It seems likely that the accumulation of bradykinin leads to persistent dry cough, a recognized side effect which occurs in 5 to 20% of patients on ACE-Is. Angioneurotic edema can occur with both ACE-Is and ARBs, although the relative frequencies and the mechanism are not clear. ARBs act by competitively antagonizing the interaction between angioten- sin II and angiotensin receptors and were first introduced as an alternative to ACE-Is in patients who had an ACE-I induced cough. ACE-Is and ARBs are valuable BP-reducing agents in CKD patients, are indicated if urinary albumin excretion is elevated and are safe to combine with most other BP-reducing agents. Clinically significant hyperkalemia and reductions in GFR can occur in patients receiving ACE-Is or ARBs, particularly in those who have renal-artery stenosis or reduced intravascular volume, or when these agents are used together with NSAIDs, COX-2 inhibitors, or potassium-sparing diuretics. The use of these drugs in women of child-bearing age should be balanced with the risk of pregnancy since they are potentially teratogenic (see The sequential marketing of ACE-Is first (captopril in 1977) and ARBs later (losartan in 1995) has influenced the design of RCTs involving these drug classes. The first large- scale RCT of RAAS blockade in diabetes involved patients with type 1 disease given captopril. By the time ARBs were introduced, the benefits of ACE-Is (in CKD patients with type 1 diabetes) were well established. Thus RCTs involving ARBs generally targeted individuals with type 2 diabetes. This has led to some bias in the evidence base underpinning recommendations for using ACE-Is or ARBs in the treatment of BP. 