Creatine and creatine analogues in hypertension and cardiovascular disease
Horjus DL, Oudman I, van Montfrans GA, Brewster LM
The Cochrane database of systematic reviews · 16 citas
Etiquetas de revisión
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Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación no declarada
Publicación
- Publicado
- 2011-11-01 · Cochrane Database Syst Rev · vol. 2011 · número 11 · pág. CD005184
- Editorial
- Elsevier BV
- Citado
- 27 citas · más que el 73% de estudios similares · 0.6× el promedio de su campo
- Referencias
- 33 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Blood Pressure and Hypertension Studies · Muscle metabolism and nutrition · Cardiovascular Function and Risk Factors
- Palabras clave
- creatine, phosphocreatine, cyclocreatine, heart failure, myocardial infarction, ischemic heart disease, essential hypertension, cardiovascular disease, ejection fraction, blood pressure, myocardial ischemia, adjunctive therapy, energy metabolism, meta-analysis of trials, quality of evidence, risk of bias
- MeSH
- humans, cardiovascular diseases, myocardial ischemia, myocardial infarction, hypertension, creatine, creatine kinase, phosphocreatine, heart failure, molecular targeted therapy
4 autores
- Deborah L. Horjus🇳🇱Amsterdam UMC Location University of Amsterdam; University of Amsterdam
- Inge Oudman🇳🇱Amsterdam UMC Location University of Amsterdam; University of Amsterdam
- Gert A. van Montfrans🇳🇱Amsterdam UMC Location University of Amsterdam; University of Amsterdam
- Lizzy M. Brewster🇳🇱Amsterdam UMC Location University of Amsterdam; University of Amsterdam
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
The creatine kinase system, the central regulatory system of cellular energy metabolism, provides ATP in situ at ATP-ases involved in ion transport and muscle contraction. Furthermore, the enzyme system provides relative protection from tissue ischaemia and acidosis. The system could therefore be a target for pharmacologic intervention.
Objectives
To systematically evaluate evidence regarding the effectiveness of interventions directly targeting the creatine kinase system as compared to placebo control in adult patients with essential hypertension or cardiovascular disease.
Search methods
Electronic databases searched: Medline (1950 - Feb 2011), Embase (up to Feb 2011), the Cochrane Controlled Trials Register (issue 3, Aug 2009), Latin-American/Caribbean databank Lilacs; references from textbooks and reviews; contact with experts and pharmaceutical companies; and searching the Internet. There was no language restriction.
Selection criteria
Randomized controlled trials comparing creatine, creatine phosphate, or cyclocreatine (any route, dose or duration of treatment) with placebo; in adult patients with essential hypertension, heart failure, or myocardial infarction. We did not include papers on the short-term use of creatine during cardiac surgery.
Data collection and analysis
The outcomes assessed were death, total myocardial infarction (fatal or non-fatal), hospitalizations for congestive heart failure, change in ejection fraction, and changes in diastolic and systolic blood pressure in mm Hg or as percent change.
Main results
Full reports or abstracts from 1164 papers were reviewed, yielding 11 trials considering treatment with creatine or creatine analogues in 1474 patients with heart failure, ischemic heart disease or myocardial infarction. No trial in patients with hypertension was identified. Eleven trials (1474 patients, 35 years or older) comparing add-on therapy of the creatine-based drug on standard treatment to placebo control in patients with heart failure (6 trials in 1226 / 1474 patients ), or acute myocardial infarction (4 trials in 220 / 1474 patients) or 1 in ischemic heart disease (28 / 1474 patients) were identified. The drugs used were either creatine, creatine phosphate (orally, intravenously, or intramuscular) or phosphocreatinine. In the trials considering heart failure all three different compounds were studied; creatine orally (Gordon 1995, Kuethe 2006), creatine phosphate via intravenous infusion (Ferraro 1996, Grazioli 1992), and phosphocreatinine orally (Carmenini 1994, Maggi 1990). In contrast, the acute myocardial infarction trials studied intravenous creatine phosphate only. In the ischemic heart disease trial (Pedone 1984) creatine phosphate was given twice daily through an intramuscular injection to outpatients and through an intravenous infusion to inpatients. The duration of the study intervention was shorter for the acute patients, from a two hour intravenous infusion of creatine phosphate in acute myocardial infarction (Ruda 1988, Samarenko 1987), to six months in patients with heart failure on oral phosphocreatinine therapy (Carmenini 1994). In the acute myocardial infarction patients the follow-up period varied from the acute treatment period (Ruda 1988) to 28 days after start of the symptoms (Samarenko 1987) or end of the hospitalization period (Zochowski 1994). In the other trials there was no follow-up after discontinuation of treatment, except for Gordon 1995 which followed the patients until four days after stopping the intervention.Only two out of four trials in patients with acute myocardial infarction reported mortality outcomes, with no significant effect of creatine or creatine analogues (RR 0.73, CI: 0.22 - 2.45). In addition, there was no significance on the progression of myocardial infarction or improvement on ejection fraction. The main effect of the interventions seems to be on improvement of dysrhythmia.
Authors' conclusions
This review found inconclusive evidence to decide on the use of creatine analogues in clinical practice. In particular, it is not clear whether there is an effect on mortality, progression of myocardial infarction and ejection fraction, while there is some evidence that dysrhythmia and dyspnoea might improve. However, it is not clear which analogue, dose, route of administration, and duration of therapy is most effective. Moreover, given the small sample size of the discussed trials and the heterogeneity of the population included in these reports, larger clinical studies are needed to confirm these observations.
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