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ACE Inhibitors and ARBs: Clinical Implications and Outcomes
ACE Inhibitors and ARBs in COVID-19
Safety Concerns and ACE2 Expression
Concerns have been raised about the safety of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in COVID-19 patients due to the hypothesis that these medications might increase ACE2 expression, the receptor for SARS-CoV-2. However, a comprehensive review of studies in both animals and humans indicates that ACEIs and ARBs do not significantly increase ACE2 expression in humans, suggesting that these medications do not elevate the risk of COVID-19 complications. Therefore, patients on ACEIs and ARBs should continue their treatment as prescribed.
Risk of Severe or Lethal COVID-19
A meta-analysis of observational studies involving nearly 10,000 hypertensive patients found no significant difference in the risk of severe or lethal COVID-19 between those treated with ACEIs or ARBs and untreated subjects. This supports the recommendation to continue these medications during the pandemic.
Prevention of Type 2 Diabetes
Efficacy in Diabetes Prevention
ACE inhibitors and ARBs have been shown to reduce the incidence of new-onset type 2 diabetes by 27% and 23%, respectively. This suggests that these medications could be beneficial for patients with pre-diabetic conditions, such as metabolic syndrome, hypertension, and impaired fasting glucose.
Pregnancy Outcomes
Risks of Prenatal Exposure
Prenatal exposure to ACEIs and ARBs has been associated with significant neonatal complications, including renal failure, oligohydramnios, and intrauterine growth retardation. The long-term outcomes for exposed children are also concerning, with only 50% showing positive results. The term "fetal renin-angiotensin system blockade syndrome" has been proposed to describe these adverse effects.
Renal and Cardiovascular Outcomes
Renoprotective Effects
ACE inhibitors and ARBs are known for their renoprotective effects, particularly in patients with chronic kidney disease (CKD). They reduce the risk of kidney failure and major cardiovascular events. ACE inhibitors also show a significant reduction in all-cause mortality compared to ARBs, suggesting they might be the preferred choice for CKD patients.
Combination Therapy in Proteinuric Renal Disease
Combining ACE inhibitors with ARBs in patients with proteinuric renal disease has been shown to further reduce proteinuria without significant adverse effects on serum potassium levels or glomerular filtration rates. This combination therapy appears safe and effective in the short term, though long-term benefits require further investigation.
Cardiovascular Outcomes in Non-Heart Failure Patients
Comparative Efficacy
In high cardiovascular risk patients without heart failure, ACE inhibitors and ARBs show similar efficacy in preventing cardiovascular death, myocardial infarction, and stroke. There is no significant difference in the risk of all-cause death, new-onset heart failure, or new-onset diabetes between the two drug classes.
Perioperative Management
Withholding vs. Continuing Therapy
For patients undergoing noncardiac surgery, withholding ACEIs or ARBs on the morning of surgery does not affect mortality or major cardiac events but is associated with a reduced incidence of intraoperative hypotension. This suggests that withholding these medications might be beneficial in managing intraoperative blood pressure.
Chronic Limb Threatening Ischemia (CLTI)
Survival and Limb Salvage
In patients with CLTI undergoing peripheral vascular interventions, ACE inhibitors and ARBs are associated with improved overall survival and amputation-free survival. However, there is no significant difference in limb salvage rates between treated and untreated groups.
Conclusion
ACE inhibitors and ARBs play a crucial role in managing various conditions, including hypertension, diabetes prevention, CKD, and cardiovascular diseases. Their use in COVID-19 patients appears safe, and they offer significant benefits in reducing the incidence of new-onset diabetes and improving renal and cardiovascular outcomes. However, caution is advised during pregnancy and perioperative periods. Further research is needed to optimize their use in specific patient populations.
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