Hypertension: Improving Treatment and Control

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Hypertension: Improving Treatment and Control

  1. 1. Improving Blood Pressure Treatment in the Community: Implications of the JNC7 Recommendations and ALLHAT Results Nathan D. Wong, PhD, FACC Professor and Director Heart Disease Prevention Program University of California, Irvine
  2. 2. Hypertension: A Significant CV and Renal Disease Risk Factor Peripheral vascular disease  Morbidity  Disability Renal disease CAD CHF LVH Stroke Hypertension National High Blood Pressure Education Program Working Group. Arch Intern Med. 1993;153:186-208.
  3. 3. At Least 65 Million Americans Require Treatment for Hypertension Nearly 1 in 3 adults (31%) in the US has hypertension Fields LE et al. Hypertension . 2004;44:398-404. Hypertension: How Big Is the Problem?
  4. 4. Risk of Cardiovascular Events by Hypertensive Status 36-Year Follow-up in Patients Aged 35-64 Years 9.5 3.3 2.4 5.0 2.0 3.5 2.1 45.4 21.3 12.4 6.2 9.9 7.3 13.9 6.3 22.7 0 10 20 30 40 50 Normotensive Hypertensive Coronary Disease Stroke Peripheral Arterial Disease Cardiac Failure Biennial Age-Adjusted Rate per 1,000 Reprinted with permission from Kannel WB. JAMA. 1996;275:1571-1576. Men Women Men Women Men Women Men Women
  5. 5. SBP-Associated Risks: MRFIT Adapted from Neaton JD et al. Arch Intern Med . 1992;152:56-64 . SBP versus DBP in Risk of CHD Mortality Diastolic BP (mm Hg) Systolic BP (mm Hg) CHD Death Rate 100+ 90–99 80–89 75–79 70–74 <70 <120 120–139 140–159 160+ 48.3 20.6 10.3 11.8 8.8 8.5 9.2 23.8 16.9 13.9 12.8 12.6 11.8 31.0 25.5 24.6 25.3 25.2 24.9 37.4 34.7 43.8 38.1 80.6
  6. 6. <40 40-49 50-59 60-69 70-79 80+ Age (y) 17% 16% 16% 20% 20% 11% Distribution of Hypertension Subtype in the untreated Hypertensive Population in NHANES III by Age Numbers at top of bars represent the overall percentage distribution of untreated hypertension by age. Franklin et al. Hypertension 2001;37: 869-874 . Frequency of hypertension subtypes in all untreated hypertensives (%) ISH (SBP  140 mm Hg and DBP <90 mm Hg) SDH (SBP  140 mm Hg and DBP  90 mm Hg) IDH (SBP <140 mm Hg and DBP  90 mm Hg) 0 20 40 60 80 100
  7. 7. <ul><li>Disease Relative Risk </li></ul><ul><li>Kidney failure (ESRD)  2.8 </li></ul><ul><li>Stroke  2.7 </li></ul><ul><li>Heart failure  1.5 </li></ul><ul><li>Peripheral vascular disease  1.8 </li></ul><ul><li>Myocardial infarction* =1.6 </li></ul><ul><li>Coronary artery disease  1.5 </li></ul>Elevated SBP Alone Is Associated With Increased Risk of Cardiovascular and Renal Disease ESRD = end-stage renal disease; SBP  165 mm Hg. *Men only. Adapted from Kannel WB. Am J Hypertens . 2000;13:3S-10S; Perry HM Jr et al. Hypertension. 1995;25(part 1):587-594; Klag MJ et al. N Engl J Med . 1996;334:13-18; Nielsen WB et al. Ugeskr Laeger . 1996;158:3779-3783; Neaton JD et al. Arch Intern Med . 1992;152:56-64.
