypertensive Options Thiazide Diuretic 2 nd or 3 rd line agent Maybe beneficial w/ CVA Not metabolically neutral Increased glucose generally minor and irrelevant Chlorthalidone and indapamide > HCTZ? Combination agents with HCTZ easy to manage Beta-Blocker Strongly indicated with systolic-hf or ischemic heart disease. Not metabolically neutral Reduced insulin sensitivity Masks hypoglycemia (?) Usually reserved for 4 th or 5 th line in absence of CVD

19 19 Combination ACEi & ARB: No More ONTARGET Trial Rampril vs Telmisartan vs Ramipril AND Telmisartan Dual RAAS blockade: No change in CVD outcomes 170% more hypotension 60% more renal impairment 20% more discontinuation VA NEPHRON-D Losartan versus Lisinopril AND Losartan Trial halted after 2.2 years No difference in CV+CKD outcomes 40% more CKD/ESRD 70% more acute kidney injury 180% more hyperkalemia Yusuf S, et al. N Engl J Med. 2008;358(15): Fried LF, et al. N Engl J Med Apr 10;358(15):

20 Diastolic BP Systolic BP 20 Resistant Hypertension in DM: Spironolactone Not at goal despite 3 maximized agents: Spironolactone 25 mg Outcomes: BP reduced ~10/4 mmhg Urine Alb:Cr reduced p<0.05 Caution with hyperk+ Caution with CKD p<0.05 Placebo Spironolactone Oxlund CS, et al. J Hypertens. 2013;31(10):

21 21 Diabetes & Hypertension: Summary 1 st Lifestyle changes 2nd 3rd 4th ACEi or ARB (CCB or diuretic if African American) CCB or Thiazide Thiazide or CCB 5th Consider spironolactone (or others)

22 22 Hypertension Case MT is a 51 year old male in clinic for routine follow-up PMH includes: DM, HTN, and dyslipidemia (no CKD) Medications: lisinopril 40 mg daily, amlodipine 10 mg daily, simvastatin 10 mg Today s vitals: 148/88 &146/84 mmhg, HR 73 bpm Which of the following would be most appropriate? A: Initiate furosemide 40 mg PO daily B: Initiate atenolol 50 mg PO daily C: Initiate hydrochlorothiazide 25 mg PO daily D: Initiate clonidine 0.2 mg TD weekly

23 23 Diabetes and Dyslipidemia Has Everything Changed?

24 24 Prior Lipid Recommendations ATP 3 Diabetes is CVD risk equivalent Target LDL < 100 Optional LDL < 70 if high risk Non-HDL < 130 If TG elevated, reduce If HDL low, increase ADA 2013 Standards Consider statin therapy to decrease LDL < 100 Overt CVD: LDL < 70 If cannot obtain LDL < 100, a decrease of 30-40% is acceptable TG < 150 and HDL > 40 Statin still preferred Combination therapy is not generally recommended

25 : ACC/AHA Instead of ATP 4 ACC/AHA Guidelines ATP 4 started in 2008 NCBLI turned process over to ACC/AHA in June 2013 Create Pooled Cohort Equation for risk estimation ASCVD 10-yr Risk Estimation Answer Critical Questions Turn the world upside-down Essentials LDL targets have no evidence base Trials usually applied therapy without titration Non-HDL targets have no evidence base Minimal evidence of benefit Cost and side effects significant

26 26 Lipids: Diet and Exercise Diet vs Exercise (12 wks) Diet + Exercise (20 wks) 14% 14% 9% 9% 4% 4% -1% LDL HDL Weight -1% LDL HDL Weight -6% -6% -11% -11% -16% Exercise Diet -16% Varady KA, et al. Lipids Health Dis. 2011;10:119 Varady KA, et al. Metabolism. 2006;55(10):

27 Moderate Intensity Statin High Intensity Statin 27 4 Groups that Benefit from Statins Secondary Prevention of ASCVD Primary Prevention w/ LDL > 190 High-Intensity lowers LDL > 50% Atorvastatin mg Rosuvastatin mg Primary Prevention with DM, age 40-75, and LDL Primary prevention 10yr risk > 7.5%, age 40-75, and LDL Moderate-Intensity lowers LDL 30-49% Atorvastatin mg Rosuvastatin 5-10 mg Pitavastatin 2-4 mg Lovastatin 40 mg Fluvastatin 80 mg Pravastatin mg Simvastatin mg

