ACE inhibitor

ACE inhibitors are a class of drugs mainly prescribed for heart and kidney conditions. They relax blood vessels and reduce blood volume, which lowers blood pressure and eases the heart’s oxygen needs. The drugs work by blocking angiotensin-converting enzyme, a key part of the renin–angiotensin system. This stops the conversion of angiotensin I into angiotensin II, a substance that narrows blood vessels, and it also prevents the breakdown of bradykinin, a peptide that widens them. Together, these effects lower blood pressure.

Because ACE inhibitors stop the breakdown of bradykinin, levels of this peptide rise, leading to increased production of prostaglandin. This process explains two common side effects: angioedema and a persistent cough. Frequently prescribed ACE inhibitors include benazepril, zofenopril, perindopril, trandolapril, captopril, enalapril, lisinopril, and ramipril.

These drugs were first approved for high blood pressure and can be used alone or with other medications. They later proved useful for other conditions, including heart attack, heart failure (specifically left ventricular systolic dysfunction), and diabetic kidney disease, where they lower blood pressure and prevent damage from excessive filtration in the kidneys. For high blood pressure, ACE inhibitors are a first-line choice. Age, frailty, and race can affect treatment decisions, and more than one drug is often needed. All ACE inhibitors except enalapril (which can be given intravenously) are taken orally. Each has different strengths and starting doses, adjusted based on response. Most can be taken once daily, except captopril. ACE inhibitors share many features with angiotensin II receptor antagonists, which are often used when patients cannot tolerate ACE inhibitor side effects. ACE inhibitors do not fully block angiotensin II formation—the effect depends on dose—so angiotensin II receptor antagonists may be useful because they block angiotensin II at the AT1 receptor but leave the AT2 receptor open, though the consequences of this need more study. Fixed-dose combinations exist, such as ACE inhibitors with thiazide diuretics.

ACE inhibitors are also used in chronic kidney failure and kidney involvement in systemic sclerosis (scleroderma renal crisis). In people with stable coronary artery disease but no heart failure, benefits are similar to other standard treatments. A 2012 meta-analysis in the BMJ found that ACE inhibitors reduce pneumonia risk compared to angiotensin II receptor blockers, with a 54% risk reduction in patients with prior stroke, 37% in those with heart failure, and 43% in people of Asian descent (versus 54% in non-Asians). However, no reduction in pneumonia-related deaths was seen. ACE inhibitors work for conditions other than high blood pressure even in people with normal blood pressure. Using maximum doses in such cases—for preventing diabetic kidney disease, heart failure, or cardiovascular events—is justified because it improves outcomes independently of blood pressure lowering. This requires careful, gradual dose adjustment to avoid dizziness or fainting from a rapid drop in blood pressure.

ACE inhibitors may also help reduce excessive water drinking in people with schizophrenia who have psychogenic polydipsia. A double-blind, placebo-controlled trial showed that enalapril reduced consumption (measured by urine output and osmolality) in 60% of participants; other ACE inhibitors have shown the same effect. In kidney transplant patients, ACE inhibitors may offer little to no benefit.

In pregnant women, ACE inhibitors taken during any trimester have been linked to birth defects, stillbirths, and newborn deaths. Common fetal problems include low blood pressure, kidney malformations, low or no urine output, low amniotic fluid, poor growth, underdeveloped lungs, a persistent ductus arteriosus, and incomplete skull bone formation. About half of newborns exposed to ACE inhibitors are affected. These drugs are classified as pregnancy category D in Australia and should be avoided in women who may become pregnant. In the U.S., they carry a boxed warning about birth defects when taken during the second and third trimesters. Use in the first trimester also raises the risk of major birth defects, especially affecting the heart and nervous system.

During breastfeeding, ACE inhibitors may be used cautiously, as small amounts appear in breast milk. Enalapril is most commonly prescribed and has the most published data. The drugs are considered safe for the mother. In children, common ACE inhibitors used for hypertension include...