|Year : 2022 | Volume
| Issue : 1 | Page : 1-9
Application of nonsteroidal anti-inflammatory drugs in aortic aneurysm
Rubén T Moro Rodríguez1, Daylin Ricardo Olivera2, Jose Luis Valdes Cantero2, Vielka Gonzalez Ferrer2
1 Head of Angiology and Vascular Surgery; Department of Vascular Surgery, Cardiocenter “Ernesto Guevara”, Villa Clara, Cuba
2 Department of Vascular Surgery, Cardiocenter “Ernesto Guevara”, Villa Clara, Cuba
|Date of Submission||30-Jun-2021|
|Date of Decision||30-Aug-2021|
|Date of Acceptance||31-Aug-2021|
|Date of Web Publication||22-Mar-2022|
Dr. Rubén T Moro Rodríguez
Head of Angiology and Vascular Surgery; Department of Vascular Surgery, Cardiocenter “Ernesto Guevara”, Villa Clara
Source of Support: None, Conflict of Interest: None
INTRODUCTION: Aortic aneurysms have among their main factor for rupture, growth, produced by the weakening of the aneurysmal wall influenced by different risk factors.
MATERIAL AND METHOD: A 5-year investigation was carried out with a group of 63 patients with aortic aneurysms who, for different reasons, were not operated on during the study period. They were divided into two groups, one called a study with 48 patients and another with 15 who use in the study group, ibuprofen-based medical treatment (non-steroidal anti-inflammatory drugs [NSAIDs) in doses of 800 mg per day and sixmonthly ultrasound controls throughout the period of the investigation, measuring the aneurysmal diameters to demonstrate the growth, detection or reduction of the same. RESULTS: The usefulness and efficacy of the use of NSAIDs in the field of medical treatment of aortic aneurysms was demonstrated, since during the investigation of the two study groups, we achieved higher survival rates for the group treated with NSAIDs.
CONCLUSIONS: Through growth control as the main rupture factor and therefore a complication that in most cases is fatal, we achieved a reduction in the aneurysmal diameter in a number of patients with higher survival rates than in the control group. Graphs up to 5 years are presented that support the results achieved.
Keywords: Aortic aneurysm, application, nonsteroidal anti-inflammatory drugs
|How to cite this article:|
Moro Rodríguez RT, Olivera DR, Valdes Cantero JL, Ferrer VG. Application of nonsteroidal anti-inflammatory drugs in aortic aneurysm. Vasc Invest Ther 2022;5:1-9
|How to cite this URL:|
Moro Rodríguez RT, Olivera DR, Valdes Cantero JL, Ferrer VG. Application of nonsteroidal anti-inflammatory drugs in aortic aneurysm. Vasc Invest Ther [serial online] 2022 [cited 2022 May 24];5:1-9. Available from: https://www.vitonline.org/text.asp?2022/5/1/1/340412
| Introduction|| |
Aortic aneurysms are abnormal dilations of the arterial wall that can be due to different etiologies, which have an alternative growth rate and level of complication, and which are greatly influenced by risk factors for arteriosclerotic disease.,,,,,,,,,,,,,,, Of different locations, the aortic ones are the most frequent and within them those located in the abdominal aorta and of this those in the V segment.,,,,,,,,, Aneurysmal disease primarily affects older, smoker, and Caucasian men. In population studies, the prevalence of aneurysms with diameters between 2.9 and 4.9 cm varies from 1.3% in men aged 45–54 years to 12.5% in those aged 75–84 years, with a male-female ratio of 4:1. Tear is a frequent cause of mortality in the general population; for example, there are 15,000 deaths/year in the United States, constituting the 15th cause of death and the 10th in men over 55 years of age. Scott et al., through a screening study with 16,000 patients, described a 4.0% prevalence of AAA >3.0 cm (7.6% in men and 1.3% in women) and a reduction in the incidence of breakage of 55%. However, due to the low prevalence of patients with surgical indication according to diameter, Greenhalgh and Smith present in their series 3.5% of AAA <4.5 cm and 0.83% of 4, 5–5.9 cm in a series of 1700 individuals aged 65–74 years,, a high relation between the diameter and the rupture index. Epidemiological studies,,,,,,, in relation to mortality and prevalence indicate that:
- USA – 1982 – 15,000 deaths per year
- USA + England – 1991 – 16,696 deaths per year
- USA (Ohio) – 1977/78 – 61.1/100,000 h/year
- England + France – 1993 – 1.3% per annum and 1992 – 1.9% per annum
- Spain – 1982 – 37.6/100,000 h/year
- World prevalence ranges from 2.1% to 8.4% population 65 years.
