Challenging the dogma of high target doses in the treatment of heart failure: is more always better?

Abstract

Current therapeutic guidelines for chronic heart failure (HF) recommend high (if possible, maximum) target doses of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers. This is based on "evidence" from large-scale trials in selected patient populations. In "real life", however, many patients receive doses below defined targets, which is usually classified as "under-treatment". When considering whether everyday practice is suboptimal, an important question arises: is more always better and should dosage recommendations be followed in all patients? The superiority of high vs. low-to-moderate doses of ACE inhibitors and beta-blockers in reducing mortality from chronic HF has not been documented convincingly. In large trials with beta-blockers, the efficacy of below-target doses was not significantly different from that of high doses. With high-dose lisinopril, a reduction in the rate of hospitalizations was achieved at the cost of more adverse events. A combination of ACE inhibitors and angiotensin receptor blockers in chronic HF may also cause more problems than benefits. The risks of high doses of spironolactone, digoxin and diuretics are well-known. Sicker elderly and multimorbid patients often do not tolerate the recommended targets but can still have a good clinical response with an improved outcome at lower doses. Therefore lower-than-target doses may not necessarily be wrong in certain patients and are better than "no doses", for example, failure to prescribe essential heart-failure drugs. Individualized doses of ACE inhibitors and beta-blockers (best in combination) are indicated in most patients with chronic HF. Less rigid application of guideline recommendations may improve their acceptance.