Presentation is loading. Please wait.

Presentation is loading. Please wait.

Practical Approaches to Managing Hypertension: Reducing Global Cardiovascular Risk John S. Banas, MD Professor Emeritus of Clinical Medicine Columbia University.

Similar presentations


Presentation on theme: "Practical Approaches to Managing Hypertension: Reducing Global Cardiovascular Risk John S. Banas, MD Professor Emeritus of Clinical Medicine Columbia University."— Presentation transcript:

1 Practical Approaches to Managing Hypertension: Reducing Global Cardiovascular Risk John S. Banas, MD Professor Emeritus of Clinical Medicine Columbia University College of Physicians and Surgeons New York, New York Dorothy and Lloyd Huck Chairman Emeritus Department of Cardiovascular Medicine Morristown Memorial Hospital Morristown, New Jersey

2 Key Question Which class of agents do you presently consider first-line treatment for patients with hypertension? 1. Diuretics 2. β-Blockers (BBs) 3. Calcium channel blockers (CCBs) 4. Angiotensin-converting enzyme inhibitors (ACEIs) 5. Angiotensin receptor blockers (ARBs) 6. All of the above Use your keypad to vote now! ?

3 Faculty Disclosure  Dr Banas: speakers bureau: Bristol-Myers Squibb Company, Pfizer Inc, sanofi-aventis Group; speakers bureau, consultant: King Pharmaceuticals, Inc.

4 Learning Objectives  State the prevalence of hypertension and its role in the cardiovascular disease continuum  Formulate hypertension management according to risk stratification  Describe the importance of targeting improvement in vascular function in patients with hypertension

5 Adapted from Dzau V, Braunwald E. Am Heart J. 1991;121: Progression of Cardiovascular Disease: The Cardiovascular Continuum Myocardial infarction Myocardial ischemia Endothelial dysfunction and atherothrombosis Ventricular dysfunction Ventricular dilation and hypertrophy Hyperlipidemia, HTN, diabetes, smoking, obesity, etc Congestive heart failure and death PAD Stroke SD

6 Time Adapted from Vasan RS, Levy D. Arch Intern Med. 1996;156: Death / Sudden Death Obesity Diabetes Smoking Dyslipidemia HF Overt heart failure Systolic dysfunction Diastolic dysfunction Subclinical left ventricular dysfunction Hypertension Risk Factors Atherothrombosis, left ventricular remodeling LVH ACS Progression From Hypertension to Heart Failure/Sudden Death

7 Development and Progression of Vascular Disease Dzau V. Hypertension. 2001;37: RISK FACTORS Smoking CLINICAL SEQUELAE Oxidative Stress Endothelial Dysfunction and Smooth Muscle Activation  NO  Local Mediators  Tissue ACE, AII Endothelin Catecholamines PAI-1, Platelet Aggregation, Tissue Factor VCAM/ICAM Cytokines Proteolysis Inflammation Growth Factors Cytokines Matrix VasoconstrictionThrombosis InflammationPlaque Rupture Vascular Lesion and Remodeling  BP Diabetes  LDL

8 Hypertension and Global CV Risk

9 What Is Global CV Risk?  Treating hypertension to goal is good  Addressing all CV risk factors is better  Achieve optimal BP level  Avoid CV and renal morbidity and mortality Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; NIH Publication No Available at:

10 JNC 7 Cardiovascular Risk Factors  Hypertension  Cigarette smoking  Obesity (BMI ≥30 kg/m 2 )  Physical inactivity  Dyslipidemia  Diabetes mellitus  Microalbuminuria or estimated GFR <60 mL/min  Age (men >55 yr; women >65 yr)  Family history of premature CVD Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; NIH Publication No Available at:

11 NCEP/Framingham Risk Scores: Estimate of 10-yr CHD Risk in Men Without CHD Reilly MP, Rader DJ. Circulation. 2003;108: Systolic BP Points (mm Hg)UntreatedTreated < – – –15912 ≥16023 HDL-C (mg/dL)Points ≥60–1 50– –49 1 <40 2 Age (y)20–3940–4950–5960–6970–79 Nonsmoker00000 Smoker85311 Points Total-CAge (y) (mg/dL)20–3940–4950–5960–6970–79 < – – – ≥ Point total: yr risk (%)< ≥30 Age (y)20–3435–3940–4445–4950–5455–5960–6465–6970–7475–79 Points–9–

12 Key Question What percentage of patients with hypertension have 2 or more additional CV risk factors? 1. 20% 2. 30% 3. 40% 4. 50% 5. >50% Use your keypad to vote now! ?