The main objective of acting on aneurysmal disease is to reduce mortality and the costs of aneurysm treatment. The ultrasound examination has a high sensitivity and specificity, it is not aggressive, and its cost is low, making it the ideal method for its early detection.,, The pathogenesis of aneurysms is very complex and a large number of components will interact in it, throughout many years of the patient's life, which will weaken the arterial wall, adding, in addition, an individual type of susceptibility.,,,,,,, The ideal treatment is surgical and within it elective, using different referral techniques for this, which is subject to factors such as:
- Quality of the institution: operating room, financial resources and materials, etc.
- Medical staff capacity: surgical experience and technical capacity of the medical equipment
- Patient characteristics: general conditions that allow the surgery to be performed and determine the surgical risk. Local conditions of the aneurysm: size, location, degree of involvement of collateral branches, etiology, etc. On occasions, when some of the aforementioned factors are not met, surgical treatment is contraindicated,,,,,,,,,, so it is necessary to implement a medical treatment that allows offering these patients a better quality of life and/or the possibility of palliative treatment appropriate to your need. Based on the results of the literature and the experience of the reviewed authors,,,,,,,,,,,,,,,,,,,,,,,,,, we decided to carry out this prospective research study in patients with aortic aneurysms, which for different reasons were not operated on and whose only treatment option is medical, using nonsteroidal anti-inflammatory drugs (NSAIDs) as drug therapy to demonstrate, with the results obtained, the effectiveness of these drugs to stop and/or reduce aneurysmal growth allowing the development of a palliative treatment method in those patients who are not subject to surgical treatment and have an aortic aneurysm.
| Objectives|| |
To demonstrate the usefulness and efficacy of NSAIDs as a current alternative in the medical treatment of aortic aneurysms, improving the quality of life, useful life, and survival of patients with aortic aneurysms who, for different reasons, are not operated on.
- Establish two working groups: a study group with the administration of NSAIDs and a control group without the drug
- Seriously check the growth rate before and after the use of NSAIDs in the study group and in the control group
- Establish the necessary doses to achieve the detection and/or reduction of the growth of the aneurysms
- Compare the results between the two study groups show the usefulness of ibuprofen (NSAIDs) as an option for the medical treatment of aortic aneurysms.
| Methodological Design|| |
Rationale for the investigation
Problem to solve
As aneurysms are tributary to surgical treatment, in many cases this is impossible and we must look for alternative methods of medical treatment that allow us to reduce their morbidity and mortality and therefore offer these patients a quality of life appropriate to their pathology.
Treatment with NSAIDs, including ibuprofen in commonly used doses (800 mg/day), allows us to offer an alternative medical treatment to these patients, achieving a symptomatic regression due to a decrease in their size or detection in their growth, this complicating factor, and therefore mortality.
Materials and methods
The sample consisted of all patients with aortic aneurysms who were not operated on for different causes, from very high risk to rejection of surgical treatment and to whom ibuprofen 400 mg tablets were administered twice a day (800 mg) and a control group without specific medication.
Both groups were under the influence of similar risk factors including age, toxic habits, sex, diet, level of emotional stress, and collateral diseases.
All of them underwent ultrasonographic studies of the aneurysm with measurement of the anteroposterior diameters in transversal and longitudinal sections, before and after the treatment at a frequency every 6 months, for the two groups, during the 5 years that the investigation lasted. The studies were carried out with ALOKA ultrasonography equipment using the 3.5 MHz transducer variables were analyzed in relation to age, sex, time of diagnosis, and permanence in both groups, as well as in the deceased the time in which death occurs, anteroposterior diameter, and complications. Measurements were taken at the neck of the aneurysm and at its largest diameter in coronal and longitudinal views by B-mode ultrasound. All data were collected in a form created for this purpose[Appendix 1], analyzed, and discussed in the group of authors, subjecting them to a statistical procedure to evaluate the results based on their analysis and offer the conclusions of the study. We evaluated as satisfactory when detection or reduction of the aneurysmal diameter demonstrated ultrasonographically was achieved and unsatisfactory when these results were not obtained.
