Does Spironolactone Have a Dose‐Dependent Effect on Left Ventricular Remodeling in Patients with Preserved Left Ventricular Function After an Acute Myocardial Infarction?
Abstract:SUMMARYAims: The aim of this study was to investigate the effects of spironolactone on left ventricular (LV) remodeling in patients with preserved LV function following acute myocardial infarction (AMI). Methods and Results: Successfully revascularized patients (n = 186) with acute ST elevation MI (STEMI) were included in the study. Patients were randomly divided into three groups, each of which was administered a different dose of spironolactone (12.5, 25 mg, or none). Echocardiography was performed within th… Show more
“…After screening the titles and abstracts of all studies, 121 full-text articles met the general inclusion criteria and were reviewed for strict inclusion or exclusion criteria. Finally, 14 RCTs were included [ 5 , 14 - 19 , 26 - 32 ]. Figure 1 Flowchart of study search and selection in this meta-analysis.…”
Section: Resultsmentioning
confidence: 99%
“…All trials (Table 1 ) were parallel arm trials, with a mean (± SD) duration of 11.75 ± 10.36 (range, 6 to39.6) months. Of the included trials, nine were conducted in HF-PEF (n = 4,127) [ 14 , 16 , 26 - 32 ] and five (n = 2,301) in MI-PEF patients [ 5 , 15 , 17 - 19 ]. Thus, a total of 6,428 participants were randomly assigned to receive MRAs (n = 3,249), placebo (n = 2,861), standard therapy (n = 301), or active comparator treatment (n = 17).…”
Section: Resultsmentioning
confidence: 99%
“…The withdrawal rates were comparable between the MRA treatment groups (9.86%) and control groups (10.79%). Spironolactone was the predominant MRA used (eight trials) [ 5 , 14 , 16 , 19 , 27 - 29 , 32 ], followed by eplerenone (four trials) [ 15 , 17 , 30 , 31 ] and canrenoate (two trials) [ 18 , 26 ]. Placebo controls were used in all except four trials.…”
Section: Resultsmentioning
confidence: 99%
“…Patients with this profile, known as HF with preserved ejection fraction (HF-PEF), have signs, symptoms, quality of life (QoL), and prognoses similar to HF patients with a reduced ejection fraction (HF-REF) [ 3 , 4 ]. Furthermore, patients with acute myocardial infarction (MI) often have preserved ejection fraction (PEF) [ 5 ]. Although many medical therapies benefit HF patients and post-MI patients with reduced LVEF [ 6 ], effective, evidence-based pharmacologic treatments are not currently available for PEF patients [ 7 ].…”
BackgroundMineralocorticoid receptor antagonists (MRAs) have been shown to be effective in patients with heart failure or myocardial infarction complicated by a reduced ejection fraction. However, the role of MRAs in patients with preserved ejection fraction (PEF) remains to be clarified. We aimed to summarize the evidence for the efficacy of MRAs in patients with either heart failure with PEF (HF-PEF) or myocardial infarction with PEF (MI-PEF).MethodsWe searched PubMed, EMBASE, Cochrane Library, and clinical trials databases for randomized controlled trials, through June 2014, assessing MRA treatment in HF-PEF or MI-PEF patients. Fourteen randomized controlled trials (MI-PEF, 5; HF-PEF, 9; n = 6,428 patients) were included.ResultsMRA treatment reduced the risk of hospitalization for heart failure (relative risk, 0.83; 95% confidence interval [CI], 0.70 to 0.98), improved quality of life (weighted mean difference [WMD], −5.16; 95% CI, −8.03 to −2.30), left ventricular end-diastolic diameter (standardized mean difference, −0.21; 95% CI, 0.32 to −0.11), and serum amino-terminal peptide of procollagen type-III level (WMD, −1.50, 95% CI, −1.72 to −1.29) in patients with PEF. In addition, MRAs reduced E/e'(an echocardiographic estimate of filling pressure for assessment of diastolic function; WMD, −1.82; 95% CI, −2.23 to −1.42) in HF-PEF patients and E/A ratio (the ratio of early to late diastolic transmitral flow; WMD, 0.12; 95% CI, 0.10 to 0.14) in MI-PEF patients. However, all-cause mortality was not improved by MRAs in either HF-PEF (P = 0.90) or MI-PEF (P = 0.27) patients.ConclusionsMRA treatment in PEF patients led to reduced hospitalization for heart failure, quantifiable improvements in quality of life and diastolic function, and reversal of cardiac remodeling, but did not provide any all-cause mortality benefit.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-014-0261-8) contains supplementary material, which is available to authorized users.
