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Blood Pressure Control Evidence and Guidelines PowerPoint Presentation

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Description : Check out this medical PowerPoint presentation titled "Blood Pressure Control Evidence and Guidelines" by Prof. J. Hanacek.

This medical PowerPoint presentation talks about Blood Pressure Control Evidence and Guidelines. High blood pressure, also known as hypertension, is a common medical condition that affects a large number of people worldwide. It is a major risk factor for cardiovascular disease, stroke, and kidney failure, among other conditions. The management of hypertension involves controlling blood pressure to reduce the risk of these complications.

The presentation talks about evidence-based guidelines and recommendations for blood pressure control.

Tags : Blood Pressure, Blood Pressure Control Evidence and Guidelines, High blood pressure, hypertension, cardiovascular disease, stroke, kidney failure, cardiology

Published on : Mar 17, 2023 | Views : 1777 | Downloads : 6

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Slide 1-

The Evidence for Current Cardiovascular Disease Prevention Guidelines: Blood Pressure Control Evidence and Guidelines American College of Cardiology Best Practice Quality Initiative Subcommittee and Prevention Committee
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Classification of Recommendations and Levels of Evidence *Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there may be a very clear clinical consensus that a particular test or therapy is useful or effective. †In 2003, the ACC/AHA Task Force on Practice Guidelines developed a list of suggested phrases to use when writing recommendations. All guideline recommendations have been written in full sentences that express a complete thought, such that a recommendation, even if separated and presented apart from the rest of the document (including headings above sets of recommendations), would still convey the full intent of the recommendation. It is hoped that this will increase readers’ comprehension of the guidelines and will allow queries at the individual recommendation level.
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Icons Representing the Classification and Evidence Levels for Recommendations
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Blood Pressure Evidence Evidence for Current Cardiovascular Disease Prevention Guidelines
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Hypertension* Prevalence (%) 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% Source: JNC-VI. Arch Intern Med 1997;157:2413-2446 51% 66% 72% 38% *Hypertension defined as blood pressure >140/90 mmHg or treatment High Blood Pressure*: Prevalence Increases with Age The prevalence of high blood pressure increases with age
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High Blood Pressure*: Prevalence in Different Patient Groups National Health and Nutrition Examination Survey (NHANES) Source: Yoon SS et al. NCHS Data Brief 2012;107:1-7 *High blood pressure defined as blood pressure 140/90 mmHg or treatment
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Risk of hypertension (%) *Residual lifetime risk of developing hypertension among people with blood pressure <140/90 mmHg starting at age 55-65 years Years Men Women Source: Vasan RS et al. JAMA 2002; 287:1003-1010 Framingham Heart Study High Blood Pressure: Lifetime Risk*
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National Health and Nutrition Examination Survey (NHANES) Blood pressureage-adjusted percentage Change in Blood Pressure Levels in the United States Over Time Source: Ford ES et al. Figure 2b, Circulation 2009;120:1181-1188
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Blood Pressure Treatment Evidence and Guidelines Evidence for Current Cardiovascular Disease Prevention Guidelines
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BP=Blood pressure, CVD=Cardiovascular disease, HTN=Hypertension Source: Chobanian AV et al. JAMA 2003;289:2560-2572 JNC VII Guidelines: Measurement of Blood Pressure
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Source: Chobanian AV et al. JAMA 2003;289:2560-2572 NSAIDs=Non-steroidal anti-inflammatory drugs JNC VII Guidelines: Causes of Secondary Hypertension
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Source: Calhoun DA et al. Circulation 2008;117:e510-526 Diagnostic and Treatment Algorithm Confirm Treatment Resistance Office BP >140/90 or 130/80 mm Hg in patients with DM or chronic kidney disease and Patient prescribed 3 or more antihypertensive medications at optimal doses, including if possible a diuretic or Office BP at goal but patient requiring 4 or more antihypertensive medications Exclude Pseudoresistance Is patient adherent with prescribed reigmen? Obtain home, work, or ambulatory BP readings to exclude white coat effect Identify/Reverse Contributing Lifestyle Factors Obesity Physical inactivity Excessive alcohol ingestion High salt, low fiber diet BP=Blood pressure, DM=Diabetes mellitus Discontinue/Minimize Interfering Substances Non-steroidal anti-inflammatory agents Sympathomimetics (diet pills, decongestants) Stimulants Oral contraceptives Licorice Ephedra Resistant Hypertension