  8. 9. Prevalence, Awareness, Treatment, and Control of Hypertension in US Adults 2003-2004 (Ong et al., Hypertension 2007; 49: 69-75)
  9. 10. Prevalence (%) of HTN in US Adults, by Disease Status (Wong et al, Arch Intern Med 2007, in press) **P <0.01 when compared to No-Disease Group ** ** ** ** ** ** ** Mean age (y): 53.5 59.3 54.8 60.5 76.1 65.9 68.2 69.3 67.2 **
  10. 11. Treatment (%) of HTN in US Adults, by Disease Status (Wong et al., Arch Intern Med 2007, in press) *P<0.05, **P <0.01 when compared to No-Disease group Treatment is in persons with HTN ** ** ** **
  11. 12. Control (all treated) (%) of HTN in US Adults, by Disease Status (Wong et al., Arch Intern Med 2007, in press) **P<0.05**P<0.01 when compared to No-Disease Group Control is in persons with HTN defined as BP < 140/90 If DM and CKD is based on BP<130/80 control is **35.3% and **23.2%, respectively. If MetS is based on BP<130/85 control is **46.7% * ** ** **
  12. 13. Minimum BP distance from goal of < 140/90 in parenthesis, even with DM & CKD *p<0.05 **p<0.01 compared to no disease Mean BP and Distance to Goal Among HTN Pts Not at Goal (Wong et al., Arch Intern Med 2007, in press) 90* (7) 154 (19) Dyslipidemia 90 (6) 155 (21*) CAD 89* (7) 157 (23** ) PAD 89** (6) 154 (22**) CHF 87** (6) 155 (22* ) Stroke 87** (7**) 155 (18 ) CKD 87** (6) 149* (14) DM 94 (5) 154 (16) MetS 93 (3) 154 (14) No Disease DBP mm Hg (Distance to Goal) SBP mm Hg (Distance to Goal)
  13. 14. Blood Pressure Classification <80 and <120 Normal 80–89 or 120–139 Prehypertension 90–99 or 140–159 Stage 1 HTN > 100 or > 160 Stage 2 HTN DBP mmHg SBP mmHg BP Classification
  14. 15. 4-Year Progression To Hypertension: The Framingham Heart Study (<120/80 mm Hg) (130/85 mm Hg) (130-139/85-89 mm Hg) Vasan, et al. Lancet 2001;358:1682-86 Participants age 36 and older
  15. 16. HOT Study: Significant Benefit From Intensive Treatment in the Diabetic Subgroup Hansson L et al. Lancet. 1998;351:1755-1762. 0 5 10 15 20 25  90  85  80 Major cardiovascular events/1,000 patient-years p =0.005 for trend mm Hg Target Diastolic Blood Pressure
  16. 17. Benefits of Lowering BP Average Percent Reduction Stroke incidence 35–40% Myocardial infarction 20–25% Heart failure 50% TROPHY Study ACC 2006: Even lowering BP in those with pre-HTN appears to reduce incidence of new HTN by up to 60%
  17. 19. Preventable CHD Events from Control of Hypertension in US Adults (Wong et al., Am Heart J 2003; 145: 888-95) PAR% = population attributable risk (proportion of CHD events preventable), NNT = number needed to treat to prevent 1 CHD event ; <0.01 comparing men and women for PAR%
  18. 20. Randomized Design of ALLHAT High-risk hypertensive patients Consent / Randomize (42,418) Amlodipine Chlorthalidone Doxazosin Lisinopril Eligible for lipid-lowering Not eligible for lipid-lowering Consent / Randomize (10,355) Pravastatin Usual care Follow for CHD and other outcomes until death or end of study (up to 8 yr). ALLHAT
  19. 21. Baseline Characteristics and Follow-up 82% Known alive 42,418 N 36 Type 2 diabetes, % 92 On antihypertensive treatment, % Person-years (% obs/exp) Lost / refused Confirmed dead Follow-up 15% 146 / 84 Mean SBP/DBP 26 History of CHD, % 22 Current smoking % 47 Women, % 99% 36 Black, % 3% 67 Mean age, y Baseline ALLHAT
