Angiotensin receptor blockers and cough
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Angiotensin Receptor Blockers (ARBs) and Cough: Comparative Incidence and Mechanisms
Cough as a Side Effect of ACE Inhibitors vs. ARBs
Angiotensin-converting enzyme inhibitors (ACE inhibitors) are well known to cause a dry, persistent cough in a significant proportion of patients, with reported rates ranging from 5% to 35% in adults, often leading to discontinuation of therapy Kamath2015Dicpinigaitis2006Borghi2023. This cough is thought to be related to the accumulation of bradykinin and substance P, which are normally broken down by ACE; when ACE is inhibited, these substances build up and can trigger cough Dicpinigaitis2006Borghi2023.
In contrast, angiotensin receptor blockers (ARBs) do not interfere with bradykinin metabolism and therefore have a much lower incidence of cough. Multiple studies and reviews have consistently shown that ARBs are associated with cough rates similar to placebo and significantly lower than those seen with ACE inhibitors Kamath2015Lam2021Pylypchuk1998+4 MORE. This makes ARBs a preferred alternative for patients who develop cough on ACE inhibitors.
Clinical Evidence: ARBs as a Replacement for ACE Inhibitors
Clinical trials and comparative studies have demonstrated that ARBs are as effective as ACE inhibitors in treating hypertension and other cardiovascular conditions, but with a much lower risk of cough Kamath2015Pylypchuk1998Contreras2003+1 MORE. In fact, ARBs are often recommended as replacement therapy for patients who cannot tolerate ACE inhibitors due to cough Kamath2015Lam2021Dykewicz2004+2 MORE. Updated clinical guidelines now suggest that either ACE inhibitors or ARBs can be used as first-line therapy, rather than requiring ACE inhibitors to be tried first .
Tolerability of ARBs in Patients with ACE Inhibitor-Induced Cough
Most patients who develop cough from ACE inhibitors can tolerate ARBs without recurrence of this side effect Dykewicz2004Contreras2003. This has been confirmed in both adult and pediatric populations, with studies showing that the incidence of cough in children receiving ARBs is also low and comparable to placebo Dykewicz2004Baker‐Smith2010.
Mechanistic Insights: Why ARBs Rarely Cause Cough
The key difference lies in the mechanism of action. ACE inhibitors block the breakdown of bradykinin, leading to its accumulation and the associated cough. ARBs, on the other hand, block the angiotensin II receptor without affecting bradykinin levels, thus avoiding this side effect Contreras2003Dina2000.
Diagnostic Considerations and Clinical Practice
Because cough is a common side effect of ACE inhibitors, patients on these drugs may undergo more diagnostic evaluations for cough-related symptoms, which can sometimes lead to unnecessary investigations . Switching to an ARB is the only uniformly effective way to resolve ACE inhibitor-induced cough .
Conclusion
In summary, angiotensin receptor blockers are as effective as ACE inhibitors for cardiovascular conditions but are much less likely to cause cough. For patients who develop cough on ACE inhibitors, ARBs are a well-tolerated and effective alternative, with a safety profile similar to placebo regarding cough incidence Kamath2015Lam2021Pylypchuk1998+5 MORE. This makes ARBs the preferred choice for individuals who experience this bothersome side effect.
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Angiotensin II-receptor antagonists: an overview.
Angiotensin II-receptor antagonists are well-tolerated and as effective as ACE inhibitors in reducing blood pressure, with fewer adverse effects.
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