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Meta-Analysis Evaluating the Effects of Renin-Angiotensin-Aldosterone System Blockade on Outcomes of Heart Failure With Preserved Ejection Fraction.
Kuno, T, Ueyama, H, Fujisaki, T, Briasouli, A, Takagi, H, Briasoulis, A
The American journal of cardiology. 2020;(8):1187-1193
Abstract
Clinical trials of renin-angiotensin-aldosterone system (RAAS) antagonists in heart failure with preserved ejection fraction (HFpEF) have suggested neutral results and treatment is focused on associated symptoms and comorbidities. MEDLINE and EMBASE were searched through October 2019 for randomized controlled studies investigating the effects of different RAAS antagonists in patients with HFpEF. The main outcomes were all-cause mortality, trial defined cardiovascular mortality, and heart failure (HF) hospitalizations. To compare different RAAS antagonists, a random-effects restricted-maximum-likelihood network meta-analysis based on a frequentist framework for indirect and mixed comparisons was used. We used p scores to rank best treatments per outcome. Our search identified 5 eligible clinical trials (PEP-CHF, perindopril; CHARM-preserved, candesartan; I-PRESERVE, irbesartan; TOPCAT, spironolactone; PARAGON-HF, sacubitril-valsartan and valsartan) enrolling a total 10,523 on RAAS antagonists and 6,259 controls. We did not identify any statistical difference in all-cause and cardiovascular mortality among RAAS antagonists and placebo. The combination of sacubitril-valsartan was associated with significantly decreased HF hospitalization risk compared with controls (odds ratio 0.73, 95% confidence interval 0.61 to 0.87) and angiotensin II receptor blockers (odds ratio 0.80, 95% confidence interval 0.71 to 0.91), without heterogeneity among studies (I2 = 0). Angiotensin receptor neprilysin inhibitor (ARNI) ranked better than other RAAS antagonists for HF hospitalizations (p value 0.9). In conclusion, RAAS antagonists do not affect mortality but the combination of sacubitril-valsartan is associated with lower HF hospitalizations in HFpEF patients.
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Effects of Mineralocorticoid Receptor Antagonists on Atrial Fibrillation Occurrence: A Systematic Review, Meta-Analysis, and Meta-Regression to Identify Modifying Factors.
Alexandre, J, Dolladille, C, Douesnel, L, Font, J, Dabrowski, R, Shavit, L, Legallois, D, Funck-Brentano, C, Champ-Rigot, L, Ollitrault, P, et al
Journal of the American Heart Association. 2019;(22):e013267
Abstract
Background Mineralocorticoid receptor antagonists (MRAs) have emerged as potential atrial fibrillation (AF) preventive therapy, but inconsistent results have been reported. We aimed to examine the effects of MRAs on AF occurrence and explore factors that could influence the magnitude of the effect size. Methods and Results PubMed, Embase, and Cochrane Central databases were used to search for randomized clinical trials and observational studies addressing the effect of MRAs on AF occurrence from database inception through April 03, 2018. We performed a systematic review and random effects meta-analyses to compute odds ratios with 95% CIs. Meta-regression was then applied to explore the sources of between-study heterogeneity. We included 24 studies, 11 randomized clinical trials and 13 observational cohorts, representing a total number of 7914 patients (median age: 64.2 years; median left ventricular ejection fraction: 49.7%; median follow-up: 12.0 months), 2843 (35.9%) of whom received MRA therapy. Meta-analyses showed a significant overall reduction in AF occurrence in the MRA-treated patients versus the control groups (15.0% versus 32.2%; odds ratio, 0.55; 95% CI, 0.44-0.70 [P<0.00001]), with the greatest benefit regarding recurrent AF episodes (odds ratio, 0.42; 95% CI, 0.31-0.59 [P<0.00001]) and with significant heterogeneity among the included studies (I2=54%; P=0.0008). Meta-regression analyses showed that effect size was significantly associated with older studies and higher AF occurrence rate in the control groups. Conclusions MRAs seem to be effective in AF prevention, especially regarding recurrent AF episodes.
