Candesartan cilexetil in cardiovascular disease

Introduction of Candesartan cilexetil

Candesartan cilexetil is an oral angiotensin II receptor blocker. Candesartan is approved by the FDA for the treatment of hypertension in adults. It is also used to treat cerebrovascular accidents or strokes, diabetic nephropathy, left ventricular hypertrophy, and migraines. It is a widely used drug for the treatment of high blood pressure and heart failure.

Hypertension is a major cardiovascular risk factor, but most patients remain asymptomatic for many years. Successful therapy not only needs to be effective, it also needs to be well tolerated. Angiotensin receptor blockers have emerged as a major therapeutic class because they meet both of these requirements. Numerous studies indicate that all approved angiotensin receptor blockers are highly selective for angiotensin-1 receptors, lower blood pressure as monotherapies, and work well in combination with other drugs - particularly diuretics. The side-effect profile of angiotensin receptor blockers is similar to that of placebo and they have not been associated with known side effects of angiotensin-converting enzyme inhibitors such as cough and angioneurotic edema.

Candesartan cilexetil is an angiotensin receptor blocker with insurmountable binding properties to the angiotensin-1 receptor, long duration of action and improved efficacy. In patients with hypertension, candesartan monotherapy has been shown to be safe and effective. Comparative data have shown similar or better results to other monotherapies in blood-pressure control, and in combination with hydrochlorothiazide it has been shown to have additive or synergistic effects. More recent data demonstrate that candesartan cilexetil is useful in the treatment of patients with heart failure and may protect against diabetic nephropathy. Studies have also shown protection from stroke, particularly in patients with isolated systolic hypertension.

Side effects of Candesartan cilexetil

The most common adverse reactions to Candesartan cilexetil were symptomatic hypotension, renal function abnormalities and hyperkalaemia. In the CHARM regimen, the incidence of symptomatic hypotension, impaired renal function (elevated creatinine) and hyperkalaemia was 18.8%, 12.5% and 6.3%, respectively. Hypotension was most common in patients with blood volume or salt deficits secondary to dietary restriction, dialysis, diarrhoea, vomiting or diuretics. Other side effects include headache, back pain, angioedema and upper respiratory tract infections, but these are clinically very rare.

Candesartan cilexetil is considered a teratogen and has a black box warning for fetal toxicity. If used in the second or third trimesters of pregnancy, medications that interfere with the renin-angiotensin-aldosterone system diminish fetal renal function. There is an increased risk of morbidity and death secondary to oligohydramnios results from decreased renal function. These neonates may develop skull hypoplasia, lung hypoplasia, hypotension, or renal failure and may ultimately expire.

References:

[1] AMY ROSS; Vasilios P. Candesartan cilexetil in cardiovascular disease.[J]. Expert Review of Cardiovascular Therapy, 2004. DOI:10.1586/14779072.2.6.829.

[2] ROBERTA MESSINA. Candesartan in migraine prevention: results from a retrospective real-world study.[J]. Journal of Neurology, 2020. DOI:10.1007/s00415-020-09989-9.