What is the therapeutic effect of Amlodipine (Norvasc) 10mg and Losartan (Losartan) 50mg in managing Hypertension with Chronic Kidney Disease (CKD) stage 3 and Impaired Renal Function?

From the Guidelines

Norvasc (amlodipine) 10mg and losartan 50mg are beneficial for chronic kidney disease (CKD) stage 3 with hypertension because they effectively lower blood pressure while providing kidney protection. This combination addresses the dual concerns of hypertension management and slowing CKD progression. Losartan, an angiotensin receptor blocker (ARB), reduces protein leakage in the urine (proteinuria) and decreases pressure within the kidney's filtering units, which helps preserve kidney function, as supported by the 2019 KDOQI US commentary on the 2017 ACC/AHA hypertension guideline 1. It also blocks the renin-angiotensin-aldosterone system that can damage kidneys over time. Norvasc, a calcium channel blocker, complements this action by dilating blood vessels throughout the body, further reducing blood pressure without negatively impacting kidney function.

The importance of controlling hypertension in CKD patients is highlighted in the 2018 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults, which notes that hypertension is the most common comorbidity affecting patients with CKD, and that treating hypertension is crucial to prevent further kidney functional decline 1. The guideline also suggests that an ACE inhibitor or an ARB is a preferred drug for treatment of hypertension if albuminuria is present. Although the evidence is mixed, the use of losartan in this context is reasonable, especially if an ACE inhibitor is not tolerated, as stated in the 2019 KDOQI US commentary on the 2017 ACC/AHA hypertension guideline 1.

Some key points to consider when using this combination include:

• Regular monitoring of blood pressure, kidney function, and potassium levels, as both medications can affect these parameters.
• Dosage adjustments may be necessary based on blood pressure response and kidney function changes over time.
• The combination of an ACE inhibitor and an ARB should be avoided due to reported harms, as noted in the 2018 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1.

Overall, the combination of Norvasc and losartan is a valuable treatment option for CKD stage 3 patients with hypertension, as it addresses both the need to control blood pressure and the need to slow CKD progression, ultimately improving morbidity, mortality, and quality of life outcomes.

From the FDA Drug Label

The antihypertensive effects of losartan were demonstrated principally in 4 placebo-controlled, 6- to 12-week trials of dosages from 10 to 150 mg per day in patients with baseline diastolic blood pressures of 95 to 115

Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells

Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure

The combination of Norvasc (Amlodipine) 10mg and Losartan 50mg is good for CKD stage 3 with hypertension because:

• Losartan has been shown to be effective in reducing blood pressure in patients with hypertension, with a dose of 50mg once daily giving statistically significant systolic/diastolic mean decreases in blood pressure compared to placebo.
• Amlodipine acts as a peripheral arterial vasodilator, reducing peripheral vascular resistance and blood pressure, and has been shown to be effective in patients with moderate hypertension.
• Both medications have been shown to be effective in reducing blood pressure, which is important for patients with CKD stage 3 to slow the progression of kidney disease.
• The combination of these two medications may provide a synergistic effect in reducing blood pressure and slowing the progression of kidney disease 2, 3. Key points:
• Blood pressure reduction: Both Losartan and Amlodipine have been shown to be effective in reducing blood pressure.
• CKD stage 3: Reducing blood pressure is important for slowing the progression of kidney disease in patients with CKD stage 3.
• Combination therapy: The combination of Losartan and Amlodipine may provide a synergistic effect in reducing blood pressure and slowing the progression of kidney disease.

From the Research

Rationale for Norvasc 10mg and Losartan 50mg in CKD Stage 3 with Hypertension

• The combination of an angiotensin II receptor antagonist (such as losartan) and a calcium channel blocker (such as amlodipine, the active ingredient in Norvasc) is a common treatment approach for patients with chronic kidney disease (CKD) and hypertension 4, 5, 6.
• Losartan has been shown to have a renoprotective effect in patients with CKD and hypertension, reducing proteinuria and slowing the progression of kidney disease 5, 6.
• The use of a calcium channel blocker such as amlodipine can help to lower blood pressure and reduce the risk of cardiovascular events in patients with CKD and hypertension 7, 8.
• The combination of losartan and amlodipine may be more effective than monotherapy with either agent alone in reducing blood pressure and proteinuria in patients with CKD and hypertension 4, 8.

Mechanism of Action

• Losartan works by blocking the action of angiotensin II, a potent vasoconstrictor that can increase blood pressure and damage the kidneys 5, 6.
• Amlodipine works by relaxing blood vessels and reducing blood pressure, which can help to reduce the strain on the kidneys and slow the progression of kidney disease 7, 8.

Clinical Evidence

• Studies have shown that the combination of losartan and amlodipine can be effective in reducing blood pressure and proteinuria in patients with CKD and hypertension 4, 8.
• The Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) study found that losartan reduced proteinuria and slowed the progression of kidney disease in patients with CKD and hypertension 5, 6.
• The 2018 guidelines for the treatment of hypertension in CKD recommend the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (such as losartan) as first-line therapy, with the addition of a calcium channel blocker (such as amlodipine) if necessary 7.