Cardiovascular Safety in the Treatment of Chronic Rheumatic Pathologies

Tamerlan Tulegenovich Zakaev^1*, Medina Vakhaevna Bakrieva¹, Rabiyat Tazhutdinovna Alkhazova², Diana Borisovna Girkina³, Anzhela Yunusovna Chagarova³, Angelina Andreevna Polyanskaya³

¹Department of Therapy, Medical Faculty of the Medical Institute of the Chechen State University, Grozny, Republic of Chechnya, Russia.

²Department of Pharmacology, Faculty of Medicine of Dagestan State University, Makhachkala, Republic of Dagestan, Russia.

³Department of Therapy, Faculty of Medicine, Stavropol State Medical University, Stavropol, Russia.

*Email: [email protected]

ABSTRACT

According to statistics from the World Health Organization (WHO), from 9 to 45% of people are susceptible to diseases of the musculoskeletal system. In addition, about 3% of people can be classified as disabled due to their condition of bones and joints, and almost every one of this 3% will experience severe pain. To eliminate pain, doctors prescribe nonsteroidal anti-inflammatory drugs (NSAIDs) to these people. Within the framework of this article, the possibility of using NSAIDs in chronic inflammatory rheumatic pathologies was considered, and their effect on the human body was also considered. In a study of patients with severe psoriatic arthritis, it was found that prevention with methotrexate led to the least number of cases of cardiovascular diseases in comparison with other methods of prevention, including traditional treatment, phototherapy, and climatotherapy. It has also been suggested that the effect of inhibitors is a defense against tumor necrosis. The method of prevention of patients with severe forms of psoriatic arthritis can greatly affect the reduction in the number of cardiovascular diseases, as a result, local studies are needed to more accurately assess the cardiovascular safety and effectiveness of systemic therapy.

Key words: Selective inhibitors, NSAIDs, Arthritis, Psoriatic arthritis, Cardiovascular diseases

INTRODUCTION

Inflammatory arthritis is a common chronic inflammatory disease that often leads to cardiovascular disease [1-3]. Inflammatory arthritis is a key problem in the pathogenesis of atherosclerosis, however, special anti-inflammatory therapy can become a key link in the treatment of atherothrombotic diseases [4]. However, the impact of systematized anti-inflammatory prevention of cardiovascular diseases in people with chronic inflammatory diseases, including rheumatoid arthritis and psoriatic arthritis, is of great interest [5].

Nonsteroidal anti-inflammatory drugs (NSAIDs) are indispensable in the treatment of pain due to the integrated role of the cyclooxygenase pathway (COX) in inflammation and pain recognition [6]. However, the disadvantage of NSAIDs is their toxicity [7]. In the 1990s, paracetamol was used as a pain reliever for osteoarthritis, but further studies have shown that paracetamol adversely affects the organs of the gastrointestinal tract (GIT). In addition, paracetamol has fewer analgesic properties than NSAIDs and cannot be a worthy alternative to NSAIDs in any inflammatory arthritis [8].

Determination of cyclooxygenase 2 (COX-2) and further use of COX-2 selective NSAID preparations was a discovery that was expected to significantly reduce side effects when administered intravenously. However, this does not apply to celecoxib, and, as it later turned out, to all COX-2-selective inhibitors when used together with ASA [9]. Selective COX-2 inhibitors inhibit renal COX-2 resulting in urinary tract fluid retention, edema, hypertension, and cardiac congestion which can be fatal [10].

The main disadvantage of selective COX-2 inhibitors has been an increase in the incidence of myocardial infarction and other cardiovascular diseases [11, 12]. Thus, the initially expected undeniable advantages of selective COX-2 inhibitors were outweighed by their possible toxicity. An analysis of the literature showed that it is possible to use a proton pump inhibitor drug with traditional NSAIDs [13]. It has also been mentioned in the literature that NSAIDs and selective COX-2 inhibitors significantly reduce gastrointestinal and peptic ulcer toxicity [14-16]. Thus, traditional NSAIDs can be considered the most preferable in the prevention of arthritis and diseases of the musculoskeletal system.

However, during the analysis of the literature data, we came across conflicting results and selective data from random studies or clinical cohorts of patients with psoriatic arthritis [17-20]. Thus, our work aimed to study the incidence of cardiovascular diseases in patients with severe psoriatic arthritis. These patients were treated with systemic therapy, i.e., biological agents (including tumor necrosis factor inhibitors and an interleukin-12/23 inhibitor), methotrexate, cyclosporine, retinoids, and other prevention methods, including traditional medicine, phototherapy, and real-life climatotherapy [21].

MATERIALS AND METHODS

Among the patients of the Dagestan diagnostic centers, a cohort study was conducted, which involved 464 patients aged 18 to 65 years. Of these, there were 252 women and 212 men. All patients were in the hospital or on home treatment with the main diagnosis of psoriatic arthritis. The study was conducted from 2014 to 2017. Patients with severe and moderate psoriatic arthritis were divided into five groups with different methods of treatment: group 1 - cyclosporine; group 2 - methotrexate; group 3 - biological products; group 4 - retinoids; and group 5 - various therapies based on traditional medicine (topical NSAIDs and/or topical vitamin D analogs), phototherapy (UVB and psoralen plus UVA), and climatotherapy. Patients were under medical supervision all the time from the moment of illness until December 31, 2017. or their recovery. Patients were regularly monitored with questionnaires and timely collection of data on their health status.

RESULTS AND DISCUSSION

This study involved 464 people, and no deaths were detected during the study. Most patients received NSAIDs that reduce the concentration of glucose, cholesterol, and antihypertensive drugs. The use of antidepressants was carried out only with severe pain syndrome. It should be noted that the development of cardiovascular diseases during treatment remained unlikely.

The number of patients in the 1st group was 82 people, in the 2nd group - 170, in the 3rd group - 16, in the 4th group - 53, and the number of people who turned to traditional medicine (5th group), amounted to 143 people. The number of cardiovascular complications was: for group 1 - 1 person; for group 2 - 3 people; for group 3 - 1 person; for a group of 4 - 4 people; for a group of 5 - 12 people (Figure 1).

It is worth noting that there were 37 patients with gastrointestinal problems out of 7027 observed people. These results allowed us to conclude that the combination of treatment with NSAIDs and selective inhibitors has become the safest method for the prevention and treatment of chronic inflammatory rheumatic pathologies.

CONCLUSION

The detection of cyclooxygenase 2 (COX-2) and the further administration of selective COX-2 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), has become a key factor in the prevention of diseases of the musculoskeletal system, but side effects on the gastrointestinal tract (GIT) should be taken into account. We did not find any evidence that celecoxib causes fewer gastrointestinal side effects than classic NSAIDs, and improvement in symptoms for COX-2 selective inhibitors is not a panacea. We also found no evidence that selective COX-2 inhibitors are more effective in preventing inflammatory arthritis than classical NSAIDs. Based on these data, we concluded that COX-2 selective inhibitors are no better than classical NSAIDs. It is also important to note that most older people require aspirin, which reacts with COX-2 to form COX-1, making it a classic NSAID. Data obtained from a literature review suggest that the combined use of NSAIDs and COX-2 significantly reduces the possibility of recurrence and ulceration, as well as reduces pain from symptoms. Thus, classic NSAIDs continue to be a good choice for the prevention of inflammatory arthritis and musculoskeletal disorders, especially when given together with a proton pump inhibitor.

ACKNOWLEDGMENTS : None

CONFLICT OF INTEREST : None

FINANCIAL SUPPORT : None

ETHICS STATEMENT : All patients sighned agreement before the start of the experiment. All additional information is available upon request from the corresponding author.