Secondary Prevention of Coronary Heart Disease

Transcription

1 Secondary Prevention of Coronary Heart Disease Samornrat Jampates, MD. Cardiology department, CCIT 6 March 2014

2 Circulation. 2011;123:

3 A B C D E S ABCDE + S Approach to Secondary CAD Prevention Antiplatelet, Anticoagulant therapy, ACEI/ARBs, Aldosterone antagonist Blood pressure control Beta -blocker Body weight management Cholesterol management Diabetes mellitus management Diet Exercise Stop smoking Shots (Influenza)

4 Indirect Comparisons of Aspirin Doses on Vascular Events in High-Risk Patients Aspirin Dose No. of Trials (%) mg Odds Ratio for Vascular Events mg mg <75 mg 3 13 Any aspirin P< Antiplatelet Better Antiplatelet Worse Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86

5 Aspirin Recommendations I IIa IIb III Start and continue indefinitely aspirin 75 to 162 mg/d in all patients unless contraindicated I IIa IIb III For patients undergoing CABG, aspirin (100 to 325 mg/d) should be started within 6 hours after surgery to reduce saphenous vein graft closure for at least 1 year to be efficacious I IIa IIb III After PCI, it is reasonable to use 81 mg per day of aspirin in preference to higher maintenance doses. AHA/ACCF Secondary Prevention: 2011update

6 Antiplatelet Therapy I IIa IIb III Clopidogrel 75 mg daily is recommended as an alternative for patients who are intolerant of or allergic to aspirin AHA/ACCF Secondary Prevention: 2011update

7 Rate of death, myocardial infarction, or stroke Clopidogrel Evidence: ACS (Non-STEMI and UA) Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) Trial 12,562 patients with a NSTEMI-ACS randomized to daily aspirin ( mg) or clopidogrel (300 mg load, 75 mg thereafter) plus aspirin ( mg) for 3-12 months (average 9 months) Aspirin + Clopidogrel Aspirin + Placebo Months of Follow Up NSTEMI-ACS=Non ST-segment elevation acute coronary syndrome P<0.001 The CURE Trial Investigators. NEJM. 2001;345:

8 Double-blind Study Design ACS (STEMI or UA/NSTEMI) & Planned PCI ASA N= 13,600 CLOPIDOGREL 300 mg LD/ 75 mg MD PRASUGREL 60 mg LD/ 10 mg MD Median duration of therapy - 12 months 1 o endpoint: CV death, MI, Stroke 2 o endpoints: CV death, MI, Stroke, Rehosp-Rec Isch CV death, MI, UTVR Stent Thrombosis (ARC definite/prob.) Safety endpoints: TIMI major bleeds, Life-threatening bleeds Key Substudies: Pharmacokinetic, Genomic

9 Conclusions Higher IPA to Support PCI Prasugrel 60 mg LD/10mg MD vs Clopidogrel 300 mg LD/ 75 mg MD Efficacy 1. A significant reduction in: CV Death/MI/Stroke 19% Stent Thrombosis 52% utvr 34% MI 24% 2. An early and sustained benefit 3. Across ACS spectrum Safety Significant increase in serious bleeding (32% increase) Avoid in pts with prior CVA/TIA Net clinical benefit significantly favored Prasugrel Optimization of Prasugrel maintenance dosing in a minority of patients may help improve the benefit : risk balance

10 PLATO study design NSTE-ACS (moderate-to-high risk) STEMI (if primary PCI) Clopidogrel-treated or -naive; randomised within 24 hours of index event (N=18,624) Clopidogrel (n=9291) If pre-treated, no additional loading dose; if naive, standard 300 mg loading dose, then 75 mg qd maintenance; (additional 300 mg allowed pre PCI) Ticagrelor (n=9333) 180 mg loading dose, then 90 mg bid maintenance; (additional 90 mg pre-pci) 6 12-month exposure Primary endpoint: CV death + MI + Stroke Primary safety endpoint: Total major bleeding

11 Conclusions Reversible, more intense P2Y 12 receptor inhibition for one year with ticagrelor in comparison with clopidogrel in patients with STEMI intended for reperfusion with primary PCI provides Reduction in composite of CV death, MI or stroke Reduction in MI and stent thrombosis Reduction in total mortality No increase in the risk of major bleeding The NNT (number needed to treat) to avoid one primary endpoint (CV death, MI or stroke) is 59 The mortality reduction is afforded on top of modern care