  20. 22. Doxazosin Arm Terminated Early <ul><li>Futility of finding a significant difference for primary CHD outcome </li></ul><ul><li>Statistically significant 20 percent higher rate of major secondary endpoint, combined CVD outcomes (80% higher rate of heart failure) </li></ul>Hypertension. 2003;42:239-246. ALLHAT
  21. 23. BP Results by Treatment Group Compared to chlorthalidone: SBP significantly higher in the amlodipine group ( ~ 1 mm Hg) and the lisinopril group ( ~ 2 mm Hg). Compared to chlorthalidone: DBP significantly lower in the amlodipine group ( ~ 1 mm Hg), similar in the lisinopril group. ALLHAT
  22. 24. Cumulative Event Rates for the Primary Outcome (Fatal CHD or Nonfatal MI) by ALLHAT Treatment Group Chlorthalidone Amlodipine Lisinopril Years to CHD Event 0 1 2 3 4 5 6 7 Cumulative CHD Event Rate 0 .04 .08 .12 .16 .2 0.81 0.99 (0.91-1.08) L/C 0.65 0.98 (0.90-1.07) A/C p value RR (95% CI) ALLHAT
  23. 25. Subgroup Comparisons <ul><li>Results were consistent across age, race, gender, and baseline diabetes subgroups, except: </li></ul><ul><ul><li>Stroke </li></ul></ul><ul><ul><ul><li>Black L/C RR (95% CI) = 1.40 (1.17 – 1.68) </li></ul></ul></ul><ul><ul><ul><li>Non-Black L/C RR (95% CI) = 1.00 (0.85 – 1.17) </li></ul></ul></ul><ul><ul><li>Combined CVD </li></ul></ul><ul><ul><ul><li>Black L/C RR (95% CI) = 1.19 (1.09 – 1.30) </li></ul></ul></ul><ul><ul><ul><li>Non-Black L/C RR (95% CI) = 1.06 (1.00 – 1.13) </li></ul></ul></ul>ALLHAT
  24. 26. Nonfatal MI + CHD Death – Subgroup Comparisons – RR (95% CI) Amlodipine Better Chlorthalidone Better 0.50 1 2 Non-Diabetic 0.97 (0.86, 1.09) Diabetic 0.99 (0.87, 1.13) Non-Black 0.97 (0.87, 1.08) Black 1.01 (0.86, 1.18) Women 0.99 (0.85, 1.15) Men 0.98 (0.87, 1.09) Age>=65 0.97 (0.88, 1.08) Age <65 0.99 (0.85, 1.16) Total 0.98 (0.90, 1.07) Lisinopril Better Chlorthalidone Better 0.50 1 2 Non-Diabetic 0.99 (0.88, 1.11) Diabetic 1.00 (0.87, 1.14) Non-Black 0.94 (0.85, 1.05) Black 1.10 (0.94, 1.28) Women 1.06 (0.92, 1.23) Men 0.94 (0.85, 1.05) Age >= 65 1.01 (0.91, 1.12) Age < 65 0.95 (0.81, 1.12) Total 0.99 (0.91, 1.08) ALLHAT
  25. 27. Predicted Cause-specific Mortality for 2 mm Hg lower SBP <ul><li>CHD -4 to -7% </li></ul><ul><li>Stroke -4 to -10% </li></ul><ul><li>Heart failure -5 to -7% </li></ul><ul><li>Higher numbers for younger hypertensives </li></ul>Prospective Studies Collaboration, Lancet 2002;360:1903-13
  26. 28. Summary of Outcomes Relative Risks and 95% CI 0.99 (0.91, 1.08) 0.98 (0.91, 1.08) CHD Lisinopril / Chlorthalidone Amlodipine / Chlorthalidone 1.19 (1.07, 1.31) 1.38 (1.25, 1.52) HF 1.10 (1.05, 1.16) 1.04 (0.99, 1.09) CCVD 1.15 (1.02, 1.30) 0.93 (0.82, 1.06) Stroke 1.05 (0.98, 1.11) 1.00 (0.94, 1.07) CCHD 1.00 (0.94, 1.08) 0.96 (0.89, 1.02) Death Amlodipine Chlorthalidone Better Better 0.50 1 2 Lisinopril Chlorthalidone Better Better 0.50 1 2 ALLHAT
  27. 29. Fasting Glucose Results * p<.05 compared to chlorthalidone Serum fasting glucose – mmol/L, mean (sd) 11.6% 4 Years Diabetes Incidence (follow-up fasting glucose  126 mg/dL) 8.1%* 9.8%* 104.4 (28.5) 4 Years 93.1 (11.7) Baseline Among baseline nondiabetics with baseline <126 mg/dL – mean (SD) 93.3 (11.8) 93.0 (11.4) 100.5 (19.5)* 103.1 (27.7) Lisinopril Amlodipine Chlorthalidone ALLHAT
  28. 30. <ul><li>Outcome results were similar in diabetic and nondiabetic participants </li></ul><ul><li>For both diabetic and nondiabetic participants, there were significant advantages for the diuretic arm </li></ul>ALLHAT Results by Baseline Diabetic Status ALLHAT
