1. Managing Blood Pressure in the Older Adult Jamie McCarrell, Pharm.D., BCPS, CGP TTUHSC School of Pharmacy

2. Objectives Describe key pharmacodynamic changes that occur as we age which impact the efficacy of certain anti-hypertensive agents State current guideline recommendations for treatment of hypertension in older adults Evaluate current literature recommendations for blood pressure treatment goals in older adults Given a patient case, develop a plan for initiating, changing, and monitoring a medication regimen for hypertension.

3. MYTH Older adults have altered response to medications because they have altered ADME (pharmacokinetic) properties.

4. PHARMACODYNAMIC AND PHYSIOLOGIC CHANGES Managing Blood Pressure in the Older Adult

5. Beta-adrenergic changes  beta-adrenergic receptors on myocardium  beta-adrenergic response to stimulus –  serum levels or noradrenalin…tachyphylaxis? Beta-blocker effects? What about HF or MI?

6. RAAS Possible decrease in ACE-inhibitor efficacy Risk of hyperkalemia due to decreased aldosterone www.mlo-online.com

7. Little Information Dihydropyridine CCBs – Will drop BP more than younger adults – No reflex tachycardia when BP drops Peripheral α-blockers – Significantly larger BP drop than younger adults with no increase in serum concentration – No reflex tachycardia when BP drops Large risk of postural hypotension with peripheral α-blockers

8. Postural Hypotension www.scimath.org

9. Isolated Systolic Hypertension Lancet 2006.

10. Pharmacokinetic Changes Phase 1 vs Phase 2 metabolism – Many common antihypertensive medications are metabolized through CYP enzymes (phase 1) – CYP enzymes can be drastically altered in older adults (number and function) – Results in clinically significant drug interactions Example: amlodipine + simvastatin – Made worse by old age??

11. TREATMENT – JNC 8 Managing Blood Pressure in the Older Adult

12. Committee Recommendations Recommendation #1 – General patient age 60+, use goal BP 150/90 – Corollary: If on therapy and SBP is < 140 with NO adverse effects, continue therapy as is (don’t back off) Recommendation #2 – General patient age < 60, use diastolic BP goal of < 90 – Age 18-29 is “expert opinion”

13. Committee Recommendations Recommendation #3 – For general patient < 60, use systolic BP goal of < 140 – Expert opinion for whole group Recommendation #4 – For patients 18+ with CKD, use BP goal < 140/90 – How defined? – What about geriatrics?

14. Committee Recommendations Recommendation #5 – In patients 18+ with diabetes, use BP goal < 140/90 Recommendation #6 – For non-black patients, initial therapy should be one of the following agents (any) Thiazide-type diuretic ACE inhibitor ARB CCB

15. Committee Recommendations Recommendation #7 – For a black patient, initial therapy should be selected from the following: Thiazide-type diuretic CCB Recommendation #8 – For patients age 18+ with CKD, the initial therapy should be an ACE or ARB Can add ACE or ARB to gain renal outcome benefit

16. Committee Recommendations Recommendation #9 – Treat to the goals…if not there after one month, maximally titrate the agent – Still not there…add and titrate a second agent as needed – Third verse, same as the first (and second) – If still not at goal, consider an additional agent not on the recommended first line list – Don’t combine an ACE and an ARB

17. JNC 8, Renal Dysfunction, and age > 60 Two JNC 8 statements – For age > 60, use goal 150/90 – For CKD, use goal 140/90 – How do you define CKD? Age < 70 with measured or calculated GFR < 60 ml/min/1.73m 2 Any age with albuminuria

18. JNC 8, Renal Dysfunction, and age > 60 What about age > 70? – If GFR is > 60, use 150/90 (unless DM) – If GFR is < 60… “The panel cannot make a recommendation for a BP goal for people aged 70 years or older with GFR less than 60…” “Thus, when weighing the risks and benefits of a lower BP goal for people aged 70 years or older…antihypertensive treatment should be individualized, taking into account frailty, comorbidities, and albuminuria.”

19. JNC 8, Renal Dysfunction, and age > 60

20. Old-old Systolic Goals JAGS. 2001.

21. HTN and survival in elderly men J Am Geriatr Soc 2001;49:367-74

22. HTN and survival in elderly women J Am Geriatr Soc 2001;49:367-74

23. SPRINT Trial NEJM late 2015 Tested SBP goal of 140 vs 120 Intensive treatment group had: – Less composite CV outcomes – Less individual outcomes for: HF Death from CV causes Death from any cause – More conversion to renal insufficiency (HR 3.49)

24. SPRINT Trial Limitations Mean age 67 with only 28% 75+ DIABETES! STROKE! Adverse events – all worse in intensive tx – Hypotension – Syncope – Electrolyte abnormalities – Acute kidney injury/failure

25. CHOOSING AN AGENT Managing Blood Pressure in the Older Adult

26. First line agents ACEs/ARBs – Generally well tolerated – Possibly reduced efficacy in older adults – Regular electrolyte measurements – Think about pill burden…daily is better than BID CCBs – Likely best “bang for your buck” in older adults – Dihydropyridine only (no verapamil/diltiazem) – Caution in HF…amlodipine may be agent of choice

27. First line agents Thiazide diuretics – HCTZ most common – Good BP-lowering – Caution with timing Risk of falls with frequent/late trips to restroom – Monitor electrolytes closely – Monitor for dehydration – TRIPLE WHAMMY

29. Beta blockers Still have a place in therapy – Post MI – Heart failure – Atrial fibrillation – Caution in diabetes…why? – Bradycardia risk, esp if already lower HR (older adults) – Don’t expect great BP reduction

30. Suboptimal therapies Alpha blockers – Terazosin, prazosin, doxazosin – Significant risk of hypotension – Significant risk of dizziness, falls, fractures – Should not be used for BPH unless using a prostate-specific agent (typically tamsulosin)

31. Suboptimal therapies Clonidine – Alpha-2 agonist centrally – Reduces sympathetic vasoconstriction – Significant risk of hypotension – Significant risk of dizziness and falls – Causes somnolence/sedation

32. PATIENT CASE Managing Blood Pressure in the Older Adult

33. Jamie McCarrell, Pharm.D., BCPS, CGP TTUHSC School of Pharmacy