What is the best treatment approach for a patient with hypertension and elevated renin levels?

From the Guidelines

For patients with hypertension and elevated renin levels, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) are the preferred first-line treatments. These medications directly target the renin-angiotensin-aldosterone system (RAAS), which is overactive in high-renin hypertension, as noted in the 2019 standards of medical care in diabetes 1. By blocking the effects of angiotensin II, they reduce vasoconstriction and decrease aldosterone production, effectively lowering blood pressure. Common ACE inhibitors include lisinopril (starting at 10mg daily), enalapril (starting at 5mg twice daily), or ramipril (starting at 2.5mg daily), while ARB options include losartan (starting at 50mg daily), valsartan (starting at 80mg daily), or olmesartan (starting at 20mg daily).

Key Considerations

• The use of ACE inhibitors or ARBs is recommended due to their ability to reduce cardiovascular events in patients with diabetes, as highlighted in both the 2018 and 2019 standards of medical care in diabetes 1.
• Multiple-drug therapy is generally required to achieve blood pressure targets, but combinations of ACE inhibitors and angiotensin receptor blockers, and combinations of ACE inhibitors or angiotensin receptor blockers with direct renin inhibitors, should be avoided 1.
• For patients treated with an ACE inhibitor, angiotensin receptor blocker, or diuretic, regular monitoring of serum creatinine/estimated glomerular filtration rate and serum potassium levels is essential, at least annually 1.
• Lifestyle interventions, including weight loss if overweight or obese, a Dietary Approaches to Stop Hypertension (DASH)-style dietary pattern, moderation of alcohol intake, and increased physical activity, should be initiated along with pharmacologic therapy when hypertension is diagnosed 1.

Monitoring and Follow-Up

Regular monitoring of blood pressure, kidney function, and electrolytes (particularly potassium) is crucial when using ACE inhibitors or ARBs, with follow-up recommended 2-4 weeks after initiation or dose adjustment. This approach ensures the safe and effective management of hypertension in patients with elevated renin levels, aligning with the recommendations from the 2019 standards of medical care in diabetes 1.

From the FDA Drug Label

Aliskiren is a direct renin inhibitor, decreasing plasma renin activity (PRA) and inhibiting the conversion of angiotensinogen to Ang I. When this rise occurs during treatment with ACEIs and ARBs, the result is increased levels of PRA During treatment with aliskiren, however, the effect of increased renin levels is blocked so that PRA, Ang I and Ang II are all reduced, whether aliskiren is used as monotherapy or in combination with other antihypertensive agents.

The best treatment approach for a patient with hypertension and elevated renin levels is to use a direct renin inhibitor such as aliskiren. This is because aliskiren directly blocks the action of renin, thereby reducing the production of angiotensin I and II, which are potent vasoconstrictors.

• Key benefits of using aliskiren in this context include:
  • Reduction of plasma renin activity (PRA)
  • Inhibition of the conversion of angiotensinogen to Ang I
  • Decrease in Ang II levels, leading to decreased vasoconstriction and blood pressure reduction
• Important consideration: Avoid combined use of aliskiren with ACE inhibitors or ARBs, particularly in patients with CrCl less than 60 mL/min 2.

From the Research

Treatment Approaches for Hypertension with Elevated Renin

• The treatment of hypertension with elevated renin levels can involve various approaches, including the use of direct renin inhibitors, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) 3, 4, 5.
• Direct renin inhibitors, such as aliskiren, have been shown to be effective in lowering blood pressure in patients with hypertension, either as monotherapy or in combination with other antihypertensive agents 4, 5.
• However, the effectiveness of aliskiren may be limited by reactive renin secretion, which can offset its ability to lower blood pressure, especially in patients with highly reactive renin levels 6.
• The use of ACE inhibitors or ARBs may be a suitable alternative for treating hypertension with elevated renin levels, as they have been shown to be effective in lowering blood pressure and are widely available 6, 7.

Comparison of Treatment Options

• A study comparing the tolerability and antihypertensive efficacy of aliskiren and lisinopril in patients with severe hypertension found that both treatments were similar in terms of adverse events and blood pressure reductions 3.
• Another study found that aliskiren was as effective as standard doses of established antihypertensive agents, including ACE inhibitors, ARBs, and calcium channel blockers, in lowering blood pressure in patients with hypertension 4.
• The combination of aliskiren with other antihypertensive agents, such as hydrochlorothiazide or amlodipine, has been shown to further decrease blood pressure in patients with hypertension 4, 5.

Considerations for Treatment

• The choice of treatment for hypertension with elevated renin levels should be based on individual patient characteristics, including the severity of hypertension, presence of comorbidities, and potential side effects of treatment 3, 6.
• Patients with highly reactive renin levels may require closer monitoring and adjustment of treatment to avoid inducing increases in blood pressure 6.
• Further research is needed to determine the optimal treatment approach for hypertension with elevated renin levels and to fully understand the benefits and limitations of direct renin inhibition 7.