What is the treatment for hypertension combined with other conditions?

Treatment for Hypertension Combined with Other Conditions

For hypertension combined with comorbidities, initiate combination therapy with a RAS blocker (ACE inhibitor or ARB) plus either a calcium channel blocker or thiazide/thiazide-like diuretic as a single-pill combination, with specific drug selection and blood pressure targets determined by the coexisting condition. 1

Initial Assessment and Risk Stratification

Before initiating treatment, determine cardiovascular disease risk and screen for target organ damage to guide therapy intensity 1:

• Chronic kidney disease (CKD): Check eGFR and urine albumin-to-creatinine ratio 1
• Diabetes: Assess for diabetic nephropathy with serum creatinine and proteinuria 2
• Heart failure: Determine ejection fraction (HFrEF, HFmrEF, or HFpEF) 1
• Cerebrovascular disease: Document history of stroke or TIA 1
• Left ventricular hypertrophy: Consider ECG or echocardiography in appropriate patients 2

Hypertension with Chronic Kidney Disease

Target systolic BP to 120-129 mmHg in patients with moderate-to-severe CKD and eGFR >30 mL/min/1.73 m², if tolerated 1:

• For diabetic or non-diabetic CKD, lower systolic BP to 130-139 mmHg as a minimum target 1
• RAS blockers (ACE inhibitors or ARBs) are the preferred agents because they reduce albuminuria more effectively than other antihypertensives 1, 2
• Add SGLT2 inhibitors for patients with CKD and eGFR >20 mL/min/1.73 m² 3
• Individualize treatment based on tolerability, renal function, and electrolyte levels 1
• Monitor serum creatinine/eGFR and potassium regularly, especially with RAS blockers 4

Hypertension with Diabetes

Target systolic BP to 120-129 mmHg if tolerated, but not below 120 mmHg 4:

• Start with RAS blocker (ACE inhibitor or ARB) plus calcium channel blocker or thiazide diuretic 1, 3
• ACE inhibitors or ARBs are particularly important in diabetic nephropathy with elevated serum creatinine and proteinuria (albumin-to-creatinine ratio ≥300 mg/g) 2
• Losartan specifically reduces progression of diabetic nephropathy, decreasing doubling of serum creatinine and end-stage renal disease 2
• Add SGLT2 inhibitors for additional cardiovascular and renal protection 3

Hypertension with Heart Failure

Heart Failure with Reduced Ejection Fraction (HFrEF)

Use ACE inhibitor (or ARB if ACE inhibitor not tolerated) or ARNI, plus beta-blocker, plus MRA, plus SGLT2 inhibitor 1:

• This combination addresses both blood pressure control and heart failure outcomes 1
• Add diuretics as needed for volume management 1
• All four medication classes have proven mortality benefit in HFrEF 1

Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF)

Follow the same regimen as HFrEF: ACE inhibitor/ARB/ARNI, beta-blocker, MRA, and SGLT2 inhibitor 1

Heart Failure with Preserved Ejection Fraction (HFpEF)

SGLT2 inhibitors are the primary recommendation for symptomatic HFpEF with hypertension 1:

• No specific drug class has proven superiority, so all major antihypertensive agents can be used 1
• If BP remains above target, consider ARBs and/or MRAs to reduce heart failure hospitalizations 1
• SGLT2 inhibitors provide modest BP-lowering along with improved outcomes 1

Hypertension with Cerebrovascular Disease

Target systolic BP to 120-130 mmHg in all hypertensive patients with ischemic stroke or TIA 1:

• For confirmed BP ≥130/80 mmHg with history of TIA or stroke, target 120-129 mmHg to reduce cardiovascular outcomes 1
• Initiate antihypertensive treatment immediately for TIA 1
• Wait several days after ischemic stroke before starting or resuming antihypertensive therapy 1

Acute Intracerebral Hemorrhage

• Do not lower BP immediately if systolic BP <220 mmHg 1
• If systolic BP ≥220 mmHg, carefully lower BP with intravenous therapy to <180 mmHg 1

Hypertension with Left Ventricular Hypertrophy

Losartan specifically reduces stroke risk in hypertensive patients with left ventricular hypertrophy 2:

• This benefit does not apply to Black patients 2
• Use standard combination therapy approach with RAS blocker plus calcium channel blocker or diuretic 1

Hypertension in Black Patients

Initial therapy should include a thiazide diuretic or calcium channel blocker, either in combination with each other or with a RAS blocker 1:

• For Black patients from Sub-Saharan Africa, use calcium channel blocker combined with either thiazide diuretic or RAS blocker 1
• Combination therapy is specifically recommended for most Black patients 1

