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Three Part Question

In [adults with moderate to severe acute left ventricular failure] are [diuretics and ace-inhibitors together better than diuretics alone] at [reducing mortality]?

Clinical Scenario

A 20 year old patient presents to the A & E department with severe pulmonary oedema of cardiac origin. You wonder whether diuretic and ace-inhibitor combination therapy is better than either of them alone.

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 (diuretics.mp. OR exp DIURETICS, OSMOTIC/ OR exp DIURETICS, THIAZIDE/ OR exp DIURETICS/ OR exp DIURETICS, SULFAMYL/ OR frusemide.mp. OR exp Furosemide/ OR furosemide.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

273 papers were found
4 were deemed relevant
3 were of sufficient quality 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
Krämer et al 1998 Germany	Various depending on particular study being reviewed	Review of diuretic therapy in congestive heart failure and discussion of mechanisms underlying diuretic resistance	Serum sodium level	Reduced when spironolactone was added to diuretic and ace-inhibitor combination therapy (exact values not given).	Details are not included of how searching for studies was done or inclusion/exclusion criteria, hence not reproducible. Quality assessment of studies not included hence reliability uncertain. Results not always presented clearly enough to allow reader to reach own conclusions (although well referenced). No sensitivity analysis.
van Vliet et al 1993 The Netherlands	21 patients all treated with diuretic and ace-inhibitor. 5 responded. 16 did not and were given additional spironolactone therapy.	Baseline controlled study	Excess fluid lost after treatment began	5/21 patients lost (mean values) 62% (0.9±0.5kg per day) excess fluid when treated with a loop diuretic and ace-inhibitor over 5 days. With spironolactone addition, 13/16 patients lost (mean values) 64% excess fluid within a week (0.61±0.2kg per day).	Small numbers used in study. Results may have been influenced by previous medication.
Sharpe 1993 New Zealand	Varied depending on studies used	Review	Benefit of combination therapy of ace-inhibitors and diuretics	Reduced mortality (more detailed measeurements not included in paper)	Paper lacks detail. Results are not present. Although references are given for theory, more needs to be presented within the paper itself.

Clinical Bottom Line

Ace-inhibitors and diuretics are more effective for treating acute heart failure when they are combined rather than only using one. The addition of spironolactone is useful in patients resistant to this combination.

References

1. Krämer B K, Schweda F, Riegger G A J, Diuretic Treatment and Diuretic Resistance in Heart Failure The American Journal Of Medicine 1999;106:90-96
2. van Vliet A A, Donker Ab J M, Nauta Jos J P et al Spironolactone in Congestive Heart Failure Refractory to High-Dose Loop Diuretic and Low-Dose Angiotensin-Converting Enzyme Inhibitor American Journal of Cardiology 1993;71:21A-28A
3. Sharpe N ACE Inhibitors Versus Diuretics: When to Choose Which Drug Cardiovascular Drugs And Therapy 1993;7(6) 877-879