Treatment of Hypertension in the Elderly: A Major Challenge

1. Treatment of Hypertension in the Elderly: A Major Challenge Thomas G Pickering MD, D Phil Behavioral Cardiovascular Health and Hypertension Program Columbia Presbyterian Hospital

2. Treating older adults: Updates and Practical Approaches Risks associated with high BP JNC 7 Guidelines Goals of treatment Choice of drugs Hypertension in the very old Non-drug treatment

3. Treating older adults: Updates and Practical Approaches Risks associated with high BP JNC 7 Guidelines Goals of treatment Choice of drugs Hypertension in the very old Non-drug treatment

4. Continuous Relation Between Blood Pressure And Risk Of CVD Stroke CHD 4 4 2 2 Relative Risk 1 1 0.5 0.5 0.25 0.25 76 84 91 98 105 76 84 91 98 105 Usual Diastolic Pressure (mm Hg) MacMahon et al. Lancet. 1990;335:765.

5. Change Of Blood Pressure With Age (NHANES - Black Women) Blood Pressure (mm Hg) Age

6. Stiffer Arteries Increase Pulse Wave Velocity And Pulse Pressure Average Blood Pressure Waveform Average Blood Pressure Waveform Shoulder Notch Notch Time (sec) Time (sec) 52-year-Old Normal Pressure Wave 81-year-Old Early Pulse Wave Reflection

7. Pulse Pressure Predicts Risk Best In Older HypertensivesA Meta-Analysis EWPHE (N=840) Syst-Eur (N=4695) Syst-China (N=2394) Diastolic Pressure (mm Hg) 2-Year Risk Of End Point Systolic Blood Pressure (mm Hg) Blacher et al. Arch Intern Med. 2000;160.

8. 60 60 50 50 40 40 30 30 20 20 Clinic 24-hr 10 10 Daytime Nighttime 0 0 190 110 130 190 150 110 170 130 150 170 Ambulatory BP and Cardiovascular Disease in the Elderly with Systolic Hypertension: The Syst-Eur Study (N = 808) Placebo Active treatment Cardiovascular disease (per 1000 patient - year) Staessen et al. JAMA 1999; 282: 539-46.

9. Consequences of Treating White Coat Hypertension (Syst-Eur study)(Fagard et al, Circ 2000; 102: 1139) Placebo Active Change of Clinic SBP mmHg White coat HTN Mild HTN Moderate HTN

10. Consequences of Treating White Coat Hypertension (Syst-Eur study)(Fagard et al, Circ 2000; 102: 1139) Placebo Active Change of Daytime SBP mmHg White coat HTN Mild HTN Moderate HTN

11. Consequences of Treating White Coat Hypertension (Syst-Eur study)(Fagard et al, Circ 2000; 102: 1139) Rate of strokes per1000 pt-years P<0.03 P=NS P=NS White coat HTN Mild HTN Moderate HTN

12. http://www.hcfa.gov/coverage/8b3-ff.htm

13. The White Coat Effect in the Real World(Little et al, BMJ 2002; 325: 254) 173 hypertensive patients in 3 general practices in the UK Clinic (MD and RN), self-monitoring, and ABPM White coat effect estimated as difference between other measures of BP and daytime BP:- Physician 19/11 mmHg Nurse 1 5/8 mmHg Nurse 2 5/6 mmHg Self-monitoring in clinic 10/13 mmHg Self-monitoring at home 5/6 mmHg

14. JNC 7: Self-Measurement of BP • Provides information on: • Response to antihypertensive therapy • Improving adherence with therapy • Evaluating white-coat HTN • Home measurement of >135/85 mmHg is generally considered to be hypertensive. • Home measurement devices should be checked regularly.

15. Analysis of The Influence of the Morning Surge of BP on Stroke Incidence (Kario, Pickering et al)

16. Analysis of The Influence of the Morning Surge of BP on Stroke Incidence (Kario, Pickering et al) Cox regression analysis for clinical stroke events Covariates RR P value Age (10 yrs) 1.80 (1.21-2.69) 0.004 Male gender 1.42 (0.76-2.67) 0.266 BMI 0.98 (0.90-1.07) 0.663 24 hr SBP 1.37 (1.16-1.63 0.003 SCI 4.40 (1.95-10.1) 0.001 Morning BP surge* 1.29 (1.10-1.51) 0.001 Nocturnal BP fall* 0.88 (0.73-1.06) 0.167 Lowest sleep BP 1.05 (0.65-1.71) 0.837 * per 10 mmHg

