Therapeutics of Hypertension Part 2

Question 1

ACC/AHA Recommendation for Choice of Initial Medication:

Answer 1

For initiation of antihypertensive drug therapy, first-line agents include thiazide diuretics, CCBs, and ACE inhibitors or ARBs.

Question 2

Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Answer 2

*42,418 patients age >55 years with HTN and 1 additional CV risk factor
*Patients randomized to: Chlorthalidone, Lisinopril-based therapy, Amlodipine, Doxazosin
*Results: Chlorthalidone > amlodipine and lisinopril-based therapy in preventing stroke, heart attacks, and heart failure
* Doxazosin arm stopped early due to increased risk of heart failure

Question 3

ALLHAT Key Takeaways

Answer 3

*Thiazide diuretics should be first-line
*For patients who cannot take a diuretic, consider prescribing a calcium channel blocker or ACE inhibitor
*Most patients with high blood pressure need more than one drug

Question 4

Combination therapy

Answer 4

target different mechanisms
*Preferred: ACEi/CCB, ARB/CCB, ACEi/diuretic, ARB/diuretic
Acceptable: CCB/diuretic

Question 5

Patient Specific Factor: Stable Ischemic Heart Disease

Answer 5

Encompass patients who have angina
First-line:
* Beta blockers (reduce CV
events and anginal symptoms)
* ACEi/ARBs (reduce MI, stroke, and CVD)
* Dihydropyridine CCBs can be used if still uncontrolled

Question 6

Patient Specific Factor: Heart Failure

Answer 6

Reduced ejection fraction: follow most recent heart failure guidelines
* Avoid non-dihydropyridine CCBs due to no clinical benefit/worse outcomes in patients with HF
Preserved ejection fraction:
* Diuretics: fluid overloaded
* ACEi/ARB: elevated BP
* Beta blockers: elevated heart rate

Question 7

Patient Specific Factor: Chronic Kidney
Disease

Answer 7

*CKD Stage 1 or 2 AND albuminuria (>300 mg/day, or >300 mg/g albumin-tocreatinine ratio): ACEi (or ARBs)
*CKD Stage 3 (eGFR<60) or higher: ACEi (or ARBs)
*Post kidney transplantation: dihydropyridine CCBs are preferred due to improved GFR and kidney survival (cause vasodilation –> increase blood flow to kidneys, don’t work in kidneys)

Question 8

Patient Specific Factor: Cerebrovascular Disease

Answer 8

Secondary stroke prevention:
* ACEi/ARBs
* Thiazide diuretic
* Combination of above
Usefulness of initiating antihypertensive treatment for BP <140/90 is not well established

Question 9

Patient Specific Factor: Diabetes

Answer 9

*All first-line classes of antihypertensive agents are useful and effective (can use a thiazide diuretic or CCB if no albuminuria)
*In the presence of albuminuria (>300 mg/day, or >300 mg/g albumin-to-creatinine ratio): ACEi or ARBs

Question 10

Patient Specific Factor: Pregnancy

Answer 10

Preferred agents:
* Methyldopa
* Nifedipine
* Labetalol
Contraindicated:
* ACEi
* ARBs
* Direct renin inhibitors
don’t want to use any agents that work in the RAAS system; thiazide diuretics cause electrolyte abnormalities

Question 11

Patient Specific Factor: Ethnicity and Race

Answer 11

In black adults with hypertension but without HF or CKD, including those with DM, initial antihypertensive treatment should include a thiazide diuretic or CCB (if not spilling protein)
* Better data for lowering BP and reducing CV events

Question 12

Stable ischemic heart disease

Answer 12

ACE-I/ARB and BB first, then CCB can be added if still not controlled

Question 13

HFrEF

Answer 13

ACE-I/ARB/ARNI, mineralocorticoid receptor antagonists, diuretics, and BB first line

Question 14

HFpEF

Answer 14

diuretics first line (if symptomatic); if persistent HTN, ACE-I/ARB or BB (if HR elevated)

Question 15

CKD

Answer 15

if albuminuria, ACE-I (ARB if intolerant) first line

Question 16

Renal transplant

Answer 16

CCB (reduces graft loss and maintains higher GFR) first line over ACE-I (anemia, hyperkalemia and lower GFR may result)

Question 17

Secondary stroke prevention

Answer 17

thiazide, ACE-I or ARB or thiazide + ACE-I
*only need to start if BP>/= 140/90

Question 18

DM

Answer 18

any first line option but ACE-I/ARB if albuminuria

Question 19

Atrial fibrillation

Answer 19

ARB may be useful for prevention of recurrence of AF

Question 20

Aortic disease

Answer 20

BB (help improve survival)

