managing hypertension in the elderly: how to best achieve control

1. Managing Hypertension in the Elderly: How to Best Achieve Control John R. Holman, MD, MPH Naval Hospital Camp Pendleton USAFP 2009

2. Disclaimer The opinions disclosed are those of the presenter and should not be construed as official or as reflecting the views of the Department of the Navy or the Department of Defense

3. Objectives Review the pathophysiology of hypertension in the elderly Review the benefits of treatment Relate unique aspects of management for older patients

4. Epidemiology Most common primary care diagnosis 35 million office visits per year Improved awareness, treatment and control over last 25 years 51 70 percent aware of HTN 31 59 percent treated for their HTN 10 34 percent with controlled HTN Goal is to achieve 50 percent in control More important to control SBP > 50 years

5. Epidemiology HTN affects 50 million US, 1 billion world If normotensive at 55, 90% lifetime risk to develop HTN The higher the BP, the greater the risk of MI, CHF, stroke, kidney disease. Age 40-70, BP 115/75 to 185/115 Increase in 20 mm SBP doubles CVD risk Increase in 10 mm DBP doubles CVD risk

6. BP Measurement Home BP checks Helpful >135/85 = HTN Check for accuracy Ambulatory BP Evaluate white-coat HTN etc HTN = 135/85 awake HTN = 120/75 asleep Normal BP falls 10-20% Better correlation with end-organ injury

7. Case #1 68 year Afri-Amer male Type 2 diabetes mellitus for 5 years No nephropathy No CV history On atorvastatin 80 mg and LDL is 80 BP is 148/98 last visit and now 150/98 Diagnosis? Stage 1 hypertension

8. Classification of BP Normal <120 and <80 Prehypertension – Rx for DM or CRF 120-139 or 80-89 Stage 1 Hypertension – begin Rx here 140-159 or 90-99 Stage 2 Hypertension > 160 or > 100

9. Classification Isolated systolic hypertension Systolic BP of > 140 mm Hg AND Diastolic BP < 90 mm Hg 76 percent of HTN patients Widened pulse pressure (more than 50) Independent CV risk factor Low diastolic BP (lower than 70) Independent CV risk factor

10. Pathophysiology Hypertension in the Elderly Increase in arterial stiffness (large arteries) Sympathetic activation Large arteries dilate and thicken Intimal hyperplasia Leads to increased systolic BP and widened pulse pressure CV mortality and morbidity

11. Pathophysiology Hypertension in the Elderly Increased total PVR Decrease in cardiac output Lability of BP due to decreased baroreceptor function Dysfunction of autoregulation in brain, heart and kidneys Affects choice of treatment for HTN

12. Pathophysiology Hypertension in the Elderly Average BP 65-94 years old Men = 133 +/- 19 / 77 +/- 11 Women = 134 +/- 19 / 76 +/- 10 White coat hypertension Occurs in 42 % of patients over 65 Hypertension at an outpatient clinic and documented BP readings below 134/90 out of clinic Prognosis and end-organ damage same as normotensive patients

13. Pathophysiology Hypertension in the Elderly Pseudohypertension Advanced arterial stiffness Arteries not compressed by arm cuff BP readings higher than direct Osler’s sign Pump arm cuff and feel brachial artery If palpable but without beats, may indicate pseudohypertension Difficult to reproduce

14. Treatment Goals of therapy Reduce CV and renal morbidity and mortality Reduce vascular dementia in elders Focus on reducing SBP Goal is <140/90, <130/80 with diabetes, renal disease

15. Benefits of Therapy Treatment decreases Stroke by 35-40% MI by 20-25% CHF by 50% NNT for stage 1 11 patients in 10 years with a 12 mm decrease in SBP to prevent 1 death. NNT with CVD etc. 9 patients

