Challenging the dogma of high target doses in the treatment of heart failure: is more always better?
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.
Follath
Ferenc
F
University Hospital Zürich, Office HAL 18/D2, Zürich, Switzerland. Ferenc.Follath@usz.ch
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D005260:Female; D019983:Guideline Adherence; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D057285:Precision Medicine; D018570:Risk Assessment; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002317:Cardiovascular Agents