Question 21

Black patients

Answer 21

thiazide or CCB unless HF or CKD

Question 22

Pregnancy

Answer 22

methyldopa, nifedipine, or labetolol

Question 23

Diuretics

Answer 23

Thiazide
* chlorthalidone, hydrochlorothiazide, indapamide, metolazone
Loop
* furosemide, torsemide, bumetanide
Aldosterone antagonists
* spironolactone, eplerenone
Potassium-sparing
* amiloride, triamterene

Question 24

Diuretics in Hypertension

Answer 24

Initial anti-hypertensive effects:
* diuresis → reduced stroke volume → increase in PVR (peripheral vascular resistance)
Chronic anti-hypertensive effects:
* Stroke volume returns to normal → decrease in PVR (below pretreatment levels)
Different sub-classes can be combined for additive/synergistic effects

Question 25

Thiazide Diuretics

Answer 25

Agents: Hydrochlorothiazide(HCTZ), chlorthalidone, indapamide, metolazone (not really used unless fluid problem)
* Chlorthalidone is the most studied and 1-2 x more potent than HCTZ (more commonly used, less expensive)
First-line for most HTN patients (ALLHAT)
More effective than loop diuretics with CrCl > 30 mL/min
Dose in the morning to avoid nocturnal diuresis

Question 26

Thiazide diuretics frequency

Answer 26

once a day in the morning

Question 27

Thiazide Diuretics AEs

Answer 27

Adverse effects:
* Hypokalemia, hypomagnesemia, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia, sexual dysfunction, increase in triglycerides/cholesterol
Drug interactions:
* Lithium toxicity with concurrent use
Contraindications:
* Sulfa allergy, anuria

Question 28

Loop Diuretics

Answer 28

Agents: furosemide (least bioavailable), torsemide, bumetanide, ethacrynic acid (used with pts who have a sulfa allergy)
NOT first line for HTN
* Preferred in heart failure for symptom management
* More effective than thiazide diuretics with CrCl < 30 mL/min
“High-ceiling” dose response curve:
* May need higher doses with severely reduced renal function or fluid overload
* Switching to another loop diuretic or from PO to IV can help
Dose in the morning or afternoon to avoid nocturnal diuresis

Question 29

Loop Diuretics frequency

Answer 29

all at least once a day in the morning
furosemide and bumetanide can be twice a day - once in morning, once in afternoon

Question 30

Loop Diuretics AEs

Answer 30

Adverse effects:
* Hypokalemia, hypomagnesemia, hypocalcemia, hyperuricemia,
ototoxicity
Contraindications:
* Sulfa allergy

Question 31

Aldosterone Antagonists

Answer 31

Agents: spironolactone, eplerenone
Spironolactone is preferred with resistant HTN (PATHWAY-2 Trial)
Gynecomastia develops in up to 10% of patients on spironolactone
* Can switch to eplerenone
Do not initiate aldosterone antagonist with potassium >5mEq/L (can cause hyperkalemia)
Dose in the morning or afternoon to avoid nocturnal diuresis

Question 32

Aldosterone Antagonists frequency

Answer 32

once or twice daily dosing in the morning or afternoon
consider holding or reducing dose if potassium > 5.5 mEg/L or SCr increase >25%

Question 33

Aldosterone Antagonists AEs

Answer 33

Adverse effects:
* Hyperkalemia, hyponatremia, gynecomastia(spironolactone)
Drug interactions:
* ACEi/ARBs/Renin inhibitors/NSAIDs- increase risk of hyperkalemia
Contraindications:
* Eplerenone:
* Impaired renal function (CrCl <50 mL/min or SCr >2 [male] or >1.8 [female])
* T2DM & proteinuria (increase risk of AKI)
Both:
* Concomitant use of potassium sparing diuretics (risk of hyperkalemia)

Question 34

Potassium-Sparing Diuretics

Answer 34

Agents: amiloride, triamterene
Minimal BP effects
* Used in combination with thiazide to minimize hypokalemia
Use with caution in patients with diabetes or CKD (GFR < 45 ml/min)
Dose in the morning to avoid nocturnal diuresis

Question 35

Potssium-Sparing Diuretics frequency

Answer 35

once or twice daily in the morning
AEs: hyperkalemia, increase uric acid (caution in pts with controlled gout), hyperglycemia

Question 36

Diuretic Monitoring

Answer 36

baseline: electrolytes, renal function
1-2 weeks after initiation
3-4 weeks after initiation (only for loop diuretics and aldosterone antagonists)
every 6-12 months

Question 37

Diuretics Clinical Pearls

Answer 37

Do not give at bedtime
Thiazides are first-line for most HTN patients
Spironolactone is first-line for patients with resistant HTN
Don’t use potassium-sparing diuretics as monotherapy for HTN
Pay attention to patient allergies (sulfa)
Check CrCl when choosing diuretic class
Important to monitor potassium (and other electrolytes)