1. Treatment of Hypertension in Patients over the age of 80 Debra Bynum, MD Associate Professor Division of Geriatric Medicine

2. The “Case”… At grand rounds, a well respected geriatrician presents an 84 year old who is functional and independent, but having falls… He has uncontrolled Systolic HTN He is not orthostatic He has evidence on scan of old cerebellar infarcts… The recommendation for antihypertensive therapy creates a stir in the audience…

3. Grand Rounds… Audience remarks:  We should focus on making him comfortable  Everyone has to die of something  Is there any evidence to support the treatment of Hypertension in patients over the age of 80?

4. Questions… Is there ageism, even among well respected physicians? What is the average life expectancy of an otherwise functional, independent 84 year old? Is there evidence to support the treatment of hypertension in patients over the age of 80? What should the goals of treatment be in patients over the age of 80?

5. Does ageism still exist?

6. What about current life expectancy?

7. The Beat goes on…

8. Life expectancy… What we can really expect At birth, average life expectancy in US: 74 for men, 79 for women But…  Average 65 y/o man will live to 82, woman to 85  Average 75 y/o man will live to 85, woman to 88  Average 85 y/o man will live to 91, woman to 92  Average 90 y/o man will live to 94, woman to 95  The older you are, the older you are likely to be…

9. Take home.. The average 80 year old is likely to live to 90 10 years… makes issues of treating or not, screening or not very real (we are not talking last year of life for most)

10. Is there evidence to support the treatment of hypertension in patients over the age of 80?

11. The controversy: Background Systolic Hypertension in the Elderly so common that once considered normal part of aging Previously : “Isolated Systolic Hypertension” 1980: JNC on HTN defined ISH as SBP >160 with DBP <90

12. JNC 7 classification… ClassificationSBPDBP Normal<120And <80 PreHypertensio n 120-139Or 80-89 Stage 1 HTN140-159Or 90-99 Stage 2 HTN>160Or >100

13. Systolic Hypertension Defined as SBP > 140 with DBP <90 No longer referred to as “Isolated”

14. How Common is Systolic Hypertension? Prevalence of HTN increases with age 67% over age 60 and ¾ of those over the age of 70 have HTN (National Health and Nutrition Examination Survey: NHANES) SH accounts for 75% of HTN in those over 65 Lifetime Risk Statistic:  Normotensive 65 year old adult who lives to age 85: 90% lifetime probability of developing stage 1 HTN (140-159/90-99) and 40% risk of stage 2 HTN (>160/100)

15. PreHypertension People over age 65: 26% four year risk of HTN if BP 120-129/80-84 Those over age 65 with BP 130-139/85-89: 50% four year risk of HTN Patients with BP 130-139/85-89 have twice the risk of CVD events compared to those with normal BP

16. Importance of the SBP Continued increase in SBP with age (likely due to increased arterial stiffness) Level/decrease in DBP with age (after 50-60) After age 50, SBP is much more important risk factor for CV events than DBP SBP more often poorly controlled than DBP (difficulty in management plus physician attitudes); Almost ALWAYS takes more than one medication…

17. SBP… Framingham data from 1976 and meta-analysis of 60 observational studies: SH major risk factor for stroke Initial concern that SBP lowering would lead to increased stroke in patients over age 80 NOT SHOWN

18. Systolic Hypertension JNC 7 clear in report: SH in patients over the age of 60 much more important than DBP SH assoicated with increased risk of CAD, LVH, renal insufficiency, stroke, and CV mortality SH more closely associated with CV risk than DBP in older patients (even in older patients with diastolic hypertension)

19. SH: Summary SH more common in older patients SH more closely correlated with CV and stroke events DBP drops with age SH more difficult to control; If SH controlled, DBP usually controlled

20. Why treat… the data SHEP trial : 1991  5000 patients, SBP 160-190, DBP <90, mean age 72  Chlorthalidone (thiazide) vs placebo  Second agents: atenolol, reserpine  Primary endpoint: stroke  Significant decrease in 5 year incidence of all strokes (8% vs 5%, ARR 3%)