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Diagnostic and Treatment Algorithm Screen for Secondary Causes of Hypertension Obstructive sleep apnea (snoring, witnessed apena, excessive daytime sleepiness) Primary aldosteronism (elevated aldosterone/renin ratio) Chronic kidney disease (CrCl <30 ml/min) Renal artery stenosis (young female, known atherosclerotic disease, worsening renal function) Pheochromocytoma (episodic hypertension, palpitations, diaphoresis, headache) Cushing’s syndrome (moon facies, central obesity, abdominal striae, inter-scapular fat deposition) Aortic coarctation (differential in brachial or femoral pulses, systolic bruit) Pharmacologic Treatment Maximize diuretic therapy, including possible addition of mineralocorticoid receptor antagonist Combine agents with different mechanisms of action Use loop diuretics in patients with chronic kidney disease and/or those receiving potent vasodilators (e.g., minoxidil) Refer to Specialist Refer to appropriate specialist for known or suspected secondary cause(s) of hypertension Refer to hypertension specialist if blood pressure remains uncontrolled after 6 months of treatment Resistant Hypertension (Continued) Source: Calhoun DA et al. Circulation 2008;117:e510-526 CrCl=Creatinine clearance
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Source: Prospective Studies Collaboration. Lancet 2002;360:1903-1913 Usual Diastolic BP (mm Hg) Usual Systolic BP (mm Hg) Ischemic Heart Disease Mortality (Floating absolute risk) 50-59 60-69 70-79 80-89 Age at Risk (Y) 40-49 256 128 64 32 16 8 4 2 1 0 120 140 160 180 50-59 60-69 70-79 80-89 Age at Risk (Y) 40-49 256 128 64 32 16 8 4 2 1 0 80 90 100 110 70 Ischemic Heart Disease Mortality (Floating absolute risk) Ischemic heart disease mortality and blood pressure BP=Blood pressure High Blood Pressure Evidence: Increased Risk with Increased Levels
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0 0.5 1.0 1.5 2.0 0.79 (0.69 to 0.90) Source: He J et al. Am Heart J 1999;138:211-219 Better than placebo Worse than placebo CHD=Coronary heart disease High Blood Pressure Evidence: Risk of CHD with Treatment
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Source: Abbott K et al. J Clin Pharmacology 2004;44:431-438 Trial (SBP Achieved) 1 1.5 2 2.5 3 3.5 4 AASK (127 mm Hg) HOT (138 mm Hg) MDRD (132 mm Hg) ABCD (127 mm Hg) UKPDS (144 mm Hg) Number of BP Meds AASK=African American Study of Kidney Disease and Hypertension, ABCD=Appropriate Blood Pressure Control in Diabetes, BP=Blood pressure, HOT=Hypertension Optimal Treatment, MDRD=Modification of Dietary Protein in Renal Disease, SBP=Systolic blood pressure, UKPDS=UK Prospective Diabetes Study High Blood Pressure Evidence: Number of Medications Needed
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33,357 patients with HTN and >1 CHD risk factor randomized to chlorthalidone, amlodipine, or lisinopril for 5 years All three BP lowering agents provide similar efficacy Rate of MI or fatal CHD Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Source: ALLHAT Investigators. JAMA 2002;288:2981-2997 Years to CHD Event BP=Blood pressure, CHD=Coronary heart disease, HTN=Hypertension, MI=Myocardial infarction Chlorthalidone Amlodipine Lisinopril Blood Pressure Lowering Therapy Evidence: Primary Prevention
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Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension Study Source: Dahlöf B et al. Lancet 2002;359:995-1003 ARB=Angiotensin receptor blocker, CV=Cardiovascular, DBP=Diastolic blood pressure, LVH=Left ventricular hypertrophy, MI=Myocardial infarction, SBP=Systolic blood pressure *Defined by SBP=160-200 mmHg or DBP=95-115 mmHg 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 (%) Atenolol 13% RRR, P=0.021 Losartan Blood Pressure Lowering Therapy Evidence: Primary Prevention 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
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19,342 high-risk hypertensive patients with 3 additional CV risk factors randomized to amlodipine (10 mg) & perindopril (8 mg) or atenolol (100 mg) & bendroflumethiazide (2.5 mg) for 5.5 years Both BP lowering regimens provide similar efficacy Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure Lowering Arm (ASCOT-BPLA) Nonfatal MI and fatal CHD (%) 6 2 4 0 1 2 3 4 5 6 0 Time since randomization (years) RRR=10%, P=0.1052 Atenolol-based regimen Amlodipine-based regimen Source: Dahlöf B et al. Lancet 2005;366:895-906 BP=Blood pressure, CV=Cardiovascular, CHD=Coronary heart disease, MI=Myocardial infarction Blood Pressure Lowering Therapy Evidence: Primary Prevention
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Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure Lowering Arm (ASCOT-BPLA) Secondary endpoints Nonfatal MI + fatal CHD 7.4 8.5 Total coronary endpoint 14.6 16.8 Total CV events/procedures 27.4 32.8 All-cause mortality 13.9 15.5 CV mortality 4.9 6.5 Fatal/nonfatal stroke 6.2 8.1 Fatal/nonfatal HF 2.5 3.0 Amlodipine-based rate/1000patient years <0.05 <0.01 <0.0001 <0.05 0.001 <0.001 NS P Amlodipine-based better Atenolol-based better 0.50 0.70 1.00 1.45 2.00 Atenolol-based rate/1000patient years Source: Dahlöf B et al. Lancet 2005;366:895-906 CHD=Coronary heart disease, CV=Cardiovascular, HF=Heart failure, MI=Myocardial infarction An amlodopine-based regimen appears to reduce the rate of other CV events Blood Pressure Lowering Therapy Evidence: Primary Prevention
