Critical Appraisal Report: Zhang et al. (2015) - Medicine Study

This report provides a critical appraisal of the study by Zhang et al. (2015), which investigated the efficacy of clopidogrel when coadministered with atorvastatin and lansoprazole in patients with non-ST-segment elevated acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). The study employed a prospective, randomized, controlled trial design, dividing patients into four groups to assess the impact of different drug combinations on platelet function and clinical outcomes. The appraisal highlights the study's methodology, including the use of a control group, blinding procedures, and patient selection criteria. The results indicated no significant differences in outcomes between the groups, leading to the conclusion that there was no major difference in outcome effect when clopidogrel is coadministered with atorvastatin or lansoprazole. The report discusses the study's strengths, such as its randomized controlled design and patient blinding, but also acknowledges limitations, including the small sample size and the lack of assessment of certain drug interactions and long-term outcomes. Overall, the appraisal offers a comprehensive overview of the study's findings and their implications.

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Critical Appraisal: Zhang, J.-r.et al., 2015. Efficacy of Clopidogrel and Clinical Outcome When
Clopidogrel Is Coadministered With Atorvastatin and Lansoprazole; A Prospective,
Randomized, Controlled Trial. Medicine, 94(50), pp. 1-8.
Student’s Name
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Instructor

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Critical Appraisal: Zhang, J.-r.et al., 2015. Efficacy of Clopidogrel and Clinical Outcome
When Clopidogrel Is Coadministered With Atorvastatin and Lansoprazole; A Prospective,
Randomized, Controlled Trial. Medicine, 94(50), pp. 1-8.
The focus of Zhang, et al. (2015) study was to determine the effectiveness of using
clopidogrel in clinical outcomes when it is administered with Atorvastatin and Lansoprazole.
This study entailed one hundred and four adult patients with the non-ST-segment elevated acute
coronary syndrome (NSTE-ACS) and had undergone percutaneous coronary intervention (PCI)
with drug-eluting stent implantation. The patients were all treated with antiplatelet therapy
(DAPT) and rosuvastatin was given as an additional drug to all patients. But after the sixth day,
the patents were divided into four different groups which were used to measure the differences in
the two groups. In a randomized control trial, there must be a general group and the control
group. In this case, the control group was based on the use of clopidogrel and rosuvastatin in
clinical outcomes for dual antiplatelet therapy.
To be called a randomized control trial, Zhong (2019, p. 53) sugges that the participants
in the study group must be randomly put in any group to avoid bias. This means that the patients
can fall either in the control group or the general group. In this study, all the patients received the
same medication as required and then they were randomly placed in four groups after the first
assessment. The index of the patients' response to drugs was then retested after 15-30 days where
all the patients that participated in the study were supposed to be maintained on the treatment for
six months. This study blinded the patients and they were not aware of the different groups that
existed.
According to Baker, et al. (2017) the success of randomized control trials is based on
analyzing the patients within the groups to which they belong to. This means that the researchers

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are supposed to analyze patients in the group that they belong to so that demographic factors that
may lead to other changes can be accounted for. Initially, the patients were analyzed within their
groups while still in the facility but they were the discharged and thus the researchers were
required to follow them up for a period of six months to determine any effects or challenges that
they may face while using the medication. This means that the main focus of this study was in
the control group which was supposed to report the effects clopidogrel when administered with
Atorvastatin and Lansoprazole.
Bondemark & Ruf (2015, p. 459) adds that in most cases, studies are supposed to focus
on reducing bias from the researcher, the patient, and even the health workers when carrying out
a randomized control study. This has been attributed to increased reliability of the data collected
because it does not give room to manipulate the results in their favor. Hrobjartsson, et al. (2014,
p. 1277) suggests that a good randomized control trial must have at least blinded patients if the
rest of the participants in the study cannot be blinded. This means that it is easy to have better
outcomes for the study if patients are blinded so that bias is not created. In some cases, blinding
of researchers and health workers is not a must due to the nature of the control group. In this
case, the effect of the control group was supposed to be based on measuring the changes between
the two groups so that a conclusion can be drawn from the study. As seen in this study, the health
workers and the researchers were not blinded and were aware of the four groups that the patients
had been put in and thus were required to record the changes as they were observed in the
patients. Non-blinding in these two groups was to ensure that inconsistencies between the two
groups are reduced.
Since this is a randomized control trial, then it means that at the beginning of the study all
the groups must be similar. The fact that two groups exist within a randomized control trial does

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not mean that the patients need to be treated differently. In randomized control trials
Broekhuizen, Pothof, Craen & Mooijaart (2015, p. 4) suggest that all the patients are supposed to
receive similar medication but the difference is only supposed to be a result of the clinical
intervention given to them. The difference between the groups comes in when the control
medication or effort is administered. In this case, the patients that qualified for this study were
supposed to be 18 years and above and had been previously diagnosed with the non-STsegment
elevated acute coronary syndrome (NSTE-ACS) and had undergone PCI in the present study. On
the other hand, patients who had angina pectoris after infarction, those using
Clopidogrel/PPIs/statins in the previous two weeks, had used CYP3A4 or CYP2C19 inhibitors or
activator had a higher risk of gastrointestinal bleeding and those that had an expected survival of
less than one year were not supposed to be included in the study. The reason why this was done
was to ensure that all the patients who participated in the study had similar clinical
characteristics to increase the validity and generalizability of the results. According to Bhide,
Shah, & Acharya (2018, p. 4) and Hrobjartsson, Emanuelsson, Thomsen, Hilden & Brorson
(2014, p. 1275) suggest that when testing the effectiveness of clinical treatment in randomized
control trials, the patients are supposed to be carefully chosen so that they are not affected by
demographic factors. For example, in most cases, factors like age and sex are in clinical studies
since they affect the way the participants are affected by the outcomes of the study. This means
that the population is purposively chosen to reflect the needs of the study.
Shaughnessy, Zechmeister & Jeanne (2011, p. 23) state that since randomized control
trials are designed around testing the effects of a certain clinical intervention, then it means that
the focus is supposed to be on the treatment group. For this study, 104 patients were initially
enrolled in the study group and received similar medication thus undergoing aspirin 100mg

