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.

Heart failure (HF) patients tend to have multiple comorbidities resulting in complex therapy regimens and medication adherence issues. Nevertheless, the evidence of pharmacists' contributions to improving clinical outcomes in HF is limited. To assess the impact of pharmacist intervention on all‐cause hospitalization, mortality, and quality of life (QoL) in HF) patients. A systematic search of PubMed, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and CINAHL was performed up to April 30, 2020. Randomized controlled trials (RCTs) evaluating pharmacist interventions compared with usual care in adult HF patients were selected. Data were extracted independently by two authors. Random effects meta‐analysis models were used to pool treatment effects and confidence intervals (CIs). Twenty‐nine trials identified 6965 predominantly HF with reduced ejection fraction (HFrEF) patients. The average age was 72.0 years (interquartile range [IQR] 66.0‐76.0) and 48% were men (IQR 40.0%‐68.0%). The majority were New York Heart Association (NYHA) Functional class (FC) II‐III with median left ventricular ejection fraction (LVEF) of 38.5% (IQR 34.5%‐49.5%). Pharmacist interventions were associated with a significant reduction of all‐cause mortality (risk ratio [RR] 0.72; 95% CI 0.58‐0.89; P = 0.003) and all‐cause hospitalizations (RR 0.87; 95% CI 0.77‐0.99; P = 0.041). A significant increase in the 36‐item Short form Health survey (SF‐36) on role physical (Mean deviation [MD], 8.5; 95% CI, 1.00 to 16.01, P = 0.026) and mental health (MD, 7.49; 95% CI, 3.88 to 11.10, P < 0.001) were observed. In addition, a significant improvement in Minnesota Living with Heart Failure Questionnaire score was observed (MD ‐3.55; 95% CI ‐6.28 to −0.82; P = 0.01). Pharmacist interventions in patients with HF significantly reduced all‐cause mortality and hospitalizations and improved QoL. Integration of a pharmacist into a HF care team or care pathway should be strongly considered as an important element of a multidisciplinary team.

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