Patients with heart failure experience various debilitating complications if their condition is poorly controlled (Bozkurt et al., 2021). The patients experience poor quality of life, including decreased functional activity, because of symptoms such as dyspnea associated with significant physical limitations (Borlaug, 2020). Patients with persevered ejection fraction also experience physical/functional limitations if the heart failure is poorly controlled (Vardeny et al., 2022). The majority of the medications in the management of heart failure have not adequately addressed such physical limitations of heart failure in patients. The study involved a randomised controlled trial of dapagliflozin on heart failure patients with preserved ejection fraction in some selected patients in the United States (Docherty et al., 2020). The knowledge gap entailed the failure of the other medications to improve symptoms/improve the quality of life of these patients. Dapagliflozin is attributed to improving some of these abnormalities/symptoms, including reducing pulmonary artery resistance/pressure and improving cardiac function (Wiviott et al., 2019). The study would help evaluate the significance of dapagliflozin in addressing some of the cardiac abnormalities and improving physical/functional activity and other symptoms in these patients. Funding for the study /randomised controlled trial involved AstraZeneca (Nassif et al., 2021). A peer review of the article was conducted by ‘Nature Medicine’. It is a reputable journal since the authors hail from recognisable institutions such as Saint Luke’s Mid-America Heart Institute and other well-recognised institutions in America. The authors also collected, analysed, interpreted data, and revised data. It is also available online( Nature Medicine). A randomised controlled trial entails an experimental study in which there are two groups(the intervention group, which is receiving the treatment under investigation) and a control group( placebo). An executive committee approved the study. The study also followed the ICH E6 Guidelines of Good Clinical Practice. The randomised study was conducted according to the Declaration of Helsinki guidelines (Nassif et al., 2021). The participants are randomly chosen for the study, which helps to eliminate bias/especially selection bias (Zabor et al., 2020). Randomised controlled studies provide comprehensive and real-time evidence or results since the study is monitored over a given period (Li et al., 2020).
Population
The population involved in the study included at the start of the study included 598 patients with heart failure ( with preserved ejection fraction). Finally, there were 324 qualified participants (Nassif et al., 2021). The other inclusion criteria included an average median age of 70 years, median duration of heart failure included three years since diagnosis and a history of hospitalisation at least once. The patients were to have NYHA class II to IV symptoms (Tomasoni et al., 2019). The patients must have also been on baseline medications such as mineralocorticoid antagonists, angiotensin-converting enzyme inhibitors, ARBs, loop diuretics and thiazide diuretics (Wintrich et al., 2020). The patients were to have high levels of natriuretic peptides such as NT pro-BNP, more than or equal to 225. The exclusion criteria were the presence of hospitalisation in the last or within seven days due to decompensated heart failure and low glomerular filtration (more than 20). Patients with type 1 diabetes and a history of diabetic ketoacidosis were excluded.
Only 324 patients qualified for the study. Randomisation was done, and finally, only 146 patients( intervention group) and 145 individuals ( placebo) completed the study (Nassif et al., 2021). The patients came from 26 selected regions in the US. The answers to the above questions do not give rise to bias or invalidate the findings. The study population adequately addressed its requirements, such as requiring patients to have heart failure with preserved ejection fraction and the above inclusion criteria.
Additionally, the sample population in the study adequately considers the appropriate age, gender distribution, genetic predisposition, and previous exposure to other interventions (Nassif et al., 2021). Some diagnostic tests were considered for the inclusion of an appropriate sample population. For instance, an echocardiogram was used to determine the participant’s ejection fraction, and the inclusion of natriuretic peptides ( NT pro-BNP) was also used to select an appropriate sample population (Cao et al., 2019). These tests align with contemporary practice. However, there was some bias in the sample population (Arias et al., 2023). The study population concentrated only in America( the selected twenty-six regions in the United States). Hence, the results from the study may not be applied to other areas; there is poor external validity of the study because these findings cannot be generalised to the rest of the world population (Fournier et al., 2019).
