Heart Attack a Public Primer on Prevention

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Published on May 6, 2008

Author: Heather

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SHAPE thanks Dr. Blumenthal for providing the following PowerPoint geared toward public education.:  SHAPE thanks Dr. Blumenthal for providing the following PowerPoint geared toward public education. Dr. Roger Blumenthal with wife, Dr. Wendy Post Blumenthal Slide2:  The ABC’s of the AHA/ACC Prevention Guidelines Alessandra Calvo-Friedman, Andrew DeFilippis, MD, Ty Gluckman MD, Dominique Ashen, CRNP, PhD, Roger Blumenthal, MD, Johns Hopkins Ciccarone Preventive Cardiology Center Slide3:  Definition Primary Prevention: Modification of risk factors or prevent their development to prevent or delay the onset of CHD. Secondary Prevention: Initiation of Rx to reduce recurrent CHD events in patients with CHD. Primary and a Half Prevention*: As individuals with subclinical CHD are identified, the distinction between primary and secondary prevention becomes blurred. *Celermajer DS. JACC 2005;45:1994-6 CHD=Coronary heart disease Slide4:  Aspirin Recommendations Aspirin (75-162 mg daily) in intermediate risk men with a 10 year risk of CHD >10%. Aspirin (75-162 mg daily) in intermediate risk women > 65 yrs with a 10 yr risk of CHD >10% Aspirin in low risk women with a 10 year risk of CHD <10%. Primary Prevention CHD=Coronary heart disease Slide5:  Aspirin Recommendations (Continued) Aspirin (75-325 mg daily) in those with known CHD or carotid artery or leg artery narrowings due to plaque. Aspirin (100-325 mg daily) in those that have undergone CABG surgery*. Secondary Prevention CABG=Coronary artery bypass graft, CHD=Coronary heart disease *To be administered within the first 48 hours after surgery in order to reduce the risk of saphenous vein graft failure. Doses >162 mg/day may be continued for up to one year. Physicians’ Health Study (PHS):  Aspirin Evidence: Primary Prevention in Men Physicians’ Health Study (PHS) 22,071 men randomized to aspirin (325mg every other day) followed for an average of 5 years Aspirin significantly reduces the risk of MI in men Physicians’ Health Study Research Group. NEJM 1989;321:129-35 CI=Confidence interval, MI=Myocardial infarction Womens’ Health Study (WHS):  Aspirin Evidence: Primary Prevention in Women Womens’ Health Study (WHS) Cumulative Incidence of MI Placebo Aspirin P=0.83 Ridker P et al. NEJM 2005; 352:1293-204 MI=Myocardial infarction Years 39,876 women randomized to aspirin (100 mg every other day) or placebo for an average of 10 years Aspirin doesn’t reduce the risk of MI in women Slide8:  Clopidogrel Evidence: Secondary Prevention Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) Trial 3 6 9 0 12 Rate of death, myocardial infarction, or stroke P<0.001 Months of Follow Up The CURE Trial Investigators. NEJM. 2001;345:494-502 DAP=Dual antiplatelet therapy, NSTE-ACS=Non ST-segment elevation acute coronary syndrome Aspirin + Clopidogrel Aspirin + Placebo 12,562 patients with a NSTE-ACS randomized to daily aspirin (75-325 mg) or clopidogrel (300 mg load, 75 mg thereafter) plus aspirin for 9 months Slide9:  ACE Inhibitor Recommendations An ACE inhibitor in those following a MI, regardless of EF or in those with CAD* along with hypertension (SBP >120 mmHg), LVSD (EF <0.40), heart failure, DM, or CKD. Optional use of an ACE inhibitor in those with low risk CAD*, well controlled CV risk factors, a normal EF, and successful revascularization. Secondary Prevention *Defined by previous MI or angiographically significant CAD. ACE=Angiotensin converting enzyme, CAD=Coronary artery disease, CKD=Chronic kidney disease, CV=Cardiovascular, DM=Diabetes mellitus, EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, SBP=Systolic blood pressure Slide10:  Days of Follow-Up CV death, MI, or stroke (%) 22% RRR, P<0.001 0.00 0.05 0.10 0.15 0.20 0 500 1000 1500 ACE Inhibitor Evidence: Secondary Prevention Placebo Ramipril HOPE Investigators. NEJM 2000;342:145-153 Heart Outcomes Prevention and Evaluation (HOPE) Study ACE-I=Angiotensin converting enzyme inhibitors, DM=Diabetes