17. Treating older adults: Updates and Practical Approaches Risks associated with high BP JNC 7 Guidelines Goals of treatment Choice of drugs Hypertension in the very old Non-drug treatment

18. JNC 7: New Features and Key Messages • Forpersons over age 50, SBP is a more important than DBP as CVD risk factor. • Starting at 115/75 mmHg, CVD risk doubles with each increment of 20/10 mmHg throughout the BP range. • Persons who are normotensive at age 55 have a 90% lifetime risk for developing HTN. • Those with SBP 120–139 mmHg or DBP 80–89 mmHg should be considered prehypertensive who require health-promoting lifestyle modifications to prevent CVD.

19. JNC 7: New Features and Key Messages • For persons over age 50, SBP is a more important than DBP as CVD risk factor. • Starting at 115/75 mmHg, CVD risk doubles with each increment of 20/10 mmHg throughout the BP range. • Persons who are normotensive at age 55 have a 90% lifetime risk for developing HTN. • Those with SBP 120–139 mmHg or DBP 80–89 mmHg should be considered prehypertensive who require health-promoting lifestyle modifications to prevent CVD.

20. JNC 7: New Features and Key Messages (Continued) • Thiazide-type diuretics should be initial drug therapy for most, either alone or combined with other drug classes. • Certain high-risk conditions are compelling indications for other drug classes. • Most patients will require two or more antihypertensive drugs to achieve goal BP. • If BP is >20/10 mmHg above goal, initiate therapy with two agents, one usually should be a thiazide-type diuretic.

21. JNC 7: New Features and Key Messages (Continued) • Thiazide-type diuretics should be initial drug therapy for most, either alone or combined with other drug classes. • Certain high-risk conditions are compelling indications for other drug classes. • Most patients will require two or more antihypertensive drugs to achieve goal BP. • If BP is >20/10 mmHg above goal, initiate therapy with two agents, one usually should be a thiazide-type diuretic.

22. Treating older adults: Updates and Practical Approaches Risks associated with high BP JNC 7 Guidelines Goals of treatment Choice of drugs Hypertension in the very old Non-drug treatment

23. BP Control Rates Trends inawareness, treatment, and control of high blood pressure in adults ages 18–74 Sources: Unpublished data for 1999–2000 computed by M. Wolz, National Heart, Lung, and Blood Institute; JNC 6.

24. Characteristics of Patients with Uncontrolled Hypertension in the US: NHANES (Hyman et al, NEJM; 2001; 345: 479) Predictors of Uncontrolled Hypertension HTN Undiagnosed HTN Diagnosed Factor Rel Risk Attrib Risk Rel Risk Attrib Risk Age >65 7.69 0.46 2.08 0.32 Male sex 1.58 0.22 1.30 0.12 Black race 1.45 0.05 - - MD visits 1.40 0.09 1.89 0.08

25. How far should BP be lowered in the elderly? Trial Starting BP Final BP HOT 170 140-144 EWPHE 183 149 SHEP 170 144 Syst-Eur 174 151 Conclude: No evidence to support lowering BP to<140 mmHg

26. Treating older adults: Updates and Practical Approaches Risks associated with high BP JNC 7 Guidelines Goals of treatment Choice of drugs Hypertension in the very old Non-drug treatment

27. Trends in Antihypertensive Drug Use(Kaplan 2003) Diuretics No. of prescriptions (millions) CCBs Beta blockers ARBs ACEI Alpha blockers Year

28. Limited Efficacy of Monotherapy in Treating Hypertension (Materson NEJM 1993; 328: 914) Patients Responding %

29. ALLHAT U.S. Department of Health and Human Services National Institutes of Health National Heart, Lung, and Blood Institute Major Outcomes in High Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) The ALLHAT Collaborative Research Group Sponsored by the National Heart, Lung, and Blood Institute (NHLBI) JAMA. 2002;288:2981-2997

30. ALLHAT 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). BP Results by Treatment Group

31. ALLHAT .2 .16 .12 Cumulative CHD Event Rate .08 .04 0 0 1 2 3 4 5 6 7 Years to CHD Event Cumulative Event Rates for the Primary Outcome (Fatal CHD or Nonfatal MI) by ALLHAT Treatment Group Chlorthalidone Amlodipine Lisinopril

32. ALLHAT .1 .08 .06 Cumulative Stroke Rate .04 .02 0 0 1 2 3 4 5 6 7 Years to Stroke Cumulative Event Rates for Stroke by ALLHAT Treatment Group Chlorthalidone Amlodipine Lisinopril

33. ALLHAT Overall Conclusions Because of the superiority of thiazide-type diuretics in preventing one or more major forms of CVD and their lower cost, they should be the drugs of choice for first-step antihypertensive drug therapy.

