15 - Hypertension

Question 1

What is the trend of age related to HTN?

Answer 1

• Males more likely than females from 35-64

- From 65 and older females become more likely

Question 2

What determines BP?

Answer 2

Cardiac output * peripheral resistance

Question 3

Why do we want to lower BP?

Answer 3

For long-term prevention of heart attacks, strokes, kidney failure, eye damage, etc.

Question 4

HTN is a significant risk factor for…?

Answer 4

• Cerebrovascular disease
• Coronary artery disease
• Congestive heart failure
• Renal failure
• Peripheral vascular disease
• Dementia
• Atrial fib
• Erectile dysfunction

Question 5

Goals of therapy for adults w/ HTN

Answer 5

• Systolic BP less than 140 mmHg
• Diastolic BP less than 90 mmHg
• Mortality greatly increases if systolic BP > 160 mmHg and/or if diastolic > 90-100 mmHg

Question 6

Benefit of HTN tx

Answer 6

• *Benefit is related to risk

- Those w/ lower CV risk will have less benefit than those w/ greater CV risk

Question 7

Describe the sprint study

Answer 7

• Studied px at high risk of CVD (average 10-year CVD risk = 20%), no DM2 (px w/ LVEF < 35% or stroke also excluded)
• Not blinded
• Studied intensive (SBP < 120) vs. standard (SBP < 140) BP control; any standard anti-hypertensive could be used; follow-up after 3.3 years
• Took 2 anti-HTN meds to get px to an average of 135/76
• Took 3 anti-HTN meds to get px to an average of 121/69 (couldn’t get them to an average of 120 SBP)

Question 8

Describe the results of the sprint study

Answer 8

• ARR (absolute risk reduction) using intensive for primary outcome (ex: MI, ACS, stroke, HF, CV death) was 1.6%; NNT = 62
• ARI (absolute risk increase) using intensive for renal (AKI or ARF) was 1.8%; NNH = 56
• ARI using intensive for >/ 30% decrease in eGFR to < 60 mL/min was 2.7%; NNH = 37
• ARI using intensive for serious adverse effects (life-threatening, permanent disability, hospitalization) was 2.2%; NNH = 46

Question 9

What are the current Canadian recommendations for HTN tx?

Answer 9

• For high-risk px aged >/ 50 years w/ SBP >/ 130 mmHg, intensive management to target a SBP < 120 mmHg should be considered
• Px selection for intensive management is recommended & caution should be taken in certain high-risk groups
• High-risk adults as candidates for intensive management:
• • Clinical or subclinical CVD or
• • Chronic kidney disease or
• • Estimated 10-year global CV risk >/ 15% or
• • Age >/ 75 years
• Px w/ >/ 1 clinical indication should consent to intensive management

Question 10

Most important drug causes of HTN

Answer 10

• NSAIDs
• Decongestants
• Alcohol
• Estrogen
• Also some herbal supplements (when mixed w/ Rx)

Question 11

What are some options for non-drug therapy for HTN?

Answer 11

• Allow 3-6 months of lifestyle modification before considering medication (in most cases)
• Examples – exercise (150 min/week of mild-moderate); diet (caffeine intake, fat intake); 1-2 cups of coffee per day isn’t a big deal; stress management; weight reduction
• DASH diet (fruits, vegetables, low-fat dairy, dietary fiber, grains, etc.)
• Reduce sodium intake toward 2000 mg (5 g of salt or 87 mmol Na) per day

Question 12

MOA of CCBs

Answer 12

Decrease contractility and vasoconstriction

Question 13

MOA of thiazide diuretics

Answer 13

Decrease sodium/water reabsorption => decrease TPR

Question 14

Describe the ALLHAT study

Answer 14

• Studied over 33,000 patients w/ HTN & at least 1 other risk factor for CHD events
• Followed them for 5 years on chlorthalidone 12.5-25 mg (thiazide), lisinopril 10-40 mg (ACE inhibitor), or amlodipine 2.5-10 mg (DHP CCB)
• Results = BP reduction chlorthalidone > amlodipine > lisinopril; however, no difference between 3 agents in fatal coronary heart disease or non-fatal MI or mortality
• *Similar efficacy overall

Question 15

Adverse reactions w/ thiazide diuretics

Answer 15

• Electrolyte imbalances
• Increased uric acid
• Decreased glucose

Question 16

Adverse reactions w/ ACE inhibitors

Answer 16

• Dry cough

- Increased potassium

Question 17

Adverse reactions w/ ARBs

Answer 17

Increased potassium and sCr

Question 18

Adverse reactions w/ beta-blockers

Answer 18

• Cold extremities
• Fatigue
• Nausea
• Decreased exercise tolerance

Question 19

Adverse reactions w/ DHP CCBs

Answer 19

• Flushing
• Ankle edema
• Headache
• Increased HR

Question 20

Are beta-blockers useful for lone HTN?

