Current Controversies with ACE Inhibitor Treatment in Heart Failure

Abstract

Although the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors on symptoms, morbidity and mortality have been proven beyond any doubt, some controversies remain. First, surveys have shown that a minority of patients in whom ACE inhibition is indicated, actually receive ACE inhibitors. Moreover, the majority of patients on ACE inhibitors use doses that are far lower than the target dose used in the large trials. These lower doses may be less effective. There is limited evidence to show that low-dose ACE inhibition is as effective as high-dose ACE inhibition. However, two ongoing trials – ATLAS and NETWORK – will determine the relative efficacy of high- and low-dose ACE inhibition. Second, the large ACE inhibitor trials have shown major variations in mortality, suggesting that differences between the efficacy of ACE inhibitors exist. However, the major differences in mortality are related mainly to the variations in inclusion criteria, suggesting a class effect of ACE inhibition. A study, assessing the relative efficacy of various ACE inhibitors seems unrealistic at this time. Third, mortality data on asymptomatic left ventricular dysfunction are conflicting, suggesting that initial treatment can wait until symptoms of heart failure appear. However, studies are consistent in showing reduction of events. Thus, early treatment in asymptomatic dysfunction may be warranted. Finally, it has been demonstrated that ACE inhibitors act favorably on volume and pressure overload, electrolytes and autonomic function. Nevertheless, the ACE inhibitor trials have failed to demonstrate that reduction of mortality is related to reduction of malignant ventricular arrhythmias/sudden death. This issue needs further study as specific antiarrhythmic strategies may be appropriate for arrhythmias.

Utilization and dosing of angiotensin-converting enzyme inhibitors for heart failure

“…In particular, physicians may not follow medication dosage protocols. While studies in progress are testing the effect of different dosages of ACE inhibitors on outcomes, 16,19,20 the Agency for Health Care Policy and Research, American Heart Association, and American College of Cardiology are currently recommending the dosages established in published trials. 12,13,19 Emphasis on adequate dosing is still needed among all specialty groups.…”

Sumatriptan (oral route of administration) for acute migraine attacks in adults

“…• Sumatriptan 100 mg versus rizatriptan 10 mg (Tfelt-Hansen 1998; Visser 1996). • Sumatriptan 100 mg versus rizatriptan 20 mg (Visser 1996).…”

“…• Sumatriptan 100 mg versus rizatriptan 40 mg (Visser 1996). In total, 2111 participants were treated with sumatriptan 25 mg, 8081 with sumatriptan 50 mg, 849 with sumatriptan 85 mg, 8094 with sumatriptan 100 mg, 460 with sumatriptan 200 mg, 454 with sumatriptan 300 mg, 7016 with placebo, 1103 with naproxen, 855 with sumatriptan 85 mg + naproxen 500 mg, 251 with sumatriptan 50 mg + naproxen 500 mg, 131 with diclofenac potassium 50…”

“…• The relative benefit of treatment compared with placebo was 1.8 (1.5 to 2.1; Analysis 4.3); the NNT was 7.5 (6.2 to 9.7). Visser 1996).…”

Wirtschaftlichkeit von Bisoprolol in der Behandlung der Herzinsuffizienz in Deutschland Eine Analyse auf der Basis der CIBIS-II-Studie

“…In den letzten Jahren haben umfangreiche Studien neue Erkenntnisse in der Behandlung der schweren Herzinsuffizienz erbracht [38,40,47,52]. Die Ergebnisse zeigen unter anderem, dass Patienten aus medizinischer Sicht von einer Therapie mit ACE-Hemmern und Bisoprolol profitieren.…”