  29. 31. Effect of 2-Year Changes in Fasting Glucose on ALLHAT Endpoints (Cox Regressions Beginning at 2 Years) 0.988 0.939 – 1.066 1.000 Heart failure 0.561 0.921 – 1.164 1.035 ESRD Per 10-Unit of Increase in Fasting Glucose (Baseline to 2 Years) 0.664 0.948 – 1.035 0.990 Total mortality 0.836 0.971 – 1.036 1.003 CCVD 0.727 0.909 – 1.069 0.986 Stroke 0.824 0.968 – 1.042 1.004 CCHD 0.327 0.979 – 1.066 1.022 CHD P 95% CI Hazard Ratio Endpoint ALLHAT
  30. 32. Diuretics, Potassium, and Glucose <ul><li>Based on 40+ years’ evidence, potassium depletion is a major factor relating thiazide treatment and abnormal glucose. </li></ul><ul><li>Both reduced insulin release and decreased insulin sensitivity have been demonstrated. </li></ul><ul><li>More attention than is often given to preventing or reversing hypokalemia is warranted, especially in patients at risk of diabetes. </li></ul><ul><li>Reference: Wilcox CS. Seminars in Nephrology, 1999;19:557-68. </li></ul>
  31. 33. Large Hypertension Trials Comparing Two or More Regimens: CVD or CV Mortality <ul><li>Trial n BP Δ Outcomes </li></ul><ul><li>CAPPP 10,985 +3/+1 captopril not superior to D/BB </li></ul><ul><li>NORDIL 10,881 +3/0 diltiazem not superior to D/BB </li></ul><ul><li>CONVINCE 16,602 0/+1 verapamil not superior to D/BB </li></ul><ul><li>STOP-2 6,628 0/-1 isradipine/felodipine & </li></ul><ul><li> 0/0 ACEIs not superior to D/BB </li></ul><ul><li>INSIGHT 6,592 0/0 nifed GITS not superior to diuretic </li></ul><ul><li>LIFE 9,193 +1/0 losartan superior to atenolol </li></ul><ul><li>ANBP-2 6,083 +1/0 ACEIs not superior to diuretics </li></ul><ul><li>ALLHAT 42,418 -3/-1 chlorthalidone superior to doxazosin , </li></ul><ul><li> -1/+1,-2/ 0 amlodipine (HF only), lisinopril </li></ul><ul><li>INVEST 22,576 0/ 0 verapamil ( + trandolapril) equivalent </li></ul><ul><li>to atenolol ( + HCTZ) </li></ul><ul><li>VALUE 15,313 +2/+2 valsartan not superior to amlodipine </li></ul>
  32. 36. Large, controlled trials have shown similar mortality or morbidity reductions with: Bendrofluazide (MRC) Chlorthalidone (SHEP, HDFP) Hydrochlorothiazide (VA, Oslo, Australian) Indapamide (PATS, PROGRESS) HCTZ/amiloride (MRC-O, STOP-H) HCTZ/triamterene (EWPHE) Conclusion Independent trial findings support the view that all thiazide diuretics are beneficial
  33. 37. ACEIs and ARBs Reduce Cardiovascular Morbidity and Mortality angiotensin-converting enzyme inhibitors (ACEI); angiotensin receptor blocker (ARB); myocardial infarction (MI); cardiovascular (CV); heart failure (HF); left ventricular hypertrophy (LVH). Yusuf S et al. N Engl J Med . 2000;342:145-153; The CONSENSUS Trial Study Group. N Engl J Med . 1987;316:1429-1435; The SOLVD Investigators. N Engl J Med. 1991;325:293-302; Granger CB et al. Lancet . 2003;362:772-776; Dahlof B et al. Lancet. 2002;359:995-1003; Cohn JN et al. N Eng J Med. 2001;345:1667-1675. HOPE CONSENSUS Placebo (n=4652) Ramipril (n=4645) Placebo (n=126) Enalapril (n=127) LIFE Atenolol (n=4588) Losartan (n=4605) CHARM-Added MI, stroke, or CV death in high-risk patients Total mortality in severe HF Death, MI, or stroke in patients aged 55–80 years with hypertension and LVH Relative Risk Reduction, % CV death or HF hospitalization in patients with chronic HF Placebo (n=1272) Candesartan (n=1276) ACEIs SOLVD Placebo (n=1284) Enalapril (n=1285) Mortality in chronic HF Val-Heft Valsartan (n=2511) Placebo (n=2499) All cause mortality and morbidity in patients with HF ARBs – 40 – 30 – 20 – 10 0