28 Death, MI Ischemia, Arrest Fatal & Non-fatal Stroke 28 Secondary Prevention: MI and Stroke MIRACL (Acute MI) MI) SPARCL (Acute Stroke) Stroke) 13.1% 20% 17.4% 14% 14.8% 12% 11.2% 15% 10% 10% 8% 6% 5% 4% 2% 0% 0% Atorva 80 mg Placebo Atorva 80 mg Placebo End LDL 72 mg/dl 146 mg/dl End LDL 73 mg/dl 132 mg/dl Schwartz GG, et al. JAMA. 2001;285(13): N Engl J Med. 2006; 355:

29 MI, Stroke, Stent/PCI 29 Primary Prevention: Diabetes Primary Prevention with DM, age 40-75, and LDL CARDS Study (2004) Moderate intensity statin DM = lower LDL = mild statin treatment per ATP 3 May use high intensity if: Secondary prevention LDL > 190 mg/dl 10-yr ASCVD risk > 7.5% Individualize therapy for < 40 and > 79 years of age 10% 8% 6% 4% 2% 0% 5.8% Atorva 10 mg Start LDL 118 mg/dl 9.0% Placebo 117 mg/dl Calhoun HM, et al. Lancet. 2004;364(9435): End LDL 81 mg/dl 121 mg/dl

30 30 Primary Prevention: LDL > 190 mg/dl Expert-based recommendation: Very high risk group No trials w/ just LDL > 190 Subgroups including LDL > 190 showed significant benefits from high intensity therapy Management Strategies High intensity statin to reduce LDL > 50% May add non-statin if 50% reduction not achieved Ezetimibe Bile acid sequestrant Work-up genetic causes

31 31 New Statin Concerns New Onset Diabetes JUPITER Trial: 270 vs 216 new diabetes cases with rosuvastatin Mostly limited to high-risk and pre-diabetes cohort Statin therapy still reduced CV events despite new onset DM Moderate to high intensity statins unmask early DM. CV risk was already being established, so they still benefit. Ridker PM, et al. N Engl J Med. 2008; 359: Impaired Cognition Data mostly from case reports and case series Meta-analysis (90 studies) 25% less cognitive impairment No increase in depression Rarely, these idiosyncratic reactions may occur. The population, at-large, still benefits from statin therapy.

32 Death, MI, Stroke 32 What about the others: Fibrates No recommendation to use gemfibrozil or fenofibrate Lack of outcomes data Statin + gemfibrozil = interactions / myopathy May still treat severe hypertriglyceridemia, but use fenofibrate if combining with a statin. 10.0% 9.0% 8.0% 7.0% 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% 0.0% ACCORD-Lipid Simva Simva + Fenofibrate N Engl J Med. 2010; 362:

33 33 What about the others: Niacin Improves HDL, no change in CVD Additional side effects: Flushing Myopathy & hepatitis Increased uric acid Increased glucose AIM-HIGH Study If initiating, obtain LFTs and uric acid. Start 100 mg TID and titrate to 3g/day (w/ ASA) DM subgroup had non-significant trend towards worse outcomes N Engl J Med. 2011;365:

34 34 Summary: Guidelines & Diabetes History of ASCVD or LDL > 190 High intensity statin DM: Age and LDL Moderate intensity statin DM: Age <40 or >80 or LDL <70 Individualize therapy

35 35 Summary: Statin Intensities High-Intensity Moderate-Intensity LDL-C 50% LDL C ~ 30% to <50% Atorvastatin mg Rosuvastatin mg Atorvastatin mg Rosuvastatin 5-10 mg Simvastatin mg Pravastatin mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg BID Pitavastatin 2-4 mg

36 36 Lipid Case MT is a 51 year old male in clinic for routine follow-up PMH includes: DM, HTN, and dyslipidemia (no CKD) Medications: lisinopril 40 mg daily, amlodipine 10 mg daily, simvastatin 10 mg Labs: A1c 8.7%; Weight 98 kg Result Ref. Result Ref. Tot Chol 220 < 200 Trig 268 <150 LDL 135 < 130 HDL 31 > 40 Which of the following would be most appropriate? A: Continue simvastatin 10 mg B: Change simvastatin to atorvastatin 20 mg C: Initiate niacin ER 500 mg HS and titrate D: Initiate fenofibrate 200 mg daily