34. ANBP2: Australian Trial of ACEI vs Diuretics in the Elderly (Wing et al NEJM, 2003; 348: 583) • Subjects were 6083 hypertensives aged 65-84 , BP >160/90 mmHg • Randomized to ACEI (Enalapril) or Diuretic (HCTZ) • Significant 11% (just) reduction in combined CV events for ACEI group (17% in men, 0 in women) • Blood Pressures were identical for the two groups throughout the study

35. Comparison of ALLHAT and ANBP2 Study Conclusions ALLHAT- Diuretics Better than ACEI ANBP2- ACEI better than Diuretics Can they be reconciled? Other studies show that ACEI prevent heart failure Higher incidence of heart failure in ALLHAT ACEI group occurred early, and may have been due to diuretic withdrawal Higher incidence of stroke in ALLHAT ACEI group may have been due to higher BP Higher percentage of blacks in ALLHAT- blacks did better with stroke, coronary endpoints, and heart failure In D than in ACEI group

36. PROGRESS & PATS: Effects of Diuretics and ACEI on Recurrent Stroke(Messerli et al, Arch Int Med 163: 2557, 2003) PROGRESS PATS PROGRESS Perindopril Indapamide Both Reduction of SBP or stroke

37. LIFE: Reduction of stroke but not MI with Losartan inIsolated Systolic Hypertension(Kjeldsen et al JAMA 2002: 288: 1491)

38. Effects of Diuretics and Beta Blockers on Cardiovascular Mortality (JNC VI) Drug Dose No. RR (95% CI) Diuretics High 11 0.78 (0.62-0.97) Diuretics Low 4 0.76 (0.65-0.89) Beta blockers 4 0.89 (0.76-1.05) 0.4 0.7 1.0 RR (95% CI) Treatment Treatment Better Worse

39. Prevention of Dementia with Calcium Channel Blocker Treatment in ISH- Syst-Eur (Forette et al, Arch Int Med 2002: 162: 2046)

40. Treating older adults: Updates and Practical Approaches Risks associated with high BP JNC 7 Guidelines Goals of treatment Choice of drugs Hypertension in the very old Non-drug treatment

41. Hypertension in the Very Old(Bulpitt J Hum Hyp 1994; 8:603) Four Reasons why Hypertension may be Different in the Elderly They are survivors Many have taken years to become ‘hypertensive’ Some have atheromatous renal artery stenosis Diastolic pressure falls in the elderly

42. BP and Survival in the Very Old(Mattila et al, BMJ 1988:296; 887) 561 Finns aged 84-102 (mean 88) Systolic Pressure mmHg 5 year survival Diastolic Pressure mmHg

43. Hypertension in the Very Elderly Trial (HYVET) 2100 hypertensives aged >80 randomised to No treatment, ACEI, or diuretic 5 year F/U Endpoint is a 40% reduction in stroke

44. HYVET: Results of Pilot Study(Bulpitt et al, J Hypertens 2003: 21: 2409) 1283 hypertensive patients aged >80 randomized to Diuretic, ACEI, or no treatment Target BP <150/80; follow-up 13 months Results: Total mortality: no effect CV mortality: no effect Stroke events: Diuretics RR 0.313, p<0.01 ACEI RR 0.629, p= 0.21

45. Treating older adults: Updates and Practical Approaches Risks associated with high BP JNC 7 Guidelines Goals of treatment Choice of drugs Hypertension in the very old Non-drug treatment

46. JNC 7: Lifestyle Modification

47. Lifestyle Modification: PREMIER(JAMA 2003: 289; 2083) Baseline 3 mo 6 mo

48. Conclusions: Hypertension in the Elderly An increasing problem with the ageing of the US population Related to increased stiffness of arteries Importance of white coat HTN, and out-of-office monitoring Diuretics drugs of choice, with addition of others- emphasis on combination Rx BP control is more important than drugs used Include lifestyle modifications Benefits of treatment in very old (>85) are unproven, but diuretics may be protective