Intervention
Dapagliflozin was the medication studied in the study. Participants in the intervention group were given oral dapagliflozin 10 mg and would take the drug once daily for the 12 weeks( study period). Additionally, patients on placebo received the same dose( 10 mg of placebo) and followed the same period. The participants were followed up through telephone calls and physical visits with adequate physical examinations and lab investigations. There was adequate consideration of the dose, frequency route and other drug and patient factors. These factors influence the validity of the study. For instance, before the study, participants were supposed to have a GFR of more than 20 and should be clinically stable. The presence of illness may require an adjustment of the dose( usually reduction), which may affect the study’s findings (Nassif et al., 2021). The patients were randomised through a double-blinded approach in which neither the researcher nor the participants knew which drug they were receiving. The randomisation was independent of the investigators. The participants were adequately followed, and only 15 patients( from the intervention group) prematurely ceased, leading to 146 patients completing the study. About thirteen patients( from the placebo group) were also prematurely discontinued from the study, with only 145 completing it. Hence, the investigator and patients knew nothing about whether they received dapagliflozin or placebo. Randomisation was conducted using a web-based tool( Sharp Clinical Services web-based IRT). The researchers and patients also remained blinded during the study, beginning from the allocation of the drug in the analysis of findings. There was no evidence of breaking the blinding system in the study (Nassif et al., 2021). Power refers to the likelihood that a given study would give an adequate result from a given population if such an effect ( of the intervention) exists in the study population. It was assumed that the loss of 10 per cent of participants yielded a sample population of 320 patients. Hence, it is justifiable based on the above study.
Control
The placebo group( 145 patients) and intervention group(146). There was no significant difference. Additionally, the patients in the placebo group had to have met the inclusion criteria before randomisation, including being clinically stable and having HF with preserved ejection fraction (Nassif et al., 2021). The placebo group also received the same dose ( of the placebo drug), 10 mg daily orally, for the 12-week study period. Hence, the study does not favour any arm over another, however, regarding the intervention period(12 weeks). The study stopped following the completion of that duration; hence, it was difficult to continue monitoring any further or long-term implication of the intervention( dapagliflozin) compared to the placebo. There was no favouritism of one group over the other during the study.
Outcomes
Outcomes measured included heart-related status using the KCCQ-CS(Kansas City Cardiomyopathy Questionnaire Clinical Summary Score) and physical/functional activity using 6MWT scoring. There was an improvement in the KCCQ-CS scores following the completion of the 12 weeks of study and an improvement in physical function (Zhao et al., 2021). There was more than a five-point improvement of the KCCQ-CS score compared to those on placebo. There was also a report of a decrease in weight helping improve cardiac function. These measures adequately reflect the condition/issue being investigated (Nassif et al., 2021). The outcomes were primary endpoints (based on the KCCQ-CS ) and secondary endpoints (analysed by the 6-minute walk test). There was improvement in both measures in the intervention group compared to placebo. The outcomes were measured at the appropriate time (after 12 weeks), which was the set duration of the study. The chosen outcome neither favours any arm of the study since all the groups were subjected to similar parameters (same study duration, similar doses, follow-up). It aimed at treating, hence no bias. The outcome measures were analysed using a Student t-test, and a comparison was made using Fisher’s exact test (Nassif et al., 2021). The results have been presented in relative risk, for instance, in comparing the primary endpoint measures( from KCCQ-CS) of dapagliflozin to placebo.
However, the findings can also determine both absolute risk and ARR. No NNHs or NNT ( Number Needed to Harm or Treat) are calculated in the study. The NNTs or NNHs cannot be verified from the study since it was based on evaluating the implication of dapagliflozin in improving cardiac function and physical function of patients with HF compared to placebo (Petrie et al., 2020). There is no justification in the study for the above measures. The current evidence-based HF treatment with preserved ejection function includes ACEIs, MRAs, ARBs/ARNIs, loop diuretics and thiazide diuretics (Gupta et al., 2021). However, these treatments do not adequately address cardiac parameters, such as reducing inflammation or oxidative stress that may precipitate heart failure (Nassif et al., 2021). Hence, the findings from the study do support that dapagliflozin( SGLT2 inhibitor) improves cardiac and physical function in these patients in addition to the current treatments for heart failure.
In conclusion, the outcomes of the study were appropriate and adequately considered in the study. Dapagliflozin (intervention) was associated with improving cardiac function and functional activity in the target patients. The intervention aimed at benefiting the target population( heart failure patients with preserved ejection fraction). However, the study’s limitation included only participants from the United States. Hence, subsequent studies involve other regions( larger and diverse sample populations) for a more comprehensive comparison. Overall, the intervention is appropriate, useful and thus is clinically transferable as it demonstrates evidence-based findings.
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