Answer 20

• Better reduction of CV events vs. placebo in < 60 y/o; no benefit in > 60 y/o
• Vs. other anti-HTN agents – beta-blockers have similar reduction of CV events in < 60 y/o, but worse in > 60 y/o (small increase in strokes)

Question 21

Should beta-blockers ever be used first line for HTN?

Answer 21

Yes, if CHF or angina, or as an option for A Fib

Question 22

What are some special considerations for anti-HTN agents?

Answer 22

• Thiazides are less effective if Clcr < 30 mL/min
• ACE inhibitors, ARBs, & beta blockers may be less effective in black patients
• CCBs have CYP 3A4 interactions

Question 23

What are some generalizations about choosing an anti-HTN agent?

Answer 23

• Efficacy, convenience, & cost are all similar

- Safety/adverse effects is what varies & what determines the agent based on pt

Question 24

Which agent should be chosen for initial thiazide therapy?

Answer 24

• HCTZ considered (at best) equal to and very likely inferior to chlorthalidone
• Therefore, consider chlorthalidone or indapamide when initiating thiazide diuretic therapy for HTN

Question 25

What is the recommendation for HTN in type 2 diabetes?

Answer 25

- Meta-analyses of over 73,000 px concluded that if SBP < 140 mmHg, further tx associated w/ increased risk of CV death, w/ no observed benefit - Didn’t persuade CHEP or CDA to change guidelines that state BP target is 130/80

Question 26

Which anti-HTN agent is best for type 2 diabetes?

Answer 26

- CHEP 2018 recommendation = ACE inhibitor, ARB, DHP CCB, or thiazide/thiazide-like diuretic (no preference) - Dipiro = ACE inhibitor or ARB

Question 27

Describe the ALLHAT study of diabetes subgroup

Answer 27

- Looked at over 13,000 px taking chlorthalidone, lisinopril, & amlodipine - No difference in incidence of end-stage renal disease between chlorthalidone & lisinopril - No difference in coronary heart disease, stroke, or combined CV disease between the 3

Question 28

Describe the role of ACE inhibitors/ARBs in renal protection for type 2 diabetes

Answer 28

- When compared to placebo or other anti-HTN in px w/o albuminuria (no kidney disease): - - ACEi are only agents shown to reduce incidence of microalbuminuria in diabetics - - No significant decrease in incidence of double of sCr or ESRD - Vs. placebo or other anti-HTN in px w/ albuminuria -> reduced progression of nephropathy -> ESRD

Question 29

Describe the general rules for HTN in type 2 diabetes

Answer 29

- Best evidence for target of DBP < 85-90 mmHg and SBP < 140 mmHg - Long-term CV protection is similar for first-line agents - For those w/o diabetic kidney disease, ACEi & ARB reduce likelihood of developing microalbuminuria but not doubling of sCr or ESRD - For those w/ diabetic kidney disease, ACEi & ARB both delay progression of nephropathy to ESRD

Question 30

Describe the research done regarding combination therapy for HTN?

Answer 30

- Summary of 354 HTN trials => using half-standard doses results in 20% less BP reduction - 119 trials compared mono vs. combo therapy => greater incidence of adverse effects w/ combo (5.2% w/ mono vs. 7.5% w/ combo)

Question 31

What is the general consensus of combination therapy in HTN?

Answer 31

- Use of 2 drugs initially generally not a rational approach - Smaller doses often do almost as good of a job at BP reduction as larger doses - Adding an agent is additive for BP reduction, but less than additive for adverse effects

Question 32

What is the importance of treating HTN in elderly?

Answer 32

- Elderly more sensitive to symp inhibition & volume depletion => increased orthostatic hypotension => increased risk of falls & morbidity - Low BP may be associated w/ dementia, cancer, HF, & MI - Age > 85 y/o w/ low SBP (< 120) associated w/ increased mortality - Age ~ 70 y/o w/ low DBP (< 65) associated w/ increased stroke & CV event risk - Isolated systolic HTN & wide pulse pressures increase risk of MI, stroke, & renal failure

Question 33

What was the HYVET study researching?

Answer 33

HTN in the very elderly

Question 34

Describe the HYVET study

Answer 34

- Over 3,000 px aged 80 y/o and older; SBP >/ 160 mmHg (baseline 173/91) - Target BP was 150/80 - Active-tx group = indapamide 1.5 mg OD + perindopril 2-4 mg OD added if necessary, vs. placebo - Placebo decreased BP to 159/84; active decreased to 144/78 (20% of placebo reached target; 48% of active reached target) - Reduction to < 150/80 decreased CV events by 3% over 3 years and decreases mortality by 2.2% -> is this worth it to the pt? probably not

Question 35

What is the general approach to treating HTN in the elderly?

Answer 35

- BP reduction in very elderly w/ HTN is beneficial - - Target = < 150/80 (likely not applicable to frail elderly) - Outcome benefits apparent w/in first year - Agent doesn’t matter; thiazide or ACEi reasonable first line options - 50% will reach target BP w/ 2 agents, but only start w/ 1 (think about tx burden)