Answer:
Introduction
This is a critical evaluation paper that uses Randomized Control Trial checklist or method to evaluate an article by Pitt et al. 2003 based on the three board issues considered when appraising RCT report:
Is the trial valid?
What are the results?
Will the results locally help?
Together with these broad, the RCTs’ ten questions will help critically appraise the article.
Screening Questions
Did The Study Ask Clearly Focused Questions?
The question is focused based on the studied population, the given intervention as well as considered outcomes. The study population was the patients with acute myocardial infarction (AMI) complicated by left ventricular dysfunction (LVD) and heart failure that were receiving optimal medical therapy (OMT). [1] Thus, by investigation the question whether the aldosterone blockade reduces death rate triggered by progressive heart failure alongside rate of abrupt death from cardiac triggers alongside hospitalization rate for heart failure amongst such patients who have severe heart failure because of dysfunction of systolic left ventricular (LV) under an ACE inhibitor treatment, the question remains focused in terms of population. [2] In terms of the intervention given EPHESUS, this question remains focused as this intervention seeks to help solve the problem suffered by the patients. In terms of the outcomes anticipated, the question remains focused by it is expected that the intervention will reduce overall patients’ mortality alongside cardiovascular mortality as well as cardiovascular events’ hospitalization. [3]
Was This A RCT And Was It Appropriate
The evaluation here primarily focuses on why the study was undertaken as the RCT; and RCT stood as a suitable approach for this question. Whereas the research did not highlight precisely the research questions, it is expressed or implied when one reads the abstract which highlights the hypothesis to be tested: eplerenone (aldosterone blocker) treatment reduces general mortality, and CVD mortality as CVD events’ hospitalization amongst these patients. [4] The method used here, therefore, was RCT. [5] This method was appropriate approach for the above hypothesis or implied study question. This is because the study involved both control and treated group using the designed Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficiency and Survival Study (EPHESIS) for hypothesis testing. Thus RCT was a suitable method in helping the authors have both the treated and control groups for comparison when the intervention was administered to the study group.
Is It Worth Continuing?
The RCT study is worth continuing because it will have great implication to the patients. Moreover, the study design is effective. The multicenter; international; randomized; double-blind; placebo-CT remained suitable in this study and would bring the anticipated results.
Detailed Questions
Were Participants Appropriately Allocated To Intervention And Control Groups?
The allocation of patients stood appropriate to both control alongside intervention cohorts. The procedure was purely random. It is clearly stated that the participants stood randomly assigned for reception of eplerenone (25 milligram daily) or matching placebo for four weeks, and then eplerenone dose stood surged to a max of 50 milligram daily. The allocation method was well described since stratification method was utilized to balance the randomization. For example, randomization remained stratified in accordance with the clinical site. The randomization schedule was also generated. For example, the investigators prepared randomization schedules using blocks (permuted) to guarantee continuing equivalence cohorts sizes. Participants were allocated to the study only after meeting certain criteria. For example, patients that met such criteria qualified for being randomized three-fourteen days following AMI:
(i) AMI as recorded by a LVEF of forty percent or less on radionuclide angiography, echocardiography or angiography of LV following the index AMI alongside before being randomized
(ii) Failure as recorded by pulmonary rales’ presence, radiography of chest indicating congestion of pulmonary venous, or 3rd heart-sound existence. [6] In participants that had diabetes but still meeting LVD criteria following AMI, the demonstration of symptoms of heart-failure was unnecessary, because those participants had a surged CVD events’ risk identical to those of patients (nondiabetic) who show symptoms of heart-failure.
(iii) Patients already received OMT that might encompass inhibitors of ACE, diuretics, angiotensin-receptor blockers, as well as beta-blockers, alongside therapy of coronary reperfusion. The differences between groups at entry to trial were reported. For example, it is reported that if at any point in the study period the serum potassium concentration (SPC) stood higher than 5.50 mmol a litre, then the study drug dose stayed decreased or treatment stood discontinued temporarily till SPC drop beneath 5.50 mmol a litre. The criteria for exclusion included the utilization of potassium-parsimonious diuretics, a serum creatinine concentration of over 2.50 mg a deciliter, and a SPC of over 5.0 mmol a liter before being randomized.
