The Effect Of Six Proton Pump Inhibitors On The Antiplatelet Effects Of Clopidogrel

Summary of the article

Heart attack is a common term for myocardial infarction, which is one of the most common forms of cardiac diseases affecting people globally. It’s estimated that myocardial infarction is the leading cause of death taking more than 17 million lives annually, according to the statistics provided by World Health Organization (WHO) (1). The cause of such kind of diseases is when the heart stops receiving blood from the body and a portion of it or completely stops functioning. The cardiac myocytes become damaged and the affected person suffers chest pain, distress which radiates into shoulder, arm, back and other extremities. The immediate affected are is the left side of the body which is adjacent to the heart.  The affected person undergoes heart-burn like sensation along with other clinical symptoms like, breath shortness, distress, loss of consciousness, diaphoresis et cetera. Myocardial infarction is also associated with acute coronary artery syndrome (2). The decreased supply of blood in the coronary arteries cause this condition in 30% of ST elevated Myocardial infarction and 25% of non-ST elevated myocardial infarction as well as 38% of unstable angina conditions. Severe conditions of myocardial infarction can lead to loss of blood supply ion the brain which leads to development of stroke. The preferred medication in these conditions of severe heart attack is Clopidogrel which inhibits blood coagulation and maintain the blood flow in the heart management. The provided paper focuses on the interaction of Clopidogrel and proton pump inhibitors. It is generally prescribed in tablet form 75mg which stays in the system for about 5 days and starts showing its effects within two hours of consumption. Clopidogrel is administered in the patients as a pro-drug which is activated by cytochrome P⁴⁵⁰ enzymes.

Clopidogrel is administered in the patients as a form of pro-drug which is activated by cytochrome P450. Deactivated form Irreversible binds to P2Y12 receptor on the platelets which in turn in inhibits the binding of adenosine diphosphate or ADP to it. Blood coagulation mediated by ADP is therefore hindered and glycoprotein GPIIb/and IIa inactivates the coagulation of platelets (4).

The authors of the article close this topic describe the above mentioned process of Clopidogrel activation and discussed the interaction or pharmacokinetics wait Proton pump inhibitors (PPI). In 2009 food and drug administration advisory board release the statement which prevented patients from using esomeprazole and Omeprazole. PPI has been proven time and again to inhibit Clopidogrel activity of platelet innovation (5). The authors investigated to find out the exact relation between PPI and Clopidogrel. The author setup a randomised control trial in Healthcare setting which consistent of consented participants who voluntarily h helped health gather evidence. The summary of the article briefly discusses the points and provides a basic background understanding of the two mentioned drugs. Also addresses the research design, materials, methods and provides a briefing of the findings which ultimately aim to provide a distinct relationship between PPI and Clopidogrel and enable readers’ to grasp for better understanding of the pharmacokinetics in the process. The researchers selected 28 healthy male participants within the age group of 18-24 and formulate a randomised controlled trial and a crossover design schedule (6). The participants underwent diagnosis for platelet aggregation with one of either pantoprazole, rabeprazole, Omeprazole, esomeprazole, laneprazole and dexlansoprazole.

Critical evaluation of the article

PPI is the most preferred treatment for gastrointestinal Reflux disease as well as irritable bowel syndrome and it’s provided to patients who are undergoing anti-platelet therapy (7). PPI is also suggested in patients who tend to suffer from gastrointestinal ulcer inflammation and bleeding disorders to facilitate the platelet coagulation (7). It came to the notice of researchers that patients who intake Clopidogrel and PPI at the same time undergo severe cardiovascular diseases.  The subgroups and other forms of PPI were identified by the FDA who wants the public about the interaction. The authors collected enough data which suggest that PPI and Clopidogrel interaction is evident in patients who have gastrointestinal disorders. The authors conducted the concise literature review of various other research articles which indicate the same report which proves the hypothesis that PPI and Clopidogrel and not to be taken together and increase the health risk of patients (8). Patients have switched two alternatives for PPI if they are at the same time administered with Clopidogrel. But the problem was that various articles suggested various mechanisms while some proved the correlation between PPI and Clopidogrel others refuted it by saying that only certain subtypes of PPI interacts with Clopidogrel and others are safe to be consumed along with Clopidogrel.

The authors conducted the study in Amherst, New York, Dent Neurologic Institute. The authors gathered approval from the University of Buffalo where the study designs was approved containing the inclusion criteria as well as proof of informed consent with respect to the legislation system of declaration of Helsinki (9). Experience of PPI what tested to interact with Clopidogrel among 23 participants who were healthy and mail. This is the author’s primary objective and their secondary objectives identify the least effective of the PPI which interacts with Clopidogrel.

The authors simulated an incomplete crossover of randomised controlled trial where each participant was provided 75 mg of Clopidogrel everyday for one week and the assessment of Threshold anti-platelet response was measured against PPI (10). The administration of PPI was randomly assigned so that each participant would have 3 different variations of PPI against Sikhs subtypes. Lifespan of platelets is generally 5 to 7 days the participants were observed till the 7th day to find out the pharmacological effect of PPI and Clopidogrel before the drug was washed down.