mellitus, CV=Cardiovascular, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction 9,297 patients with DM or vascular disease plus one additional CV risk factor, but without HF or known LVSD randomized to ramipril (10 mg) or placebo for 5 years ACE-I reduce CV events in high-risk individuals Slide11:  Digitalis: Recommendations Digitalis in those with symptomatic HF and LVSD (EF <45%) to reduce hospitalizations for HF*. Digitalis in those with asymptomatic LVSD and normal sinus rhythm. Secondary Prevention EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic function *Contraindications include significant sinus or atrioventricular block unless a permanent pacemaker is present. Slide12:  ACE Inhibitor Evidence: Secondary Prevention Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial Primary End Point (%)* 30 25 20 15 10 5 0 0 1 2 3 4 5 6 Years After Randomization Placebo Trandolapril PEACE Trial Investigators. NEJM 2004;351:2058-2068 *Includes death from cardiovascular causes, myocardial infarction, or coronary revascularization 8,290 patients with stable coronary artery disease and normal left ventricular function randomized to trandolapril (4 mg) or placebo for 5 years ACE-I do not reduce CV events in low-risk individuals Slide13:  ACE Inhibitor Evidence: Secondary Prevention Comparison between the HOPE and PEACE trials Patients enrolled in the PEACE trial were at lower risk* MI, Cardiac death, or Stroke (%) Braunwald, E. et al., NEJM 2004;351:2058-68. CHD=Coronary heart disease, MI=Myocardial infarction *Reflects greater blood pressure control, revacularization, and use of other risk-reducing medications (i.e., antiplatelet therapy, b-blocker, lipid-lowering medication) Years Slide14:  Years Probability of Event OR: 0.74 (0.66–0.83) 0.1 Flather MD, et al. Lancet. 2000;355:1575–1581 SAVE Radionuclide EF £ 40% AIRE Clinical and/or radiographic signs of HF TRACE Echocardiogram EF £ 35% ACE Inhibitor Evidence: Secondary Prevention ACE-I=Angiotensin converting enzyme inhibitors, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, OR=Odds ratio ACE-I provide substantial benefit in post-MI LVSD Slide17:  JNC VII Guidelines for Measurement of BP BP=Blood pressure, CVD=Cardiovascular disease, HTN=Hypertension Chobanian AV et al. JAMA. 2003;289:2560-2572 Slide18:  Percent hypertensive 18-29 National Health and Nutrition Examination Survey (NHANES) III 30-39 40-49 50-59 60-69 70-79 80+ Age 3% 9% 18% JNC-VI. Arch Intern Med. 1997;157:2413-2446 Blood Pressure: Risk Increases with Age 51% 66% 72% 38% Hypertension defined as blood pressure >140/90 mmHg or treatment Slide19:  Prospective Studies Collaboration. Lancet. 2002;360:1903-1913 Usual Diastolic BP (mm Hg) Usual Systolic BP (mm Hg) Ischemic Heart Disease Mortality 50-59 60-69 70-79 80-89 Age at Risk (Y) 40-49 50-59 60-69 70-79 80-89 Age at Risk (Y) 40-49 Blood Pressure: Lower is Better Ischemic Heart Disease Mortality Ischemic Heart Disease Mortality BP=Blood pressure Slide20:  JNC VII Causes of Secondary Hypertension Chobanian AV et al. JAMA. 2003;289:2560-2572 NSAIDS=Non-steroidal anti-inflammatory drugs Slide21:  JNC VII Lifestyle Modifications for BP Control Chobanian AV et al. JAMA. 2003;289:2560-2572 BMI=Body mass index, SBP=Systolic blood pressure Slide22:  JNC VII Guidelines for Management and Treatment and or or or ACEI=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker, BB=b-blocker, BP=Blood pressure, CCB=Calcium channel blocker, DBP=Diastolic blood pressure, SBP=Systolic blood pressure Chobanian AV et al. JAMA. 2003;289:2560-2572 *Treatment determined by highest blood pressure category. †Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. ‡Treat patients with chronic kidney disease or diabetes mellitus to blood pressure goal of <130/80 mmHg. Slide23:  Blood Pressure Recommendations Secondary Prevention Initiation or maintenance of lifestyle modification in those with a BP >120/80 mmHg. Use of an ACE inhibitor and/or b-blocker in those with a BP >140/90 mmHg*. Other drugs (i.e., thiazide diuretics) should be added in order to achieve the desired BP. ACE=Angiotensin converting enzyme, BP=Blood pressure, CKD=Chronic kidney disease, DM=Diabetes mellitus *A BP >130/80 mmHg should be