13 26% 25% 8% RF = risk factor. Adapted from Kannel WB. Am J Hypertens. 2000;13:3S-10S. MenWomen 2 RFs 3 RFs 1 RF No Additional RFs 4 or More RFs 27% 24% 12% 2 RFs 3 RFs 1 RF No Additional RFs 4 or More RFs >50% of Hypertension Occurs in Presence of 2 or More Risk Factors CV Risk Factor Clustering With Hypertension: Framingham Offspring, Aged 18 to 74 Years 19% 22% 17% 20%

14 Risk of CHD in Mild Hypertension by Intensity of Associated Risk Factors SBP mm Hg TC mg/dL− HDL-C mg/dL−−++++ Diabetes−−−+++ Cigarette smoking−−−−+ + ECG-LVH−−−−− Year Probability of Event (%) Adapted from Kannel WB. Am J Hypertens. 2000;13:3S-10S. Risk Factors

15 NORMAL PREHYPERTENSION STAGE 1 STAGE 2 SBP <120 mm Hg and DBP <80 mm Hg SBP mm Hg or DBP mm Hg SBP mm Hg or DBP mm Hg SBP  160 mm Hg or DBP  100 mm Hg Treatment recommended Consider treatment in those with diabetes or renal disease who fail lifestyle modification JNC 7 Classification of Blood Pressure Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; NIH Publication No Available at:

16 LIFESTYLE MODIFICATIONS Not at Goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease) Without Compelling Indications With Compelling Indications Stage 1 Hypertension Thiazide-type diuretics for most; may consider ACEI, ARB, BB, CCB, or combo Stage 2 Hypertension 2-drug combos for most (usually thiazide-type diuretics and ACEI, or ARB, or BB, or CCB) Compelling Indications Other drugs (diuretic, ACEI, ARB, BB, CCB) as needed If not at goal BP, optimize dosages or add drugs until goal BP achieved; consider consultation with hypertension specialist INITIAL DRUG CHOICES JNC 7: Algorithm for Hypertension Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; NIH Publication No Available at:

17 Adapted from: Stevens VJ et al. Ann Intern Med. 2001;134:1-11; Messerli FH et al. In: Griffin BP et al, eds Manual of Cardiovascular Medicine. 2nd ed; Whelton SP et al. Ann Intern Med. 2002;136: ; Cutler JA et al. Am J Clin Nutr. 1997;65(suppl):643S-651S; Xin X et al. Hypertension. 2001;38: ; Whelton PK et al. JAMA. 1997;277: BP Decrease (mm Hg) SBPDBP Exercise Low-Salt Diet Alcohol Reduction Nonpharmacologic Interventions and BP Reduction Weight Loss (19.4 lb)

18 Antihypertensive Medications: Mechanism of Action Drug ClassMechanism of Action Diuretics  Rid body of excess fluids and sodium  May enhance effect of other BP medications ACEIs  Lower levels of angiotensin II  Dilate blood vessels ARBs  Block angiotensin II receptors  Dilate blood vessels BBs  Decrease heart rate and cardiac output CCBs  Interrupt movement of calcium into heart and vessel cells Aldosterone Receptor Blockers  Decrease salt and water retention Renin Inhibitors  Block action of renin, decreasing formation of angiotensin I American Heart Association. December 11, Available at:http://www.americanheart.org/presenter.jhtml?identifier=

19 JNC 7: Compelling Indications for Antihypertensive Drug Classes Recommended Drugs Aldo Compelling IndicationDiureticACEI BBARBCCB ANT Heart failure Post MI High coronary disease risk Diabetes Chronic kidney disease Recurrent stroke prevention Aldo ANT = aldosterone antagonist. Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; NIH Publication No Available at:

20 Key Question On average, how many drugs will a patient need to control hypertension? Use your keypad to vote now! ?

21 Multiple Antihypertensive Agents Frequently Required to Achieve BP Goal Patients had either diabetes or renal impairment. Bakris GL et al. Am J Kidney Dis. 2000;36: ; Brenner BM et al. N Engl J Med. 2001;345: ; Lewis EJ et al. N Engl J Med. 2001;345: Average No. of BP Medications UKPDS (<150/85 mm Hg) MDRD (<92 mm Hg, MAP) HOT (<80 mm Hg, diastolic) AASK (<92 mm Hg, MAP) RENAAL (<140/90 mm Hg) IDNT (  135/85 mm Hg) 4321