“…After screening the titles and abstracts of all studies, 121 full-text articles met the general inclusion criteria and were reviewed for strict inclusion or exclusion criteria. Finally, 14 RCTs were included [ 5 , 14 - 19 , 26 - 32 ]. Figure 1 Flowchart of study search and selection in this meta-analysis.…”
Section: Resultsmentioning
confidence: 99%
“…All trials (Table 1 ) were parallel arm trials, with a mean (± SD) duration of 11.75 ± 10.36 (range, 6 to39.6) months. Of the included trials, nine were conducted in HF-PEF (n = 4,127) [ 14 , 16 , 26 - 32 ] and five (n = 2,301) in MI-PEF patients [ 5 , 15 , 17 - 19 ]. Thus, a total of 6,428 participants were randomly assigned to receive MRAs (n = 3,249), placebo (n = 2,861), standard therapy (n = 301), or active comparator treatment (n = 17).…”
Section: Resultsmentioning
confidence: 99%
“…The withdrawal rates were comparable between the MRA treatment groups (9.86%) and control groups (10.79%). Spironolactone was the predominant MRA used (eight trials) [ 5 , 14 , 16 , 19 , 27 - 29 , 32 ], followed by eplerenone (four trials) [ 15 , 17 , 30 , 31 ] and canrenoate (two trials) [ 18 , 26 ]. Placebo controls were used in all except four trials.…”
Section: Resultsmentioning
confidence: 99%
“…Patients with this profile, known as HF with preserved ejection fraction (HF-PEF), have signs, symptoms, quality of life (QoL), and prognoses similar to HF patients with a reduced ejection fraction (HF-REF) [ 3 , 4 ]. Furthermore, patients with acute myocardial infarction (MI) often have preserved ejection fraction (PEF) [ 5 ]. Although many medical therapies benefit HF patients and post-MI patients with reduced LVEF [ 6 ], effective, evidence-based pharmacologic treatments are not currently available for PEF patients [ 7 ].…”
BackgroundMineralocorticoid receptor antagonists (MRAs) have been shown to be effective in patients with heart failure or myocardial infarction complicated by a reduced ejection fraction. However, the role of MRAs in patients with preserved ejection fraction (PEF) remains to be clarified. We aimed to summarize the evidence for the efficacy of MRAs in patients with either heart failure with PEF (HF-PEF) or myocardial infarction with PEF (MI-PEF).MethodsWe searched PubMed, EMBASE, Cochrane Library, and clinical trials databases for randomized controlled trials, through June 2014, assessing MRA treatment in HF-PEF or MI-PEF patients. Fourteen randomized controlled trials (MI-PEF, 5; HF-PEF, 9; n = 6,428 patients) were included.ResultsMRA treatment reduced the risk of hospitalization for heart failure (relative risk, 0.83; 95% confidence interval [CI], 0.70 to 0.98), improved quality of life (weighted mean difference [WMD], −5.16; 95% CI, −8.03 to −2.30), left ventricular end-diastolic diameter (standardized mean difference, −0.21; 95% CI, 0.32 to −0.11), and serum amino-terminal peptide of procollagen type-III level (WMD, −1.50, 95% CI, −1.72 to −1.29) in patients with PEF. In addition, MRAs reduced E/e'(an echocardiographic estimate of filling pressure for assessment of diastolic function; WMD, −1.82; 95% CI, −2.23 to −1.42) in HF-PEF patients and E/A ratio (the ratio of early to late diastolic transmitral flow; WMD, 0.12; 95% CI, 0.10 to 0.14) in MI-PEF patients. However, all-cause mortality was not improved by MRAs in either HF-PEF (P = 0.90) or MI-PEF (P = 0.27) patients.ConclusionsMRA treatment in PEF patients led to reduced hospitalization for heart failure, quantifiable improvements in quality of life and diastolic function, and reversal of cardiac remodeling, but did not provide any all-cause mortality benefit.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-014-0261-8) contains supplementary material, which is available to authorized users.
