Can a patient be on both Valsartan (Angiotensin II Receptor Blocker) and Lisinopril (Angiotensin-Converting Enzyme Inhibitor) simultaneously?

From the Guidelines

It is not recommended to take both valsartan and lisinopril together due to the increased risk of adverse effects and lack of significant additional benefits for most patients. Valsartan is an angiotensin II receptor blocker (ARB) while lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, both of which target the renin-angiotensin-aldosterone system but at different points, ultimately reducing blood pressure by preventing blood vessel constriction. According to the 2017 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 1, drug combinations that have similar mechanisms of action or clinical effects should be avoided, including the combination of ACE inhibitors and ARBs. This is because high-quality RCT data demonstrate that simultaneous administration of RAS blockers (i.e., ACE inhibitor with ARB) increases cardiovascular and renal risk.

Some key points to consider when evaluating the use of both valsartan and lisinopril together include:

• The increased risk of side effects such as dangerously low blood pressure, high potassium levels, and kidney problems
• The lack of significant additional benefits for most patients
• The potential for increased cardiovascular and renal risk
• The recommendation to avoid combining ACE inhibitors and ARBs, as stated in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1
• The results of the ONTARGET and ALTITUDE trials, which found that the combination of an ACE inhibitor and an angiotensin receptor blocker was accompanied by a significant excess of cases of end-stage renal disease (ESRD) and stroke 1

In specific cases, such as certain heart failure patients or those with significant proteinuria, a doctor might prescribe this combination under close monitoring, but this is not common practice. If your blood pressure is not well-controlled on a single medication, your doctor would typically increase the dose of your current medication or add a different class of blood pressure medication like a calcium channel blocker or diuretic rather than combining an ACE inhibitor with an ARB.

From the FDA Drug Label

7.3 Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy [see Clinical Studies (14. 3)]. In general, avoid combined use of RAS inhibitors. 7.4 Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. In most patients no benefit has been associated with using two RAS inhibitors concomitantly In general, avoid combined use of RAS inhibitors.

Concomitant use of valsartan and lisinopril is not recommended due to the increased risk of hypotension, hyperkalemia, and changes in renal function. The benefits of using both drugs together do not outweigh the risks, and alternative treatment options should be considered 2 3.

From the Research

Combination Therapy with Valsartan and Lisinopril

• The study 4 compared the efficacy and safety of combination therapy with valsartan and lisinopril versus high-dose monotherapy in patients with hypertension and microalbuminuria.
• The results showed that the combination of valsartan and lisinopril provided a significantly better reduction in urine albumin creatinine ratio and more than doubled the rate of patients with normalized urine albumin creatinine ratio compared to lisinopril alone.
• Another study 5 compared the risk-benefit profile of valsartan with lisinopril in patients with mild to severe hypertension, and found that both treatments were highly effective in controlling blood pressure, but valsartan was associated with a significantly reduced risk of adverse events.

Safety and Efficacy of Combination Therapy

• The study 4 found that all treatments, including the combination of valsartan and lisinopril, were safe and well tolerated.
• The study 6 also found that the combination of amlodipine and valsartan was well tolerated and efficacious in patients with stage 2 hypertension.
• However, the study 7 found that in patients with chronic heart failure, the addition of valsartan to conventional therapy, including ACE inhibitors, was associated with an increased risk of adverse events, including dizziness, renal impairment, and hypotension.

Blood Pressure Reduction

• The study 5 found that both valsartan and lisinopril were highly effective in reducing blood pressure in patients with mild to severe hypertension.
• The study 6 found that the combination of amlodipine and valsartan was effective in reducing blood pressure in patients with stage 2 hypertension.
• The study 4 found that the combination of valsartan and lisinopril provided a significant reduction in urine albumin creatinine ratio, but the difference in blood pressure reduction between the groups was not statistically significant.