22 Hypertension and Diabetes: Global CV Risk Reduction With Evidence-Based Intervention

23 Adapted from Curb JD et al. JAMA. 1996;276: ; Hansson L et al. Lancet. 1998;351: ; Tuomilehto J et al. N Engl J Med. 1999:340: DM Approximately Doubles CVD Risk in Patients With Hypertension Study Patients With Diabetes Patients Without Diabetes Ratio (events per 1000 pt-yr) SHEP CV events Stroke CHD events Syst-Eur CV events Stroke CHD events HOT (DBP <90 mm Hg) CV events

24 Patients with hypertension received nitrendipine  enalapril or HCTZ. N = DM = 492. Syst-Eur = Systolic Hypertension in Europe; CV = cardiovascular. Adapted from Tuomilehto J et al. N Engl J Med. 1999;340: Syst-Eur: CV Protection Resulting From BP Lowering Was Greatest in Patients With Diabetes Reduction in Event Rate for Active Treatment Group (%) Overall Mortality CVD Mortality All CV Events Fatal and Nonfatal Stroke Fatal and Nonfatal Cardiac Events 0 –10 –20 –30 –70 –40 –50 41% P =.09 8% P =.55 70% P =.01 16% P =.37 62% P = % P =.02 69% P =.02 36% P =.02 –60 57% P =.06 22% P =.10 DiabeticNondiabetic

25 Target DBP (mm Hg) Stroke, MI, or CV Death (per 1000 patient-years)  80  85  P =.005 Patients with hypertension and diabetes were given baseline felodipine, plus other agents in a 5-step regimen. Study N = 18790; diabetes n = HOT = Hypertension Optimal Treatment; MI = myocardial infarction. Adapted from Hansson L et al, for the HOT Study Group. Lancet. 1998;351: HOT Study: Fewer Major CV Events in Patients With Diabetes Randomized to Lower BP Goal

26 UKPDS: Tight Glucose Versus Tight BP Control and CV Outcomes Patients had hypertension and Type 2 diabetes. N = Tight glucose control (goal <6.0 mmol/L or 108 mg/dL) Tight BP control (average 144/82 mm Hg) *P <.05 compared to tight glucose control Stroke Any Diabetic Endpoint DM Deaths Microvascular Complications Relative Risk Reduction (%) 32% 37 % 10% 32% 12% 24 % 5% 44% * * * * UKPDS = United Kingdom Prospective Diabetes Study. Bakris GL et al. Am J Kidney Dis. 2000;36:

27 Antihypertensive Medications: Mechanism of Action Drug ClassMechanism of Action Diuretics  Rid body of excess fluids and sodium  May enhance effect of other BP medications ACEIs  Lower levels of angiotensin II  Dilate blood vessels ARBs  Block angiotensin II receptors  Dilate blood vessels BBs  Decrease heart rate and cardiac output CCBs  Interrupt movement of calcium into heart and vessel cells Aldosterone Receptor Blockers  Decrease salt and water retention Renin Inhibitors  Block action of renin, decreasing formation of angiotensin 1 American Heart Association. December 11, Available at:

28 Adapted with permission from Brown NJ et al. Circulation. 1998;97: ; Endemann DH. J Am Soc Nephrol. 2004;15: The Renin-Angiotensin-Aldosterone System (RAAS)  Blood Pressure  Vascular Proliferation  Oxidative Stress  Vascular Inflammation  Thrombogenesis  Aldosterone ACE Angiotensinogen Renin Angiotensin I Angiotensin II AT1 Kininogen Kallikrein Bradykinin Inactive Peptides

29 Adapted with permission from Brown NJ et al. Circulation. 1998;97: ; Endemann DH. J Am Soc Nephrol. 2004;15: The Renin-Angiotensin-Aldosterone System (RAAS)  Blood Pressure  Vascular Proliferation  Oxidative Stress  Vascular Inflammation  Thrombogenesis  Aldosterone ACE ACEIs Angiotensinogen Renin Angiotensin I Angiotensin II AT1  ARBs  Kininogen Kallikrein Bradykinin Inactive Peptides Nitric Oxide   Renin Inhibitors

