What is the treatment algorithm for uncontrolled hypertension (HTN)?

Treatment Algorithm for Uncontrolled Hypertension

For patients with uncontrolled hypertension, a systematic approach using combination therapy with ACE inhibitors/ARBs, calcium channel blockers, and diuretics, followed by the addition of mineralocorticoid receptor antagonists if needed, is recommended to achieve target blood pressure below 130/80 mmHg. 1

Initial Assessment and Optimization

• Confirm true uncontrolled hypertension by using out-of-office measurements (home BP monitoring or ambulatory BP monitoring) to rule out white coat hypertension 1
• Assess medication adherence and optimize current regimen before adding new medications 1
• Review and address lifestyle factors: sodium restriction, weight loss, regular physical activity, and limited alcohol intake 2
• Discontinue substances that may interfere with BP control (NSAIDs, certain supplements) 2

Step-by-Step Treatment Algorithm

Step 1: Optimize First-Line Combination Therapy

• Start with a low-dose combination of two first-line agents 1:
  • ACE inhibitor or ARB (e.g., lisinopril) 3
  • Long-acting calcium channel blocker (dihydropyridine class) 1
  • If BP remains uncontrolled after 1-3 months, proceed to Step 2 1

Step 2: Triple Combination Therapy

• Add a thiazide diuretic to the ACE inhibitor/ARB and calcium channel blocker 1
• Use maximally tolerated doses of all three medications 1
• Reassess BP control after 1-3 months 1
• If BP remains uncontrolled, proceed to Step 3 1

Step 3: Management of Resistant Hypertension

Resistant hypertension is defined as BP that remains above target despite concurrent use of three antihypertensive agents including a diuretic 2

• Add spironolactone as fourth-line agent (most effective option for resistant hypertension) 1, 4, 2
• Monitor for hyperkalemia, especially in patients with chronic kidney disease or diabetes 1
• If spironolactone is not tolerated, consider alternatives:
  • Eplerenone (may need higher doses of 50-200 mg) 1
  • Beta-blockers (preferably vasodilating types like carvedilol, labetalol, or nebivolol) 1
  • Alpha-blockers (e.g., doxazosin) 2

Step 4: Further Options for Truly Resistant Cases

• Consider amiloride, centrally acting agents (clonidine), or vasodilators 1, 2
• Hydralazine can be effective but may provoke angina in patients with coronary artery disease 1
• Minoxidil should only be considered if all other agents prove ineffective due to multiple side effects 1

Special Considerations for Comorbidities

Coronary Artery Disease

• Target BP should be <130/80 mmHg 1
• Use beta-blockers and ACE inhibitors/ARBs as first-line therapy for compelling indications (previous MI, stable angina) 1
• Add dihydropyridine CCBs for patients with angina and persistent uncontrolled hypertension 1

Heart Failure with Preserved Ejection Fraction

• First manage volume overload with diuretics 1
• For persistent hypertension after volume management, use ACE inhibitors/ARBs and beta-blockers to achieve SBP <130 mmHg 1

Chronic Kidney Disease

• Target BP should be <130/80 mmHg 1
• ACE inhibitors or ARBs are preferred first-line agents 1

Common Pitfalls to Avoid

• Inadequate dosing: Nearly half of patients with resistant hypertension have inadequate dosing or suboptimal combinations 5
• Failure to assess adherence: Poor medication adherence is a major cause of uncontrolled hypertension 6
• Ignoring white coat effect: Confirm elevated office readings with home or ambulatory BP monitoring 1
• Not addressing lifestyle factors: Sodium restriction, weight loss, and physical activity are essential components of management 2
• Overlooking secondary causes: Consider screening for conditions like primary aldosteronism, chronic kidney disease, or sleep apnea in resistant cases 2, 5
• Not using single-pill combinations: These can improve adherence and simplify regimens 1

By following this algorithm and addressing these common pitfalls, clinicians can significantly improve blood pressure control rates in patients with uncontrolled hypertension 1.