PROSPERO (CRD42015026069).

No abstract

Introduction: Caregivers of women with breast cancer in low-and-middle-income countries experience significant physical and economic burdens. The review aimed to map the evidence of studies that had reported on the experiences of family caregivers of women diagnosed with breast cancer. Methods: A systematic literature search was conducted in CINAHL, PubMed, PsycINFO, Scopus, and Web of Science databases using a combination of key search terms and medical subject heading terms such as "family caregiver," "breast cancer," "home care," "low-and-middle-income countries," "experience," "effect," and "coping mechanism." A total of 1781 articles were retrieved and screened. Nineteen studies addressing caregiving experiences were included in the final review based on the inclusion and exclusion criteria. Results: The systematic review yielded 19 studies that focused on caregivers' motivation, needs of caregivers, intervention for caregivers, and consequences of caregiving. The most significant correlates of the quality of life among caregivers were disease severity, functional status of patients, and family income. The challenges encountered by caregivers were mostly psychosocial. Conclusions: Caregivers play a crucial role in the management of women with breast cancer. However, they are faced with increasing challenges in their caregiving roles. Understanding the nature and extent of the burden experienced by family caregivers in developing countries will facilitate the development of appropriate interventions that can help improve caregivers' quality of life. Gaps in recent studies were identified, and suggestions for future research were also addressed in this review. Systematic review registration: PROSPERO CRD42019118391

SUMMARYIntroduction: Statins are known to prevent heart failure (HF). However, it is unclear whether statins as class or type (lipophilic or hydrophilic) improve outcomes of established HF. Aims: The current meta-analysis was performed to compare the treatment effects of lipophilic and hydrophilic statins on inflammation and cardiac function in HF. Outcomes were indicators of cardiac function [changes in left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP)] and inflammation [changes in highly sensitive C-reactive protein (hsCRP) and interluekin-6 (IL-6)]. Method: We conducted a search of PubMed, EMBASE, and the Cochrane databases until December 31, 2014 for randomized control trials (RCTs) of statin versus placebo in patients with HF. RCTs with their respective extracted information were dichotomized into statin type evaluated and analyzed separately. Outcomes were pooled with random effect approach, producing standardized mean differences (SMD) for each statin type. Using these pooled estimates, we performed adjusted indirect comparisons for each outcome. Results: Data from 6214 patients from 19 trials were analyzed. Lipophilic statin was superior to hydrophilic statin treatment regarding follow-up LVEF (SMD, 4.54; 95% CI, 4.16-4.91; P < 0.001), BNP (SMD, À1.60; 95% CI, À2.56 to À0.65; P < 0.001), hsCRP (SMD, À1.13; 95% CI, À1.54 to À0.72; P < 0.001), and IL-6 (SMD, À3.75; 95% CI, À4.77 to À0.72; P < 0.001) in HF. Conclusions: Lipophilic statin produces greater treatment effects on cardiac function and inflammation compared with hydrophilic statin in patients with HF. Until data from adequately powered head-to-head trial of the statin types are available, our meta-analysis brings clinicians and researchers a step closer to the quest on which statin-lipophilic or hydrophilic-is associated with better outcomes in HF.

Lipophilic statin treatment shows significant decreases in all-cause mortality, cardiovascular mortality and hospitalization for worsening HF compared with rosuvastatin treatment. This meta-analysis provides preliminary evidence that lipophilic statins offer better clinical outcomes in HF till data from head to head comparisons are available.