used for individuals with CKD or DM Slide24:  Blood Pressure Evidence: Primary Prevention Rate of MI or fatal CHD Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) ALLHAT Investigators. JAMA. 2002;288:2981-97 Years to CHD Event BP=Blood pressure, CHD=Coronary heart disease, HTN=Hypertension, MI=Myocardial infarction Chlrothalidone Amlodipine Lisinopril 33,357 patients with HTN and >1 CHD risk factor randomized to chlorthalidone, amlodipine, or lisinopril for 5 years There is similar efficacy among BP lowering agents Slide25:  0 6 12 18 24 30 36 42 48 54 60 66 Study Month 4 8 12 16 0 Proportion with CV death, MI, or stroke (%) Blood Pressure Evidence: Primary Prevention Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension Study Dahlöf B et al. Lancet. 2002;359:995-1003. Atenolol Losartan 13% RRR, P=0.021 ARBS=Angiotensin receptor blocker strategy, CV=Cardiovascular, DBP=Diastolic blood presure, LVH=Left ventricular hypertrophy, MI=Myocardial infarction, SBP=Systolic blood pressure *Defined by SBP=160-200 mmHg or DBP=95-115 mmHg 9,193 high-risk hypertensive* patients with LVH randomized to losartan (100 mg) or atenolol (100 mg) for 5 years An ARB provides greater efficacy in patients with LVH Slide26:  Nissen S et al. JAMA 2004;292:2217-26. Blood Pressure Evidence: Secondary Prevention Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis (CAMELOT) Trial *Includes CV death, MI, cardiac arrest, coronary revascularization, hospitalization for HF or angina pectoris, stroke, TIA, development of PAD CV event rate* 0 0.25 0.20 0.10 0.05 6 12 18 24 0.15 0 Placebo Amlodipine Enalapril Months Follow-up BP (mmHg) 125/77 124/77 130/78 BP=Blood pressure, CAD=Coronary artery disease, CV=Cardiovascular, DBP=Diastolic blood pressure, HF=Heart failure, MI=Myocardial infarction, PAD=Peripheral arterial disease, TIA=Transient ischemic attack 1,991 patients with CAD and a DBP <100 mmHg randomized to amloidipine (10 mg), enalapril (20 mg), or placebo for 2 years A BP <130/80 mmHg is associated with fewer CV events Slide27:  A b-blocker in all patients following a MI. A beta-blocker in all patients with LVSD. A b-blocker in those with other forms of CV disease or DM, unless contraindicated. *Relative contraindications include asthma, chronic obstructive pulmonary disease, insulin dependent diabetes mellitus, severe peripheral arterial disease, and a PR interval >0.24 seconds. CV=Cardiovascular, DM=Diabetes mellitus, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction b-blocker Recommendations* Secondary Prevention Slide28:  Phase of Treatment Acute treatment Secondary prevention Overall Total # Patients 28,970 24,298 53,268 0.5 1.0 2.0 RR of death b-blocker better RR (95% CI) Placebo better 0.87 (0.77-0.98) 0.77 (0.70-0.84) 0.81 (0.75-0.87) b-blocker Evidence: Secondary Prevention 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, 1168. Summary of Secondary Prevention Trials of b-blocker Therapy CI=Confidence interval, RR=Relative risk Slide29:  Secondary Prevention Cholesterol Management Guidelines Restriction of saturated fat (<7% of total calories) and cholesterol (<200 mg/day) in all patients. Promotion of daily physical activity and weight management in all patients. Increase in w-3 fatty acid consumption in all patients. LDL-C=Low density lipoprotein cholesterol Slide30:  Secondary Prevention Cholesterol Management Guidelines (Continued) Initiation or intensification of LDL-C lowering drug therapy in those with a baseline or on-treatment LDL-C level >100 mg/dl. Initiation of LDL-C lowering drug therapy in those with a baseline LDL-C level <100 mg/dl based on clinical judgment. LDL-C=Low density lipoprotein cholesterol Slide31:  Cholesterol Management Guidelines (Continued) As set forth by the Adult Treatment Panel III (ATP III) National Cholesterol Education Program (NCEP) Obtain a fasting lipid profile in all patients. For those with a myocardial infarction, a fasting lipid profile should be obtained within 24 hrs of admission. Start therapeutic lifestyle changes in all patients, including: Reduced intakes of saturated fats (<7% of total calories) and cholesterol (<200 mg/day) Addition of plant stanols/sterols (2 