Heart failure (HF) is a cardiac structural and/or functional abnormality leading to failure of the heart to deliver oxygen at a rate commensurate with the requirements of the metabolizing tissues . Diagnosis of HF is confirmed based on clinical history, physical examination (Framingham criteria), chest X-ray and echocardiography findings and laboratory exams specifically plasma B-type Natriuretic Peptide and N-terminal B-type Natriuretic Peptide measurement [2, 3]. Clinical outcomes among patients with HF were mortality (all-cause and HF specific death), hospitalization, readmission and morbidity endpoints used in different trials and taken as definition by the European Society of Cardiology HF association consensus document .
Globally, about 26 million people were living with HF with poor patient outlook and worse survival . HF put significant stress on patients, caregivers and the health care system. The five year mortality rate of systolic HF patients ranged from 25% to 75% due to sudden death from ventricular arrhythmia . In a longitudinal study on community-living older persons from Cardiovascular Health Study, the rate of hospitalization was 7.9/10 person-years .
Multidisciplinary health professionals including nurses, pharmacists and dietitian’s intervention on patient education, medication teaching and nutrition guidance, respectively, proved to have positive outcomes and lowered mortality . Lower educational status was associated with an increased hospitalization of HF patients . Low health literacy, which can be defined as Brief Health Literacy Screen ≤ 9, was associated with higher risk of mortality and increased risk of hospital readmission . Heart failure patients who have higher literacy have better understanding of their disease state, self efficacy and self care, thus patients with low literacy level were associated with worse HF related quality of life (QoL) .
Comparison of QoL among the healthy old age group versus ill old age HF patients showed a lesser QoL in the later ones. Using physical symptom as strongest measure, older adults with HF had poorer physical and emotional symptoms, poorer functional status and more worse health perception . Using the German version generic QoL measure (SF-36) containing eight dimensions, scores of five of the eight QoL domains were reduced to around one-third in NYHA class III patients . In the study conducted in Serbia, the poor QoL were due to lower income, longer history of chronic HF, longer hospital stay, multiple medications, higher NYHA class, depression and cognitive impairment .
Communicating hospitalized HF patients effectively at the time of discharge regarding their future clinical status improved QoL of patients . In this case, the involvement of pharmacists demonstrated better medication adherence compared to other health professionals and had greater impact on the ability to inform, solve problem and support patients directly . The pooled data of the systematic review and meta-analysis study on the pharmacist-led medication reconciliation programs, showed a significant reduction in adverse drug event-related hospital and emergency department visits, reduction in hospital readmissions and improved medication adherence [17, 18]. Overall, pharmacists significantly improved health related quality of life (HRQoL) through pharmaceutical care interventions in terms of general health, social and physical functioning 
Importance of this review
Pharmacists can review medication charts and make interventions such as medication reconciliation for discharged patients and correct medication discrepancies, dealing with barriers to medication documentation and interdisciplinary communication . Pharmacist-led medication review and reconciliation were effective in improving medication adherence and patient outcomes, as well as in reducing hospitalization improving post-hospital medication safety and health care utilization [17, 18]. Pharmacists play significant roles in handling HF patients by minimizing disease symptoms, improving medication compliance and enhancing chronic disease management .
Clinical pharmacists can identify and resolve pharmaceutical care issues and provide optimal care when working in collaboration with other health care professionals . Clinical pharmacists lower prescription errors and medication discrepancies through the discharge service to HF patients. The clinical pharmacist’s activities includes: review of medications, communication with cardiologists, general practitioners and community pharmacists, providing patient information and preparing written overview of discharge medication .
Pharmacists decreased readmission of HF patients and improved care through continuum of care such as discharge counseling services and resolving medication reconciliation discrepancies. Patients discharged with the diagnosis of HF who received continuum of care had lower 30-day all-cause readmission rate .
Providing pharmaceutical care service to patients with HF had significant clinical and humanistic benefits. Pharmacist-led pharmaceutical care programs were shown to improve exercise tolerance (2-min walk test), forced vital capacity, medication adherence and HRQoL measured by the Minnesota living with heart failure questionnaire .
The systematic review and meta-analysis study demonstrated multidisciplinary interventions for HF reduced both hospital admission and all-cause mortality . Pharmaceutical care interventions significantly improved HRQoL measures. However, the pooled data on HF- specific measures indicated no significant impact of pharmaceutical care utilization . Therefore the aim of this systematic review and meta-analysis is to investigate whether pharmacist intervention is effective on quality of life and clinical outcomes among patients with HF.
The aim of this study protocol is to provide a clear way to review systematically from various indexing databases and synthesize the data that whether pharmacist intervention is effective on HRQoL and clinical outcomes compared to usual/standard care. This review will address systematic literature search strategy, describe data sources identified in the review, set inclusion and exclusion criteria for the study, describe data extraction process, assess quality measures for the systematic review, and describe statistical procedures for the quantitative analysis. We aim to address our key research question that whether pharmacist intervention is effective on improving HRQoL and clinical outcomes (in terms of reduced hospitalization and mortality) among patients with HF compared to usual/standard care.