Therapeutics of Hypertension Part 2 Flashcards
ACC/AHA Recommendation for Choice of Initial Medication:
For initiation of antihypertensive drug therapy, first-line agents include thiazide diuretics, CCBs, and ACE inhibitors or ARBs.
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
*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
ALLHAT Key Takeaways
*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
Combination therapy
target different mechanisms
*Preferred: ACEi/CCB, ARB/CCB, ACEi/diuretic, ARB/diuretic
Acceptable: CCB/diuretic
Patient Specific Factor: Stable Ischemic Heart Disease
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
Patient Specific Factor: Heart Failure
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
Patient Specific Factor: Chronic Kidney
Disease
*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)
Patient Specific Factor: Cerebrovascular Disease
Secondary stroke prevention:
* ACEi/ARBs
* Thiazide diuretic
* Combination of above
Usefulness of initiating antihypertensive treatment for BP <140/90 is not well established
Patient Specific Factor: Diabetes
*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
Patient Specific Factor: Pregnancy
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
Patient Specific Factor: Ethnicity and Race
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
Stable ischemic heart disease
ACE-I/ARB and BB first, then CCB can be added if still not controlled
HFrEF
ACE-I/ARB/ARNI, mineralocorticoid receptor antagonists, diuretics, and BB first line
HFpEF
diuretics first line (if symptomatic); if persistent HTN, ACE-I/ARB or BB (if HR elevated)
CKD
if albuminuria, ACE-I (ARB if intolerant) first line
Renal transplant
CCB (reduces graft loss and maintains higher GFR) first line over ACE-I (anemia, hyperkalemia and lower GFR may result)
Secondary stroke prevention
thiazide, ACE-I or ARB or thiazide + ACE-I
*only need to start if BP>/= 140/90
DM
any first line option but ACE-I/ARB if albuminuria
Atrial fibrillation
ARB may be useful for prevention of recurrence of AF
Aortic disease
BB (help improve survival)
Black patients
thiazide or CCB unless HF or CKD
Pregnancy
methyldopa, nifedipine, or labetolol
Diuretics
Thiazide
* chlorthalidone, hydrochlorothiazide, indapamide, metolazone
Loop
* furosemide, torsemide, bumetanide
Aldosterone antagonists
* spironolactone, eplerenone
Potassium-sparing
* amiloride, triamterene
Diuretics in Hypertension
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
Thiazide Diuretics
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
Thiazide diuretics frequency
once a day in the morning
Thiazide Diuretics AEs
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
Loop Diuretics
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
Loop Diuretics frequency
all at least once a day in the morning
furosemide and bumetanide can be twice a day - once in morning, once in afternoon
Loop Diuretics AEs
Adverse effects:
* Hypokalemia, hypomagnesemia, hypocalcemia, hyperuricemia,
ototoxicity
Contraindications:
* Sulfa allergy
Aldosterone Antagonists
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
Aldosterone Antagonists frequency
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%
Aldosterone Antagonists AEs
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)
Potassium-Sparing Diuretics
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
Potssium-Sparing Diuretics frequency
once or twice daily in the morning
AEs: hyperkalemia, increase uric acid (caution in pts with controlled gout), hyperglycemia
Diuretic Monitoring
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
Diuretics Clinical Pearls
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)