30 Adapted with permission from Brown NJ et al. Circulation. 1998;97: ; Endemann DH. J Am Soc Nephrol. 2004;15: The Renin-Angiotensin-Aldosterone System (RAAS)  Blood Pressure  Vascular Proliferation  Oxidative Stress  Vascular Inflammation  Thrombogenesis  Aldosterone ACE Angiotensinogen Renin Angiotensin I Angiotensin II AT1 ARBs Kininogen Kallikrein Bradykinin Inactive Peptides  Renin Inhibitors

31 Adapted with permission from Brown NJ et al. Circulation. 1998;97: ; Endemann DH. J Am Soc Nephrol. 2004;15: The Renin-Angiotensin-Aldosterone System (RAAS)  Blood Pressure  Vascular Proliferation  Oxidative Stress  Vascular Inflammation  Thrombogenesis  Aldosterone ACE Angiotensinogen Renin Angiotensin I Angiotensin II AT1 ARBs  Kininogen Kallikrein Bradykinin Inactive Peptides AT2

32 VALUE: Hazard Ratios for Prespecified Analyses in Patients With Hypertension at High CV Risk Favors ValsartanFavors Amlodipine Hazard Ratio Valsartan/Amlodipine Primary cardiac composite endpoint Cardiac mortality Cardiac morbidity All myocardial infarction All congestive heart failure All stroke All-cause death New-onset diabetes Patients had hypertension and were at high CV risk. VALUE = Valsartan Antihypertensive Long-term Use Evaluation. Julius S et al, for the VALUE trial group. Lancet. 2004;363:

33 Adapted with permission from Brown NJ et al. Circulation. 1998;97: ; Endemann DH. J Am Soc Nephrol. 2004;15: The Renin-Angiotensin-Aldosterone System (RAAS)  Blood Pressure  Vascular Proliferation  Oxidative Stress  Vascular Inflammation  Thrombogenesis  Aldosterone ACE ACEIs Angiotensinogen Renin Angiotensin I Angiotensin II AT1  Kininogen Kallikrein Bradykinin Inactive Peptides Nitric Oxide 

34 EUROPA Investigators. Lancet. 2003;362: ; HOPE Study Investigators. N Engl J Med. 2000;342: ; PEACE Trial Investigators. N Engl J Med. 2004;351: ; Pitt B, et al. Am J Cardiol. 2001;87: PEACE: CV Death/MI/CABG/PCI HOPE: CV Death/MI/Stroke Placebo Ramipril 10 mg Time (years) Percent % Risk Reduction HR = 0.78 (0.70–0.86) P < Time (years) Placebo Perindopril 8 mg EUROPA: CV Death/MI/Cardiac Arrest 20% Risk Reduction HR = 0.80 (0.71–0.91) P = Placebo Quinapril 20 mg Time (years) 1 4% Risk Increase HR = 1.04 (0.89–1.22) P = QUIET: All CV Events Time (years) Trandolapril 4 mg Placebo % Risk Reduction HR = 0.96 (0.88–1.06) P =.43 Percent ACEI Trials in CAD Without HF: Primary Outcomes

35 MICRO-HOPE, PERSUADE: CV Events in Patients With Diabetes MICRO-HOPE = Microalbuminuria, Cardiovascular, and Renal Outcomes (Heart Outcomes Prevention Evaluation); PERSUADE = Perindopril Substudy in Coronary Artery Disease and Diabetes. HOPE Study Investigators. Lancet. 2000;355: ; Daly CA et al. Eur Heart J. 2005;26: Follow-Up (years) Primary Outcome (%) MICRO-HOPE (n = 3577) CV death/MI/stroke Ramipril 10 mg Placebo 25% RRR P = Follow-Up (years) PERSUADE (n = 1502) CV death/MI/cardiac arrest Perindopril 8 mg Placebo 19% RRR P =.13 5

36 MICRO-HOPE: Albuminuria in Patients With Diabetes HOPE Study Investigators. Lancet. 2000;355: P =.001 P =.02 Placebo Ramipril Mean Albumin/Creatinine Ratio (urine) Time (y)