21. SHEP… Reduction in Heart Failure  2.3% vs 4.4 %  ARR 2%  NNT 48

22. SHEP trial… 32 % Relative Risk Reduction and 5% Absolute Reduction in total combined CV events (secondary outcome) NNT: need to treat 18 people over 5 years to prevent 1 major cardiovascular or cerebrovascular event ?underestimation: goal BP only reached in 70% treatment group; 44% placebo group also treated (intention to treat analysis)

23. Additional data… Systolic Hypertension in Europe Systolic Hypertension in China All demonstrated decreased risk of stroke and combined CV events in older patients treated for SH None powered to demonstrate difference in all cause or cardiovascular mortality

24. Treatment of SH decreased strokes… SHEP data: both hemorrhagic and ischemic strokes decreased Immediate effect on bleeds seen 2 years needed to see full effect of reduction in ischemic stroke

25. Treatment of ISH in the elderly: Meta-analysis of outcome trials SHEP Syst-Eur Syst-China EWPHE (European Working Party on High Blood Pressure in the Elderly) HEP (HTN in Elderly Patients in Primary Care) STOP (Swedish Trial in Old Patients with HTN) MRC1 (Medical Research Council trials in mild HTN) MRC2 (in older adults)  Lancet 2000

26. Meta-analysis 8 trials, over 15,000 patients with SH Median follow up 3.8 years Treatment decreased mortality by 13%, stroke by 30%

27. NNT for 5 years to prevent one major CV event….

28. Summary… Treatment of SH in older patients with SBP over 160 is beneficial Largest benefit when treating patients over age 70, men, and those with prior cardiac events (higher risk=highest benefit)

29. Will lowering the BP too much cause harm? 1. Decreasing SBP 2. Decreasing DBP 3. Increasing PP (pulse pressure)

30. SBP Longitudinal studies show elderly with the lowest SBPs may have higher mortality (J curve) Problem: Patients with the lowest SBP may be more likely to have more serious underlying comorbidities

31. INVEST International Verapamil SR Trandolapril Study Comparing beta blockers (atenolol) vs ca channel blockers Over 2000 of the 22,000 patients were over the age of 80

32. INVEST Overall greatest proportion of patients with primary outcome (mortality/nonfatal MI/CVA) found in those over 80 (23%) J shaped relationship between BP and outcome SBP <140 and DBP <70 associated with increased HR

33. Will lowering the DBP cause harm? Population studies suggested lower DBP in older patients associated with worse outcomes

34. Low DBP… Meta-analysis of 8 trials, over 15,000 patients from Lancet 2000 DBP inversely correlated with total mortality (independent of SBP)

35. Pulse pressure… Observation studies show patients with highest PP (difference between SBP and DBP), especially when over 50, have worse outcomes Trials: those who had CV event on treatment were more likely to have lower DBP and higher pulse pressure (DBP 50) than those without CV event in tx group SHEP: increase in CV events in treatment group if DBP <60

36. Is “overtreatment” risky? Patients with lower DBP and high PP who were in placebo group also had higher rates of vascular events Risk of events in patients with lower DBP on treatment still less than that in the placebo group! Lower DBP and Higher PP likely more of a marker for bad outcomes (stiffness of arteries)

37. Back to the question: Should we treat those over the age of 80? Observation that the very old with low BP have higher mortality Fear of increased risk of side effects (orthostasis and falls) JAGS 2007: retrospective cohort study of VA patients over age 80 found lower 5 year survival in patients with lower BPs Concern that association between SH and stroke is not as strong in those over 80 compared to those 65-80 INDANA subgroup meta-analysis (Lancet 1999): reduced stroke and heart failure but 14% increase in all cause mortality; Used high dose diuretics and beta blockers…

39. There is always a Big But… But…This group has highest ABSOLUTE risk of CV event, heart failure and stroke -- leading to possible greater ARR with treatment (risk- treatment paradox)

40. HYVET: Hypertension in the Very Elderly Trial RCT of nearly 4000 patients from Europe, China, Australia, Tunisia Age over 80 SBP > 160 Indapamide vs placebo ACE inhibitor (perindopril) or placebo added as second agent when needed Primary endpoint: stroke

41. HYVET… Mean age : 83 Mean standing BP: 173/90 12% had hx of CV disease 1.8 year follow up Treatment group: 15/6 lower BP

