What medications are recommended for cardiorenal protection?

From the Guidelines

The most effective medications for cardiorenal protection are SGLT2 inhibitors and GLP-1 receptor agonists, which have demonstrated significant benefits in reducing heart failure hospitalizations, progression of kidney disease, and cardiovascular death. These medications are recommended as first-line therapy for patients with diabetes, chronic kidney disease, or heart failure to maximize cardiorenal protection 1. The use of SGLT2 inhibitors, such as empagliflozin (10-25mg daily), dapagliflozin (10mg daily), and canagliflozin (100-300mg daily), has been shown to reduce MACE, HF, and improve kidney outcomes in people with established CVD or CKD 1. GLP-1 receptor agonists, such as semaglutide (0.25-1mg weekly), dulaglutide (0.75-4.5mg weekly), and liraglutide (0.6-1.8mg daily), also offer cardiorenal protection by improving glycemic control, promoting weight loss, and reducing inflammation 1. Additionally, ACE inhibitors (like lisinopril 10-40mg daily) and ARBs (such as losartan 25-100mg daily) provide protection by blocking the renin-angiotensin-aldosterone system, which reduces blood pressure, proteinuria, and fibrosis in both heart and kidney tissues 1. Key considerations for medication selection include:

• The presence of established CVD, CKD, or HF
• The level of kidney function, as measured by eGFR
• The presence of albuminuria, as measured by UACR
• The patient's age, reproductive potential, and other comorbidities
• The potential for medication interactions and side effects. In general, selection of medications to improve cardiovascular and kidney outcomes should not differ for older people, and in younger people with diabetes, consider early combination therapy 1.

From the FDA Drug Label

In two placebo controlled, 12-week clinical studies compared the addition of lisinopril up to 20 mg daily to digitalis and diuretics alone. The combination of lisinopril, digitalis and diuretics reduced the following signs and symptoms of heart failure: edema, rales, paroxysmal nocturnal dyspnea and jugular venous distention In one of the studies, the combination of lisinopril, digitalis and diuretics reduced orthopnea, presence of third heart sound and the number of patients classified as NYHA Class III and IV; and improved exercise tolerance. A large (over 3,000 patients) survival study, the ATLAS Trial, comparing 2. 5 mg and 35 mg of lisinopril in patients with systolic heart failure, showed that the higher dose of lisinopril had outcomes at least as favorable as the lower dose

Medications for cardiorenal protection include:

• Lisinopril: an angiotensin-converting enzyme (ACE) inhibitor that has been shown to reduce signs and symptoms of heart failure and improve exercise tolerance 2.
• Spironolactone: an aldosterone antagonist that can cause hyperkalemia, but may be used for cardiorenal protection in certain patients, such as those with heart failure 3.

Key points:

• Lisinopril has been shown to reduce blood pressure and improve outcomes in patients with heart failure.
• Spironolactone can cause hyperkalemia and should be used with caution in patients with impaired renal function.
• The combination of lisinopril, digitalis, and diuretics can reduce signs and symptoms of heart failure.

From the Research

Medications for Cardiorenal Protection

Medications that provide cardiorenal protection are crucial for patients with hypertension and chronic kidney disease. The following medications are recommended:

• Angiotensin-converting enzyme (ACE) inhibitors: These medications have been shown to have beneficial effects on proteinuria and declining renal function, and are recommended as a first-line antihypertensive approach in patients with chronic kidney disease 4, 5.
• Angiotensin receptor blockers (ARBs): ARBs have similar benefits to ACE inhibitors and are recommended for patients who are intolerant to ACE inhibitors 4, 5.
• Calcium channel antagonists: These medications can be used in combination with ACE inhibitors or ARBs to reduce blood pressure and preserve renal function 4, 6.
• Diuretics: Diuretics can be used in combination with ACE inhibitors or ARBs to reduce blood pressure and preserve renal function 4, 6.

Specific Medications

Some specific medications that have been shown to be effective for cardiorenal protection include:

• Manidipine: A third-generation dihydropyridine calcium channel antagonist that has been shown to have beneficial effects on intrarenal haemodynamics, proteinuria, and other measures of renal functional decline 4.
• Verapamil and diltiazem: These calcium channel antagonists have been shown to have long-term cardioprotective effects after a myocardial infarction 6.

Guideline Recommendations

Guidelines recommend the use of ACE inhibitors and ARBs as first-line therapy for patients with hypertension and chronic kidney disease 5, 7. However, the implementation of these guidelines in clinical practice is unclear, and studies have shown that these medications are not always prescribed as recommended 7.