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Practical Approaches to Managing Hypertension: Reducing Global Cardiovascular Risk Randall M. Zusman, MD Associate Professor of Medicine Harvard Medical.

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Presentation on theme: "Practical Approaches to Managing Hypertension: Reducing Global Cardiovascular Risk Randall M. Zusman, MD Associate Professor of Medicine Harvard Medical."— Presentation transcript:

1 Practical Approaches to Managing Hypertension: Reducing Global Cardiovascular Risk Randall M. Zusman, MD Associate Professor of Medicine Harvard Medical School Director Division of Hypertension and Vascular Medicine Massachusetts General Hospital Boston, Massachusetts

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 Zusman: advisory board member, research support, speakers bureau: AstraZeneca, Bristol- Myers Squibb Company, Forest Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc, sanofi-aventis Group, Sankyo Co., Ltd.

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 Hypertension and Global CV Risk

6 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:

7 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:

8 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! ?

9 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%

10 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

11 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:

12 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 Potassium Supplement Nonpharmacologic Interventions and BP Reduction Weight Loss (19.4 lb)

13 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:

14 Goal BP Recommendations for Patients With DM or Renal Disease OrganizationYear Goal BP (mm Hg) Canadian Hypertension Society2007<130/80 American Diabetes Association2006<130/80 National Kidney Foundation2004<130/80 British Hypertension Society /80 JNC 72003<130/80 World Health Organization/ International Society of Hypertension 2003<130/80 Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; NIH Publication No Available at:

15 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 and Aldo Ant = aldosterone antagonist. Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; NIH Publication No Available at:

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

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

18 Patients had hypertension and at least 1 other CHD risk factor. N = Adapted from Cushman WC et al. J Clin Hypertens. 2002;4: Baseline6 Months3 Years5 Years 1 Drug2 Drugs 3 Drugs % Controlled <140/90 mm Hg Patients (%) Year Multiple Antihypertensive Agents Needed to Achieve BP Goal: ALLHAT

19 Multiple Antihypertensive Agents Needed to Achieve BP Goal: Diabetes/Renal Impairment 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

20 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

21 Target DBP (mm Hg) Stroke, MI, or CV Death (per 1000 patient-years) 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

22 Patients with hypertension received nitrendipine enalapril or HCTZ. N = 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 With DiabetesWithout Diabetes

23 UKPDS: Tight Glucose Versus Tight BP Control and CV Outcomes 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% * * * * Patients had hypertension and type 2 diabetes. N = Bakris GL et al. Am J Kidney Dis. 2000;36:

24 Currently Available Antihypertensive Medications: Mechanism of Action Drug ClassMechanism of Action Diuretics Rid the body of excess fluids and sodium through urination May enhance the effect of other BP medications ACEIs Lower levels of angiotensin II Expand blood vessels ARBs Block angiotensin II receptors Expand blood vessels BBs Decrease heart rate and cardiac output CCBs Interrupt movement of calcium into heart and vessel cells American Heart Association. December 11, Available at:

25 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) ACEI Blood Pressure Vascular Proliferation Oxidative Stress Vascular Inflammation Thrombogenesis ARB ACE ACEIs Angiotensinogen Renin Angiotensin I Angiotensin II AT1 ARBs ARBs Kininogen Kallikrein Bradykinin Inactive Peptides Nitric Oxide

26 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 ACE Angiotensinogen Renin Angiotensin I Angiotensin II AT1 ARBs Kininogen Kallikrein Bradykinin Inactive Peptides Renin Inhibitors

27 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:

28 Val-HeFT: HF Morbidity With ARB in Patients Not Receiving ACEIs Valsartan (n = 185) Placebo (n = 181) Event-Free Probability (%) Months Risk Reduction 44% (P <.001) ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; HF = heart failure. Maggioni AP et al. J Am Coll Cardiol. 2002;40:

29 VALIANT: ARBs in Secondary Prevention Valsartan Valsartan and captopril Captopril All-Cause Mortality (probability) Months Valsartan vs captopril: HR = 1.00; P =.982 Valsartan + captopril vs captopril: HR = 0.98; P =.726 Patients had post-MI HF or LVSD (EF <0.40). N = EF = ejection fraction; LVSD = left ventricular systolic dysfunction; MI = myocardial infarction; RAS = renin-angiotensin system; VALIANT = Valsartan in Acute Myocardial Infarction Trial. Pfeffer M et al. N Engl J Med. 2003;349: Acute dual RAS blockade provides no significant benefit

30 Carvedilol n = 1511; metoprolol n = COMET = Carvedilol or Metoprolol European Trial. Poole-Wilson PA et al. Lancet. 2003;362:7-13. Time (years) COMET: Primary Endpoint of Mortality All-Cause Mortality (%) HR = % CI, P =.0017 Metoprolol Carvedilol

31 ACEI Versus Placebo: Effect on MI Patients had HF and/or LVD. Strauss MD, Hall A. Circulation. 2006;114: CONSENSUS II AIRE TRACE SOLVD-Treatment SOLVD-Prevention SAVE Total (95% CL) OR (95% CL) for the Occurrence of MI Years

32 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

33 MICRO-HOPE, PERSUADE: CV Events in Patients With 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

34 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)

35 The Data Support Global CV Risk Management CV disease remains the leading cause of death in both men and women in the United States Framingham data show that CV risk factors tend to clusterand that risk of death from CHD and stroke increases proportionately Endothelial dysfunction seems to be a key factor in the development of CV disease Recent clinical trials have given us a wealth of information with which to manage global CV risk

36 Adherence

37 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)

38 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 patients lifestyle and needs Use motivational interviewing techniques Look for: Different ways to approach patients based on individual patient attitudes Allies in patient carefamily, 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:

39 Practical Tips to Improve Adherence Use systematic approaches Disease management programs Periodic review of electronic medical records or manual chart audits Group/shared medical appointmentsblend 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:

40 Case Study

41 Case Study: 55-Year-Old Asian Man With Hypertension and Type 2 Diabetes 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

42 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! ?

43 Decision Point The patients 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! ?

44 Q & A

45 PCE Takeaways

46 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 enemydon't settle for "close enough"

47 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! ?


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