Effects of Statin Treatment on Inflammation and Cardiac Function in Heart Failure: An Adjusted Indirect Comparison Meta-Analysis of Randomized Trials.
BACKGROUND
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.


OBJECTIVE
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)].


METHODS
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, -1.60; 95% CI, -2.56 to -0.65; P < 0.001), hsCRP (SMD, -1.13; 95% CI, -1.54 to -0.72; P < 0.001), and IL-6 (SMD, -3.75; 95% CI, -4.77 to -0.72; 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.
School of Medicine and Health Sciences, Monash University, Bandar Sunway, Selangor DE, Malaysia.|Pharmacy Department, Accident and Emergency Directorate, Komfo Anokye Teaching Hospital, Kumasi, Ghana.
Kwadwo Osei
KO
Bonsu
School of Medicine and Health Sciences, Monash University, Bandar Sunway, Selangor DE, Malaysia.
Daniel Diamond
DD
Reidpath
School of Medicine and Health Sciences, Monash University, Bandar Sunway, Selangor DE, Malaysia.
Amudha
A
Kadirvelu
D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D013318:Stroke Volume; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D002317:Cardiovascular Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
Adjusted indirect comparison; Heart failure; Hydrophilic statin; Lipophilic statin; Meta-analysis