g/day) and viscous fiber (10-25 g/day) to enhance LDL-C lowering Weight reduction Increased physical activity Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486. Slide32:  Cholesterol Management Guidelines (Continued) As set forth by the Adult Treatment Panel III (ATP III) National Cholesterol Education Program (NCEP) For primary and secondary prevention, HMG-coA reductase inhibitors (statins) should be first-line in order to achieve the LDL-C goal. For those that remain above the LDL-C goal, statin therapy should be intensified along with the addition of a second LDL-C lowering agent if needed. If the TG level is >150 mg/dl or HDL-C level is <40 mg/dl, emphasize weight management, physical activity, and smoking cessation. If the TG level is 200-499 mg/dl after initiation of LDL-C lowering therapy, consider adding nicotinic acid or a fibrate. If the TG level is >500 mg/dl, consider adding nicotinic acid or a fibrate before LDL-C lowering therapy. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486. TG=Triglyceride Slide33:  CAD or Risk Equivalent** Risk Profile Assessment for LDL-C Lowering A risk assessment tool* is needed for individuals with >2 RFs Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486. CAD=Coronary artery disease, CHD=Coronary heart disease, DM=Diabetes mellitus, RF=Risk factor **Includes DM, non-coronary atherosclerotic vascular disease, and >20% 10-year CHD risk by the FRS *Such as the Framingham Risk Score (FRS) 10-year CHD Risk Slide34:  Passed torch: President and Mrs. Clinton exit McDonald’s after his symbolic passage of leadership. Slide35:  Step 1: Age Points Framingham Risk Score: Men Step 2: Total Cholesterol Points Step 3: HDL-C Points Step 4: SBP Points Step 5: Smoking Status Points Step 6: Sum of Points Step 7: 10-year CHD Risk Slide36:  Step 1: Age Points Framingham Risk Score: Women Step 2: Total Cholesterol Points Step 3: HDL-C Points Step 4: SBP Points Step 5: Smoking Status Points Step 6: Sum of Points Step 7: 10-year CHD Risk Slide37:  Grundy, S. et al. Circulation 2004;110:227-39. ATP III LDL-C Goals and Cut-points for Drug Therapy ATP=Adult Treatment Panel, CHD=Coronary heart disease, LDL-C=Low-density lipoprotein cholesterol, TLC=Therapeutic lifestyle changes *Risk factors for cardiovascular disease include: cigarettes smoking, hypertension (blood pressure >140/90 mmHg or on antihypertensive medication, HDL-C <40 mg/dl (>60 mg/dl is a negative risk factor), family history of premature CHD, age >45 years in men or >55 years in women. Slide38:  Primary Therapies to Lower LDL-C Slide39:  Illingworth DR. Med Clin North Am. 2000;84:23-42. HMG-CoA Reductase Inhibitor: Dose-Dependent Effect The Rule of 6’s Each doubling of the statin dose produces an additional 6% reduction in the LDL-C level Slide40:  HMG-CoA Reductase Inhibitor: Primary Prevention West of Scotland Coronary Prevention Study (WOSCOPS) CHD=Coronary heart disease, MI=Myocardial infarction, RRR=Relative risk reduction Shepherd J et al. NEJM 1995;333:1301-1307 Placebo 7.5 Pravastatin 9 6 3 0 5.3 P<0.001 31% RRR Rate of MI or CHD death (%) 6,595 men with moderate hypercholesterolemia randomized to pravastatin (40 mg) or placebo for 5 years Statins provide significant benefit in those with average cholesterol levels Slide41:  Rate of MI, unstable angina, or SCD (%) Placebo 5.5 Lovastatin 6 4 2 0 3.5 HMG-CoA Reductase Inhibitor: Primary Prevention Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) P<0.001 37% RRR MI=Myocardial infarction, RRR=Relative risk reduction, SCD=Sudden cardiac death Downs JR et al. JAMA 1998;279(20):1615–1622 6,605 patients with average LDL-C levels randomized to lovastatin (20-40 mg) or placebo for 5.2 years Statins provide significant benefit in those with average LDL-C levels Slide42:  Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA) Sever PS et al. Lancet. 