Pharmacological interventions for heart failure with preserved ejection fraction (HFpEF) have failed to reduce mortality and hospitalization. Evidence for mineralocorticoid antagonists (MRAs), β-adrenoceptor blockers (β-blockers), and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs)-to reduce clinical outcomes in HFpEF remains unclear. We conducted a systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov for randomized controlled trials (RCTs) assessing pharmacological treatments in HFpEF diagnosed according the recommendations of the European Society of Cardiology (ESC) 2016 guidelines from inception to August, 2017. The study outcomes were mortality, hospitalization, changes in indexes of cardiac structure and function, biomarkers, and indexes of functional capacity-quality of life (QoL) assessment and 6-min walk distance test (6-MWD). The random-effects models were used to estimate pooled relative risks (RRs) for the binary outcomes and standardized mean differences for continuous outcomes, with 95% CI. A network meta-analysis using a random-effects model was employed to estimate the comparative efficacy of treatments. We included data from 15 RCTs comprising 5930 patients. There was no significant effect seen with all treatments compared with placebo and comparative efficacy of any two treatments on all outcomes assessed. However, mineralocorticoid antagonist spironolactone demonstrated a trend towards reducing mortality compared with placebo (RR 0.92; 95% CI 0.79-1.08), sildenafil (0.14; 0.01-2.78), perindopril (0.87; 0.59-1.28), and eplerenone (0.91; 0.25-3.33). Similar trends in treatment effect were observed with spironolactone on surrogate outcomes while eplerenone demonstrated a trend of superior effect in reduction of hospitalizations compared with all other drug treatment. No drug treatment demonstrated statistically significant improvement in clinical and surrogate outcomes in HFpEF diagnosed according to the ESC 2016 guideline. Spironolactone and eplerenone showed clinically relevant reduction in mortality and hospitalization respectively compared with other drug treatments. Further trials with MRAs are warranted to confirm treatment effects in HFpEF.

BackgroundStatins are known to reduce cardiovascular morbidity and mortality in primary and secondary prevention studies. Subsequently, a number of nonrandomised studies have shown statins improve clinical outcomes in patients with heart failure (HF). Small randomised controlled trials (RCT) also show improved cardiac function, reduced inflammation and mortality with statins in HF. However, the findings of two large RCTs do not support the evidence provided by previous studies and suggest statins lack beneficial effects in HF. Two meta-analyses have shown statins do not improve survival, whereas two others showed improved cardiac function and reduced inflammation in HF. It appears lipophilic statins produce better survival and other outcome benefits compared to hydrophilic statins. But the two types have not been compared in direct comparison trials in HF.Methods/designWe will conduct a systematic review and meta-analysis of lipophilic and hydrophilic statin therapy in patients with HF. Our objectives are:1. To determine the effects of lipophilic statins on (1) mortality, (2) hospitalisation for worsening HF, (3) cardiac function and (4) inflammation.2. To determine the effects of hydrophilic statins on (1) mortality, (2) hospitalisation for worsening HF, (3) cardiac function and (4) inflammation.3. To compare the efficacy of lipophilic and hydrophilic statins on HF outcomes with an adjusted indirect comparison meta-analysis.We will conduct an electronic search of databases for RCTs that evaluate statins in patients with HF. The reference lists of all identified studies will be reviewed. Two independent reviewers will conduct the search. The inclusion criteria include:1. RCTs comparing statins with placebo or no statin in patients with symptomatic HF.2. RCTs that employed the intention-to-treat (ITT) principle in data analysis.3. Symptomatic HF patients of all aetiologies and on standard treatment.4. Statin of any dose as intervention.5. Placebo or no statin arm as control.The exclusion criteria include:1. RCTs involving cerivastatin in HF patients.2. RCTs with less than 4 weeks of follow-up.DiscussionWe will perform an adjusted indirect comparison meta-analysis of lipophilic versus hydrophilic statins in patients with HF using placebo or no statin arm as common comparator.

Statins lower serum cholesterol and are employed for primary and secondary prevention of cardiovascular events. Clinical evidence from observational studies, retrospective data, and post hoc analyses of data from large statin trials in various cardiovascular conditions, as well as small scale randomized trials, suggest survival and other outcome benefits for heart failure. Two recent large randomized controlled trials, however, appear to suggest statins do not have beneficial effects in heart failure. In addition to lowering cholesterol, statins are believed to have many pleotropic effects which could possibly influence the pathophysiology of heart failure. Following the two large trials, evidence from recent studies appears to support the use of statins in heart failure. This review discusses the role of statins in the pathophysiology of heart failure, current evidence for statin use in heart failure, and suggests directions for future research.