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11,506 high-risk hypertensive patients randomized to benazepril (40 mg) and amlodipine (10 mg) or benazepril (40 mg) and HCTZ (25 mg) for 36 months* An amlodipine-based regimen provides greater benefit Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) Benazepril/HCTZ Benazepril/Amlodipine Composite of CV death, MI, stroke, hospitalization for angina, sudden cardiac arrest, and coronary revascularization (%) 20% RRR, HR=0.80, P=0.0002 Source: Jamerson K et al. NEJM 2008;359:2417-2428 0.16 0.14 0.12 0.10 0.08 0.06 0.04 0.02 0.00 0 200 400 600 800 1000 1200 1400 *The study was prematurely stopped Blood Pressure Lowering Therapy Evidence: Primary Prevention CV=Cardiovascular, MI=Myocardial infarction
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3,845 patients >80 years with SBP >160 mm Hg randomized to treatment to indapamide (1.5 mg) and perindopril (2-4 mg if needed) vs. placebo for 2 years Blood pressure control in patients >80 years of age provides benefit Hypertension in the Very Elderly (HYVET) Trial Source: Beckett NS et al. NEJM 2008;358:1887-1898 CV=Cardiovascular, CVA=Cerebrovascular accident Rate/1000 patient years (%) P=0.06 P=0.05 P=0.02 P<0.001 P<0.001 (Primary end point) Blood Pressure Lowering Therapy Evidence: Primary Prevention Indapamide + perindopril Placebo
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22,576 patients with HTN and CAD randomized to a BP lowering strategy with verapamil SR (240 mg) or atenolol (50 mg) for 2.7 years Both a CAS and NCAS provide similar efficacy International Verapamil-Trandolapril Study (INVEST) Months RR=0.98, P=0.57 Calcium antagonist strategy (CAS)* Non-calcium antagonist strategy (NCAS)* Source: Pepine CJ et al. JAMA 2003;290:2805-2816 *Trandolapril (up to 4 mg) was added in those with diabetes mellitus, chronic kidney disease, or heart failure Incidence of all cause death, nonfatal MI, or nonfatal stroke BP=Blood pressure, CAS=Calcium antagonist strategy, HTN=Hypertension, MI=Myocardial infarction, NCAS=Non-calcium antagonist strategy Blood Pressure Lowering Therapy Evidence: Secondary Prevention 0 20 10 15 5
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Favors valsartan Favors amlodipine Primary cardiac composite endpoint Cardiac mortality Cardiac morbidity All myocardial infarction All congestive heart failure All stroke All-cause death New-onset diabetes 0.5 1 2 Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) Trial Source: Julius S et al. Lancet 2004;363:2022-2031 BP=Blood pressure, CV=Cardiovascular, HTN=Hypertension 15,245 patients with untreated HTN and high CV risk randomized to a BP lowering strategy with valsartan (160 mg) or amlodipine (10 mg) for 4.2 years Both blood pressure lowering regimens provide similar efficacy Blood Pressure Lowering Therapy Evidence: Secondary Prevention
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Source: Nissen S et al. JAMA 2004;292:2217-2226 Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis (CAMELOT) Trial *Includes CV death, myocardial infarction, cardiac arrest, coronary revascularization, hospitalization for heart failure or angina pectoris, stroke, transient ischemic attack, development of peripheral arterial disease 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 1,991 patients with CAD and a DBP <100 mmHg randomized to amlodipine (10 mg), enalapril (20 mg), or placebo for 2 years Treatment with amlodipine results in reduced CV events Blood Pressure Lowering Therapy Evidence: Secondary Prevention
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Source: Hansson L et al. Lancet 1998;351:1755-1762 Hypertension Optimal Treatment (HOT) Study Diastolic BP goal Patients without Diabetes Major CV events per 1000 patient-years Patients with Diabetes Diastolic BP goal 18,790 patients with a baseline diastolic BP of 100-115 mm Hg randomized to a target diastolic BP of <90 mm Hg, <85 mm Hg, or <80 mm Hg More intensive blood pressure control provides greater benefit in diabetics Blood Pressure Lowering Therapy Evidence: Effect of Intensive Blood Pressure Control BP=Blood pressure, CV=Cardiovascular
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Source: Verdecchia P et al. Lancet 2009;374:525-533 Cardio-SIS Trial AF=Atrial fibrillation, ESRD=End stage renal disease, CHF=Congestive heart failure, CVA=Cerebrovascular accident, LVH=Left ventricular hypertrophy, MI=Myocardial infarction, PAD=Peripheral artery disease, SBP=Systolic blood pressure, TIA=Transient ischemic attack Incidence of LVH (%) Usual Control 17.0 Tight Control 21 14 7 0 11.4 P=0.013 Composite of CV events* (%) Usual Control 9.4 Tight Control 15 10 5 0 4.8 P=0.003 *Composite of death, MI, CVA, TIA, CHF, angina, new AF, revascularization, aortic dissection, PAD, and ESRD 1,111 patients >55 years with SBP >150 mm Hg randomized to treatment to achieve usual BP control (SBP <140 mm Hg) or intensive BP control (SBP <130 mm Hg) More intensive blood pressure control provides greater benefit Blood Pressure Lowering Therapy Evidence: Effect of Intensive Blood Pressure Control