2003;361:1149-1158 0 1 2 3 4 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Atorvastatin 90 mg/dl* Placebo 126 mg/dl* P=0.0005 Cumulative incidence of MI and fatal CHD (%) Follow-up (yr) 36% RRR *Post-treatment LDL-C level 10,305 patients with hypertension randomized to atorvastatin (10 mg) or placebo for 5 years Statins provide significant benefit in moderate- to high-risk individuals by lowering LDL-C levels below current goals CHD=Coronary heart disease, RR=Relative risk HMG-CoA Reductase Inhibitor: Primary Prevention Slide43:  Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering Trial (MIRACL) HMG-CoA Reductase Inhibitor: Secondary Prevention 17.4% 14.8% RR=0.84, P=0.048 Combined cardiovascular event rate (%)* Weeks *Includes death, myocardial infarction, resuscitated cardiac arrest, recurrent symptomatic myocardial ischemia requiring emergency rehospitalization. 4 8 12 16 0 Atorvastatin Placebo Schwartz GG et al. JAMA 2001;285:1711-1718 4,162 patients with an ACS randomized to atorvastatin (80 mg) or pravastatin (40 mg) for 24 months Acute intensive therapy significantly reduces the event rate Slide44:  Follow-up (months) 3 6 9 12 15 18 21 24 27 30 30 25 20 15 10 5 0 P =0.005 Recurrent MI or Cardiac Death 16% RRR Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT)—TIMI 22 Study Atorvastatin Pravastatin ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk reduction Cannon CP et al. NEJM 2004;350:1495-1504 HMG-CoA Reductase Inhibitor: Secondary Prevention 4,162 patients with an ACS randomized to atorvastatin (80 mg) or pravastatin (40 mg) for 24 months Acute intensive therapy significantly reduces the event rate Slide45:  HMG-CoA Reductase Inhibitor: Secondary Prevention Scandinavian Simvastatin Survival Study (4S) Mortality (%) Placebo 11.5 Simvastatin 12 8 4 0 8.2 P<0.001 30% RRR 4S Group. Lancet 1994;344:1383–1389 MI=Myocardial infarction, RRR=Relative risk reduction 4,444 patients with angina pectoris or previous MI randomized to simvastatin (20-40 mg) or placebo for 5.4 years Statins provide significant benefit in those with average LDL-C levels Slide46:  HMG-CoA Reductase Inhibitor: Secondary Prevention Cholesterol and Recurrent Events (CARE) Study Placebo 13.2 Pravastatin 15 10 5 0 10.2 P=0.003 24% RRR Rate of MI or CHD death (%) Sacks FM et al. NEJM 1996;335:1001–1009 CHD=Coronary heart disease, MI=Myocardial infarction, RRR=Relative risk reduction 4,159 patients with a history of MI randomized to pravastatin (40 mg) or placebo for 5 years Statins provide significant benefit in those with average cholesterol levels Slide47:  Event Rate Ratio (95% CI) Statin Better Statin Worse 0.76 (0.72–0.81) P<0.0001 Heart Protection Study (HPS) HMG-CoA Reductase Inhibitor: Secondary Prevention 20,536 patients with CAD, other occlusive arterial disease, or DM randomized to simvastatin (40 mg) or placebo for 5.5 years Statins provide significant benefit across a broad range of LDL-C levels CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus, HPS Collaborative Group. Lancet 2002;360:7-22 Slide48:  Illingworth DR. Med Clin North Am. 2000;84:23-42. HMG-CoA Reductase Inhibitor: Dose-Dependent Effect The Rule of 6’s Each doubling of the statin dose produces an additional 6% reduction in the LDL-C level Slide49:  HMG-CoA Reductase Inhibitor: Primary Prevention West of Scotland Coronary Prevention Study (WOSCOPS) CHD=Coronary heart disease, MI=Myocardial infarction, RRR=Relative risk reduction Shepherd J et al. NEJM 1995;333:1301-1307 Placebo 7.5 Pravastatin 9 6 3 0 5.3 P<0.001 31% RRR Rate of MI or CHD death (%) 6,595 men with moderate hypercholesterolemia randomized to pravastatin (40 mg) or placebo for 5 years Statins provide significant benefit in those with average cholesterol levels Slide50:  Rate of MI, unstable angina, or SCD (%) Placebo 5.5 Lovastatin 6 4 2 0 3.5 HMG-CoA Reductase Inhibitor: Primary Prevention Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) P<0.001 37% RRR MI=Myocardial infarction, RRR=Relative risk reduction, SCD=Sudden cardiac death Downs JR et al. JAMA 1998;279(20):1615–1622 6,605 patients with average LDL-C levels randomized to lovastatin (20-40 mg) or placebo for 5.2 years Statins provide significant benefit in those with average LDL-C levels Slide51:  Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA) Sever PS et al. Lancet. 