37 Multiple Mechanisms of ACEI in Cardiovascular Disease Blood pressure lowering Cardioprotective effects   Preload and afterload   LV mass   Sympathetic stimulation   Reperfusion injury  Improved myocardial remodeling Metabolic syndrome  Lipid neutral  Improved glucose metabolism  Increases adiponectin  Decreased insulin resistance Modified from: Lonn E et al. Eur Heart J Suppl. 2003;5:A43-A48. Vasculoprotective effects  Direct antiatherogenic  Enhance endogenous fibrinolysis  Inhibit platelet aggregation  Antimigratory for mononuclear cells   Matrix formation  Improve endothelial function  Antioxidant  Anti-inflammatory  Protection from plaque rupture  Improved arterial compliance and tone

38 Definition of the Metabolic Syndrome Abdominal Obesity Waist Circumference Men: >40 in (>102 cm); (>94 cm [37 in]) Women: >35 in (>88 cm); (>80 cm [32 in]) Plus Two Risk Factors  Triglycerides ≥150 mg/dL (1.7 mmol/L)  HDL cholesterol Men: <40 mg/dL (<1.0 mmol/L) Women: <50 mg/dL (<1.3 mmol/L)  BP ≥30/85 mm/Hg  Glucose ≥110 mg/dL (>6.1 mmol/L); (≥100 mg/dl) (≥5.6 mmol/L) Grundy SM et al. Circulation. 2004;109: IDF Consensus. Berlin 2005.

39 Large (Visceral/Peritoneal) Insulin-Resistant Adipocytes Metabolic Syndrome (cont’d)

40 Decreased Adiponectin* Resistin FFA* TNF-alpha* Leptin* IL-6 (CRP)* Tissue Factor* PAI-1* Retinol-binding protein Adipsin Angiotensinogen* Acylation-stimulating protein *Probable CAD Risk Factor Relationship Between Visceral Adipose Tissue and Insulin Action Banerji M et al. Am J Physiol. 1997;273:E425-E432.

41 Characteristics of the Metabolic Syndrome: NCEP-ATP III National Cholesterol Educational Program (NCEP); Adult Treatment Panel (ATP) III; Abdominal obesity Glucose intolerance/ Insulin resistance Hypertension Atherogenic dyslipidemia Proinflammatory/ Prothrombotic state Diabetes CVD

42 AHA/ACC Guidelines Update in Patients With Atherosclerotic CV Disease Medication Recommendations as Supplements* to Lifestyle Modification (TLC) (DASH, weight loss, exercise, smoking cessation):  Lipid-lowering therapy to achieve LDL-C of <100 mg/dL (optional: <70 mg/dL); non-HDL <130 mg/dL (optional: <100 mg/dL)  Antiplatelet therapy, aspirin and/or clopidogrel  Antihypertensive therapy to achieve BP of <140/90 mm Hg  <130/80 mm Hg in the patient with diabetes  Ideal BP  120/80 (JNC 7)  Hypoglycemic therapy to achieve near normal fasting glucose (HbA1C <7%) (ADA: <6.5)  ACE inhibitor  Beta-blocker  Influenza vaccine Updated from: AHA/ACC. Circulation. 2001;104: ; Braunwald E et al. J Am Coll Cardiol. 2002;40: ; Grundy SM et al. Circulation. 2004;110: ; Krumholz HM et al. Circulation. 2006;113: ; Smith S et al. J Am Coll Cardiol. 2006;47: *In the absence of specific contraindications

43 Adherence

44 CV Risk Factor Control Among Adults With Diagnosed Diabetes *LDL-C and TG not evaluated. Saydah SH, et al. JAMA. 2004;291: Fewer than half of adults with diabetes achieve treatment goals for CV risk factors A1C Level <7% Blood Pressure <130/80 mm Hg Total Cholesterol* <200 mg/dL Achieved All 3 Treatment Goals Adults (%) NHANES III, (n = 1204) NHANES (n = 370)

45 Factors Which Contribute to Poor Adherence  Lack of understanding  Dementia/senility  Side effects  Lack of discharge planning  Cost  Lack of symptoms  Complexity of Rx regimen  Poor mobility  Little or no support system Modified from: Vermeire E, et al. J Clin Pharm and Ther. 2001;26: ; Cheng JWM, et al. Pharmacotherapy. 2001;21:

46 Practical Tips to Improve Adherence  Talk to your patient  Explain the condition and why specific therapy is important  Ask about adherence  Involve the patient as a partner in treatment  Provide clear written and oral instructions  Tailor the regimen to the patient’s lifestyle and needs  Use motivational interviewing techniques  Look for  Different ways to approach patients based on individual patient attitudes  Allies in patient care—family, friends  Ways to simplify the regimen  Refill dates (if the patient has not refilled the prescription, the medication is not being taken) Ockene IS et al. J Am Coll Cardiol. 2002;40:

