However, recent studies have uncovered some worrying problems with ARBs. Although better tolerated in more patients than ACE inhibitors, their associated side-effects can be serious and, in some patients, lead to paradoxical effects. This means that they can sometimes cause the very conditions they’re meant to be treating: heart attack and kidney failure.
It seems that, where ARBs are concerned, an antihypertensive action has been confused with vascular protection. Researchers find that, despite their beneficial effects on reducing blood pressure, ARBs – unlike ACE inhibitors – are either neutral or increase the chances of a heart attack (BMJ, 2004; 329: 1248-9).
The double-blind, randomised Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial compared valsartan with the ACE inhibitor amlodipine for lowering blood pressure in 15,245 high-risk patients. Both drugs lowered blood pressure, and both had similar outcomes in terms of heart protection (Lancet, 2004; 363: 2022-4). However, the earlier Heart Outcomes Prevention Evaluation (HOPE) study had linked valsartan with a 19 per cent increase in heart attacks (Lancet, 2001; 358: 2130-1).
Likewise, the Candesartan in Heart Failure-Assessment of Reduction in Morbidity and Mortality (CHARM)-Alternative trial showed a 36-per-cent increase in heart attacks with candesartan vs a placebo, again despite a reduction in blood pressure (Lancet, 2003; 362: 772-6). And in the Study on Cognition and Prognosis in the Elderly (SCOPE), candesartan, while combating hypertension, was associated with a 10-per-cent increase in heart attacks (J Hypertens, 2003; 21: 875-6).
In a recent review of large-scale controlled trials investigating the effects of ARBs on the risk of heart attack in nearly 32,000 high-risk cardiovascular patients, the authors admitted that, although ARBs are theoretically better tolerated and better at inhibiting angiotensin II than ACE inhibitors, they offer no real advantage. Indeed, it’s been suggested that ARBs may even confer a risk of harm through their association with heart attacks (BMJ, 2005; 331: 873).
As for the paradoxical effects of ARBs on kidney function, one double-blind trial comparing valsartan with the ACE-inhibitor captopril in patients with heart conditions found that kidney dysfunction and hypotension were more common in those taking valsartan (N Engl J Med, 2003; 349: 1893-906).
In another review of randomised clinical trials, the most common side-effects of valsartan included kidney impairment (as well as elevated serum creatinine and potassium levels, and dizziness). The authors concluded that patients experiencing these adverse events while taking ACE inhibitors are also likely to experience them with valsartan (Ann Pharmacother, 2005; 39: 460-9).