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HR=1.15, p=0.036 International Verapamil-Trandolapril Study (INVEST)—DM Substudy BP=Blood pressure, CV=Cardiovascular Blood Pressure Lowering Therapy Evidence: Effect of Intensive Blood Pressure Control Source: Cooper-DeHoff RM et al. JAMA 2010;304:61-68 6,400 diabetic patients from the INVEST study grouped by tight (<130 mm Hg), usual (>130 to <140 mm Hg), or uncontrolled (>140 mm Hg) blood pressure Tight BP control is not associated with reduced adverse CV events
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Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial Total stroke HR=0.88 95% CI (0.73-1.06) HR=0.59 95% CI (0.39-0.89) Nonfatal MI, nonfatal stroke, or CV death BP=Blood pressure, DM=Diabetes mellitus, HR=Hazard ratio, SBP=Systolic blood pressure ACCORD study group. NEJM 2010;362:1575-1585 4,733 diabetic patients randomized to intensive BP control (target SBP <120 mm Hg) or standard BP control (target SBP <140 mm Hg) for 4.7 years Intensive BP control in DM does not reduce a composite of adverse CV events, but does reduce the rate of stroke Blood Pressure Lowering Therapy Evidence: Effect of Intensive Blood Pressure Control
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2-drug combination for most† (usually thiazide-type diuretic and ACE-I or ARB or BB or CCB). Yes >100 >160 Stage 2 Hypertension Drug(s) for compelling indications.‡ Other antihypertensive drugs (as needed). Thiazide-type diuretics for most. May consider ACE-I, ARB, BB, CCB, or combination of these. Yes 90–99 140–159 Stage 1 Hypertension Drug(s) for compelling indications.‡ No antihypertensive drug indicated. Yes 80–89 120–139 Prehypertension Encourage <80 <120 Normal With compelling indications Without compelling indications Initial drug therapy Lifestyle modification DBP* mmHg SBP* mmHg BP classification and or or or Source: Chobanian AV et al. JAMA 2003;289:2560-2572 ACE-I=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker, BB=Beta-blocker, BP=Blood pressure, CCB=Calcium channel blocker, DBP=Diastolic blood pressure, SBP=Systolic blood pressure *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 JNC VII Guidelines: Management and Treatment
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Source: Chobanian AV et al. JAMA 2003;289:2560-2572 BMI=Body mass index, BP=Blood pressure, SBP=Systolic blood pressure JNC VII Guidelines: Lifestyle Modifications for BP Control
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Clinical-Trial Basis Compelling Indication ALLHAT, HOPE, ANBP2,LIFE, CONVINCE High CAD Risk ACC/AHA Post-MI Guidelines, BHAT, SAVE, Capricorn, EPHESUS Post-MI MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, Val-HeFT, RALES Initial Therapy Options Diuretic, BB, ACE-I, CCB BB, ACE-I, Aldo ANT Diuretic, BB, ACE-I,ARB, Aldo ANT Heart Failure Recurrent Stroke Prevention PROGRESS Diuretic, ACE-I NKF-ADA Guideline,UKPDS, ALLHAT NKF Guidelines, Captopril Trial, RENAAL, IDNT, REIN, AASK Diuretic, BB, ACE-I,ARB, CCB ACE-I, ARB Diabetes Mellitus Chronic Kidney Disease Source: Chobanian AV et al. JAMA 2003;289:2560-2572 ACE-I=Angiotensin converting enzyme inhibitor, Aldo ANT=Aldosterone antagonist, ARB=Angiotensin receptor blocker, BB=Beta-blocker, CAD=Coronary artery disease, CCB=Calcium channel blocker, MI=Myocardial infarction JNC VII Guidelines: Compelling Indications for Drug Classes
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Optimize dosages or add additional drugs until goal BP is achieved. Consider consultation with hypertension specialist. Lifestyle modifications Initial drug choices Not at goal BP Not at goal BP (<140/90 mm Hg)(<130/80 mm Hg for those with diabetes mellitusor chronic kidney disease) WITH compelling indications WITHOUT compelling indications Stage 1 hypertension (SBP 140–159 mm Hg or DBP 90–99 mm Hg): Thiazide-type diuretic for most. May consider ACEI, ARB, BB, CCB, or combo. Stage 2 hypertension(SBP ³160 or DBP ³100 mm Hg): Two-drug combination for most (usually thiazide-type diuretic and ACEI or ARB or BB or CCB). Drugs for compelling indications: Other antihypertensive drugs (diuretic, ACEI, ARB, BB, CCB)as needed. Source: Chobanian AV et al. JAMA 2003;289:2560-2572 ACEI=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker, BB=Beta-blocker, BP=Blood pressure, CCB=Calcium channel blocker, DBP=Diastolic blood pressure, SBP=Systolic blood pressure JNC VII Guidelines: Blood Pressure Treatment Algorithm
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Counsel regarding the need for lifestyle modification: weight control; increased physical activity; alcohol moderation; sodium reduction; and emphasis on increased consumption of fresh fruits, vegetables, and low-fat dairy products. Source: Smith SC Jr. et al. JACC 2011;58:2432-2446 Blood Pressure Recommendations Primary and Secondary Prevention