  34. 38. Implications for Your Practice and Your Patients <ul><li>The blood pressure goal for most patients with hypertension is <140/90 mm Hg. </li></ul><ul><li>Initial drug therapy for most should be either thiazide-type diuretic alone or combined with other drug classes. </li></ul><ul><li>Most patients with uncontrolled Stage 1 or Stage 2 hypertension should experience better blood pressure control and better long term CVD risk when the medication regimen includes a thiazide-type diuretic. </li></ul>
  35. 39. Algorithm for Treatment of Hypertension Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease) Initial Drug Choices Lifestyle Modifications Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. With Compelling Indications Stage 2 Hypertension (SBP > 160 or DBP > 100 m mHg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB) Stage 1 Hypertension (SBP 140 –159 or DBP 90–99 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Without Compelling Indications Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist.
  36. 40. AHA Scientific Statement Recommendations: General CVD Prevention, High CAD Risk, Stable and Unstable Angina, NSTEMI, STEMI, LVD (Circulation 2007; 115: 2761-2788)
  37. 41. AHA 2007 Statement Recommendations <ul><li>A target BP of <130/80 mmHg is reasonable for individuals with any of the following (Class IIa, level of evidence B): </li></ul><ul><ul><li>Diabetes mellitus </li></ul></ul><ul><ul><li>Chronic renal disease </li></ul></ul><ul><ul><li>Coronary artery disease (CAD) </li></ul></ul><ul><ul><li>CAD risk equivalents </li></ul></ul><ul><ul><li>Carotid artery disease </li></ul></ul><ul><ul><li>Peripheral artery disease </li></ul></ul><ul><ul><li>Abdominal aortic aneurysms </li></ul></ul><ul><ul><li>High risk pts defined as >=10% 10-year risk from FRS </li></ul></ul>
  38. 42. Compelling Indications for Individual Drug Classes ACEI, ARB Chronic kidney disease THIAZ , ACEI Recurrent stroke prevention THIAZ , BB, ACEI, ARB, CCB Diabetes THIAZ , BB, ACEI, CCB High CAD Risk BB, ACEI, ALDO ANT Post myocardial infarction THIAZ , BB, ACEI, ARB, ALDO ANT Heart failure Initial Therapy Option Compelling Indication
  39. 43. Renin Inhibition With Aliskiren Binding of Angiotensinogen Prevented Rahuel J et al. J Struct Biol. 1991;107:227-236. <ul><li>Angiotensinogen </li></ul>Aliskiren binds to a pocket in the renin molecule, blocking angiotensinogen from being cleaved by renin
  40. 44. Aliskiren Suppresses the Entire System—Targets the Point of Activation <ul><li>(Pro)Renin Receptor </li></ul><ul><li>Actions: </li></ul><ul><li>Binding of (Pro)Renin </li></ul><ul><li>Increased renin catalytic activity </li></ul><ul><li>Activates VSMC ERK1/2 </li></ul>Renin Ang II Angiotensinogen ARBs AT 1 receptor Ang I Target cell renin-angiotensin-aldosterone system (RAAS); vascular smooth muscle cells (VSMC); extracellular singal-regulated kinases (ERK 1/2); angiotensin (Ang); angiotensin-converting enzyme (ACE); angiotensin-converting enzyme inhibitor (ACEI); angiotensin receptor blockers (ARB); type 1 angiotensin II receptor (AT 1 ) . Aliskiren <ul><li>Vasoconstriction </li></ul><ul><li>Remodelling </li></ul>Vessels Kidney Heart Aldosterone Ang III + IV ACE ACEIs Non-ACE pathways Aliskiren (Pro)Renin receptor
