Renin angiotensin system blockers
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Renin-Angiotensin System Blockers: Types and Mechanisms
Renin-angiotensin system (RAS) blockers include several drug classes: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), renin inhibitors, and aldosterone receptor antagonists. These medications are widely used to manage hypertension, heart failure, and other cardiovascular and kidney diseases by interfering with the RAS pathway, which regulates blood pressure and fluid balance Riet2015Li2017.
Efficacy in Heart Failure and Left Ventricular Dysfunction
For patients with heart failure with reduced ejection fraction (HFrEF) or left ventricular dysfunction, RAS blockers are proven to reduce mortality and hospitalizations. Among these, angiotensin receptor–neprilysin inhibitors (ARNIs) show the greatest reduction in all-cause mortality and heart failure hospitalizations, followed by aldosterone receptor antagonists and ACEIs. Adding an aldosterone receptor antagonist to standard therapy further reduces mortality and hospitalization risk without significantly increasing discontinuation rates .
Use in Cardiac Surgery and Acute Myocardial Infarction
RAS blockers, including ACEIs, ARBs, and antialdosterones, have demonstrated cardioprotective effects in cardiac surgery patients, reducing ischemic events and improving outcomes in heart failure and after acute myocardial infarction. However, evidence from perioperative studies is limited and sometimes conflicting, highlighting the need for more research on their impact on mortality and major complications in surgical settings .
Impact on Critically Ill Cancer Patients
In critically ill patients with solid tumors, both ARBs and ACEIs are associated with improved survival during intensive care unit (ICU) stays. Notably, ARBs are linked to better one-year survival rates, suggesting a potential benefit of RAS blockers in this high-risk population .
RAS Blockers in Diabetes and Hypertension
For people with diabetes, RAS blockers are not superior to other antihypertensive drugs (such as thiazides, calcium channel blockers, and beta-blockers) in reducing the risk of death, cardiovascular events, or end-stage renal disease. This supports guidelines recommending the use of various antihypertensive agents in diabetic patients without kidney disease . In cases of severe acute hypertension, RAS blockers are often underused, despite their established role in chronic hypertension management .
Comparison of Renin Inhibitors and ARBs
Direct comparisons between renin inhibitors (like aliskiren) and ARBs in patients with mild primary hypertension show little to no difference in mortality, adverse events, or blood pressure reduction. Both drug classes are similarly effective and well-tolerated, but more long-term studies are needed to assess differences in cardiovascular outcomes .
Additional Benefits and Considerations
RAS blockers are a cornerstone in hypertension treatment and are especially important for resistant hypertension, with mineralocorticoid receptor antagonists playing a key role. The choice of RAS blocker may depend on individual factors such as age, sex, ethnicity, salt intake, and genetic background . In Parkinson’s disease patients with hypertension, ARBs (but not ACEIs) may help slow cognitive decline .
Safety During the COVID-19 Pandemic
Despite concerns about ACE2 upregulation and COVID-19 risk, current evidence does not support discontinuing RAS blockers due to coronavirus infection. In fact, some data suggest potential protective effects on the lungs and cardiovascular system .
Expanding Understanding of the Renin-Angiotensin System
The RAS is more complex than previously thought, with multiple axes beyond the classic pathway. This expanding knowledge may lead to new therapeutic options for cardiovascular, hypertensive, and kidney diseases .
Conclusion
Renin-angiotensin system blockers are essential in managing heart failure, hypertension, and other cardiovascular conditions. Their benefits are well-established in heart failure and certain high-risk populations, while their role in diabetes and acute hypertension is more nuanced. Ongoing research continues to refine their use and explore new therapeutic possibilities within the broader RAS pathway.
Sources and full results
Most relevant research papers on this topic
Survival Benefit of Renin-Angiotensin System Blockers in Critically Ill Cancer Patients: A Retrospective Study
Renin-angiotensin system blockers (ARBs) improve in-ICU survival and decrease one-year mortality in critically ill cancer patients, while ACEis do not.
Diabetes mellitus as a compelling indication for use of renin angiotensin system blockers: systematic review and meta-analysis of randomized trials
In people with diabetes, RAS blockers are not superior to other antihypertensive agents in reducing the risk of hard cardiovascular and renal endpoints.
A plea for renin-angiotensin system blockers as first-line treatment in cases of severe acute hypertension.
Renin-angiotensin system blockers should be the first-line treatment for severe acute hypertension, as current recommendations result in underuse of these drugs.
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