47 Practical Tips to Improve Adherence  Use systematic approaches  Disease management programs  Periodic review of electronic medical records or manual chart audits  Group/shared medical appointments blend care, education, social support  Other techniques  Follow-up (telephone/mail/ ) and reminder cards  Signed agreements/contracts  Self-monitoring tools (eg, tape measure, pedometer, home testing devices)  Patient assistance programs  Support patients where medication costs are a barrier to adherence Fonarow GC et al. Am J Cardiol. 2001;87: ; Ockene IS et al. J Am Coll Cardiol. 2002;40: ; NCEP ATP III. September NIH publication no ; Pfizer Helpful Answers Web site. Available at:

48 Summary: The Case for Global CV Risk Management  CV disease remains the leading cause of death in both men and women in the United States  Data from the Framingham Heart Study have demonstrated “clustering” of risk factors—and that risk of death from CHD and stroke increases further with each added risk factor  Hypertension, a pivotal risk factor for CV disease, should prompt the search for the presence of additional risk factors  Recent clinical trials have provided the “evidence” supporting a “standard of care” for the management of global CV risk

49 Case Study

50 Case Study: 55-Year-Old Man From India With Hypertension and Type 2 Diabetes The patient is in for a checkup  History  Hypertension  Type 2 diabetes  Nonsmoker  No symptoms  Physical examination  BP: 148/96 mm Hg  Height: 64"  Weight: 178 lb  BMI: 30 kg/m 2  Waist circumference: 38"  Cardiac dysfunction status: normal ventricular function (LVEF 68%)  Laboratory values  Glucose: 148 mg/dL (fasting)  A1C: 8.8%  Creatinine: 1.5 mg/dL  Urinalysis: 1+ proteinuria  Lipid profile (mg/dL): TC: 268; LDL-C: 168; HDL-C: 42; TG: 296  Medications  HCTZ 25 mg/d  Glyburide 5 mg/d

51 NCEP/Framingham Risk Scores: Estimate of 10-yr CHD Risk in Men Without CHD VBWG Systolic BP Points (mm Hg)UntreatedTreated < – – –15912 ≥16023 HDL-C (mg/dL)Points ≥60–1 50– –49 1 <40 2 Age (y)20–3940–4950–5960–6970–79 Nonsmoker00000 Smoker85311 Points Total-CAge (y) (mg/dL)20–3940–4950–5960–6970–79 < – – – ≥ Reilly MP, Rader DJ. Circulation. 2003;108: Point total: yr risk (%)< ≥30 Age (y)20–3435–3940–4445–4950–5455–5960–6465–6970–7475–79 Points–9–

52 Decision Point What is the JNC 7 goal for this patient who has hypertension, diabetes, and renal disease? 1. <120/80 mm Hg 2. <130/80 mm Hg 3. <140/80 mm Hg 4. <140/90 mm Hg Use your keypad to vote now! ?

53 Decision Point The patient’s BP is 148/96 mm Hg while taking HCTZ 25 mg/d and glyburide 5 mg/d. To bring BP down to <130/80 mm Hg, you would add a(n): 1. BB 2. CCB 3. ARB 4. ACE Use your keypad to vote now! ?

54 PCE Takeaways

55 1. Patients with hypertension often present with multiple cardiac risk factors 2. Be vigilant in your investigation of all clinical indicators 3. Creatively address patient adherence; not everyone responds to the same interventions 4. Clinical inertia is the enemy—don't settle for "close enough"

56 Key Question How important is using an antihypertensive agent with proven risk reduction (reducing morbidity and mortality) when choosing medications for your patients with hypertension? 1. Not important 2. Slightly important 3. Somewhat important 4. Extremely important Use your keypad to vote now! ?