  41. 45. Lifestyle Modifications <ul><li>Most patients will experience better control if they modify diet and exercise. </li></ul><ul><li>Physician advice sometimes works and should always be given along with a follow-up visit appointment to monitor both blood pressure and lifestyle change efforts. </li></ul><ul><li>Most of us do not do lifestyle counseling beyond simple advice and admonishment – the time factor is a problem. </li></ul><ul><li>Nevertheless, lifestyle modification is at the top of the JNC7 algorithm. </li></ul>
  42. 47. Lifestyle Modification 2-4 mmHg Moderation of alcohol consumption 4-9 mmHg Physical activity 2-8 mmHg Dietary sodium reduction 8-14 mmHg Adopt DASH eating plan 5-20 mmHg / 10 kg weight loss Weight reduction Approximate SBP reduction (range) Modification
  43. 48. The Japanese Diet and Lifestyle
  44. 49. Keys to Physician Influence in Lifestyle Modification <ul><li>Advice giving and follow-up monitoring are a minimum (many pts are not adequately titrated to goal BP) </li></ul><ul><li>Some evidence that brief behavioral counseling aimed at matching messages to patient readiness to change and eliciting the patient’s own motivation to change can move the patient along a continuum of change </li></ul>
  45. 50. Physician Influence in Lifestyle Modification- What to Do PICM <ul><li>P ermission: Ask the patient for permission to talk about lifestyle change and get preference for beginning with diet or exercise </li></ul><ul><li>I nterest: Ask the patient about readiness to change – How interested are you on a scale of 1-10. Ask why they are not a lower number – to elicit a motivational statement from the patient. </li></ul><ul><li>C onfidence: Ask how sure they are that they can do the behavior – again ask why not a lower number </li></ul><ul><li>M atch a message to interest and confidence </li></ul>
  46. 51. Summary: For better long-term CVD risk for your patients <ul><li>Focus on blood pressure control for both SBP and DBP (<140/90 mm Hg - <130/80 for patients with diabetes or chronic renal disease) </li></ul><ul><li>Follow the JNC7 treatment guidelines: Use a thiazide-type diuretic as first line treatment and in combination for uncontrolled HTN </li></ul><ul><li>Do your part to disseminate these evidence-based guidelines </li></ul><ul><li>Make a renewed effort to encourage lifestyle change </li></ul>
  47. 52. Tools to Enhance BP Control <ul><li>For use with patients: </li></ul><ul><li>Physician-patient hypertension treatment planning pad for exam rooms </li></ul><ul><li>Poster for exam rooms </li></ul><ul><li>The DASH Eating Plan (also on CD & NHLBI.ORG) </li></ul><ul><li>Brief behavioral counseling steps and patient monitoring tools </li></ul><ul><li>For your reference: </li></ul><ul><li>Pocket card (palm format downloadable from ALLHAT.ORG) </li></ul><ul><li>ALLHAT results paper; Setting the Record Straight paper </li></ul><ul><li>Newsletter </li></ul><ul><li>JNC7 reference card (also on CD & NHLBI.ORG) </li></ul>
  48. 53. Web site www.nhlbi.nih.gov/
  49. 54. DASH Fact Sheet
  50. 55. Your Guide to Lowering Blood Pressure
  51. 56. Reference Card
  52. 57. Thank you for your attention! For more information contact the UCI Heart Disease Prevention Program at: www.heart.uci.edu 949-824-5561

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