Can aliskiren help with hypertension or heart failure treatment?

Aliskiren for Hypertension and Heart Failure: Limited Role with Significant Contraindications

Aliskiren can lower blood pressure effectively as monotherapy or combined with thiazide diuretics or calcium channel blockers in uncomplicated hypertension, but it should NOT be used in diabetic patients taking ACE inhibitors or ARBs, and it has no proven benefit for heart failure or cardiovascular outcomes. 1

Blood Pressure Lowering Efficacy

Aliskiren is FDA-approved for hypertension treatment in adults and pediatric patients ≥6 years weighing ≥50 kg. 2

When used as monotherapy:

• Aliskiren 150-300 mg daily reduces systolic blood pressure by 12-16 mm Hg and diastolic blood pressure by 2-12 mm Hg in patients with mild-to-moderate hypertension 1
• Its efficacy is comparable to angiotensin receptor blockers (irbesartan 150 mg, valsartan 80-320 mg) 1

When used in combination therapy:

• Aliskiren provides greater antihypertensive effects when combined with thiazide diuretics, calcium channel blockers, or other RAS blockers 1
• The combination with hydrochlorothiazide or calcium antagonists produces additive blood pressure reduction 1

Critical Contraindications and Safety Concerns

Absolute contraindication in diabetic patients on ACE inhibitors or ARBs:

• The ALTITUDE trial was stopped early due to increased adverse events including stroke, hyperkalemia, hypotension, and end-stage renal disease when aliskiren was added to ACE inhibitors or ARBs in diabetic patients 1
• The FDA issued a contraindication in April 2012 against using aliskiren with ACE inhibitors or ARBs in patients with diabetes due to risks of kidney impairment, hypotension, and hyperkalemia 1
• The manufacturer (Novartis) recommends stopping aliskiren in diabetic patients treated with ACE inhibitors or ARBs 1

Contraindication in bilateral renal artery stenosis:

• Direct renin inhibitors like aliskiren should be avoided in severe bilateral renal artery stenosis as they may cause acute renal failure 3

Lack of Cardiovascular Outcome Data

No proven benefit on hard endpoints:

• No trials demonstrate that aliskiren reduces cardiovascular or renal morbidity and mortality in hypertension 1
• The APOLLO trial (evaluating cardiovascular outcomes in elderly patients) was stopped, though without evidence of harm 1
• No aliskiren-based trials with hard endpoints are expected in the near future 1

No benefit in heart failure:

• Adding aliskiren to standard heart failure treatment showed no beneficial effect on mortality or hospitalization 1

Appropriate Clinical Use

Aliskiren may be considered for:

• Uncomplicated mild-to-moderate hypertension as an alternative when first-line agents (ACE inhibitors, ARBs, calcium channel blockers, thiazides) are contraindicated or not tolerated 1
• Combination therapy with thiazide diuretics or calcium channel blockers (but NOT with ACE inhibitors or ARBs in diabetic patients) 1
• Patients who develop dry cough with ACE inhibitors and need an alternative RAS-blocking agent 1

Dosing:

• Start with 150 mg once daily; may increase to 300 mg once daily if needed 2

Common Pitfalls to Avoid

• Never combine aliskiren with ACE inhibitors or ARBs in diabetic patients - this is an FDA contraindication with proven harm 1
• Do not use in bilateral renal artery stenosis - risk of acute renal failure 3
• Do not prescribe expecting cardiovascular outcome benefits - unlike ACE inhibitors and ARBs, aliskiren lacks outcome trial data showing reduction in cardiovascular events 1
• Avoid in patients with moderate renal dysfunction without careful monitoring - limited safety data in this population 1
• Monitor for hyperkalemia and hypotension, especially when combined with other RAS-acting drugs 1

Adverse Effects

The most common adverse effects include headache, fatigue, dizziness, diarrhea, and nasopharyngitis, with an overall tolerability profile similar to placebo 1