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Source: Buse JB et al. Circulation 2007;115:114-126 BP should be measured at every routine visit. Patients with a SBP >130 mm Hg or DBP >80 mm Hg should have BP confirmed on a separate day. Patients should be treated to a SBP <130 mm Hg and a DBP <80 mm Hg. Patients with a SBP of 130-139 mm Hg or a DBP of 80-89 mm Hg should initiate lifestyle modification* alone for a maximum of 3 months. If, after these efforts, targets are not achieved, treatment with pharmacological agents should be initiated. *Includes weight control, increased physical activity, alcohol moderation, sodium reduction, and emphasis on increased consumption of fresh fruits, vegetables, and low-fat dairy products AHA=American Heart Association, BP=Blood pressure, CV=Cardiovascular, DBP=Diastolic blood pressure, DM=Diabetes mellitus, SBP=Systolic blood pressure AHA Primary Prevention of CV Disease in DM Blood Pressure Recommendations Primary Prevention
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Source: Buse JB et al. Circulation 2007;115:114-126 Multiple-drug therapy is generally required to achieve BP targets. In elderly hypertensive patients, BP should be lowered gradually to avoid complications. Orthostatic measurement of BP should be performed when clinically indicated. Patients not achieving target BP despite multiple-drug therapy should be referred to a physician specializing in the care of patients with hypertension. AHA=American Heart Association, BP=Blood pressure, CV=Cardiovascular, DM=Diabetes Mellitus AHA Primary Prevention of CV Disease in DM Blood Pressure Recommendations (Continued) Primary Prevention
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BP should be measured at every routine DM visit. Patients found to have a SBP >130 mm Hg or a DBP >80 mm Hg should have BP confirmed on a separate day. A repeat SBP >130 mm Hg or a repeat DBP >80 mm Hg confirms a diagnosis of hypertension. Patients with DM should be treated to a SBP <130 mm Hg. Patients with DM should be treated to a DBP <80 mm Hg. Patients with a SBP 130-139 mm Hg or a DBP 80-89 mm Hg may be given lifestyle therapy alone for a maximum of 3 months, and then if targets are not achieved, patients should have pharmacologic agents added. Source: American Diabetes Association. Diabetes Care 2010;33:S11-61 ADA=American Diabetes Association, BP=Blood pressure, DBP=Diastolic blood pressure, DM=Diabetes mellitus, SBP=Systolic blood pressure ADA Blood Pressure Recommendations for Patients with Diabetes Mellitus Primary Prevention
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Patients with more severe hypertension (SBP >140 mm Hg or DBP >90 mm Hg) at diagnosis or follow-up should receive pharmacologic therapy in addition to lifestyle therapy. Lifestyle therapy for hypertension consists of weight loss if overweight, DASH-style dietary pattern including reducing sodium and increasing potassium intake, moderation of alcohol intake, and increased physical activity. Source: American Diabetes Association. Diabetes Care 2010;33:S11-61 ACE=Angiotensin converting enzyme, ADA=American Diabetes Association, BP=Blood pressure, DBP=Diastolic blood pressure, DM=Diabetes mellitus, GFR=Glomerular filtration rate, SBP=Systolic blood pressure ADA Blood Pressure Recommendations for Patients with Diabetes Mellitus (Continued) Primary Prevention
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Pharmacologic therapy for patients with DM and hypertension should be paired with a regimen that includes either an ACE inhibitor or an ARB. If one class is not tolerated, the other should be substituted. If needed to achieve BP targets, a thiazide diuretic should be added to those with an estimated GFR >30 ml/min and a loop diuretic with an estimated GFR <30 ml/min. Multiple drug therapy (two or more agents at maximal doses) is generally required to achieve BP targets. Source: American Diabetes Association. Diabetes Care 2010;33:S11-61 ACE=Angiotensin converting enzyme, ADA=American Diabetes Association, ARB=Angiotensin receptor blocker, BP=Blood pressure, DM=Diabetes mellitus, GFR=Glomerular filtrate rate ADA Blood Pressure Recommendations for Patients with Diabetes Mellitus (Continued) Primary Prevention
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Use of an ACE inhibitor and/or beta-blocker in those with BP >140/90 mmHg*. Other drugs 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 Source: Smith SC Jr. et al. JACC 2011;58:2432-2446 Blood Pressure Recommendations Secondary Prevention
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Angiotensin Converting Enzyme Inhibitor Evidence and Guidelines Evidence for Current Cardiovascular Disease Prevention Guidelines
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Angiotensin II Kininase II Angiotensin I Angiotensinogen ACE Renin Bradykinin Inactive Fragments Sympathetic Vasopressin Aldosterone Vasoconstriction ACE=Angiotensin converting enzyme Kininogen Kallikrein Vasodilation Prostaglandins tPA Inhibitor ACE Inhibitor: Mechanism of Action
