What is the best treatment for hypertension?

Best Treatment for Hypertension

For most adults with confirmed hypertension, initiate combination therapy with two medications from the start—specifically a RAS blocker (ACE inhibitor or ARB) combined with either a dihydropyridine calcium channel blocker or thiazide/thiazide-like diuretic, preferably as a single-pill combination, targeting a systolic blood pressure of 120-129 mmHg if tolerated. 1, 2

Initial Pharmacological Treatment Strategy

Start with dual combination therapy immediately rather than monotherapy for confirmed hypertension (BP ≥140/90 mmHg). 1, 2 The European Society of Cardiology explicitly recommends against monotherapy as initial treatment, as combination therapy is more effective from the outset. 2

Preferred First-Line Combinations:

• ACE inhibitor or ARB + dihydropyridine calcium channel blocker (e.g., amlodipine) 1, 3
• ACE inhibitor or ARB + thiazide/thiazide-like diuretic (e.g., chlorthalidone or hydrochlorothiazide) 1, 3

Use fixed-dose single-pill combinations when available to improve adherence. 1, 2

Race-Specific Considerations:

• For Black patients: Initial therapy should include a diuretic or calcium channel blocker, either in combination or with a RAS blocker. 1 The combination of calcium channel blocker + thiazide diuretic may be more effective than calcium channel blocker + RAS blocker in this population. 1, 4

• For non-Black patients: The standard sequence is RAS blocker + calcium channel blocker or RAS blocker + thiazide diuretic. 1, 4

Blood Pressure Targets

• Standard target: 120-129 mmHg systolic if well tolerated 1, 2
• Minimum acceptable target: <140/90 mmHg for most patients 5, 2, 3
• For patients ≥60 years: <150 mmHg systolic reduces mortality, stroke, and cardiac events 5
• For patients with diabetes: <130/80 mmHg 5, 1
• For patients with prior stroke/TIA: Consider <140 mmHg systolic to reduce recurrent stroke 5

Treatment Escalation Algorithm

Step 1: Two-Drug Combination

RAS blocker (ACE inhibitor or ARB) + calcium channel blocker OR thiazide diuretic, preferably as single-pill combination. 1, 2

Step 2: Three-Drug Combination

If BP remains uncontrolled, add the third agent: RAS blocker + dihydropyridine calcium channel blocker + thiazide/thiazide-like diuretic. 1, 4 This represents guideline-recommended triple therapy with complementary mechanisms targeting volume reduction, vasodilation, and renin-angiotensin system blockade. 4

Step 3: Four-Drug Combination (Resistant Hypertension)

Add spironolactone 25-50mg daily as the preferred fourth-line agent if BP remains uncontrolled despite optimized triple therapy. 1, 4, 6 Spironolactone provides additional BP reductions of 20-25/10-12 mmHg when added to triple therapy and is the most effective treatment for resistant hypertension. 4, 6

Essential Lifestyle Modifications (Concurrent with Pharmacotherapy)

Never delay pharmacological treatment while attempting lifestyle modifications alone—both should be initiated simultaneously. 2

• Weight reduction to BMI 20-25 kg/m² through reduced fat and total calorie intake 1, 2, 3
• Sodium restriction to <2,300 mg/day (ideally <2g/day) by eliminating excessively salty foods 1, 2, 3
• DASH diet pattern: 8-10 servings of fruits/vegetables daily and 2-3 servings of low-fat dairy products 1
• Regular aerobic physical activity (predominantly dynamic like brisk walking) 1, 2
• Alcohol limitation: ≤2 drinks/day for men, ≤1 drink/day for women 1
• Complete tobacco cessation with referral to smoking cessation programs 1
• Elimination of sugar-sweetened beverages and restriction of free sugar to maximum 10% of energy intake 1

Lifestyle modifications can lower systolic BP by 3.5-20 mmHg and reduce cardiovascular disease risk by approximately 30%, providing additive effects to pharmacological therapy. 3, 7, 8

Monitoring and Follow-Up

• Confirm diagnosis with out-of-office BP measurements (home BP ≥135/85 mmHg or 24-hour ambulatory BP ≥130/80 mmHg) before initiating treatment 2
• Achieve target BP within 3 months of treatment initiation or modification 1, 2
• Monitor serum potassium and creatinine 2-4 weeks after initiating RAS blockers or diuretics 1, 2
• See patients frequently (every 1-3 months) until BP is controlled 2
• Maintain treatment lifelong, even beyond age 85, if well tolerated 1

Critical Pitfalls to Avoid

• Never use monotherapy as initial treatment for confirmed hypertension—combination therapy is recommended from the outset 2
• Never combine two RAS blockers (ACE inhibitor + ARB)—this increases adverse events like hyperkalemia and acute kidney injury without additional cardiovascular benefit 1, 4
• Never add a beta-blocker as third-line agent unless there are compelling indications (angina, post-MI, heart failure with reduced ejection fraction, or need for heart rate control) 4
• Do not add a fourth drug class before maximizing doses of the current three-drug regimen—this violates guideline-recommended stepwise approaches 4
• Verify medication adherence before assuming treatment failure—non-adherence is the most common cause of apparent treatment resistance 4, 8

Evidence Supporting Blood Pressure Reduction

An SBP reduction of 10 mmHg decreases risk of cardiovascular events by approximately 20-30%. 3 The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality have also been seen regularly. 9, 10, 3 High-quality evidence shows that treating hypertension in older adults to moderate targets (<150/90 mmHg) reduces mortality, stroke, and cardiac events. 5