16. Evidence for Elderly and ISH Treat 19 for 5 years Prevent 1 CV event Treat 50 for 5 years Prevent 1 CV death Treat 63 for 5 years Prevent 1 all cause death May not hold true for the old-old. HYVET study of HTN in patients over 80 is ongoing. Analysis of 1st year of data showed 19 strokes prevented with the cost of 20 extra all cause deaths. Stroke rate RRR 34% for over 80s, Nonfatal CV events RRR 22%, HF RRR is 39% - 1999 meta analysis of RCTs. Increase in all cause death by 6% (non statistically significant)May not hold true for the old-old. HYVET study of HTN in patients over 80 is ongoing. Analysis of 1st year of data showed 19 strokes prevented with the cost of 20 extra all cause deaths. Stroke rate RRR 34% for over 80s, Nonfatal CV events RRR 22%, HF RRR is 39% - 1999 meta analysis of RCTs. Increase in all cause death by 6% (non statistically significant)

17. Benefits of Therapy

18. Treatment Treatment goals in elderly Controversial – How low is too low? HOT trial – 1998 (mean age 61.5) Best effect at 130-140/80-85 SHEP trial – 2000 (mean age 71.6) No increase stroke protection from 150-140 SBP DBP <55 – twice the rate of CV events PATE-Hypertension – 2000 SBP <130 – increase CV events

19. Ogihara et al. Guidelines for treatment of hypertension in the elderly - 2002 revised version. Hypertens Res 2003;26:1-36. Treatment Possible goals Patients with overt CAD – lower BP Patients with diabetic nephropathy – more MIs if DBP lower than 85.Patients with overt CAD – lower BP Patients with diabetic nephropathy – more MIs if DBP lower than 85.

20. Case #1 68 year Afri-Amer male Type 2 diabetes mellitus for 5 years No nephropathy No CV history On atorvastatin 80 mg and LDL is 80 BP is 148/98 last visit and now 150/98 Treatment? Lifestyle, medications

21. Treatment Lifestyle modifications Weight reduction - C DASH eating plan (rich in K+ and Ca++) www.nhlbi.nih.gov - A Reduce dietary sodium Increase physical activity - A Moderate alcohol consumption Smoking cessation - A DASH eating plan is similar to monotherapy for BP reduction Has not been shown in RCTs to decrease risk of death or major CV events. May not be cost effective, when considering indirect costs > $50,000 per year of life saved. Has not been shown in RCTs to decrease risk of death or major CV events. May not be cost effective, when considering indirect costs > $50,000 per year of life saved.

22. Treatment Paced breathing 14/8 mm Hg reduction after 4 weeks Evidence – Case reports Uncontrolled studies Not better than placebo with T2DM All studies small Very low risk!

23. Treatment Pharmacologic treatment These meds have been shown to work ACE inhibitors Thiazide diuretics Beta blockers Calcium channel blockers Angiotensin-receptor blockers

24. Treatment Thiazide diuretics Basis of most outcome trials “Unsurpassed in preventing CV complications of HTN.” – JNC VII Enhance the efficacy of multidrug regimens Do not widen pulse pressure in ISH Affordable but underused 2004 meta analysis by Psaty – no difference in HCTZ vs chlorthalidone HCTZ 12.5-50 mg, no benefit in higher doses, increase electrolyte problems2004 meta analysis by Psaty – no difference in HCTZ vs chlorthalidone HCTZ 12.5-50 mg, no benefit in higher doses, increase electrolyte problems

25. Treatment First line medications – uncomplicated hypertension THIAZIDE DIURETICS!!! Consider ACE Inhibitor ARB CCB Beta-blocker Combination Especially good for African Americans and patients over 65.Especially good for African Americans and patients over 65.