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Source: HOPE Investigators. NEJM 2000;342:145-153 Heart Outcomes Prevention and Evaluation (HOPE) Study ACE=Angiotensin converting enzyme, 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 an additional CV risk factor, but without HF or known LVSD randomized to ramipril (10 mg) or placebo for 5 years An ACE inhibitor provides benefit in high-risk individuals ACE Inhibitor Evidence: Secondary Prevention
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Cardiovascular death (0.86; 0.72-1.03) Non-fatal MI (0.78; 0.20-0.90) Cardiac arrest (0.54; 0.20-1.47) Combined endpoint (0.80; 0.71-0.91) European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) Favors Perindopril Favors Placebo Source: EUROPA Investigators. Lancet 2003;362:782-788 12,218 patients with CAD and presumed normal LV function randomized to perindopril (8 mg) or placebo for 4 years An ACE inhibitor provides benefit in intermediate-risk individuals ACE=Angiotensin converting enzyme, CAD=Coronary artery disease, CV=Cardiovascular, MI=Myocardial infarction ACE Inhibitor Evidence: Secondary Prevention
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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 Source: The PEACE Trial Investigators. NEJM 2004;351:2058-2068 *Includes death from cardiovascular causes, myocardial infarction, or coronary revascularization Trandolapril 8,290 patients with stable CAD and normal LV function randomized to trandolapril (4 mg) or placebo for 5 years An ACE inhibitor does not provide benefit in lower-risk individuals ACE Inhibitor Evidence: Secondary Prevention ACE=Angiotensin converting enzyme, CAD=Coronary artery disease, LV=Left ventricular
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Comparison between the HOPE and PEACE trials Patients enrolled in the PEACE trial were lower risk* MI, Cardiac death, or Stroke (%) Source: The PEACE Trial Investigators. NEJM 2004;351:2058-2068 CHD=Coronary heart disease, MI=Myocardial infarction *Reflects better blood pressure control, revascularization, and use of other risk-reducing medications (i.e., antiplatelet therapy, beta-blocker, lipid-lowering medication) Years HOPE, placebo HOPE, active drug (ramipril) PEACE, placebo ACE Inhibitor Evidence: Secondary Prevention
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Clinical Trial HOPE 9,297 1051 0.4 0.6 0.8 1.0 1.2 1.4 1.6 N ACE-I Better Placebo Better EUROPA 12,218 795 PEACE 8,290 633 HR=0.89 P=0.13 HR=0.89 P=0.10 HR=0.84 P=0.005 Deaths All Trials 33,960 >3000 HR=0.86 P<0.001 Sources: Danchin N et al. Arch Intern Med 2006;166:787-796 The HOPE Trial Investigators. NEJM 2000;342:145-153 The EUROPA Study. Lancet 2003; 362: 782-788 The PEACE Trial Investigators. NEJM 2004;351:2058-2068 Meta-Analysis of the HOPE, EUROPA, and PEACE Trials* RR of Mortality *7 RCTs, 33,960 randomized patients, and 4.4 years of mean follow-up. Other findings include a CV mortality HR=0.81, MI HR=0.82, and stroke HR=0.77 ACE-I=Angiotensin converting enzyme inhihbitor, MI=Myocardial infarction ACE Inhibitor Evidence: Secondary Prevention
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Years Probability of Event ACE-I Placebo OR 0.74 (0.66–0.83) Source: Flather MD et al. Lancet 2000;355:1575–1581 SAVERadionuclideEF <40% AIREClinical and/or radiographic signs of HF TRACEEchocardiogramEF <35% ACE-I=Angiotensin converting enzyme inhibitor, EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction, OR=Odds ratio An ACE-I provides substantial benefit in post-MI LVSD ACE Inhibitor Evidence: Secondary Prevention
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An ACE inhibitor should be started and continued indefinitely in all patients with left ventricular ejection fraction <40% and in those with hypertension, DM, or CKD, unless contraindicated An ACE inhibitor in all other patients ACE=Angiotensin converting enzyme, CKD=Chronic kidney disease, DM=Diabetes mellitus, LVSD=Left ventricular systolic dysfunction Source: Smith SC Jr. et al. JACC 2011;58:2432-2446 ACE Inhibitor Recommendations Secondary Prevention
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Source: Buse JB et al. Circulation 2007;115:114-126 Patients with a SBP >140 mm Hg or DBP >90 mm Hg should receive drug therapy in addition to lifestyle and behavioral therapy. All patients with hypertension should be treated with a regimen that includes an ACE inhibitor or an ARB. If one class is not tolerated, the other should be substituted. Other drug classes* that have been demonstrated to reduce CVD events should be added as needed to achieve BP targets. If ACE inhibitors, ARBs, or diuretics are used, renal function and serum potassium levels should be monitored within the first 3 months. If stable, follow-up could occur every 6 months. ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, BP=Blood pressure, CV=Cardiovascular, CVD=Cardiovascular disease, DBP=Diastolic blood pressure, DM=Diabetes mellitus, SBP=Systolic blood pressure *Includes beta-blockers, thiazide diuretics, and calcium channel blockers AHA Primary Prevention of CV Disease in DM Blood Pressure Recommendations Primary Prevention