Were participants, staff, and study personnel “blind” to” participants” study group
They were “blind” to “subjects’ study cohort. Every necessary efforts was undertaken to achieve blinding. For example, they only had a complete access to the data following the unbinding. The blinding was achieved by having a double-blind controlled trial. [7] Moreover, all Eps stood arbitrated by the blinded important-events committee.
Were All Of Participants Who Entered The Trial Accounted For At Its Conclusion?
Subjects that made entry into trial never accounted for study’s conclusion. All the participants were randomized and followed for central status as well as hospitalizations three months till end of study. There was no intervention-group subjects that go a control-group option or reverse. All the outcomes from subjects stood analyzed on the basis of cohorts initially assigned. Additional information I would like to have seen about this group is age and the sex of the participants. Also, I would have liked to see replacement done for those who discontinued the treatment and those who died. This would have been drawn from the control group. 12 patients at each treatment cohort never took any study medication. 1021 patients (528 in eplerenone cohort and 493 in placebo cohort) discontinued permanently from study medication and hence did not account for the study conclusion. Also, 17 patients; seven in placebo group alongside ten in eplerenone cohort showed known essential status at the study end. The surviving patients (99%) of them stood contacted or seen. Sixteen months stood as the mean follow-up period. 478 participants in intervention cohort alongside 554 participants in placebo cohort died at end point (EP) and hence never accounted for the study conclusion. The death EP from CVD triggers as well as CVD events’ hospitalization stayed hit by eight hundred and eighty-five participants in intervention cohort while 993 participants were from placebo cohort.
Were The Participants In All Groups Followed Up And Data Collected In Same Way?
The subjects in both groups stood followed up and data gathered similar way. This enabled the data to be analyzed and helpful discussion making the outcomes to be applicable locally.
Did The Study Have Enough Participants To Minimize The Play Of Chance?
Adequate participants took part in the study for minimization of chance’s play. The randomization of a total of 6642 stood done at 674 centers in 37 nations. This was an adequate number since 3313 were placebo-assigned whereas 3319 were eplerenone-assigned, whereas merely ten participants were excluded from the analysis prior to un-blinding. This was effectively done due to problems with quality of data a 1 centre.
How The Results Are Presented And What Is The Main Result?
The presentation of the results is performed as patients’ proportion witnessing a risk outcome. Results indicate that in the course of the mean follow up, 478 deaths stood reported in eplerenone group while placebo group documented 554 deaths (comparative risk, 0.850; 95.0% CI, 0.750 to 0.960; P=0.0080). 407 of deaths in intervention cohort while 483 deaths in placebo cohort were attached to CVD triggers (comparative risk, 0.830; 95.0% CI, 0.720 to 0.0050). In respect of death due to CVD triggers/ CVD events’ hospitalization (primary end point (PEP)), it stood decreased by intervention (comparative risk, 0.870; 95.0% CI, 0.790 to 0.950; P=0.0020). The secondary death EP triggered by any hospitalization or cause showed (comparative risk, 0.920; 95.0% CI, 0.860 to 0.980; P=0.020). A decrease in rate of sudden death from cardiac triggers was recorded (comparative risk, 0.790; 95.0% CI, 0.640 to 0.970; P=0.030). Serious hyperkalemia rate stood at 5.5% in eplerenone group while placebo cohort had 3.90% (P=0.0020). The hypokalemia rate stood at 8.40% and 13.10% in intervention and control group respectively with (P=0.0010). The size of the outcomes is large enough for generalization. The results are quite meaningful and has great implication to practitioners and patients. This is because with the approximated quantity required for the treatment of fifty for saving a single life yearly and the approximated quantity required for treating thirty-three to bar a single death from CVD triggers or a single CVD event’s hospitalization yearly, the eplerenone introduction to therapy greatly underwrites to ongoing enhancement in endurance as well as rates of hospitalization amongst these patients. The bottom-line result of the trial can be summed up in a single sentence as; “the eplerenone reduces overall mortality and death rate arising from cardiovascular causes or hospitalization for the cardiovascular events amongst patients with AMI being complicated by LVD alongside heart failure”.
How Precise Are These Results?