2003;361:1149-1158 0 1 2 3 4 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Atorvastatin 90 mg/dl* Placebo 126 mg/dl* P=0.0005 Cumulative incidence of MI and fatal CHD (%) Follow-up (yr) 36% RRR *Post-treatment LDL-C level 10,305 patients with hypertension randomized to atorvastatin (10 mg) or placebo for 5 years Statins provide significant benefit in moderate- to high-risk individuals by lowering LDL-C levels below current goals CHD=Coronary heart disease, RR=Relative risk HMG-CoA Reductase Inhibitor: Primary Prevention Slide52:  Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering Trial (MIRACL) HMG-CoA Reductase Inhibitor: Secondary Prevention 17.4% 14.8% RR=0.84, P=0.048 Combined cardiovascular event rate (%)* Weeks *Includes death, myocardial infarction, resuscitated cardiac arrest, recurrent symptomatic myocardial ischemia requiring emergency rehospitalization. 4 8 12 16 0 Atorvastatin Placebo Schwartz GG et al. JAMA 2001;285:1711-1718 4,162 patients with an ACS randomized to atorvastatin (80 mg) or pravastatin (40 mg) for 24 months Acute intensive therapy significantly reduces the event rate Slide53:  Follow-up (months) 3 6 9 12 15 18 21 24 27 30 30 25 20 15 10 5 0 P =0.005 Recurrent MI or Cardiac Death 16% RRR Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT)—TIMI 22 Study Atorvastatin Pravastatin ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk reduction Cannon CP et al. NEJM 2004;350:1495-1504 HMG-CoA Reductase Inhibitor: Secondary Prevention 4,162 patients with an ACS randomized to atorvastatin (80 mg) or pravastatin (40 mg) for 24 months Acute intensive therapy significantly reduces the event rate Slide54:  HMG-CoA Reductase Inhibitor: Secondary Prevention Scandinavian Simvastatin Survival Study (4S) Mortality (%) Placebo 11.5 Simvastatin 12 8 4 0 8.2 P<0.001 30% RRR 4S Group. Lancet 1994;344:1383–1389 MI=Myocardial infarction, RRR=Relative risk reduction 4,444 patients with angina pectoris or previous MI randomized to simvastatin (20-40 mg) or placebo for 5.4 years Statins provide significant benefit in those with average LDL-C levels Slide55:  HMG-CoA Reductase Inhibitor: Secondary Prevention Cholesterol and Recurrent Events (CARE) Study Placebo 13.2 Pravastatin 15 10 5 0 10.2 P=0.003 24% RRR Rate of MI or CHD death (%) Sacks FM et al. NEJM 1996;335:1001–1009 CHD=Coronary heart disease, MI=Myocardial infarction, RRR=Relative risk reduction 4,159 patients with a history of MI randomized to pravastatin (40 mg) or placebo for 5 years Statins provide significant benefit in those with average cholesterol levels Slide56:  Event Rate Ratio (95% CI) Statin Better Statin Worse 0.76 (0.72–0.81) P<0.0001 Heart Protection Study (HPS) HMG-CoA Reductase Inhibitor: Secondary Prevention 20,536 patients with CAD, other occlusive arterial disease, or DM randomized to simvastatin (40 mg) or placebo for 5.5 years Statins provide significant benefit across a broad range of LDL-C levels CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus, HPS Collaborative Group. Lancet 2002;360:7-22 Slide57:  Change from Baseline Goldberg A et al. Am J Cardiol 2000;85:1100-1105 500 HDL-C LDL-C TG –9% –14% –22% –21% –17% 30% 30% 26% 22% 15% 10% –28% –35% –44% –39% –11% –5% Nicotinic Acid: Efficacy at Raising HDL-C 1000 1500 2000 2500 Dose (mg) 3000 Slide58:  Frick MH et al. NEJM 1987;317:1237-1245 Manninen V et al. Circulation 1992;85:37-45 BIP Study Group. Circulation 2000;102:21-27 Rubins HB et al. NEJM 1999;341:410-418 *Post hoc analysis of subgroup with TG >200 mg/dL and HDL-C <42 mg/dL. **Post hoc analysis of subgroup with TG 200 mg/dL and HDL-C <35 mg/dL. ***Difference between placebo and Rx for primary endpoint was statistically significant (p < 0.05). % CHD Death/Nonfatal MI Rx Placebo 2.7 4.1*** 2.7 8.0 13.6 15.0 13.0 22.3 17.3 21.7*** 66% 34% 9% 42% 22% PRIMARY PREVENTION SECONDARY PREVENTION HHS HHS* BIP BIP** VA-HIT Fibrate: Primary and Secondary Prevention Slide59:  Complete cessation No environmental tobacco smoke exposure Cigarette Smoking Cessation Guidelines Ask about tobacco use at every visit. In a clear, strong, and personalized manner, advise the patient to stop smoking. Urge avoidance of exposure to secondhand smoke at work and home. Assess the patient’s willingness to quit smoking. Develop a plan for smoking cessation and arrange follow-up. Provide