Angiotensin receptor blockers: Therapeutic targets and cardiovascular protection

Abstract

In the prevention and treatment of cardiovascular disease, pharmacological treatment strategies should have several aims: (i) in individuals without overt cardiovascular disease, but with risk factors such as hypertension and/or diabetes, pharmacotherapy should prevent or delay disease development; (ii) in patients who have already progressed to cardiovascular disease, pharmacotherapy should help either to prevent or regress target organ damage (TOD); and (iii) in patients with TOD, pharmacotherapy should prevent events. Any medication intended for long-term therapy also should be well tolerated. Inhibiting the renin-angiotensin system has proven a successful therapeutic strategy in cardiovascular and renal medicine. Angiotensin-converting enzyme (ACE) inhibitors have demonstrated important advantages over conventional agents such as beta-blockers and thiazide diuretics, and have become a relevant part of treatment for heart failure post-myocardial infarction, left ventricular dysfunction and renal disease. Tolerability concerns may prevent their use in some patients, however. Angiotensin AT1 receptor blockers (ARBs) provide a different form of blockade of the renin-angiotensin system and a growing body of evidence suggests that this alternative approach may confer additional cardiovascular protection for some patient subgroups. In addition, ARBs generally are better tolerated than ACE inhibitors, enhancing patient compliance and persistence with long-term therapy. Furthermore, evidence in favour of combining an ACE inhibitor and an ARB in certain circumstances is continuously growing.

Telmisartan and Irbesartan Therapy in Type 2 Diabetic Patients Treated with Rosiglitazone: Effects on Insulin-Resistance, Leptin and Tumor Necrosis Factor-.ALPHA.

“…Activation of angiotensin type 1 (AT 1 ) receptors leads to vasoconstriction, stimulation of the release of catecholamines and antidiuretic hormone, and promotion of the growth of vascular and cardiac muscle. AT 1 receptor blockers thereby relax vascular smooth muscle, increase salt excretion, decrease cellular hypertrophy and induce antihypertensive effects without modifying heart rate or cardiac output ( 3 ). Most of the AT 1 receptor blockers in use are able to control BP with a oncedaily dose, without evidence of producing tolerance to the antihypertensive effect and with a low incidence of side effects even when used over the long term.…”

Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation

“…In other words, if there were significant Ang II synthesis in tissues by alternate pathways, such as chymase in the heart, this would limit the efficacy of ACEIs (but not of ARBs) through a mechanism postulated to contribute to the "escape" phenomenon following long-term ACE inhibition. [116] In contrast to the ACEIs, ARB therapy actually results in an increase in Ang II levels [117]. As with ACE inhibition, blockade of the AT1 receptor inhibits the negative feedback loop, leading to increased renin secretion and thus to increased synthesis of Ang I.…”

Sartans: differences, similitudes and costs

“…Gli effetti indesiderati di norma sono lievi: può comparire ipotensione sintomatica (con un'incidenza compresa fra 1/1000 e 1/100 per valsartan, fra 1/10 e 1/100 per candesartan, fra 1/10.000 a 1/1000 per olmesartan e inferiore a 1/10.000 per eprosartan) e ipercaliemia (con un'incidenza compresa fra 1/1000 e 1/100 per valsartan ed eprosartan, fra 1/10 e 1/100 per candesartan, fra 1/10.000 a 1/1000 per olmesartan e pari a circa l'1,5% per losartan [4][5][6][7][11][12][13][14][15] Per quanto riguarda l'abbandono della terapia, nello studio Val-HeFT, il 9,9% dei pazienti riceventi il sartano ha interrotto il trattamento a causa della comparsa di eventi avversi rispetto al 7,2% nel gruppo placebo [42]; nel CHARM l'interruzione definitiva del trattamento a causa dell'insorgenza di eventi avversi è risultato del 21,0% nel gruppo trattato con candesartan e del 16,7% nel gruppo placebo [43].…”

“…Gli ARB attualmente a disposizione del medico, pur mantenendo diversi aspetti peculiari, condividono tra loro alcune caratteristiche farmacologiche: l'alta affinità per i recettori AT 1 (mentre è quasi nulla l'affinità per i recettori di tipo 2) e l'elevato legame con le proteine plasmatiche (Tabella I) [3][4][5][6].…”