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Three Part Question

In [patients with an acute episode of heart failure] does [the addition of an ACE inhibitor to standard therapies] improve [outcome].

Clinical Scenario

A 72-year-old man with a known history of ischaemic heart disease presents to the emergency department in the early hours of the morning with acute dyspnoea. He is diaphoretic and on examination has crepitations on both middle and lower zones of his chest. A chest radiograph shows cardiomegaly and increased shadowing consistent with pulmonary oedema. He remains unwell despite the administration of oxygen, nitrates, diuretics and opiates and, knowing that ACE inhibitors have proven benefit in chronic heart failure, you wonder if he would receive benefit from this drug in the acute setting.

Search Strategy

Medline via Ovid 1966 to Apr 2009
[exp Heart Failure, Congestive/ OR heart failure.mp. OR congestive cardiac failure.mp. OR ccf.mp. OR exp Ventricular Dysfunction, Left/ or lvf.mp. OR acute dyspnoea.mp. OR exp Pulmonary Edema/ OR cardiac insufficiency.mp. OR failing heart.mp. OR left ventricular failure.mp. OR exp Pulmonary Edema/ OR pulmonary oedema.mp. ] AND [ACE inhibitor.mp. OR exp Angiotensin-Converting Enzyme Inhibitors/ OR captopril.mp. OR exp Captopril/ OR enalapril.mp. OR exp Enalapril/ OR benazepril.mp. OR cilazapril.mp. or exp Cilazapril/ OR fosinopril.mp. OR exp Fosinopril/ OR lisinopril.mp. OR exp Lisinopril/ OR moexipril.mp. OR perindopril.mp. OR exp Perindopril/ OR quinapril.mp. OR ramipril.mp. OR exp Ramipril/ OR trandolapril.mp. OR enalaprilat.mp. or exp Enalaprilat/] AND
[morbidity.mp. OR exp Morbidity/ OR mortality.mp. OR exp Hospital Mortality/ OR exp Mortality/ OR Survival/ OR survival.mp. OR exp Survival Rate/ OR outcome.mp. OR exp Treatment Outcome] LIMIT to humans and English language and "therapy(sensitivity)".

Search Outcome

459 papers were found of which 2 were relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Haude et al, 1990, Germany	24 patients who had been admitted to the ICU with severe dominant left heart failure (NYHA Class III or IV). Patients were required to have a cardiac index of ≤2.5 l/min/m2 and a diastolic pulmonary artery pressure of ≥20 mm Hg to be included.25 mg captopril vs 0.8 mg nitroglycerin. Following this, they were given the other drug and observed for a further 3 h.	Experimental	Average change in cardiac index(cardiac output/body surface area)	Captopril: baseline 2.0 (0.4) l/min/m2 increased to 2.6 (0.6) l/min/m2.Nitroglycerin: baseline 2.1 (0.4) l/min/m2 increased to 2.4 (0.6) l/min/m2 (p<0.001).	Small study. Patients were not representative of patients who attend with an acute heart failure, 9/24 patients had dilative cardiomyopathy and were selected according to haemodynamic findings.
			Average change in blood pressure	Decreased by 16% following captopril and by 15% following nitroglycerin. No significant difference between drugs.
			Average change in pulmonary arterial pressure	Decrease after captopril 22.1%, decrease after nitroglycerin 19.1%.
			Change in heart rate	No significant change in heart rate with either drug.
Hamilton et al, 1996, USA	57 patients presenting to the emergency department with the clinical appearance of acute pulmonary oedema. All patients received oxygen, sublingual nitroglycerin, intravenous morphine, furosemide and, if necessary, nitrates at the attending physician’s discretion.Captopril vs placebo.	PRCT	Reduction in average APEX score at 30 minutes	Captopril group 57% of original (95% CI 47-67%), Placebo group 75% of original (95% CI 65-85%)	The APEX scoring system has not been validated though it is likely to reflect the patients symptoms given its components. A larger study may have demonstrated a benefit of reduced requirements for ventilation. The size of the patient group also allowed significant differences in the characteristics for example the rate of myocardial infarction was 26% in the captopril group versus 36% in the placebo group. There is no mention of longer term outcomes for these patients e.g. mortality.
			Reduction in average APEX score at 120 minutes	Both groups around 30% of original, no significant difference
			Need for mechanical ventilation	9% for captopril group vs. 20% for placebo group, (p=0.10, Fishers exact test)

Comment(s)

There are limited data suggesting a possible short-term benefit from the use of ACE inhibitors in patients with acute pulmonary oedema. This group of patients is difficult to study because they are often extremely ill at the time of initial presentation. Treatment of these patients also tends to be multimodal, and it can be difficult to isolate which drug is causing which effect. The diagnosis of heart failure is essentially a clinical one with various different potential pathologies and different underlying mechanisms of producing the same set of symptoms. Demonstrating benefit by improving haemodynamic measurements is of limited value.

Clinical Bottom Line

There is no clear evidence of a significant clinical benefit to administrating an ACE inhibitor to patients with acute heart failure in addition to standard therapy.

Level of Evidence

Level 3 - Small numbers of small studies or great heterogeneity or very different population.

References

1. Haude M, Steffen W, Erberl R, Meyer J. Sublingual administration of captopril versus nitroglycerin in patients with severe congestive heart failure. International Journal of Cardiology 1990 (27) 351-359.
2. Hamilton RJ, Carter WA, Gallagher EJ. Captopril for Acute Pulmonary Edema. Acad. Emerg. Med. 1996 (3); 205-212.