Subscribe: Latest / All - Designed by Dr James P Howard (Google+)
RALES TRIAL |
|
|---|---|
| Problem | CCF (NYHA III & IV) |
| Format | Double-blinded multi-center RCT |
| Treatment | Spironolactone |
| Control | Placebo |
| Population | 1663 |
| Inclusion criteria | Must have all of: New York Heart Association (NYHA) class IV heart failure within the six months before enrolment In NYHA class III or IV at the time of enrolment Diagnosis of heart failure at least six weeks before enrolment Being treated with an ACE inhibitor (if tolerated) and a loop diuretic Had a left ventricular ejection fraction of no more than 35 percent within the six months before enrollment (with no clinically significant intercurrent event) Treatment with digitalis and vasodilators was allowed, but potassium-sparing diuretics were not permitted. |
| Exclusion criteria | Primary operable valvular heart disease (other than mitral or tricuspid regurgitation with clinical symptoms due to left ventricular systolic heart failure) Congenital heart disease Unstable angina Primary hepatic failure Active cancer Any life-threatening disease (other than heart failure) Those undergone or awaiting heart transplant Serum creatinine concentration of more than 2.5 mg per deciliter (221 Î_mol per liter) Serum potassium concentration of more than 5.0 mmol per liter |
| Follow-up | Mean 24 months |
| Primary endpoint | Death from any cause |
| Secondary endpoint(s) | Death from cardiac causes Hospitalisation for cardiac causes Combined incidence of death from cardiac causes or hospitalization for cardiac causes Change in NYHA class The effect of spironolactone was also assessed with the use of six prerandomization variables: left ventricular ejection fraction, the cause of heart failure, the serum creatinine concentration, age, the use of ACE inhibitors, and the use of digitalis. |
| Details | Patients started on 25mg, could be uptitrated to 50mg @ 8 weeks if progression of disease without hyperkalaemia If patients developed hypokalaemia, dose reduced to 25mg alternating days - however, advice was to adjust other medications first |
| Brief summary: | Spironolactone reduced mortality and symptoms in NYHA 3+ |
| PAPER: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators | |
|---|---|
| Date | 2 Sep 1999 |
| Journal | N Engl J Med. 1999 Sep 2;341(10):709-17. |
| Information | Trial stopped early due to 30% relative risk reduction (p<0.001) In patients with severe HF and LVEF < 35%, spironolactone vs. placebo: -Significant reduction in all cause mortality --Significant reduction in sudden death and progression of CCF --Similar across all subgroups -NYHA improved significantly more and worsened in significantly fewer Benefits independent of age, EF, aetiology of HF and other therapy |