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daily, clopidogrel 75mg daily plus rosuvastatin 10g daily. After the sixth day, they were assigned
to four groups of A=27, B=26, C=26, and D=25 participants respectively. This was supposed to
be the outcome of the clinical assessment after day 15 of the clinical intervention. From this flow
of clinical events we can see the clinical outcome of the study coming out clearly. In group A,
patients received asprin+clopidogel+ lansoprazole+ atorvastatin, in group B, they received
asprin+clopidogel+ atorvastatin, in group C, they received asprin+clopidogel+
lansoprazole+rosuvastatin and in group D, they received asprin+clopidogel+ rosuvastatin. It is to
note that group D is the control group which was based on receiving all three drugs that are being
tested in the study. From here the primary outcome of the study can be identified as testing the
effectiveness of using clopidogrel in clinical outcomes and its effectiveness when it is
administered with Atorvastatin and Lansoprazole. Spieth, et al. (2016, p. 1343) argue that a
clearly focused randomized control trial is supposed to be easily identifiable by design. This
means that the reader can understand the differences between the groups in the study and at the
same time note the objective of the study by determining what will be entailed in the control
trial. Thus the focus of these trials is to measure the differences between the control group and
the general group.
The results of this study showed that there were no significant differences between the
groups (P>0.05). Thus the study concluded that there is no major difference in outcome effect
when clopidogrel is coadministered with atorvastatin or lansoprazole. This means that the control
group did not have any significant effects on the change as compared to the other three groups.
In statistical analysis (P>0.05). In hypothesis testing when the P value is equal to or less than the
significant value, then the null hypothesis of the study is supposed to be rejected (Wasserstein &
Lazar 2016, p. 131; Creswell, 2012, p. 25). In this case, the control group outcomes are rejected

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since the effects are not significant enough to be used in clinical outcomes. However, the
differences between the results of ADP-IPA%, MAADP, P-selectin, and sCD40L at each time
point are significant (P<0.05, respectively). This means that the platelet aggregation that is
induced by ADP and platelet activation decrease. Thus this reported that the response of patients
increased over time which showed the significant differences in the use of clopidogrel increased
as patients continued to use the medication.
According to Twisk, Bosman, Hoeskstra, Rijnhart, Welten & Heymans (2018, p. 83) the
results of a good study can be applicable to other studies if their validity and confidence levels
are high. The results of this study are applicable in different contexts because it included a wide
range of patient demographics. By having patients who do not fall within one cohort, the
researchers increase the generalizability of the study since it covered all the patients' ages that
fall within the group. This study reflects the patients that exist in general life situations because
they covered the participants that were available for the study. According to Stuart, Bradshaw, &
Leaf (2015, p. 479) suggests that the strength of randomized control trials lies in the use of
control groups to test the treatment effect and the blinding of participants to increase
generalizability. Thus this study can be generalized to other populations since it used a wide
range of patients while at the same did not have one group but had four groups which were used
to compare their effects with the control group. On the other hand, the patients were blinded to
increase the validity of the results and at the same time reduce bias. Thus the results of this study
can be replicated to clinical outcomes since the participants of the study reflect the nature of the
patients that were used in the study.
However, the sample size of the study was small and may have failed to cover a large
number of patients that is applicable to randomized control trials. Tweel, et al. (2012, P. 140)

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argue that the size of the sample in randomized control trials varies from scenario to scenario and
thus this is supposed to be a representative of the whole population. However, this study used a
purposive sample with inclusion-exclusion criteria that led to 104 patients for the study. This
sample may fail to adequately reflect the generalizability of the sample to the whole population.
Further, this study was also limited by the fact that the study failed to address any interactions
between high doses of other drugs and clopidogrel was not clear. This means that the study
reported the outcomes without considering the effects of other drugs that the patients were using.
This study also failed to measure the platelet function and the concentration of platelet activation
markers when the study was completed at six months. The measures at this stage could have
given a better indicator for the study thus leading to better clinical outcomes of the study.
Susukida, Crum, Ebnesajjad, Stuart, & Mojtabai (2018, p. 1213) argues that the success of these
trials is based on assessing the patients to the last level of study. This means that if the study
period is six months, then the measures at six months are important in determining how these
relate to the intended outcomes.
Colquitt & George (2011, p. 433) suggests that a good grand research is supposed to offer
direction for future research. This study failed to give recommendations that can be used in the
field of study. This study reported no significant differences between the groups (P>0.05) but the
findings of the study indicated that the control group had better effects since the efficacy of
clopidogrel did not decrease and the adverse effects of the drug were not reported in any of the
patients. This implies that the drugs may have been effective but they need further research to
refine their effects on the patient population. The findings of this study are related to Manach, et
al. (2014, p. 4), Mantz et al. (2011, p. 910) & Zisman (2010, p. 619) who argue that withdrawal
of aspirin early enough increases the restoration of platelet functions since this is related to

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variable platelet recovery. Despite that, there were no reported effects of the use of
Coadministered with Atorvastatin and Lansoprazole in the control group. I, therefore, feel that
the findings of this study need to be considered to determine how the low significant value of the
study can be improved to increase the clinical outcomes of the study.

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