counseling, pharmacologic therapy, and referral to formal smoking cessation programs as indicated. Slide60:  Smoking Cessation Pharmacotherapy* *Pharmacotherapy combined with behavioral support provides the best success rate **Other nicotine replacement therapy options include: nicotine gum, lozenge, inhaler, nasal spray Slide61:  Jorenby DE et al. NEJM 1999;340:685-91 Cigarette Smoking Cessation: Primary Prevention ap<0.001 when compared to placebo bp=0.001 when compared to NRT cp<0.001 when compared to NRT dp=0.37 when compared to buproprion ep=0.22 when compared to buproprion NRT=Nicotine replacement therapy 893 smokers randomized to 9 weeks of buproprion (150 mg a day for 3 days and then 150 mg twice daily), NRT (21 mg patch weeks 2-7, 14 mg patch week 8, and 7 mg patch week 9), bupropion and NRT, or placebo Bupropion with or without NRT provides the greatest benefit Slide62:  JAMA 2006:296:47-55 and JAMA 2006;296:56-63 Smoking Cessation Pharmacotherapy: Varenicline Two trials compared treatment with varenicline, a nicotine acetylcholine receptor agonist, to treatment with buproprion or placebo. These trials included a total of almost 700 participants. The mean duration of smoking was 25 years. Varenicline yielded higher rates of smoking cessation than buproprion or placebo. Slide63:  Calculate BMI* and measure waist circumference as part of evaluation. Monitor response of BMI and waist circumference to therapy. BMI 18.5 to 24.9 kg/m2 Women: <35 inches Men: <40 inches Weight Management Guidelines Start weight management and physical activity as appropriate. If BMI and/or waist circumference is above goal, initiate caloric restriction, measures to increase caloric expenditure, and treatment strategies for the metabolic syndrome. BMI=Body mass index *BMI is calculated as the weight in kilograms divided by the body surface area in meters2. Overweight state is defined by BMI=25-30 kg/m2. Obesity is defined by a BMI >30 kg/m2. 10% weight reduction within the first year of therapy Slide64:  Prevalence of Obesity in U.S. Adults 1996 2003 % State Population No Data <10% 10%–14% 15%–19% 20%–24% ≥25% Source: CDC Overweight and Obesity Slide65:  Mhurchu N et al. Int J Epidemiol 2004;33:751-758 CV Risk Increases with Body Mass Index CV=Cardiovascular Body mass index is calculated as the weight in kilograms divided by the body surface area in meters2. Slide66:  Diabetes Mellitus Guidelines Goal HbA1C <7% Intensive lifestyle modification to prevent the development of DM (especially in those with the metabolic syndrome) Aggressive management of CV risk factors (i.e., tobacco use, hypertension, dyslipidemia, physical inactivity, and overweight and obese states) Hypoglycemic therapy to achieve normal to near normal fasting plasma glucose as defined by the HbA1C (<7%) Weight reduction and exercise Oral hypoglycemic agents Insulin therapy Coordination of diabetic care with the patient’s primary physician and/or endocrinologist. CV=Cardiovascular, DM=Diabetes mellitus, HbA1C=Glycosylated hemoglobin Slide67:  Consists of a constellation of major risk factors, life-habit risk factors, and emerging risk factors Over-represented among populations with cardiovascular disease Often occurs in individuals with a distinctive body-type including an increased abdominal circumference The Metabolic Syndrome Slide68:  Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497 ATP III Definition of the Metabolic Syndrome Defined by presence of >3 risk factors HDL-C=High-density lipoprotein cholesterol Slide69:  Tuomilehto J et al. NEJM 2001;344:1343-1350 Intervention Control 11% 23% % with Diabetes Mellitus Metabolic Syndrome: Risk of Developing DM Finnish Diabetes Prevention Study †Defined as a glucose >140 mg/dl 2 hours after an oral glucose challenge 522 overweight (mean BMI=31 kg/m2) patients with impaired fasting glucose† randomized to intervention‡ or usual care for 3.2 years Lifestyle modification reduces the risk of developing DM ‡Aimed at reducing weight (>5%), total intake of fat (<30% total calories) and saturated fat (<10% total calories); increasing uptake of fiber (>15 g/1000 cal); and physical activity (moderate at least 30 min/day) Slide70:  