“…Aldosterone is thought to generate in the adrenal zone through the classical reninangiotensin-aldosterone system, and it is also synthesized by myocardial RAAS itself, including infarcted myocardium. [7,8] Meanwhile, angiotensin II could promote the synthesis of aldosterone in the myocardium. Some studies [9,10] demonstrated that the myocaridium could uptake aldosterone to induce ventricular remodeling in the acute phase of myocadial infarction.…”
BACKGROUND: Few studies have reported the effect of aldosterone receptor antagonist (ARA) on myocardial remodeling after acute myocardial infarction (AMI). This study was undertaken to investigate the preventive effect of ARA on myocardial remodeling after AMI. METHODS: A total of 616 patients who had been admitted into the CCU of the First Affiliated Hospital of Harbin Medical University from January 2008 to January 2010 were studied prospectively. Only 528 patients were observed completely, including 266 of the control group and 262 of the treatment group. There was no statistical difference in age, gender, medical history, admission situation, and treatment between the two groups (P>0.05). The preventive effects of spironolactone on cardiac remodeling, left ventricular function, renal function and blood levels of potassium were evaluated by echocardiography, serum potassium and serum creatinine at one-month and one-year follow-up. RESULTS: The echocardiography indicators such as LVESD, LVEDD, LVEF, LAD-ML and LAD-SI were signifi cantly improved in the treatment group compared with the control group at one year (P<0.05). In the treatment group, LVESD, LVEDD, LVPWT, LVEF, LAD-ML and LAD-SI were more significantly improved at one year than one month (P<0.05, P=0.007 to LVEF), and in the control group LVEF was more signifi cantly improved at one year than one month (P=0.0277). There were no signifi cant differences in serum potassium and serum creatinine levels between the two groups. CONCLUSION: On the basis of conventional treatment, the early combination of low-dose spironolactone (20 mg/d) could inhibit cardiac remodeling at late stage and prevent heart failure.
IMPORTANCE Treatment with aldosterone antagonists is recommended and has been shown to have beneficial effects in patients with ST-segment elevation myocardial infarction (STEMI) and left ventricular ejection fraction (LVEF) less than 40%. However, the role of aldosterone antagonists in patients with ejection fraction greater than 40% or without congestive heart failure is not well known. OBJECTIVES To perform a systematic review and meta-analysis using standard techniques to determine the role of therapy with aldosterone antagonists in this patient population. DATA SOURCES PubMed, Embase, CINAHL, and Cochrane Central databases were searched and a manual search for relevant references from the selected articles and published reviews was performed from database inception through June 2017. STUDY SELECTION Randomized clinical trials that evaluated treatment with aldosterone antagonists in patients with STEMI without clinical heart failure or LVEF greater than 40% were included. DATA EXTRACTION AND SYNTHESIS Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used to conduct and report the meta-analysis, which used a random-effects model. Two investigators independently performed the database search and agreed on the final study selection. A manual search was performed for relevant references from the selected articles and published reviews. MAIN OUTCOMES AND MEASURES The outcomes analyzed were mortality, new congestive heart failure, recurrent myocardial infarction, ventricular arrhythmia, and changes in LVEF, serum potassium level, and creatinine level at follow-up. RESULTS In all, 10 randomized clinical trials with a total of 4147 unique patients were included in the meta-analysis. In patients who presented with STEMI without heart failure, treatment with aldosterone antagonists compared with control was associated with lower risk of mortality (2.4% vs 3.9%; odds ratio [OR], 0.62; 95% CI, 0.42-0.91; P = .01) and similar risks of myocardial infarction (1.6% vs 1.5%; OR, 1.03; 95% CI, 0.57-1.86; P = .91), new congestive heart failure (4.3% vs 5.4%; OR, 0.82; 95% CI, 0.56-1.20; P = .31), and ventricular arrhythmia (4.1% vs 5.1%; OR, 0.76; 95% CI, 0.45-1.31; P = .33). Similarly, treatment with aldosterone antagonists compared with control was associated with a small yet significant increase in LVEF (mean difference, 1.58%; 95% CI, 0.18%-2.97%; P = .03), a small increase in serum potassium level (mean difference, 0.07 mEq/L; 95% CI, 0.01-0.13 mEq/L; P = .02), and no change in serum creatinine level (standardized mean difference, 1.4; 95% CI, −0.43 to 3.24; P = .13). CONCLUSIONS AND RELEVANCE Treatment with aldosterone antagonists is associated with a mortality benefit in patients with STEMI with LVEF greater than 40% or without heart failure.
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