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Recommendations Concerning ARBs

Angiotensin receptor blockers should not be considered equivalent or superior to ACE inhibitors in the treatment of HF, and thus, they should not be used for the treatment of HF in patients who have no prior use of an ACE inhibitor and should not be substituted for ACE inhibitors in patients who are tolerating ACE inhibitors without difficulty. Hence, ACEIs the first choice for inhibition of the renin-angiotensin system in chronic HF, but ARBs can now be considered a reasonable alternative.

Candesartan improved outcomes in patients with preserved LVEF who were intolerant of ACEIs in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM)67.

Angiotensin receptor blockers are as likely to produce hypotension, worsening renal function, and hyperkalemia as ACEIs. Although angioedema is much less frequent with ARBs, there are cases of patients who developed angioedema to both ACEIs and later to ARBs. There is little information available about the addition of ARBs to therapy with both ACEIs and aldosterone antagonists, but risks of renal dysfunction and hyperkalemia would be further increased. Until further information is available, the routine combined use of all 3 inhibitors of the renin-angiotensin system cannot be recommended.

Practical use of ARBS

Many of the considerations with ARB are similar to those with initiation of an ACEI, as discussed above.

Blood pressure (including postural blood pressure changes), renal function, and potassium should be reassessed within 1 to 2 weeks after initiation and followed closely after changes in doses.

Patients with systolic blood pressure below 80 mm Hg, low serum sodium, diabetes mellitus, and impaired renal function merit particular surveillance during therapy with inhibitors of the renin-angiotensin-aldosterone system.

Titration is generally achieved by doubling doses. For stable patients, it is reasonable to add therapy with beta-blocking agents before full target doses of either ACEIs or ARBs are reached. The risks of treatment with ARBs are those attributed to suppression of angiotensin stimulation, as discussed above for ACEIs. These risks of hypotension, renal dysfunction, and hyperkalemia are greater when combined with another inhibitor of this axis, such as ACEIs or aldosterone antagonists.

67 Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003;362:772-6.

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