26. Treatment Second line medications THIAZIDE DIURETICS!!! Addition of ACE Inhibitor ARB CCB Beta-blocker Consider 2 drugs initially when BP is more than 20/10 above goal

27. Treatment Trials ALLHAT – Double blind RCT Sponsored by NHLBI 42,418 age >55 with one CHD risk factor Amlodipine or lisinopril or doxazosin VS. Chlorthalidone Step 2 – Atenolol or clonidine or reserpine Step 3 - Hydralazine

28. Treatment Trials ALLHAT Doxazosin terminated early due to much higher incidence of CHF Nearly 5 year follow up of other arms No difference in primary endpoint of combined fatal CHD or nonfatal MI Diverse population, high percent with DM 35% African American 47% women Secondary analysis also support thiazides. ACEI, CCBs and alpha blockers less effective in preventing HF ACEI and alpha blockers inferior in stroke prevention No additional protective effects beyond BP lowering noted with newer agents. Secondary analysis also support thiazides. ACEI, CCBs and alpha blockers less effective in preventing HF ACEI and alpha blockers inferior in stroke prevention No additional protective effects beyond BP lowering noted with newer agents.

29. Treatment Trials ANBP2 – Open label RCT Sponsored by Australian Dept of Health and Merck, Sharp, Dohme 6083 65-84 with low CV risk profile ACEI (enalapril) vs. Diuretic (HCTZ) Step 2 – ß blocker or a blocker or CCB Step 3 – Nonstep 2 drugs or diuretic in ACEI Step 4 – Nonstep 2 or 3 drugs

30. Sawicki. Have ALLHAT, ANBP2 ASCOT-BPLA, and so forth improved our knowledge about better hypertension care? Hypertension 2006;48:1-7. Treatment Trials ANBP2 Followed for median 4.1 years Primary endpoint changed Initial protocol – Total CV events including CV death; secondary endpoints-death & CHD events Final pub – All CV events and all cause death Marginally lower primary endpoint for ACEI 56.1 vs 59.8 per 1000 patient years Lower stroke rate for diuretic

31. Treatment Trials ANBP2 Validity issues Question of primary endpoints measured Open label design may have induced bias as data collection supported by sponsor/maker of ACEI Diuretic use was permitted in the ACEI group Superiority of ACEI over diuretics not demonstrated 95% white, 7% DM, 49% men95% white, 7% DM, 49% men

32. Treatment Trials ASCOT-BPLA – Open label RCT Sponsored by Pfizer 19,257 40-79, > 3 CV risk factors Amlodipine vs. atenolol Step 2 – Add perindopril vs. thiazide + K Step 3 - Doxazosin

33. Treatment Trials ASCOT-BPLA Followed for 5.5 years, terminated early Primary endpoint nonfatal MI + fatal CHD Amlodipine 8.2 per 1000 PY vs. atenolol 9.1 per 1000 PY, p = 0.105 Reduction noted in all cause mortality – secondary endpoint Amlodipine 13.9 per 1000 PY vs. atenolol 15.5 per 1000 PY, p = 0.025 Improved BP control in amlodipine arm led to better stroke, CV mortality, PAOD, total coronary endpoint and total CV events

34. Sawicki. Have ALLHAT, ANBP2, ASCOT-BPLA and so forth improved our knowledge about better hypertension care? Hypertension 2006;48:1-7. Treatment Trials ASCOT – BPLA Validity issues Protocol listed statistical significance for secondary endpoints as 0.01 Lipophilic ß blocker – less effective Only 55% of patients with ß blocker + diuretic Open label design may have introduced bias Premature termination of trial may influence outcome Does not prove superiority of amlodipine based regimen 95% white, 27% DM, 77% men95% white, 27% DM, 77% men

35. Thiazide Diuretics Bendroflumethiazide Chlorothiazide Chlorthalidone Hydrochlorothiazide Hydroflumethiazide Methyclothiazide Metolazone Polythiazide Quinethazone Trichlormethiazide

36. Thiazide Diuretics Chlorthalidone vs HCTZ Chlorthalidone basis of landmark studies HCTZ more commonly prescribed Chlorthalidone longer acting Chlortalidone 1.5-2 times more potent More effective BP control No head to head studies