Resistant Hypertension (Uncontrolled on Three Drugs)

Add low-dose spironolactone (25-50 mg daily) to existing treatment 1:

• First, reinforce lifestyle measures, especially sodium restriction to <2 g/day 1
• If spironolactone is not tolerated or ineffective, use eplerenone, amiloride, higher-dose thiazide/thiazide-like diuretic, or loop diuretic 1
• Next-line options include bisoprolol or doxazosin 1
• Consider catheter-based renal denervation at high-volume centers after multidisciplinary assessment and shared decision-making 1

Core Pharmacological Strategy

First-Line Agents

ACE inhibitors, ARBs, dihydropyridine calcium channel blockers, and thiazide/thiazide-like diuretics (chlorthalidone, indapamide) are the proven first-line agents 1, 3, 5:

• These classes have demonstrated the most effective reduction in BP and cardiovascular events 1, 3
• Amlodipine (calcium channel blocker) reduces cardiovascular morbidity and mortality 6
• Losartan (ARB) lowers risk of fatal and nonfatal cardiovascular events 2
• Hydrochlorothiazide (thiazide diuretic) is indicated for hypertension management 7

Combination Therapy Approach

Start with two-drug combination for most patients with confirmed hypertension (BP ≥140/90 mmHg) 1, 3:

• Preferred combinations: RAS blocker + calcium channel blocker OR RAS blocker + thiazide/thiazide-like diuretic 1, 3
• Use fixed-dose single-pill combinations to improve adherence 1, 3
• If BP not controlled, escalate to three-drug combination: RAS blocker + calcium channel blocker + thiazide/thiazide-like diuretic 1, 3
• Never combine two RAS blockers (ACE inhibitor + ARB)—this is potentially harmful 1, 3

Beta-Blockers

Reserve beta-blockers for specific compelling indications: angina, post-myocardial infarction, HFrEF, or heart rate control 1, 3

Blood Pressure Targets by Condition

Condition	Systolic BP Target	Key Considerations
General hypertension	120-129 mmHg [1,3]	If not tolerated, use ALARA principle [3]
Diabetes	120-129 mmHg, not <120 [4]	Monitor for hypoglycemia
CKD (eGFR >30)	120-129 mmHg [1,3]	Monitor renal function and electrolytes
CKD (general)	130-139 mmHg [1,4]	Individualize based on eGFR
Stroke/TIA history	120-130 mmHg [1]	Proven to reduce CVD outcomes
Age ≥85 years	Maintain treatment if tolerated [1,3]	Test for orthostatic hypotension

Essential Lifestyle Modifications

All patients require comprehensive lifestyle intervention regardless of medication use 1, 3, 5:

Dietary Changes

• Adopt Mediterranean or DASH diet 1, 3, 4
• Reduce sodium to approximately 2 g/day (equivalent to 5 g salt/day) 1, 3
• Restrict free sugar consumption to maximum 10% of energy intake; avoid sugar-sweetened beverages 1
• Increase potassium intake through fresh fruits and vegetables 5

Weight Management

• Target BMI 20-25 kg/m² and waist circumference <94 cm (men) or <80 cm (women) 1, 3
• Weight loss has additive BP-lowering effects with medications 5

Physical Activity

• Moderate-intensity aerobic exercise ≥150 minutes/week (30 minutes, 5-7 days/week) 1
• Add low- or moderate-intensity resistance training 2-3 times/week 1

Alcohol and Tobacco

• Limit alcohol to <100 g/week of pure alcohol; preferably avoid completely 1, 3
• Stop tobacco smoking immediately and refer to cessation programs 1, 3, 4

Implementation and Adherence Strategies

Take medications at the most convenient time of day to establish habitual patterns 1, 3:

• Use multidisciplinary approaches including physicians, nurses, pharmacists, dietitians, and physiotherapists 3
• Implement home BP monitoring to improve control and patient empowerment 3
• Address five dimensions of adherence: socio-economic, health system, therapy-related, condition-related, and patient-related factors 3
• Maintain BP-lowering treatment lifelong, even beyond age 85, if well tolerated 1, 3, 4

Critical Pitfalls to Avoid

• Do not delay combination therapy in patients with confirmed hypertension ≥140/90 mmHg 3
• Do not use monotherapy when combination therapy would be more effective 3
• Never combine ACE inhibitor with ARB—this increases harm without benefit 1, 3
• Do not fail to screen for secondary hypertension in adults diagnosed before age 40 3
• Do not discontinue treatment prematurely—BP control requires lifelong management 3
• Do not ignore orthostatic hypotension before starting or intensifying treatment, especially in older adults 3