What are the considerations for antihypertensive medications in patients with comorbid (co-existing) conditions?

From the Guidelines

When managing blood pressure in patients with comorbidities, it is essential to consider the specific condition and choose medications that provide additional benefits beyond blood pressure control, as recommended by the most recent guidelines 1.

Key Considerations

• For patients with diabetes, ACE inhibitors (like lisinopril 10-40mg daily) or ARBs (such as losartan 25-100mg daily) are preferred due to their renoprotective effects, as supported by the 2020 International Society of Hypertension global hypertension practice guidelines 1.
• In heart failure patients, a combination of ACE inhibitors/ARBs, beta-blockers (metoprolol succinate 25-200mg daily), and aldosterone antagonists (spironolactone 25-50mg daily) is recommended to reduce mortality and improve cardiac function, as outlined in the 2020 ACC/AHA guideline 1.
• For those with coronary artery disease, beta-blockers and calcium channel blockers (amlodipine 5-10mg daily) are beneficial due to their anti-ischemic properties, as noted in the 2020 International Society of Hypertension global hypertension practice guidelines 1.
• In chronic kidney disease, ACE inhibitors or ARBs help slow disease progression, but require monitoring of potassium and creatinine levels, as recommended by the British Hypertension Society guidelines 1.

Special Considerations

• For patients with asthma or COPD, calcium channel blockers or ARBs are preferred as beta-blockers may worsen bronchospasm, as cautioned in the 2020 International Society of Hypertension global hypertension practice guidelines 1.
• In elderly patients, starting with lower doses and gradually titrating is important to prevent orthostatic hypotension, with calcium channel blockers or thiazide diuretics (hydrochlorothiazide 12.5-25mg daily) often well-tolerated, as recommended by the 2020 International Society of Hypertension global hypertension practice guidelines 1.

Treatment Approach

• Consider monotherapy in low-risk grade hypertension and in patients aged >80 years or frail, and simplify regimen with once daily dosing and single pill combinations, as suggested by the 2020 International Society of Hypertension global hypertension practice guidelines 1.
• For non-black patients, consider low dose ACEI/ARB, increasing to full dose, and adding thiazide/thiazide-like diuretic, as outlined in the 2020 International Society of Hypertension global hypertension practice guidelines 1.
• For black patients, consider low dose ARB, increasing to full dose, and adding DHP-CCB or DHP-CCB thiazide/thiazide-like diuretic, as recommended by the 2020 International Society of Hypertension global hypertension practice guidelines 1.

From the FDA Drug Label

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). Losartan is indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes and a history of hypertension Lisinopril tablets USP are indicated to reduce signs and symptoms of systolic heart failure Amlodipine besylate tablets is indicated for the symptomatic treatment of chronic stable angina.

Special considerations for comorbid conditions include:

• Diabetes management: patients with diabetes may benefit from more aggressive treatment to a lower blood pressure goal 2
• Hyperlipidemia: patients with hyperlipidemia may benefit from more aggressive treatment to a lower blood pressure goal 2
• Heart failure: lisinopril is indicated to reduce signs and symptoms of systolic heart failure 3
• Angina: amlodipine is indicated for the symptomatic treatment of chronic stable angina 4
• Diabetic kidney disease: losartan is indicated for the treatment of diabetic nephropathy 2
• Black patients: some antihypertensive drugs have smaller blood pressure effects in black patients 2, 3, 4

From the Research

Blood Pressure Medications and Comorbid Conditions

• The treatment of hypertension often involves the use of multiple antihypertensive agents, with four main classes of medications being used in combination therapy: thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) 5.
• In patients with heart failure with reduced ejection fraction, initial treatment should include a beta blocker and an ACEI or ARB, followed by add-on therapy with a mineralocorticoid receptor antagonist and a diuretic based on volume status 5.
• For patients with chronic kidney disease and proteinuria, treatment should include an ACEI or ARB plus a thiazide diuretic or a calcium channel blocker 5.
• Patients with diabetes mellitus should be treated similarly to those without diabetes unless proteinuria is present, in which case combination therapy should include an ACEI or ARB 5.

Special Considerations for Comorbid Conditions

• In black patients, at least one agent should be a thiazide diuretic or a calcium channel blocker 5.
• ACEIs and ARBs should not be used simultaneously 5.
• The use of angiotensin II receptor antagonists (ARBs) in patients with heart failure has been evaluated in several clinical trials, with results showing that ARBs have haemodynamic effects similar to ACE inhibitors, but differ in their mechanism of action and certain adverse effects 6.
• A review of guidelines for the management of patients with cardiovascular disease found that ACE inhibitors are recommended as first-choice therapy, while ARBs are considered an alternative for ACE inhibitor-intolerant patients 7.

Combination Therapy

• Fixed-dosed combination regimens consisting of a calcium channel blocker and an angiotensin II type 1 receptor blocker have been shown to be effective in the management of hypertension, with complementary effects on blood pressure 8.
• Clinical trials have demonstrated that the combination of amlodipine (a calcium channel blocker) and an angiotensin II receptor blocker is well tolerated and produces greater reductions in blood pressure compared to individual agents or other combination therapies 8.