37. Treatment Trials in Elderly 12 Studies reviewed Average BP drop 17/8 mm Hg ~30 % decrease in relative risk for CV disease CAD CHF Total CV diseases

38. Treatment Trials in Elderly SHEP 1991, 4739 patients, 57% women SBP 160-190, DBP<90 72 years 177/77 143/68, p<0.001 NNT to prevent stroke is 50 NNT to prevent CV event is 20 Agents Chlorthalidone, atenolol, reserpine

39. Treatment Trials in Elderly Sys-Eur 1997, 4695 patients, 67% women SBP 160-219, DBP<95 70 years 174/85 151/78, p<0.001 NNT to prevent stroke is 100 NNT to prevent CV event is 50 Agents Nitrendipine, enalapril, HCTZ

40. Treatment Trials in Elderly Sys-China 1998, 2394 patients, 35% women SBP 160-219, DBP<95 66 years 170/86 150/81, p<0.001 NNT to prevent stroke is 50 NNT to prevent CV event is 50 Agents Nitrendipine, captopril, HCTZ

41. Choice of Medications STOP – 2 - 2000 6614 patients, 70-84 years old Diuretics/Beta vs. ACEI vs. CCB No difference in outcomes or BP lowering SHELL - 2003 1882 patients, >60 Diuretic vs CCB No difference in outcomes or BP lowering

42. Choice of Medications NICS – EH - 1999 414 patients, > 60 years CCB vs. diuretic No difference in outcomes or BP lowering SCOPE - 2003 4964 patients, 70-89 years Candesarten vs. placebo and usual care No difference in BP lowering Decrease in non-fatal stroke in ARB

43. Treatment of the “Old” Old HYVET – 2008 Nearly 4000 patients Over 80 years old Systolic BP at least 160 mm Hg Target BP was 150/80 Agents vs. placebo Indapamide SR 1.5 mg +/- Perindopril 2 – 4 mg

44. Treatment of the “Old” Old HYVET Primary endpoint – any stroke Secondary – all cause mortality, CV mortality, cardiac death Beneficial effects seen within 1 year No increase in serious adverse events Different from pilot study reported in 2006

45. Treatment of the “Old” Old HYVET Total of 2.1 years of therapy Lowered BP by 15/6 mm Hg 30% decrease in primary endpoint (p=0.06) 39% decrease in stroke deaths (p=0.046) 21% decrease in all cause deaths (p=0.02) 23% decrease in CV deaths (p=0.06) 64% decrease in rate of HF (p<0.001) Fewer adverse events in Rx group (p=0.001)

46. Treatment of the “Old” Old HYVET – Recommendations Screen for HTN in elderly like anyone else Begin treatment if SBP is >160 mm Hg Indapamide +/- perinodopril Questions Indapamide = HCTZ or chlorthalidone? Perindopril = lisinopril or ramipril? Is there a better agent for “old” old? Are results due to BP lowering alone? What is the ideal BP for “old” old?

47. Follow up After treatment begun Monthly visits until control achieved More frequently as needed Check K+/Cr 1-2 times a year BP in control, F/U 3-6 months Low dose ASA ONLY when in control to avoid stroke

48. Choice of Medications Quality of Life Complex, multifactorial, hard to measure Treatment not associated with significant impairment in QOL and can improve No class is clearly superior ACEI and ARBs Cognition – dementia and memory, not learning or perceptual processing Sexual activity

49. SOLVD/SAVE, CIBIS, CAPRICORN, COPERNICUS, RALES, EPHESUS, MERIT-HF, CHARM Special Consideration Hypertension with heart failure Diuretic - A Beta blocker - A ACE inhibitor – A, NNT = 43 ARB - A Aldosterone antagonist – A, NNT = 50

50. BHAT, Norwegian Multi Center Study, PEACE, TRACE, SMILE, HOPE, EUROPA Special Consideration Hypertension post MI Beta blocker – Std of Care - A ACE inhibitor – A, stable & normal LV fxn Aldosterone antagonist – B