Biostatistical analysis of the results obtained in the two groups was carried out and conclusions were offered in this regard. In all cases, informed consent was obtained from the patients to participate in the research [Appendix 2], also establishing inclusion and exclusion criteria.
These corresponded with the refusal of patients to participate in the study; cases that developed allergy to the drug, contraindications to the use of NSAIDs such as bleeding ulcers, cancer of the digestive tract, esophageal varices, severe HT and those who were operated.
The study included all patients with a diagnosis of aortic aneurysm who for different reasons, whether medical or not, have contraindicated surgical treatment by conventional methods and agreed to be included in the research, both for the study group and for the group control, the latter being made up of patients allergic to ibuprofen and who agreed to participate, as well as patients who refused medical treatment, as well as surgery.
We will reliably contribute to the center's investigations and those carried out in the context of aneurysmal disease with high morbidity and mortality in our population and in fact we will be the pioneers, in the country, in teaching this modality of medical treatment of the aneurysm, in addition to confirming one more utility of NSAIDs. In addition, work will be done on the priority program for chronic noncommunicable diseases in MINSAP.
Once the effectiveness of NSAIDs has been demonstrated in the medical treatment of aortic aneurysms, its indication will allow at a very low cost to offer a better perspective and quality of life to these patients.
Here in really lies the importance of the research since the results obtained support the implementation of NSAIDs as a therapy in those cases in which for various reasons they cannot be operated on, wait for it, or decide not to undergo surgical treatment of their aneurysm. Once the diameter is reduced or the growth of the aneurysm is stopped, we can establish palliative measures that effectively improve the quality of life of these patients, increasing the years of useful life. The decrease in morbidity and mortality due to aneurysm is an important part of the social impact of the research.
| Results|| |
[Table 1] and [Table 2] show us the results in relation to sex and age. There was a clear predominance of males for both groups in a 2-to-1 ratio. The minimum age of presentation of the aneurysm was established very similarly for the two groups, with 42 years for the control group and 44 for the study group, with the oldest being 90 years for the control group and 86 for the study group. Expressing the average ages in equality. All the authors reviewed offer similarity to those reached in this research, in relation to these two variables.
[Table 3] shows the accompanying pathologies of the aortic aneurysms diagnosed in the patients that constituted in all cases similarity for both groups, factors that exclude surgical treatment, being scheduled for the conduct of the investigation, that is, the application of NSAIDs, as an alternative palliative treatment in these cases. Known by all that the main determining factor of rupture in aneurysms and therefore mortality, is the growth to which they are subjected, regardless of the degree of laminar thrombosis produced in the wall as a response of the body to try to avoid it, at a larger diameter achieved, the greater the possibility of complication and breakage. Acting on this growth constitutes a preventive action, which, if achieved, we would obtain an increase in life expectancy and quality of life in these patients. The research showed that the expected growth in the control group behaved as established in multiple trend analyses in aortic aneurysms with 86.7% and only 8.3% for the study group with a very significant statistical difference of P less than 0.01, while the analysis in those that did not grow showed 72.9% for the study group and only 13.3% for the control group, also with a very high statistical significance and P less than 0.01 in favor of the study group, which reliably demonstrates the action of NSAIDs on the growth of aneurysms [Figure 1]. It should be noted that in relation to a decrease in diameter, this was not achieved in any case of the control group, while in the study group, 18.8% of the cases showed an appreciable decrease in the aneurysmal diameter, which although it does not have a high statistical significance, the fact that a group of patients achieved its reduction is a positive achievement of the research. The analysis of the deceased during the period that the investigation lasted showed 12.5% for the study group and 53.3% for the control group, reaching a greater survival in those patients who were treated with NSAIDs as shown in [Figure 2]. The analysis of mean years of survival with a confidence interval of 95% showed estimation values of 2.8 for the control group with a lower limit of 2.2 and an upper limit of 3.4, while in the study group, the value of the estimate reached 4.7, with the lower and upper limits being 4.4 and 4.9, respectively, which means that those patients who received NSAIDs survived a longer time than those who did not receive them, with the upper limit of control group below the lower limit of the study group, thus demonstrating the usefulness and efficacy of NSAIDs in the treatment of aortic aneurysms [Table 4]. If we analyze what is shown in [Figure 3] with the Kaplan-Meier estimate of survival time between the control and study groups, we see that at 5 years only patients from the study group arrived for 70%, at 4 years for 83%, at 3 years for 90%, and 98% for 2 and 1 years.
|Figure 3: Kaplan-Meier estimates of survival time between the study group and the control group|
Click here to view
In the control group, survival reached 36% for 3 years, 59% for 2 years, and 93% for 1 year, we have the evidence of the objectives set by the research, showing that NSAIDs can become an option but for the treatment of the aneurysmal disease that takes so many lives to humanity.
