The aim of this study is to perform a systematic review of the costing methodological approaches adopted by published cost-of-illness (COI) studies. A systematic review was performed to identify cost-of-illness studies of heart failure published between January 2003 and September 2015 via computerized databases such as Pubmed, Wiley Online, Science Direct, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Costs reported in the original studies were converted to 2014 international dollars (Int$). Thirty five out of 4972 studies met the inclusion criteria. Nineteen out of the 35 studies reported the costs as annual cost per patient, ranging from Int$ 908.00 to Int$ 84,434.00, while nine studies reported costs as per hospitalization, ranging from Int$ 3780.00 to Int$ 34,233.00. Cost of heart failure increased as condition of heart failure worsened from New York Heart Association (NYHA) class I to NYHA class IV. Hospitalization cost was found to be the main cost driver to the total health care cost. The annual cost of heart failure ranges from Int$ 908 to Int$ 40,971 per patient. The reported cost estimates were inconsistent across the COI studies, mainly due to the variation in term of methodological approaches such as disease definition, epidemiological approach of study, study perspective, cost disaggregation, estimation of resource utilization, valuation of unit cost components, and data sources used. Such variation will affect the reliability, consistency, validity, and relevance of the cost estimates across studies.
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.