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Aldosterone Antagonist Therapy and Mortality in Patients With ST-Segment Elevation Myocardial Infarction Without Heart Failure: A Systematic Review and Meta-analysis.
Dahal, K, Hendrani, A, Sharma, SP, Singireddy, S, Mina, G, Reddy, P, Dominic, P, Modi, K
JAMA internal medicine. 2018;(7):913-920
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Abstract
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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A comparative systematic review of Yasmin (drospirenone pill) versus standard treatment options for symptoms of polycystic ovary syndrome.
Li, J, Ren, J, Sun, W
European journal of obstetrics, gynecology, and reproductive biology. 2017;:13-21
Abstract
OBJECTIVES To systematically review the impact of Yasmin (drospirenone pill) compares with other standard treatments for symptoms of Polycystic Ovary Syndrome (PCOS). STUDY DESIGN The relevant studies of the randomized controlled trials in women with PCOS treated with drospirenone were retrieved and the systematic evaluation was conducted. RESULTS Eighteen articles were included. Compared with drospirenone (DRSP) monotherapy, DRSP plus metformin was better in reducing body mass index (BMI), luteinizing hormone (LH) and low-density lipoprotein cholesterol (LDL-C). Compared with metformin, DRSP was better in modulating serum total testosterone (T), sex hormone-binding globulin (SHBG), follicle stimulating hormone (FSH) and free androgen index (FAI), while metformin was more effective in reducing BMI, total cholesterol (TC), LDL-C and Triglyceride (TG). DRSP was superior to cyproterone acetate (CPA) in reducing TC and homeostasis model assessment of insulin resistance (HOMA-IR). DRSP shows better effect in modulating LDL-C and high-density lipoprotein cholesterol (HDL-C) compared with desogestrel (DSG). CONCLUSIONS The available data suggested that DRSP was effective in modulating hormones, insulin and lipid metabolism in women with PCOS. Compared with commonly used drugs for symptoms of PCOS as CPA and DSG, DRSP shows identical or better effect in improving symptoms and protect cardiovascular system. For the PCOS patients with IR, obesity or high LH/FSH ratio, DRSP combines with metformin maybe more effective than use DRSP alone.
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The Effects of Aldosterone Antagonists in Patients With Resistant Hypertension: A Meta-Analysis of Randomized and Nonrandomized Studies.
Dahal, K, Kunwar, S, Rijal, J, Alqatahni, F, Panta, R, Ishak, N, Russell, RP
American journal of hypertension. 2015;(11):1376-85
Abstract
BACKGROUND A few studies have shown aldosterone antagonists (AA) to be effective therapy in patients with resistant hypertension (RH). We performed a meta-analysis of randomized and nonrandomized studies of AA in patients with RH. METHODS We searched PUBMED, EMBASE, and CENTRAL for studies on the use of AA in patients with RH. Meta-analysis was performed using random-effects model. The change in office and ambulatory blood pressures (BP), effects on biochemical profile, change in the number of antihypertensive agents, and adverse events were main outcomes. RESULTS We included 15 studies (3 randomized controlled trials, 1 nonrandomized comparative study, and 11 single-arm studies) with 1,204 total patients in the meta-analysis. In comparative studies, AA reduced systolic BP (SBP) by 24.26 mm Hg (95% CI: 8.65-39.87, P = 0.002) and diastolic BP (DBP) by 7.79 mm Hg (3.79-11.79, P = 0.0001). Similarly, AA reduced SBP by 22.74 mm Hg (18.21-27.27, P < 0.00001) and DBP by 10.49 mm Hg (8.85-12.13, P < 0.00001) in single-arm studies. AA resulted in significant change in serum electrolytes in single-arm studies but not in comparative studies. Significantly more adverse events were noted in single-arm studies but not in comparative studies. CONCLUSIONS On the basis of the current meta-analysis, we conclude that AA is safe and effective therapy in patients with RH.