51. Special Consideration Hypertension with high CAD risk Diuretic - A Beta blocker - A ACE inhibitor - B CCB - B

52. Special Consideration Hypertension with diabetes Diuretic – thiazide induced DM is more benign Beta blocker - B ACE inhibitor - A CCB - B ARB - A

53. Special Consideration Hypertension with chronic kidney disease ACE inhibitor - A ARB – A Combine ARB and ACEI

54. PROGRESS Special Consideration Hypertension & recurrent CVA prevent Diuretic - A ACE inhibitor - B Perindopril + indapamide – B, RRR 43%

55. Question 1

56. Improving Control Atmosphere of trust in relationship Understanding cultural beliefs of patient Agreement on BP goals Overcome clinical inertia to achieve goals Consider cost and complexity of care

57. Improving Control Increase knowledge In 2001, 41% of primary care providers were not familiar with JNC 7 Identify and treat Only 30-49 percent controlled in US Less than 10 percent in developing countries Focus on widespread and cost-effective HTN care, not what agent is “best”

58. Resistant HTN Failure to reach goal on 3 drugs including a diuretic Exclude potential identifiable causes Explore reasons why goal not met May need higher doses of diuretics with kidney disease Consider referral to HTN specialist

59. BPLTTC, STOP-2 Conclusions Persons over 50, SBP is more important Thiazide diuretics are the mainstay of treatment, tailor to medical conditions Most patients will need 2 or more drugs Patients and providers must be motivated Lowering BP in patients and populations is more important than agent Small lowering of BP has large effect. Decrease BP by 5 mm Hg will decrease mortality due to stroke by 14%, cardiac mortality by 9% and all cause mortality by 7%.Small lowering of BP has large effect. Decrease BP by 5 mm Hg will decrease mortality due to stroke by 14%, cardiac mortality by 9% and all cause mortality by 7%.

60. Questions

61. Case #1 68 year Afri-Amer male Type 2 diabetes mellitus for 5 years No nephropathy No CV history On atorvastatin 80 mg and LDL is 80 BP is 148/98 last visit and now 150/98 Diagnosis? Evaluation? Treatment

62. Case #1 Diagnosis Stage 1 HTN Evaluation Check for smoking other CV risks Exam normal Labs are normal (CBC, chem, UA, ECG) Treatment DASH HCTZ vs ACEI vs CCB

63. Question #2

64. Case #2 75 year old Latino female Type 2 diabetes for 10 years, poor control LDL at 167, no treatment No CV history, non smoker On metformin 1000 bid BP is 165/88, then 163/80 Diagnosis? Evaluation? Treatment?

65. Case #2 Diagnosis Stage 2 ISH Assessment Exam normal except obese Normal labs except UA + for protein and ECG with evidence of LVH Treatment DASH HCTZ vs ACEI vs ARB vs CCB

66. Question 3

67. HTN and LVH PRESERVE Enalapril = nifedipine gts LIVE Indapamide SR > enalapril LIFE Losarten > atenolol In reversing hypertensive LVH

68. Case #3 69 year old white male No medical history BP 145/105, 147/102 No meds Diagnosis? Evaluation? Treatment?

69. Case #3 Diagnsis Stage 2 HTN Evaluation No CV risk factors Exam normal Labs normal except K= 2.1, repeat =2.0 No diuretics Further work up

70. Case #3 Diagnosis Stage 2 HTN Secondary HTN Aldosteronism Primary – adrenal adenoma, hyperplasia Secondary – high renin, accelerated HTN Plasma renin – Low Saline load – high aldosterone CT scan – no adenoma Hyperplasia

71. Case #3 Treatment Sodium restriction Antimineralocorticoids Sprinonolactone 25-100 mg tid If adenoma seen, surgery BP normal for last two years