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Angiotensin II receptor antagonists

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Angiotensin mediates its effects through two receptors. The AT-1 receptor mediates the vasoconstrictive and aldosterone stimulating effects of angiotensin II. The action of angiotensin II at the AT-2 receptor tends to antagonize the pressor effects of the AT-1 receptor.

  • angiotensin Receptor Blockers (ARB) specifically block the action of angiotensin II at the AT-1 receptor.
  • the antihypertensive efficacy of ARBs (e.g. Losartan) appears to be equal to that of atenolol or ACE inhibitors; ARBs and thiazide diuretics may be combined, resulting in additive hypotensive effects. The combination of an ACE inhibitor and an angiotensin II receptor antagonist is unlikely to have an additive effect.
  • there is a lower incidence of cough in patients taking ARBS as compared to patients taking ACE inhibitors
    • owing to their receptor selectivity for the AT-1 receptor, and their lack of potentiation of bradykinin and possibly other vasoactive peptides, cough and angio-oedema are much less likely to occur than with ACE inhibitors (2)
  • there is evidence that ARBs are renoprotective in patients with type 2 diabetes mellitus and nephropathy. This effect was beyond that attributable to blood pressure control (2,3)

It had been stated that the clearest indication for use of angiotensin-II-receptor antagonists was in patients among whom coughing has limited the use of ACE inhibitors, but for whom blockade of the renin-angiotensin system offers particular benefit (5). However the British Hypertension Society have included both ARBs and ACE inhibitors in the step 1 of their A/CD guideline of blood pressure management (2).

Effectivity of ARB if intolerant of ACE inhibitor in reduction of cardiovascular risk:

  • ACE inhibitors reduce major cardiovascular events, but are not tolerated by about 20% of patients
    • a study (TRANSCEND) assessed whether the angiotensin-receptor blocker telmisartan would be effective in patients intolerant to ACE inhibitors with cardiovascular disease or diabetes with end-organ damage
    • there was no significant benefit with respect to the study primary outcome (composite of cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure) in the ARB treated group

The summary of product characteristics should be consulted before prescribing specific angiotensin II receptor antagonists.

Reference:


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