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If an ACE inhibitor, ARB, or diuretic is used, kidney function and serum potassium levels should be closely monitored. In pregnant patients with DM and chronic hypertension, BP target goals of 110-129/65-79 mm Hg are suggested in the interest of long-term maternal health and minimizing impaired fetal growth. An ACE inhibitor and ARB are contraindicated during pregnancy. Source: American Diabetes Association. Diabetes Care 2010;33:S11-61 ACE=Angiotensin converting enzyme, ADA=American Diabetes Association, ARB=Angiotensin receptor blocker, BP=Blood pressure, DM=Diabetes mellitus ADA Blood Pressure Recommendations for Patients with Diabetes Mellitus (Continued) Primary Prevention
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Angiotensin Receptor Blocker Evidence and Guidelines Evidence for Current Cardiovascular Disease Prevention Guidelines
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Receptors AT II Receptor Blocker Antiproliferative Action Vasodilation Proliferative Action Vasoconstriction ATII ATI Angiotensinogen Other Pathways Renin AT I Receptor Blocker Angiotensin I Angiotensin II ACE Angiotensin Receptor Blocker: Mechanism of Action
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2,028 patients with symptomatic HF, LVSD (EF <40%), and intolerance to ACE inhibitor randomized to candesartan (32 mg) or placebo for 34 months An ARB provides benefit in those intolerant of an ACE inhibitor 0 1 2 3 Years 50 HR 0.77 p=0.0004 0 40 30 20 10 Candesartan Placebo Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) Alternative Trial Source: Granger CB et al. Lancet 2003;362:772-777 ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, CV=Cardiovascular, EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction CV Death or Hospitalization for HF Angiotensin Receptor Blocker Evidence: Secondary Prevention
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Source: Pfeffer M et al. NEJM 2003;349:1893-1906 Valsartan in Acute Myocardial Infarction Trial (VALIANT) 0.0 0.1 0.2 0.3 0.4 0 6 12 18 24 30 36 Valsartan Valsartan and Captopril Captopril All Cause Mortality Months Valsartan vs. Captopril: HR = 1.00; P = 0.982 Valsartan + Captopril vs. Captopril: HR = 0.98; P = 0.726 ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction Angiotensin Receptor Blocker Evidence: Secondary Prevention 14,703 patients with post-MI HF or LVSD (EF <0.40) randomized to captopril (50 mg tid), valsartan (160 mg bid), or captopril (50 mg tid) plus valsartan (80 mg bid) for 2 years An ARB provides similar efficacy to an ACE inhibitor in Post-MI LVSD
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0 1 2 3 0 10 20 30 40 50 HR 0.85, p=0.011 Candesartan Placebo CV Death or Hospitalization for HF Years Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) Added Trial ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction Source: McMurray JJ et al. Lancet 2003;362:767-771 Angiotensin Receptor Blocker Evidence: Secondary Prevention 2,548 patients with symptomatic HF and LVSD (EF <40%) randomized to candesartan (32 mg) or placebo in addition to an ACE inhibitor for 34 months Addition of an ARB to an ACE inhibitor may provide benefit in those with LVSD
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Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) Source: ON TARGET Investigators. NEJM 2008;358:1547-1559 ACE-I=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker, CVD=Cardiovascular disease, DM=Diabetes mellitus, MI=Myocardial infarction Angiotensin Receptor Blocker Evidence: Secondary Prevention 25,620 patients with CVD or DM randomized to ramipril (10 mg), telmisartan (80 mg), or a combination of both for 56 months An ARB provides similar efficacy to an ACE-I in high risk patients
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Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) Source: ON TARGET Investigators. NEJM 2008;358-1547-1559 CVD=Cardiovascular disease, DM=Diabetes mellitus, MI=Myocardial infarction, RAS=Renin angiotensin system CV Death, MI, Stroke, or Hospitalization for Heart Failure 0.20 0.15 0.10 0.05 0.00 0 1 2 3 4 5 Follow-up (years) Telmisartan Ramipril Telmisartan plus ramipril* *Dual RAS blockade leads to greater renal impairment HR=1.33 (p<0.001) Angiotensin Receptor Blocker Evidence: Secondary Prevention 25,620 patients with CVD or DM randomized to ramipril (10 mg), telmisartan (80 mg), or a combination of both for 56 months Dual RAS blockade provides no additional benefit but leads to greater renal impairment
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Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (TRANSCEND) Percent of patients P=0.216 P=0.048 P=0.055 Source: TRANSCEND Investigators. Lancet. 2008;372:1174-83 *Primary endpoint is a composite of CV death, MI, stroke or heart failure hospitalization Angiotensin Receptor Blocker Evidence: Secondary Prevention * ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, CV=Cardiovascular, MI=Myocardial infarction 5,926 high risk patients intolerant to ACE inhibitors randomized to telmisartan (80 mg) or placebo for 56 months An ARB is well tolerated in those unable to take an ACE inhibitor