The outcomes remained highly clear-cut to draw rational conclusion/decision. It is clear from the results that the intervention reduced mortality and death rate. Also, the results precisely show a decrease in CVD mortality alongside rate of death rate from hospitalization or other triggers in the intervention group. For example, it is clear that 1-year mortality among patients in placebo is higher (13.6%) than those in eplerenone group (8.4%). This leads to a decision that intervention remains effective in decreasing the death rate as well as mortality among these patients. [8] The results led to a decision that the greater utilization of beta-blockers accounts for the differences in death rate and mortality in both groups. The results also led to the identification of LVD severity, heart failure degree as well as background therapy degree as the imperative variables in the determination of absolute mortality and therapeutic agents’ effectiveness. However, there is no clarity on the mechanisms through which this intervention offers myocardial safeguard in these patients. Also, where the study acknowledges that aldosterone blockers have effects on plasma volume alongside excretion of electrolyte, the study is silent on mentioning how such effects could have contributed to benefit eplerenone provided, and even totally quiet on highlighting the non-renal mechanism said to may have remained significant. A CL stood documented and the deduction about whether or not to utilize eplerenone was never similar at lower/upper confidence borders. The upper boundaries stood prioritized on making the decisions. A p-value stood reported in cases of CI’s absentia.
Were All Important Outcomes Considered So The Results Can Be Applied?
The study took into consideration all significant outcomes and hence the outcomes remain applicable. The participants in trial are similar to the population and hence would always generate similar outcomes as the participants were drawn from different areas and countries and hence can be generalized. [9] There was no significant difference from my local setting from that of trial and hence same treatment could be given to my setting. From individual level, the outcomes are beneficial in treating such patients and would reduce both death and mortality. From the policy maker and professionals, the realization of the effectiveness of eplerenone would make it easy to be integrated in the treatment of this diseases alongside OMT. [10] From family or carers, this intervention brings hope to the family as their patients will be treated and get well whereas the carers will feel less relieved as their clients will not suffer much. The wider community will be happy as the intervention will ensure a reduction in mortality and death rate. The reported benefits from this study i.e. the death rates and mortality’s decreases outweighs harm of adverse events and even the cost of intervention. The policy and practice need to change as a consequent of the evidence entailed in this trial. Henceforth, the eplerenone should be given to these patients alongside the OMT to increase the effectiveness of reducing death rates and mortality.
Conclusion
From this critical evaluation, the article clearly adheres to the checklist or method of RCT critical evaluation. Both detailed and screening questions are met and well answered. The three broad issues considered when appraising RCT report including; “is the trial valid”; “what are the results”, as well as “will the results help locally” are met.
References
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Brunssen, C., Johannes R., Heike L., Anja H., Annika F., Andreas D., Mirko P., et al. “Impact of Eplerenone on Vascular Function in LOX-1 Overexpressing Mice on High-Fat Diet.” (2015): A543-A543.
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Montalescot, G., Bertram P., Esteban L., Christian W. H., Marcus F., Freek V., Harry S., et al. “Early eplerenone treatment in patients with acute ST-elevation myocardial infarction without heart failure: the Randomized Double-Blind Reminder Study.” European heart journal 35, no. 34 (2014): 2295-2302.
Pitt, B., Stefan D. A., Michael B., Mihai G., Lars K., Henry K., Aldo P. M., et al. “Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study?Heart Failure (ARTS?HF): a randomized study of finerenone vs. eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease.” European journal of heart failure 17, no. 2 (2015): 224-232.
Pitt, B., Willem R., Faiez Z., James N., Felipe M., Barbara R., Richard B., Steve H., Jay K., and Marjorie G. “Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.” New England Journal of Medicine 348, no. 14 (2003): 1309-1321. https://www.nejm.org/doi/full/10.1056/NEJMoa030207#t=article
Raman, S.,V., Kan N. H., Wojciech M., Nancy J. H., John T. K., Xin H., Tam T., et al. “Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial.” The Lancet Neurology 14, no. 2 (2015): 153-161.
Rossignol, P. Daniela D., John J.V.M., Karl S., Henry K., Dirk, J.V., Harry S., et al. “Incidence, determinants, and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo additional to optimal medical therapy: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF).” Circulation: Heart Failure (2013): CIRCHEARTFAILURE-113.