Why not use acei and arb together
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The Risks of Combining ACE Inhibitors and ARBs: A Comprehensive Review
Introduction to ACE Inhibitors and ARBs
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly prescribed medications for managing hypertension and providing renoprotective effects. Both drug classes target the renin-angiotensin-aldosterone system (RAAS), albeit through different mechanisms. ACEIs inhibit the conversion of angiotensin I to angiotensin II, while ARBs block the angiotensin II receptors. Given their complementary actions, there has been interest in combining these drugs to enhance therapeutic outcomes. However, recent studies have raised concerns about the safety and efficacy of this combination therapy.
Lack of Mortality and Cardiovascular Benefits
A systematic review of 85 trials involving 21,708 patients found no significant reduction in all-cause mortality or fatal cardiac-cerebrovascular outcomes when comparing ACEI versus placebo, ARB versus placebo, ACEI versus ARB, or combined ACEI and ARB therapy versus monotherapy1. This suggests that the combination does not offer additional benefits in terms of reducing mortality or severe cardiovascular events.
Renal Outcomes and Albuminuria
The same review highlighted that while both ACEIs and ARBs independently reduced the progression of microalbuminuria to macroalbuminuria and the development of end-stage kidney disease, the combination therapy did not show superior renal protection compared to monotherapy1. Another study focusing on patients with macroalbuminuric diabetic nephropathy found that combination therapy did not significantly reduce proteinuria and was associated with a higher risk of worsening proteinuria and increased urinary inflammatory cytokines5.
High Incidence of Adverse Effects
Combination therapy has been associated with a high rate of adverse effects. In a study involving patients with diabetic nephropathy, 28.5% of participants experienced significant side effects, and the risk of worsening proteinuria was higher in the combination therapy group5. This raises concerns about the safety of using both ACEIs and ARBs together, especially in populations with advanced kidney disease.
COVID-19 Considerations
The COVID-19 pandemic has brought additional scrutiny to the use of ACEIs and ARBs. Several studies have investigated whether these medications affect COVID-19 susceptibility and outcomes. A meta-analysis found no association between ACEI/ARB use and increased risk of COVID-19 infection, severity, or mortality3 4 6 7. In fact, some studies suggested that ACEI/ARB use might be associated with lower mortality rates among COVID-19 patients with hypertension8 9 10. However, these findings do not directly address the safety of combining ACEIs and ARBs.
Conclusion
The current body of evidence does not support the combined use of ACEIs and ARBs due to the lack of additional benefits in reducing mortality, cardiovascular events, or renal outcomes, coupled with a higher incidence of adverse effects. While both drug classes are effective independently, their combination does not appear to offer superior protection and may pose additional risks. Therefore, clinicians should exercise caution and consider monotherapy with either ACEIs or ARBs rather than combining them. Further research is warranted to explore alternative therapeutic strategies that might offer enhanced benefits without the associated risks.
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Most relevant research papers on this topic
Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and combined therapy in patients with micro- and macroalbuminuria and other cardiovascular risk factors: a systematic review of randomized controlled trials.
ACEI and ARB provide independent renal and nonfatal cardiovascular benefits, but their effects on mortality and fatal cardiovascular disease remain uncertain, and their combination therapy is not supported by evidence.
Systematic Review
Highly CitedShould ACE inhibitors and ARBs be used in combination in children?
Combination ACEI/ARB therapy may be beneficial in treating hypertension and renoprotective effects in children with incomplete angiotensin blockade on one agent.
Literature Review
Rigorous JournalACEI/ARB use and risk of infection or severity or mortality of COVID-19: A systematic review and meta-analysis
ACEI/ARB use is not associated with a higher risk of COVID-19 infection, severity, or mortality, supporting current guidelines not to discontinue these drugs during the pandemic or in COVID-19 patients.
Meta-AnalysisRigorous JournalHighly CitedRisks of ACE Inhibitor and ARB Usage in COVID‐19: Evaluating the Evidence
ACE inhibitors and ARBs do not increase ACE2 expression and do not increase the risk of complications from COVID-19, so patients should continue their use for approved indications.
Systematic ReviewRigorous JournalHighly CitedACEI and ARB combination therapy in patients with macroalbuminuric diabetic nephropathy and low socioeconomic level: a double-blind randomized clinical trial.
Combination therapy of ACEI and ARB may not provide superior renoprotection compared to enalapril in advanced diabetic nephropathy patients with severe proteinuria and poor metabolic control.
RCTSystematic review and meta-analysis of the clinical outcomes of ACEI/ARB in East-Asian patients with COVID-19
ACEI/ARB treatment in East-Asian COVID-19 patients is associated with reduced mortality and shorter hospital stays, without adverse clinical outcomes.
Meta-AnalysisThe Effect of Prior ACEI/ARB Treatment on COVID-19 Susceptibility and Outcome: A Systematic Review and Meta-Analysis
Prior ACEI/ARB treatment does not increase COVID-19 susceptibility or disease severity, supporting current medical guidelines that ACEI/ARB should not be discontinued.
Meta-AnalysisEffects Of ARBs And ACEIs On Virus Infection, Inflammatory Status And Clinical Outcomes In COVID-19 Patients With Hypertension: A Single Center Retrospective Study.
ARBs/ACEIs may reduce inflammation and death rates in COVID-19 patients with preexisting hypertension, supporting their use in this population.
Very Rigorous JournalHighly CitedAssociation of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19
Inpatient use of ACEI/ARB is associated with a lower risk of all-cause mortality in COVID-19 patients with hypertension compared to nonusers.
Observational StudyRigorous JournalHighly CitedAssociation of ACEi/ARB Use and Clinical Outcomes of COVID-19 Patients With Hypertension
ACEi/ARB use in COVID-19 patients with hypertension is not associated with an increased risk of disease severity compared to patients without ACEi/ARB.
Observational Study