12 P2Y12 inhibitor therapy I IIa IIb III In patients receiving a stent (BMS or DES) or after ACS, P2Y12 inhibitor therapy should be given in combination with aspirin for at least 12 months. Options include: clopidogrel 75 mg daily, prasugrel 10 mg daily, and ticagrelor 90 mg twice daily. *The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily. AHA/ACCF Secondary Prevention: 2011update

13 Anticoagulation Recommendations I IIa IIb III If there is a compelling indication for warfarin or other vitamin K antagonists combination with aspirin. The aspirin should be reduced to low dose (75-81 mg daily) I IIa IIb III Use of warfarin in conjunction with aspirin and/or clopidogrel is associated with increased risk of bleeding and should be monitored closely AHA/ACCF Secondary Prevention: 2011update

14 Probability of Event ACE Inhibitor Evidence: Post MI with LVD or HF SAVE Radionuclide EF 40% AIRE Clinical and/or radiographic signs of HF TRACE Echocardiogram EF 35% Placebo ACE-I Flather MD, et al. Lancet. 2000;355: decrease in mortality Years OR: 0.74 ( ) ACE-I=Angiotensin converting enzyme inhibitors, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, OR=Odds ratio 4

15 ACE Inhibitor Recommendations I IIa IIb III ACE inhibitors should be given and continued indefinitely for all patients with LV dysfunction (LVEF 40%), hypertension, or diabetes mellitus or CKD, unless contraindicated. I IIa IIb III Consider for all other patients AHA/ACCF Secondary Prevention: 2011update

16 All Cause Mortality ARB Evidence: Post MI with LVD or HF Valsartan in Acute Myocardial Infarction Trial (VALIANT) 14,703 patients with post-mi HF or LVSD (EF <0.40) randomized to captopril (50 mg three times daily), valsartan (160 mg twice daily), or captopril (50 mg three times daily) plus valsartan (80 mg twice daily) over 2 years Captopril Valsartan Valsartan and Captopril Valsartan vs. Captopril: HR = 1.00; P = Valsartan + Captopril vs. Captopril: HR = 0.98; P = Months Pfeffer M et al. NEJM 2003;349:

17 Angiotensin Receptor Blocker (ARBs) I IIa IIb III Use in patients who are intolerant of ACEI with HF or post MI with LVEF 40% I IIa IIb III Consider in other patients who are ACE inhibitor intolerant AHA/ACCF Secondary Prevention: 2011update

18 Aldosterone antagonist I IIa IIb III Use of aldosterone blockade in Post MI patients without renal dysfunction(gfr< 30 ml/min) or hyperkalemia(k > 5mEq/L) is recommended in patients who are already receiving therapeutic doses of an ACE inhibitor and beta-blocker, who have a LVEF 40%, and who have either diabetes or heart failure AHA/ACCF Secondary Prevention: 2011update

19 Beta Blockers Summary of Secondary Prevention Trials of b-blocker Therapy Phase of Treatment Acute treatment Secondary prevention Overall Total # Patients 28,970 24,298 53,268 RR (95% CI) 0.87 ( ) 0.77 ( ) 0.81 ( ) CI=Confidence interval, RR=Relative risk RR of death b-blocker better Placebo better Antman E, Braunwald E. Acute Myocardial Infarction. In: Braunwald E, Zipes DP, Libby P, eds. Heart Disease: A textbook of Cardiovascular Medicine, 6th ed., Philadelphia, PA: W.B. Sanders, 2001,

20 b-blocker Evidence: Benefit in HF and LVSD Study Drug HF Severit y CIBIS Bisoprolol* Moderat e-severe CIBIS-II Bisoprolol* Moderat e-severe BEST Bucindolol* Moderat e-severe MERIT-HF MDC Metoprolol succinate # Metprolol tartrate* Mild- Moderat e Mild- Moderat e Patient s (n) Followup (years) Mean Dosage mg/day 2, mg/day 2, mg/day 3, mg/day mg/day CAPRICORN Carvedilol Mild 1, mg/day US Carvedilol Carvedilol Mild- Moderat e 1, mg/day COPERNICUS Carvedilol Severe 2, mg/day Effects on Outcomes All cause mortality 22% (p=ns) All cause mortality 34% (P<0.0001) All cause mortality 10% (p=ns) All cause mortality 34% (P=0.0062) Death or Need for Tx 30% (P=NS) All cause mortality 23% (P =0.03) All-cause mortality 65% (P=.0001) All-cause mortality 35% (P =0.0014) *Not an approved indication Not a planned end point. # Not approved for severe HF or mortality reduction alone