57

58 NCEP-ATP-III. JAMA. 2001;285: Age, yPoints TotalAgeAgeAgeAgeAge Cholesterol <  AgeAgeAgeAgeAge HDL mg/dLPoints  <402 Systolic BP If If mm HgUntreatedTreated <  Point Total10-Year Risk, % <0<  17  30 6 Estimate of 10-Year Risk for Men (Framingham Point Scores) Nonsmoker00000 Smoker

59 Estimate of 10-Year Risk for Women (Framingham Point Scores) Age, yPoints TotalAgeAgeAgeAgeAge Cholesterol <  AgeAgeAgeAgeAge HDL mg/dLPoints  <402 Systolic BP If If mm HgUntreatedTreated <  Point Total10-Year Risk, % <9<  25  30 Nonsmoker00000 Smoker NCEP-ATP-III. JAMA. 2001;285:

60 RESULTS Patients experiencing the primary endpoint (CV death, MI, or cardiac arrest): 10% of patients in the placebo group 8% of patients in the perindopril group Among patients with stable CHD without apparent HF, perindopril can significantly improve outcome EUROPA = EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease. EUROPA Trial Investigators. Lancet. 2003;362: Study Design: EUROPA perindopril 8 mg/day n = 6110 STUDY N = 13,655 Patients had previous MI, angiographic evidence of CAD, coronary revascularization, or a positive stress test placebo n = 6108 Randomized; mean follow-up 4.2 years

61 HOPE = Heart Outcomes Prevention Evaluation. Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342: Study Design: HOPE Ramipril 10 mg/day n = 651 Randomized 2x2 factorial study also evaluated effects of vitamin E STUDY N = 9297 Aged  55 years Patients were at high risk for CV events (evidence of vascular disease or diabetes + 1 other CV risk factor) but did not have LVD or HF Placebo n = 826 RESULTSCV DEATHMISTROKEALL-CAUSE DEATH PLACEBO GROUP8.1%12.3%4.9%12.2% TREATMENT GROUP6.1%9.9%3.4%10.4%

62 RESULTS CV events per 1000 pt/yrs, nondiabetic patients: 9.9 for DPB goal  90 mm Hg; 9.3 for DPB goal  80 mm Hg CV events per 1000 pt/yrs, diabetic patients: 24.4 for DPB goal  90 mm Hg; 11.9 for DPB goal  80 mm Hg BP lowering is particularly beneficial in patients with DM HOT = Hypertension Optimal Treatment. Hansson L, et al, for the HOT Study Group. Lancet. 1998;351: Study Design: HOT  90 mm Hg n = 6264 Patients received the CCB felodipine 5 mg/day To reach randomized BP goal, patients were also given ACE inhibitors or beta-blockers; doses were increased as necessary STUDY N = 18,790 Aged years, DBP mm Hg Randomized to DBP goals  85 mm Hg n = 6264  80 mm Hg n = 6262

63 HOPE = Heart Outcomes Prevention Evaluation. Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342: Study Design: MICRO-HOPE (a substudy of HOPE) Ramipril 10 mg/day n = x2 factorial study also evaluated the effects of vitamin E Follow-up 4.5 years; study stopped early because of consistent benefit STUDY N = 3577 Aged  55 years Patients were at high risk for CV events and at least 1 other CV risk factor Placebo n = 1760 RESULTSCOMBINED PRIMARY OUTCOME* MICV DEATH REVASCULAR- IZATION TREATMENT GROUP  25%  22%  37%  17% *MI, stroke, or CV death

64 PEACE = Prevention of Events with Angiotensin-Converting Enzyme Inhibition PEACE Trial Investigators. N Engl J Med. 2004;351: Study Design: PEACE Trandolapril 4 mg/day n = 4158 Double blind, randomized, placebo controlled Follow-up 4.8 years STUDY N = 8290 Patients had stable CAD and normal or slightly reduced left ventricular function Placebo n = 4132 RESULTS Patients experiencing the primary endpoint (CV death, MI, or coronary revascularization): 22.5% of patients in the placebo group 21.9% of patients in the trandolapril group

65 RESULTS Patients experiencing the primary endpoint (CV death, nonfatal MI, or resuscitated cardiac arrest): 15.5% of patients in the placebo group 12.6% of patients in the perindopril group (nonsignificant) Relative magnitude was similar to the 20% risk reduction in EUROPA PERSUADE = PERindopril SUbstudy in coronary Artery Disease and diabEtes. Daly CA, et al. Eur Heart J. 2005;26: Study Design: PERSUADE (a substudy of EUROPA) perindopril 8 mg/day n = 721 STUDY N = 1502 Patients had diabetes with known CAD and no HF placebo n = 781 Randomized, double-blind Follow-up was a median of 4.3 years

