Can enalapril (Angiotensin-Converting Enzyme (ACE) inhibitor) be given with telmesartan (Angiotensin Receptor Blocker (ARB))?

Combination of Enalapril and Telmisartan is Not Recommended

The combination of enalapril (ACE inhibitor) and telmisartan (ARB) should not be used together due to increased risk of adverse events including hyperkalemia, hypotension, and acute kidney injury without additional cardiovascular or mortality benefit. 1, 2

Rationale Against Dual RAAS Blockade

The 2017 ACC/AHA hypertension guidelines explicitly state that simultaneous use of an ACE inhibitor and ARB is potentially harmful and not recommended for treating adults with hypertension 1. This recommendation carries a Class III: Harm designation with Level of Evidence A, indicating strong evidence against this practice.

The FDA label for telmisartan specifically warns about dual blockade of the renin-angiotensin-aldosterone system, citing the ONTARGET trial which enrolled 25,620 patients and found that:

• Patients receiving the combination of telmisartan and ramipril did not obtain any additional benefit on cardiovascular outcomes
• The combination led to increased incidence of clinically important renal dysfunction (acute renal failure) compared to monotherapy with either agent 2

Specific Risks of Combination Therapy

When ACE inhibitors and ARBs are used together, patients face increased risks of:

1. Hyperkalemia - Both drug classes can elevate potassium levels
2. Acute kidney injury - Particularly in patients with bilateral renal artery stenosis or compromised renal function
3. Hypotension - Additive blood pressure lowering effects can cause symptomatic hypotension
4. Syncope - Due to excessive blood pressure reduction 3

Alternative Approaches for Hypertension Management

Instead of combining an ACE inhibitor and ARB, the guidelines recommend:

• Choose one RAAS blocker: Either an ACE inhibitor OR an ARB, not both
• Add complementary agents from different classes when BP targets aren't met:
  • Thiazide or thiazide-like diuretics
  • Calcium channel blockers
  • If appropriate, mineralocorticoid receptor antagonists 1, 3

Monitoring Recommendations

When using a single RAAS blocker (either ACE inhibitor OR ARB):

• Monitor serum creatinine and potassium within 2-4 weeks after initiation or dose change
• Continue therapy unless serum creatinine rises by more than 30%
• Perform annual monitoring of serum creatinine/eGFR and potassium 3

Special Considerations

For patients with diabetic nephropathy who might benefit from RAAS blockade:

• Use a single agent (either ACE inhibitor OR ARB) at the maximum tolerated dose
• Titrate to the highest approved dose that is tolerated before considering other agents 3
• For patients with resistant hypertension, consider adding a mineralocorticoid receptor antagonist rather than combining ACE inhibitors and ARBs 3

Conclusion

While both enalapril and telmisartan are effective antihypertensive agents individually, their combination is contraindicated due to increased risks without additional benefit. Choose one agent based on patient-specific factors and add medications from complementary classes if blood pressure targets are not achieved.