The author is utilised impendence aggregometry to measure the responsiveness of platelet collected from the whole blood samples of the participants (11). The threshold for impedance observed in normal population ranges from 6 to 24 Omega according to the Havertown PA protocol. The healthy male participants aging from 18 to 24 provided adequate response 2 ATP binding of platelet receptors during aggregation mechanism without the effect of Clopidogrel. It was previously known that the threshold value for Clopidogrel induced platelet inactivation was less than 4 Omega. The patients were provided informed consent after which their administrated with the drug and your authors found data that suggested cytochrome P activity is influenced by the action of progesterone and oestrogen levels in females during menstrual cycle or use of contraceptives (12). This was the reason that male participants were chosen to exclude the effect of Clopidogrel administration. Participants who showed abnormality in their blood war excluded from the study to avoid unwanted complications. Exclusion criteria also contain exclusion of participants who had history of hypertension alcoholism as both conditions internet did platelet activity and to minimise the number of variables of the study. The authors made sure that the participants please Train themselves from smoking or use of illicit drugs two weeks prior to the study of 2.5 to 7 days of completion r of the study. The patients who had associated co morbidities were also included from the sample (6).

Design

Participants who made all the inclusion criteria were selected randomly and administers web three different types of PPI used individually 1 per day. Undertook Latin square model design where each participant was provided three different PPI for one week each over the course of the study. The PPI was used approximately 12 times 23 out of 30 people. Specific data sample was recorded and a sorted according to their name identity ID number and placed in the sequence of allocation after which it was all gathered in the report form (6).

The author selected are model for analysing the found data and used fixed effect model to compare the treatment groups according to the threshold and measured in comparison to normal drug-free patients (13). The authors identified the data using random effects model and segregated the treatment type legends of capital grill or absence of Clopidogrel.

The authors Cabot the finding by comparing interquartile median range of data which range from 2.5 Ohm to 0m. The participants, who exuded higher than 4 ohm of response was assessed. 3 participants were excluded based on the mismatch of inclusion criteria and 2 participants showed resistance towards tutorial and 1 had low platelet count which left 27 active participants.The authors display the results in the form of regression model.

Pantoprazole Omeprazole and rabeprazole showed greater than 6 Ohm. Omeprazole expressed highest level of difference with Clopidogrel but still it did not match the statistical significance and dexlansoprazole short least amount of interaction (14). Some participants short as 12 metric results in spite of providing Clopidogrel along with PPI and their tutorial content matched with their baseline results. The author failed to find any statistical difference between the aggregation along with Clopidogrel and PPI.

 64% of the participants showed adverse drug reactions. 51% of the participants reported susceptibility to bruising. Number of participants who did not wish to continue with this study was 6. After the completion of the study the authors conducted linear regression model which food analyse the effect of time on their research and it was assured there was an insignificant search in the impedance statistic every two weeks.

Researchers failed to find statistical significance that would prove there hypothesis. It is indicated that clinical circumstances can lead to interaction between PPI and Clopidogrel which can affect the functionality of cytochrome P iso-enzyme that react with Clopidogrel (15). The choice of technique for measurement of places aggregation was quite apt and would help future researchers have a better understanding.

The author stated their limitations in the research as the following the difference between the baseline Omeprazole and Clopidogrel not up to the mark. The researchers stated that are more effective and Powerful observation and statistical study would have enhanced the importance of the research. The authors also stated in the paper that they have not considered the role of genomics in the pharmacological effect of the drugs (16). Since the genomic expression plays an important role in the development of metabolic interactions in individual the subtypes of genes alleles play a significant role in pharmacotherapy. Additionally there are other weaknesses that can be pointed out in the research. The sample size selected is very small to gather effective and statistically significant information to prove the hypothesis (17). The experiment was conducted by the authors in one particular Healthcare setting weight limits the transferability of information and comparison to form a more descriptive research data (18).

One strength indicated by the authors was the use of Impedance Aggrometry which analyses aggregation of cells when administered within agonist and antagonist in a physical environment (11). The whole blood sample collection also provided enhancement in the research since in this kind of Aggrometry technique manipulation of whole blood is not required to obtain results.

Previous research has shown that the larger the number of sample size the most statistical significance results can be found. The study also excludes female participants but this shows bias towards gender inequality in Clopidogrel, which is also administered in women who suffer cardiac diseases (19). More research can be done to investigate the actual process to prove or refute the hypothesis that PPI or its subtypes affect the action of Clopidogrel. It also gives room for investigation to find out if ascertain variant of the ll responsible for cytochrome p interacts with Clopidogrel along with PPI which could mean that this interaction is purely molecular.

The overall evaluation of the research paper makes it clear that the authors were unable to prove their hypothesis and needed more evidence. Larger sample size would have proved more efficient to simulate an effective research data. The inclusion gender bias short in the research paper excludes half the population who are affected by myocardial infarction and will be excluded from study. Propagation of a research requires transferability of information between different reset settings together or more effective and descriptive data (20). As of now it is safer father patients if they avoid the use of Clopidogrel and PPI.

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