21 Beta Blockers I IIa IIb III Beta-Blocker therapy should be used in all patients with LVEF 40% with heart failure or prior myocardial infarction, unless contraindicated. (Use should be limited to carvedilol, metoprolol succinate, or bisoprolol, which have been shown to reduce mortality.) *Precautions but still indicated include mild to moderate asthma or chronic obstructive pulmonary disease, insulin dependent diabetes mellitus, severe peripheral arterial disease, and a PR interval >0.24 seconds. AHA/ACCF Guidelines 2011update

22 Beta Blockers I IIa IIb III Beta-Blocker therapy should be started and continued for 3 years in all patients with normal left ventricular function who have had myocardial infarction or ACS AHA/ACCF Guidelines 2011update

23 b-blocker Recommendations I IIa IIb III It is reasonable to continue beta-blockers beyond 3 years as chronic therapy in all patients with normal left ventricular function who have had myocardial infarction or ACS I IIa IIb III It is reasonable to give Beta-blocker therapy in patients with left ventricular systolic dysfunction (LVEF 40%) without heart failure or prior myocardial infarction AHA/ACCF Secondary Prevention: 2011update

24 Benefits of Lowering BP Average Percent Reduction Stroke incidence 35 40% Myocardial infarction 20 25% Heart failure 50%

25 Classification and Management of BP for adults BP classification SBP* mmhg DBP* mmhg Lifestyle modification Without compelling indication Initial drug therapy With compelling indications Normal <120 and <80 Encourage Prehypertension or Yes No antihypertensive drug indicated. Drug(s) for compelling indications. Stage 1 Hypertension Stage 2 Hypertension or Yes Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. >160 or >100 Yes Two-drug combination for most (usually thiazide-type diuretic and ACEI or ARB or BB or CCB). Drug(s) for the compelling indications. Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. *Treatment determined by highest BP category. Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmhg.

26 JNC-7 Report: Treatment Algorithm Initial Drug Choices No Compelling Indication Stage 1 HTN SBP mm Hg DBP mm Hg Usually thiazide-type diuretic Also consider ACEI, ARB, BB, or CCB alone or in combination Stage 2 HTN SBP 160 mm Hg DBP 100 mm Hg 2-drug combination Usually thiazide-type diuretic and ACEI, ARB, BB, or CCB Chobanian AV, et al. JAMA. 2003;289: Copyright 2003 American Medical Association. All rights reserved.

27 Recommended Drug Classes for Adults with Hypertension and a Related Comorbidity Compelling Indicator* Diuretic b-blocker ACE Inhibitor ARB CCB Aldosterone Antagonist Heart failure Prior myocardial infarction High risk of coronary disease Diabetes Chronic kidney disease Prior stroke *Based on documented benefits from outcome studies or on existing clinical guidelines; each compelling indicator is managed in parallel with hypertension. ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; CCB = calcium channel blocker Chobanian AV, et al. JAMA. 2003;289: Copyright 2003 American Medical Association. All rights reserved.

28 JNC 8

29 2014 Guideline for Management of High Blood Pressure (JNC 8) condition Goal(mmHg) class General <140/90 A DM <140/90 E CKD <140/90 E Elderly ( 60Y) SBP 150 <150/90 SBP <140(well tolerated) A E

30 2013 ESH/ESC Guidelines for the management of arterial hypertension condition Goal (mmhg) class General < 140/90 I DM <140/80-85 I CAD, CVA, CKD < 140/90 IIa CKD with proteinuria <130/90 IIb Elderly (< 80Y, 80Y) SBP 160 Fit elderly (<80Y) SBP /90 I < 140/90 IIb

31 Hazard Ratio CV Risk Increases with Body Mass Index 4.0 Hemorrhagic Stroke 4.0 Ischemic Stroke 4.0 Ischemic Heart Disease CV=Cardiovascular Mhurchu N et al. Int J Epidemiol 2004;33: Body Mass Index (kg/m 2 )* Body mass index is calculated as the weight in kilograms divided by the body surface area in meters 2.

