BACKGROUND: Statins 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/DESIGN: We 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.
DISCUSSION: We 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.