Metabolic Syndrome: Risk of Developing DM Diabetes Prevention Program (DPP) Knowler WC et al. NEJM 2002;346:393-403 *Includes 7% weight loss and at least 150 minutes of physical activity per week Placebo Metformin Lifestyle modification Incidence of DM (%) 0 20 30 10 40 0 0 1 4 2 3 Years 3,234 patients with elevated fasting and post-load glucose levels randomized to placebo, metformin (850 mg twice daily), or lifestyle modification* for 2.8 years Lifestyle modification reduces the risk of developing DM Slide71:  Assess risk, preferably with exercise test, to guide prescription. Encourage aerobic activity (e.g., walking, jogging, cycling) supplemented by an increase in daily activities (e.g., walking breaks at work, gardening, household work). Encourage resistance training (e.g., weight machines, free weights) 2 days a week (Class IIb, Level C) Encourage cardiac rehabilitation for patients with chronic stable angina, recent myocardial infarction, left ventricular systolic dysfunction, or recent coronary artery bypass graft surgery. Minimum: 30 minutes, 5 days per week Optimal: 30 minutes daily Exercise Guidelines Slide72:  Ejection Fraction Guidelines Echocardiography in those following a STEMI to re-evaluate ventricular function when results are used to guide therapy*. Echocardiography or radionuclide angiography in those following a NSTE-ACS when results are used to guide therapy*. *Includes use of an aldosterone antagonist, digitalis, and/or an implantable cardioverter defibrillator NSTE-ACS=Non-ST-segment elevation acute coronary syndrome, STEMI=ST-segment elevation myocardial infarction Secondary Prevention Slide73:  Digitalis: Recommendations Digitalis in those with symptomatic HF and LVSD (EF <45%) to reduce hospitalizations for HF*. Digitalis in those with asymptomatic LVSD and normal sinus rhythm. Secondary Prevention EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic function *Contraindications include significant sinus or atrioventricular block unless a permanent pacemaker is present. Slide74:  54-60 >60 50 40 30 20 10 0 <30 31-35 36-45 46-53 Cardiac Mortality % Brodie B et al. Am J Cardiol 1992;69:1113 Relationship Between EF* and Mortality Ejection Fraction (%) *Post myocardial infarction EF=Ejection fraction Slide75:  Pitt B et al. NEJM 1999;341:709-717 RR = 0.70, P<0.001 Months Survival (%) 36 33 30 27 24 21 18 15 12 9 6 3 0 1.00 .90 .80 .70 .60 .50 0 Aldosterone Antagonist: Secondary Prevention Randomized Aldactone Evaluation Study (RALES) EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, NYHA=New York Heart Association Spironolactone Placebo 1,663 patients with NYHA Class III or IV HF and LVSD (EF <0.35) randomized to spironolactone (25 mg) or placebo (50 mg) for 24 months Aldosterone inhibition provides significant benefit in patients with advanced heart failure Slide76:  RR = 0.85, P=0.008 All Cause Mortality (%) Month Aldosterone Antagonist: Secondary Prevention Eplerenone Poct-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) Eplerenone Placebo 3,313 patients with evidence of heart failure and LVSD (EF <0.40) after a MI randomized to eplerenone (50 mg) or placebo for 16 months Aldosterone inhibition provides significant benefit in patients with post-MI heart failure and LVSD Pitt B et al. NEJM 2003;348:1309-21 EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction Slide77:  ICD Algorithm EF < 30% EPS Yes + NEJM 349:1836,2003 EF 31-40% No EF > 40% - At least one month following a myocardial infarction EF=Ejection fraction, EPS=Electrophysiology study, ICD=Implantable cardioverter defibrillator, Rx=Treatment, SCD=Sudden cardiac death, Slide78:  1 Moss AJ. N Engl J Med. 1996;335:1933-1940 2 Buxton AE. N Engl J Med. 1999;341:1882-1890 3 Moss AF. N Engl J Med. 2002;346:877-883 1 2 3 54% 75% 55% 73% 31% 61% 27 Months 39 Months 20 Months % Mortality Reduction w/ ICD Rx ICD: Secondary Prevention* *Primary prevention of sudden cardiac death Overall death Arrhythmic death EF <35% EF <40% EF <30% Prevention Pyramid:  Prevention Pyramid ACE-1 = angiotensin converting enzyme inhibitor; ASA = aspirin Secondary Primary Primordial

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