66 RESULTS Quinapril did not significantly affect the overall frequency of ischemic events or the progression of coronary atherosclerosis QUIET = Quinapril Ischemic Event Trial. Pitt B, et al. Am J Cardiol. 2001;87: Study Design: QUIET quinapril 20 mg/day Study duration a mean of 27  0.3 months STUDY N = 1750 Patients did not have systolic left ventricular dysfunction Placebo

67 RESULTS: 5-year major CVD rate was lower by 34% for active treatment compared with placebo for both diabetic and nondiabetic patients Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients SHEP = Systolic Hypertension in the Elderly Program. Curb JD et al. JAMA. 1996;276: Study Design: SHEP STUDY N = 4736 Aged  60 years; SBP  160 mm Hg; DBP <90 mm Hg Pts with noninsulin-dependent diabetes n = 583; nondiabetic pts n = 4149 Active treatment: Chlorthalidone mg/d with step-up to atenolol mg/d or reserpine mg/d if needed Placebo (or antihypertensive drugs prescribed by patient’s private physician for persistently high BP) Trial was double blind, randomized, placebo controlled Follow-up 5 years

68 RESULTS In patients receiving active treatment, reductions in overall mortality, mortality from CVD, and all CV events were significantly larger among diabetic vs nondiabetic patients All CV events:  69% in diabetic vs  26% in nondiabetic patients Fatal/nonfatal strokes:  73% in diabetic vs  38% in nondiabetic patients Syst-Eur = Systolic Hypertension in Europe Tuomilehto J, et al. New Engl J Med. 1999;340: Study Design: Syst-Eur Nitrendipine mg/day with addition or substitution of enalapril 5-20 mg/day or hydrochlorothiazide mg/day or both STUDY N = 4695 Aged  60 years; SBP mm Hg; DBP <95 mm Hg; patients with diabetes n = 492 Placebo

69 RESULTS Risk reductions in group assigned to tight control vs less-tight control: 24% in diabetes-related end points 32% in deaths related to diabetes 44% in strokes 37% in microvascular end points UKPDS = United Kingdom Prospective Diabetes Study. UK Prospective Diabetes Study Group. BMJ. 1998;317: ; Bakris GL, et al. Am J Kidney Dis. 2000;36: Study Design: UKPDS Tight BP control n = 758 Randomized; median follow-up 8.4 years STUDY N = 1148 Type 2 diabetes Mean age 56 years, mean BP 160/94 mm Hg Less-tight BP control n = 390

70 RESULTS BP  with both treatments Primary endpoint (composite of cardiac mortality and morbidity) occurred in valsartan 10.6% vs amlodipine 10.4%, HR 1.04 Amlodipine effects were more pronounced in the early period BP  4.0/2.1 mm Hg in amlodipine after 1 month VALUE = Valsartan Antihypertensive Long-term Use Evaluation. Julius S, et al. Lancet. 2004;363: Study Design: VALUE Step 1: valsartan 80 mg/day Step 2: valsartan 160 mg/day n = 7649 Both regimens included HCTZ in steps 3 and 4 Further drugs could be given to achieve BP control Randomized, double-blind, parallel group comparison STUDY N = 15,245 Aged  50 years; With treated or untreated hypertension and high risk of cardiac events Step 1: amlodipine 5 mg/day Step 2: amlodipine 10 mg/day n = 7596

71 ICD-9 Code Metabolic Syndrome Abdominal Obesity Waist Circumference Men: >40 in (>102 cm); (>94 cm [37in]) Women: >35 in (>88 cm); (>80 cm [32in]) Plus Two Risk Factors  Triglycerides >150 mg/dL (1.7 mmol/L)  HDL cholesterol Men: <40 mg/dL (<1.0 mmol/L) Women: <50 mg/dL (<1.3mmol/L)  BP >130/85 mm/Hg  Glucose >110 mg/dL (>6.1 mmol/L); (≥100 mg/dl) (>5.6 mmol/L) Grundy SM et al. Circulation. 2004;109: IDF Consensus. Berlin 2005

72 Large (Visceral / Peritoneal) Insulin-Resistant Adipocytes Insulin-Resistant Adipocytes


Download ppt "Practical Approaches to Managing Hypertension: Reducing Global Cardiovascular Risk John S. Banas, MD Professor Emeritus of Clinical Medicine Columbia University."

Similar presentations


Ads by Google