42. HYVET: results EndpointTreatment (rate per 1000 patient-year/# events) Placebo Stroke12.4 (51)17.7 (69) Death from stroke6.5 (27)10.7 (42) Mortality47.2 (196)59.6 (235) Death from CV cause23.9 (99)30.7 (121) Any MI2.2 (9)3.1 (12) p=.45 Any heart failure5.3 (22)14.8 (57) Any CV event33.7 (138)50.6 (193) Any CV event:Death from CV cause, stroke, MI, CHF

43. HYVET results… 30% decrease in rate of fatal or nonfatal stroke 39% decrease in rate of death from stroke 21 % decrease in all cause mortality 23% decrease in CV death 64% decrease in heart failure Fewer adverse events in treatment group

44. HYVET… additional points Target SBP of <150 Only 50% treatment group reached target SBP Excluded patients with SBP over 200 Followed standing BP to keep over 140 7.9% in treatment group vs 8.8% in placebo group had orthostatic hypotension

45. HYVET: Take Home points Overall number of events small (healthy population of elderly) Stroke: ARR of almost 1% (NNT near 100 over 2 years to prevent one stroke) Older patients more likely to die from stroke All cause mortality (secondary outcome): ARR 1.2 % (NNT about 80): Some concern about this finding based upon results of other studies…

46. Recent Meta-analysis of Treatment of patients over the age 80 Primary outcome: total mortality Secondary outcomes: coronary events, CV events, CVA, CHF, cause specific mortality Over 6000 patients in 7 studies  Journal of HTN 2010

47. Meta-analysis of patients over 80… Biggest differences:  Decrease in CVA (35% RRR)  Decrease in CV events (27% RRR)  50% decrease in CHF ARR 3 % over 5 years for stroke prevention Did not show improvement in mortality, but also did NOT show worse mortality….

48. Treating over 80: summary There is evidence that those over 80 have similar reductions in bad outcomes as in those 60-80 (and may have greater absolute reductions) Although mortality may or may not be improved, there is a consistent theme of decreased risk of stroke, CHF, and CV events

49. What should the target BP in those over 80? JNC 7: recommends overall similar treatment guidelines for the elderly (goal SBP under 140) But, NO study has looked at patients with baseline BP of <160 Average SBP achieved in large RCTS: 143 No trial achieved average SBP of <140

50. Valsartan in Elderly Isolated Systolic Hypertension Study (VALISH) Compared CV mortality and morbidity in eldelry patients with SH with strict control (SBP<140) vs moderate control (140-150) goals 3000 patients (70-85), 2.8 year follow up SBP 136 in tight control, 142 in moderate control group achieved No difference in outcomes…

51. Target BP HYVET: Target SBP of 150 INVEST: increased risk seen with SBP <140 (not compared to placebo….) VALISH: no difference in outcomes with stricter control Reasonable goal of SBP 150

52. Summary Systolic hypertension in older patients is common and difficult to treat There is strong evidence that treatment of SH in patients over 65 reduces risk of CVA and CHF There is now strong evidence that treating SH in patients over the age of 80 also reduces the risk of stroke and heart failure Although the evidence is not strong that treating decreases mortality, there is no evidence that treatment increases mortality in those over 80

53. Summary… The association between stroke and SH may not as strong in older patients as those in midlife, but the higher absolute risk of stroke and heart failure push toward treating Balance risk of orthostasis and falls – but patients in the HYVET study who were not orthostatic benefited with SBP in the 140 - 150 range! Stroke reduction is not insignificant in a patient who on average may live another 10 years, reducing the potential for disability and placement in addition to mortality

54. Summary: Patients with the highest risk (those over 70, men, those with prior CV events, and those with a high PP) actually may stand to gain the most from treatment… Even modest treatment goals may have significant benefit

55. Recommendations… Check and follow BP while standing Remember diet/lifestyle changes Treat patients with SBP >160 with medications (start with thiazide or ACE or Ca channel blockers) Target BP in those over 80: 150 Recognize that patients with DBP 50 have a higher risk of CV events, but not clear if this can be modified

56. Questions and Discussion…