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Three Part Question

In [adults with moderate to severe acute left ventricular failure] are [nitrates better than ace-inhibitors] at [impoving outcome]?

Clinical Scenario

A 60 year old woman presents to the A & E department with acute heart failure symptoms. The SHO wonders whether the administration of nitrates or ace-inhibitors would be most beneficial.

Search Strategy

Medline 1966 to June 2005 week 4
(exp Heart Failure, Congestive/ OR exp Adult/ OR exp Cardiac Output, Low/ OR cardiac failure.mp/ OR ccf.mp/ OR exp Pulmonary Edema/ OR exp Cardiotonic Agents/ OR exp Acute Disease/ OR exp Natriuretic Peptide, Brain/ OR pulmonary edema.mp/ OR pulmonary oedema.mp/ OR exp Ventricular Dysfunction, Left/ OR acute systolic failure.mp/ OR shortness of breath.mp/ OR exp Dyspnea/ OR dyspnoea.mp/ OR exp Morphine/ OR left ventricular failure.mp/ OR lv failure.mp/ OR left ventricular heart failure.mp/ OR lvf.mp.) AND 2. (nitrates.mp. OR exp NITRATES/ OR exp Coronary Vessels/ OR exp Vasodilator Agents/ OR exp Nitroglycerin/ OR gtn.mp. OR exp Heart/ OR glyceryl trinitrate.mp.) AND (ace inhibitors.mp. OR exp Angiotensin-Converting Enzyme Inhibitors/ OR angiotensin converting enzyme inhibitors.mp. OR captopril.mp. OR exp CAPTOPRIL/)

Search Outcome

293 papers were found
2 were deemed relevant and are included in the BET

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Haude M, Steffen W, Erbel R, Meyer J 1990 Germany	24 patients with severe left heart failure (NYHA Classification Class III or IV) in the intensive care setting.	Randomized crossover study. Patients all monitored using a pulmonary artery thermodilution catheter. Randomized to receive either 25mg captopril or 0.8mg nitroglycerin sublingually then monitored for 3h. After parameters had returned to base-line levels the patients received the other treatment arm and were again monitored for 3h.	Pre- and after-load parameters	Nitroglycerin and captopril improved parameters to significantly (P<0.001 for each)	Not clear how patients were recruited for this study. Method of randomisation not explained. No blinding. No sample size estimate. No mention of ethical approval. Clinical outcomes only mentioned briefly - 22/24 patients reported improvement, 5/24 patients reported headache with nitroglycerin, no other side effects.
			Increase in cardiac index	Captopril increased this significantly more than nitroglycerin (+49.2% vs. +25% P<0.001)
			Peak onset	Captopril 47-84 minutes vs. nitroglycerin at 25-55 minutes (P<0.001)
			Duration of action	Captopril 117-162 minutes vs nitroglycerin at 68-120 minutes (P<0.001)
Adigun AQ et al 1998 Nigeria	17 patients presenting to an Emergency Department with severe, acute left ventricular failure.	Prospective, randomised trial. Randomised to receive either 50mg captopril and 1mg prazosin orally or 30mg hydralazine intravenously and 30mg isosorbide dintrate orally. Patients required to be hypertensive with pulmonary oedema on the chest x-ray and a dilated heart.	Systolic and diastolic blood pressure	Significant drop in both values in each group. (P<0.001). No significant difference between treatments.	Study carried out in Nigeria where LVF is often secondary to malignant hypertension rather than to coronary artery disease. Recruitment not clearly described, only 17 patients recruited in 2y. No power calculation. Clinical outcome described only briefly: 4 patients from captopril group and 4 patients from hydralazine group required dialysis for renal failure. One of the patients from the hydralazine group died before his dialysis could be commenced. No other patients died.
			Respiratory rate	Both treatments produced significant drop in respiratory rate (P=0.001). Captopril/prazosin group had significantly greater drop in respiratory rate (P=0.034).

Comment(s)

In patients with heart failure it is beneficial to decrease the cardiac pre-load and after-load. Both of these agents are effective in creating these actions. Nitrates produce the maximal effect more quicly than ACE inhibitors though ACE inhibitors have a more prolonged effect. There is no evidence produced by this search regarding any benefit of one agent over the other in terms of clinical benefit for the patients.

Clinical Bottom Line

Both ACE inhibitors and nitrates produce benificial effects in the treatment of acute heart failure. No evidence was found to recommend one drug type over the other.

Level of Evidence

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

References

1. Haude M, Steffen W, Erbel R, Meyer J Sublingual administation of captopril versus nitroglycerin in patients with severe congestive heart failure International Journal of Cardiolgoy 27 (1990) 351-359
2. Adigun AQ, Ajayi OE, Sofowora GG, Ajayi AA Vasodilator therapy of hypertensive acute left ventricular failure: Comparison of captopril-prazosin with Hydralazine-isorbide dinitrate International Journal of Cardiology 67 (1998) 81-86