If before we had to wait, tied hands and feet, the arrival of death in patients not operated on for an aneurysm, now we can offer them even the consolation of a possible longer survival and therefore a better quality of life.
| Discussion|| |
There is currently no scientific evidence of the influence of drug treatment in the control of aneurysmal growth. The progressive knowledge of the etiopathogenesis of the process opens up new therapeutic perspectives that should be evaluated in future studies. Interference in the inflammatory process has been described with the use of NSAIDs in patients with aneurysms, observing a reduction in growth compared to controls, probably mediated by the decrease in metalloproteinases (MMP-9).,
What are nonsteroidal anti-inflammatory drugs?
NSAIDs are a large family of drugs, named to differentiate them from the other large family of anti-inflammatory drugs, that formed by cortisone and its derivatives, called steroids or glucocorticoids. They are very popular medications and are commonly used to combat pain, reduce swelling, and eliminate fever. For this reason, they are the group of drugs most used in Europe and the United States. It is estimated that 30 million people consume them every day in developed countries.,, The so-called NSAIDs that are used today, the vast majority inhibit the activities of cyclooxygenase 1 (Cox-1) present in various tissues and which mediates a physiological reaction, and Cox-2 present in tissue injured.
NSAIDs include very diverse compounds, which, although almost never have any chemical relationship, do share therapeutic activities and side effects. This vast group includes anti-inflammatory, analgesic, antipyretic drugs and, at present, their antiplatelet effect should be considered within their pharmacological actions. As there is no proven and effective medical treatment for aortic aneurysm, all the authors consider that studies in this regard are sufficient motivation to undertake clinical trials in patients with small aneurysms to assess the effect of drugs on the growth of the aneurysmal sac to establish whether angiotensin-converting enzyme (ACE) inhibitors, NSAIDs, and SARTANs are capable of modifying the natural history of the disease. Authors, such as Vetto, Hirsch et al., Cronenwett et al., Lederle et al., Walton et al., and Mosorin et al. among others, have published works in which reference is made to the use of NSAIDs by different causes, in cases with aneurysms of different locations, achieving a certain degree of symptomatic regression of the aneurysm as well as in relation to the size and degree of complication thereof.
More recently, Hackam et al. highlighted the action of ACE inhibitors on aneurysmal growth. The growth rate differs according to the initial diameter at the time of diagnosis. Thus, annual growth in aneurysms <4.0 cm ranges between 1 and 4 mm. In those of 4.0–6.0 cm, the annual growth is between 4 and 5 mm and, in older ones, the growth reaches up to 8 mm/year. Diameter is accepted as the main predictor of rupture, with a practically zero annual risk for aneurysms <4 cm. The annual risk of rupture increases to 0.5%–5% in AA of 4–5 cm or 3%–15% in those of 5–6 cm, or to 20%–40% in aneurysms of 7–8 cm and reaching 50% annual breakage in those >8 cm. The growth rate: 4 mm × year on average.
Recent studies,,,,,,,,,,, offer averages on:
- 1.3% as a cause of death (rupture) in men over 65 years of age
- Elective operative mortality <5%
- Broken 30%–60% only one-third of them survive the acute episode.
Our results show that in the control group, the aneurysms grew as expected in 86.7%, no growth in 13.3% and there was no decrease in diameter in any case, as well as the rupture index behaved as established for these cases.
In the group where ibuprofen was administered, at the previously established doses of 800 mg daily, growth was halted in 72.9%, the decrease in 18.8% and only 8.3% increased. The variables age and sex behaved for both groups very similar to all the series reviewed, as well as the associated diseases chronic obstructive pulmonary disease and previous acute myocardial infarction with left ventricular ejection fraction <30%. Authors such as Riambau et al., Szilagyi, and Miller et al. offer similar results.