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33 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults Goal: BMI kg/m2 Assess BMI and/or waist circumference on each visit and consistently encourage weight maintenance/ reduction through an appropriate balance of physical activity, caloric intake, and formal behavioral programs when indicated. Initial goal of weight loss : 5% - 10% of baseline within 6 months.

34 Weight Loss and Physical Activity Benefits for Those Overweight or Obese (or with Insufficient Daily Activity) From Manson JE, Skerrett PJ, Greenland P, VanItallie TB: The escalating pandemics of obesity and sedentary lifestyle: A call to action for clinicians. Arch Intern Med 164:249, = strong decrease in risk; = moderate decrease in risk; = slight decrease in risk; = no benefit.

35 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults Diets for Weight Loss Any 1 of the following methods energy intake target less than energy balance :1,200 1,500 kcal/day for women and 1,500 1,800 kcal/day for men (usually adjusted for the individual s BW) Prescribe a 500 kcal/day or 750 kcal/day energy deficit; or Prescribe one of the evidence-based diets that restricts certain food types (such as high-carbohydrate foods, low-fiber foods, or high-fat foods) in order to create an energy deficit by reduced food intake. High levels of physical activity (i.e., minutes/week) Refer for High Intensity Comprehensive Lifestyle Intervention Adding Pharmacotherapy Bariatric Surgical Treatment for Obesity : BMI 40 or BMI 35 with obesity-related comorbid conditions

36 Mortality log odds ratio Gould AL et al. Circulation. 1998;97: Meta-analysis of primary and secondary intervention trials % decrease in LDL-C reduces CHD risk by 1% Total mortality (p=0.004) CHD mortality (p=0.012) % in cholesterol reduction 40

37 Event (%) HMG-CoA Reductase Inhibitor: Secondary Prevention Relationship between LDL Levels and Event Rates in Secondary Prevention Trials of Patients with Stable CHD Statin Placebo HPS CARE 4S LIPID LIPID CARE HPS TNT (atorvastatin 10 mg/d) TNT (atorvastatin 80 mg/d) 4S LDL-C (mg/dl) LDL-C=Low density lipoprotein cholesterol; TNT=Treating to New Targets; HPS=Heart Protection Study; CARE=Cholesterol and Recurrent Events Trial; LIPID=Long-term Intervention with Pravastatin in Ischaemic Disease; 4S=Scandinavian Simvastatin Survival Study. LaRosa JC et al. NEJM. 2005;352:

38 Major Risk Factors That Modify LDL Goals 1. Cigarette smoking 2. Hypertension (BP 140/90 mmhg or on antihypertensive medication) 3. Low HDL cholesterol (<40 mg/dl) 4. Family history of premature CHD CHD in male first degree relative <55 years CHD in female first degree relative <65 years 5. Age (men 45 years; women 55 years) HDL cholesterol 60 mg/dl counts as a negative risk factor if presence removes one risk factor from the total count Adult Treatment Panel (ATP III Guidelines)2004

39 CHD Risk Equivalents Diabetes peripheral arterial disease abdominal aortic aneurysm symptomatic carotid artery disease Multiple risk factors that confer a 10-year risk for CHD >20% ATP III Guidelines

40 LDL-C level NCEP ATP III: LDL-C Goals High Risk CHD or CHD risk equivalents (10-yr risk >20%) goal 100 mg/dl or optional 70 mg/dl* Moderatel y High Risk 2 risk factors (10-yr risk 10-20%) goal 130 mg/dl or optional 100 mg/dl* Moderate Risk 2 risk factors (10-yr risk <10%) goal 130 mg/dl Lower Risk <2 risk factors goal 160 mg/dl 70 mg/dl=1.8 mmol/l; 100 mg/dl=2.6 mmol/l; 130 mg/dl=3.4 mmol/l; 160 mg/dl=4.1 mmol/l Grundy SM et al. Circulation 2004;110:

41 Lipid management I IIa IIb III If TG 200 mg/dl, non-hdl-c should be < 130 mg/dl I IIa IIb III Patients who have triglycerides > 500 mg/dl should be started on fibrate therapy in addition to statin therapy to prevent acute pancreatitis. AHA/ACCF Secondary Prevention: 2011update

42 2011 Very high risk known CVD type 2 diabetes or type 1 diabetes with microalbuminuria 10 year risk SCORE 10% chronic kidney disease Class I (A) 70 mg/dl) or at least a 50% relative reduction from baseline LDL-C.