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An ARB in patients who have HF or who have had a MI with left ventricular ejection fraction <40% and who are ACE-inhibitor intolerant An ARB in other patients who are intolerant of an ACE inhibitor Use of an ARB in combination with an ACE inhibitor is not well established in those with systolic heart failure ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, HF=Heart failure, MI=Myocardial infarction Source: Smith SC Jr. et al. JACC 2011;58:2432-2446 Angiotensin Receptor Blocker Recommendations Secondary Prevention
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Source: Buse JB et al. Circulation 2007;115:114-126 Patients with a SBP >140 mm Hg or DBP >90 mm Hg should receive drug therapy in addition to lifestyle and behavioral therapy. All patients with hypertension should be treated with a regimen that includes an ACE inhibitor or an ARB. If one class is not tolerated, the other should be substituted. Other drug classes* that have been demonstrated to reduce CVD events should be added as needed to achieve BP targets. If ACE inhibitors, ARBs, or diuretics are used, renal function and serum potassium levels should be monitored within the first 3 months. If stable, follow-up could occur every 6 months. ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, BP=Blood pressure, CV=Cardiovascular, CVD=Cardiovascular disease, DBP=Diastolic blood pressure, DM=Diabetes mellitus, SBP=Systolic blood pressure *Includes beta-blockers, thiazide diuretics, and calcium channel blockers AHA Primary Prevention of CV Disease in DM Blood Pressure Recommendations Primary Prevention
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If an ACE inhibitor, ARB, or diuretic is used, kidney function and serum potassium levels should be closely monitored. In pregnant patients with DM and chronic hypertension, BP target goals of 110-129/65-79 mm Hg are suggested in the interest of long-term maternal health and minimizing impaired fetal growth. An ACE inhibitor and ARB are contraindicated during pregnancy. Source: American Diabetes Association. Diabetes Care 2010;33:S11-61 ACE=Angiotensin converting enzyme, ADA=American Diabetes Association, ARB=Angiotensin receptor blocker, BP=Blood pressure, DM=Diabetes mellitus ADA Blood Pressure Recommendations for Patients with Diabetes Mellitus (Continued) Primary Prevention
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Beta-blocker Evidence and Guidelines Evidence for Current Cardiovascular Disease Prevention Guidelines
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Parasympathetic Nerve Terminal Sympathetic Cholinergic Nerve Terminal a1 M2 M2 M2 a1 b2 b2 b2 b1 a2 a2 a2 NE ACh Sympathetic Nerve Terminal + + + _ NE NE _ + _ _ Heart Blood Vessel Inotropy Chronotropy Dromotropy Vasoconstriction Vasoconstriction Vasodilation Vasodilation b1 selective blocker b non-selective blocker b non-selective blocker with a1 blocking activity a=Alpha receptor, Ach=Acetylcholine, b=Beta receptor, M=Muscarinic receptor, NE=Norepinephrine Source: Klabunde, RE (ed) Cardiovascular Physiology Concepts LWW 2001 Beta-blocker: Targets and Receptor Selectivity
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Placebo-controlled post-MI trials* using oral beta-blockers *Includes the largest trials performed to date †Patients received IV followed by oral metoprolol MI=Myocardial infarction, NA=Not applicable, NS=Not significant Beta-blocker Evidence: Secondary Prevention
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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 Beta-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) Source: 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 beta-blocker therapy CI=Confidence interval, RR=Relative risk Beta-blocker Evidence: Secondary Prevention
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*Not an approved indication, †Not a planned end point #Not approved for severe HF/mortality reduction alone HF=Heart failure, LVSD=Left ventricular systolic dysfunction, NS=Not significant, TX=Transplant Beta-blocker Evidence: Benefit in HF and/or LVSD
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Beta-blocker should be used in all patients with LVSD (ejection fraction <40%) with HF or prior MI, unless contraindicated*. (Use should be limited to carvedilol, metoprolol succinate, or bisoprolol, which have been shown to reduce mortality.) Beta-blocker for 3 years in all patients with normal left ventricular function who have had a MI or ACS Beta-blocker beyond 3 years as chronic therapy in all patients with normal left ventricular function who have had a MI or ACS *Relative contraindications include asthma, chronic obstructive pulmonary disease, insulin dependent diabetes mellitus, severe peripheral arterial disease, and a PR interval >0.24 seconds ACS=Acute coronary syndrome, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction Source: Smith SC Jr. et al. JACC 2011;58:2432-2446 Beta-Blocker Recommendations Secondary Prevention
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Beta-blocker in patients with LVSD (ejection fraction <40%) without HF or prior MI Beta-blocker as chronic therapy for all other patients with coronary or other vascular disease HF=Heart failure, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction Source: Smith SC Jr. et al. JACC 2011;58:2432-2446 Beta-Blocker Recommendations (Continued) Secondary Prevention