Mortality in the control group showed figures of 53.3%, while in the study group, it only reached 12.5%, with the mean survival time being greater, both for the upper and lower limits in favor of the group in treatment, which shows the positive effect that NSAIDs have on aortic aneurysms. Survival analysis applying the KaplanMeier method shows in all the years that the research lasted, percentages higher for the patients in the study group, reaching 83% for 4 years and 70% for 5 years, there being no control group patient who reached these years of survival.
| Conclusions|| |
In the study group, growth arrest was detected in 33 cases for 72.9%, a decrease in diameter in 9 for 18.8% and only in 6 cases there was growth as expected. For the control group, 86.7% grew as expected, the remaining 13.3% did not grow, and in no case did the aneurysm diameter decrease. The research allowed us to demonstrate the efficacy of NSAIDs as a medical treatment option for aneurysms. The study has shown that NSAIDs can become part of the therapeutic drug arsenal in the treatment of aortic aneurysms.
We believe that other researches on other aspects of the medical treatment of aortic aneurysms will clear the way and make this therapy more effective, giving a greater and better beam of life to all patients with aortic aneurysms who have not been able to achieve the benefits of the surgical treatment, either by conventional means or by endoprosthetic methods.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
CARDIOCENTER ERNESTO CHE GUEVARA ENDORSEMENT OF THE SCIENTIFIC COUNCIL.
The Scientific Council of the Ernesto Che Guevara Cardiocentro in plenary session on June 01, 2020, analyzes the request of Dr. Rubén T Moro Rodriguez_ to obtain the corresponding GUARANTEE for the titled research;
USE OF NSAIDS IN THE TREATMENT OF AORTA ANEURYSMS. Given:
First: The qualities of the partner, from the scientific, teaching, and care point of view, endorsed by his professional career in addition to technical-scientific improvement through scientific events, publications, and teaching development.
Second: The importance of the results achieved in this research that demonstrated the degree of effectiveness of NSAIDs in aortic aneurysms, reducing their morbidity and mortality and therefore significantly improving the quality of life of these patients – we consider appropriate:
Approve: ____X__________ Reject: _______________.
As stated in agreement Number 1–11 on investigations taken by this council.
Given in Santa Clara on January 6, 2020.
Secretary C. Scientific
Dr. C. M. Javier Vázquez
RESEARCH ETHICS COMMITTEE CERTIFICATE
In Santa Clara, on February 14, 2020, the members of the Ethics Committee of the Ernesto Che Guevara Cardiocenter of Villa Clara meet to learn about the request of Dr. Rubén Tomas Moro Rodriguez in his capacity as principal investigator regarding the investigation:
USE OF NSAIDS IN THE TREATMENT OF AORTA ANEURYSMS
As a result of the analysis and discussion of said research, this Ethics Committee estimates that the study presented was compliant.
- The methodology established in this regard
- I respect the integrity of the patients and the right to voluntariness
- Has the informed consent model
- It did not affect the environment
- The invasiveness of the patient was minimal when administering doses of drugs (NSAIDs) established worldwide
- The exclusion and inclusion criteria were foreseen. Therefore, in the use of the powers conferred on this committee, we declare: (1) Approve the results of the Investigation Use of NSAIDs in the Treatment of Aortic Aneurysms by complying with the ethical requirements established in the Declaration of Helsinki, the latest version corresponding to the World Medical Assembly held in Edinburgh/Scotland 2000.
For the record, sign this
Dr. Rosendo Ibargollin Hernández President
| Appendices|| |
Data collection form.
Name Age Sex race
Assistance unit Assistant doctor
Diagnosis time of aneurysm
Time of permanence in the investigation.
Informed consent form patient:
Sex Direction: _____________________ In the use of my physical and mental faculties, I express and sign this for being duly informed of all the risks involved in this research, agreeing to participate in it in accordance with all the risks derived from it.
Santa Clara of the _____________________ month of the __________________________ year.
Physician Signature: __________________ Patient Signature: _____________
Conflicts of interest:
There are no conflicts of interest between the participating authors of the research, as well as with the assistance center where the same was carried out.All patients gave their informed consent to participate in the investigation.There are no conflicts of interest between students and researchers.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]