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44 2013 ACC/AHA Blood Cholesterol Guideline 4 Statin Benefit Groups Clinical Atherosclerotic cardiovascular disease (ASCVD) LDL C >190 mg/dl, Age >21 years Primary prevention - Diabetes: Age years, LDL C mg/dl Primary prevention - No Diabetes**: 7.5% 10-year ASCVD risk, Age years, LDL C mg/dl **Requires discussion between clinician and patient before statin initiation Statin therapy may also be considered in those with 5-<7.5% 10-year ASCVD risk or when a risk-based treatment decision is uncertain 2013 ACC/AHA Blood Cholesterol Guideline

45 High-Intensity Statin Therapy High- Moderate- and Low-Intensity Statin Therapy (Used in the RCTs reviewed by the Expert Panel)* Moderate-Intensity Statin Therapy Low-Intensity Statin Therapy Daily dose lowers LDL C on average, by approximately 50% 30% -50% <30% Atorvastatin (40 ) 80 mg Rosuvastatin 20 (40) mg Atorvastatin 10 (20) mg Rosuvastatin (5) 10 mg Simvastatin mg Pravastatin 40 (80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2 4 mg Simvastatin 10 mg Pravastatin mg Lovastatin 20 mg Fluvastatin mg Pitavastatin 1 mg Statins and doses that are approved by the U.S. FDA but were not tested in the RCTs reviewedare listed in italics ACC/AHA Blood Cholesterol Guideline

46 New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury Simvastatin 80 mg should not be started in new patients. Simvastatin 80 mg should be used only in patients who have been taking this dose for 12 months or more without evidence of muscle injury (myopathy). This information has been updated in the December 15, 2011

47 New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury This information has been updated in the December 15, 2011

48 2013 ACC/AHA Blood Cholesterol Guideline

49 Initiating statin therapy in individuals with clinical ASCVD 2013 ACC/AHA Blood Cholesterol Guideline

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52 Diabetes Mellitus Recommendations I IIa IIb III Lifestyle modifications including daily physical activity, weight management, BP control, and lipid management are recommended for all patients with diabetes I IIa IIb III IIa Metformin is an effective first-line pharmacotherapy and can be useful if not contraindicated AHA/ACCF Secondary Prevention: 2011update

53 American Diabetes Association. Standards of medical care in diabetes Diabetes Care 2014;37(suppl 1):S42 ADA 2014 : Glycemic goals in adults Less-stringent A1C goals (such as <8%) may be appropriate for patients with (B) history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbid conditions longstanding diabetes in whom the general goal is difficult to attain despite diabetes self-management education, appropriate glucose monitoring, and effective doses of multiple glucose lowering agents including insulin

54 ADA 2014 Recommendations for cardiovascular disease In patients with symptomatic heart failure, avoid thiazolidinedione treatment (C) In patients with stable CHF, metformin may be used if renal function is normal but should be avoided in unstable or hospitalized patients with CHF (B) American Diabetes Association. Standards of medical care in diabetes Diabetes Care 2014;37(suppl 1):S42

55 ADA 2014 Recommendations for cardiovascular disease consider ACE inhibitor (C) and use aspirin and statin therapy (A) (if not contraindicated) to reduce the risk of cardiovascular event prior MI, β-blockers should be continued for at least 2 years after the event (B) American Diabetes Association. Standards of medical care in diabetes Diabetes Care 2014;37(suppl 1):S42

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57 Physical Activity Goal: 30 minutes 7 days/week, minimum 5 days/week I IIa IIb III For all patients, the clinician should encourage 30 to 60 minutes of moderate-intensity aerobic activity, such as brisk walking, supplemented by an increase in daily lifestyle activities (eg, walking breaks at work, gardening, household work) to improve cardiorespiratory fitness and move patients out of the least fit AHA/ACCF Secondary Prevention: 2011update

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59 Cigarette Smoking Goal : Complete Cessation and No Exposure to Environmental Tobacco Smoke Ask about tobacco use status at every visit. Advise every tobacco user to quit. Assess the tobacco user s willingness to quit. 5 A Assist by counseling and developing a plan for quitting. Arrange follow-up, referral to special programs, or pharmacotherapy (including nicotine replacement and bupropion. Urge avoidance of exposure to environmental tobacco smoke at work and home.

60 Influenza I IIa IIb III An annual influenza vaccination is recommended for patients with cardiovascular disease.