Cardiovascular Risk of Synthetic, Non-Biologic Disease-Modifying Anti- Rheumatic Drugs (DMARDs)

2020 ◽  
Vol 18 (5) ◽  
pp. 455-462 ◽  
Author(s):  
Iordanis S. Mourouzis ◽  
Antonis S. Manolis ◽  
Constantinos Pantos

Patients with rheumatoid diseases have an increased risk of cardiovascular disease (CVD) and CVD-related death compared with the general population. Both the traditional cardiovascular risk factors and systemic inflammation are contributors to this phenomenon. This review examines the available evidence about the effects of synthetic, non-biologic disease-modifying antirheumatic drugs (DMARDs) on CVD risk. This is an important issue for clinicians when deciding on individual treatment plans in patients with rheumatic diseases. Evidence suggests that synthetic, non-biologic DMARDs such as methotrexate, sulfasalazine, hydroxychloroquine, leflunomide and tofacitinib show decreased CVD morbidity and mortality. However, the strongest data in favour of a reduction in CVD events in rheumatoid patients are shown with methotrexate, which has been the focus of most studies. Adequate proof for a favourable effect also exists for hydroxychloroquine. Larger, prospective studies and randomized clinical trials are needed to better characterize the effect of synthetic, non-biologic DMARDs on CVD outcomes in these patients. Design of future studies should include areas with lack of evidence, such as the risk for heart failure, arrhythmias and valvular heart disease. The clinically relevant question whether synthetic, non-biologic DMARDs are inferior to biologic DMARDs in terms of CVD outcomes remains not adequately addressed.

BMJ Open ◽  
2017 ◽  
Vol 7 (12) ◽  
pp. e019468 ◽  
Author(s):  
Bongani Brian Nkambule ◽  
Zibusiso Mkandla ◽  
Tinashe Mutize ◽  
Phiwayinkosi Vusi Dludla

IntroductionThe incidence of cardiovascular disease (CVD) is now at least threefold higher in HIV-infected patients as compared with the general population. Although platelet activation and reactivity are implicated in the development of CVDs in HIV-infected patients, its precise role remains inconclusive. We aim to assess the association between platelet activation and selected cardiovascular risk factors in HIV-1-infected individuals on highly active antiretroviral treatment (HAART).MethodsThis will be a systematic review and meta-analysis of published studies evaluating the association between platelet activation and CVD risk factors in HAART-treated adults. The search strategy will include medical subject headings words for MEDLINE, and this will be adapted to Embase search headings (Emtree) terms for the EMBASE database. The search will cover literature published between 1 January 1996 to 30 April 2017. Studies will be independently screened by two reviewers using predefined criteria. Relevant eligible full texts will be screened; data will be extracted, and a qualitative synthesis will be conducted. Data extraction will be performed using Review Manager V.5.3. To assess the quality and strengths of evidence across selected studies, the Grading of Recommendations Assessment Development and Evaluation approach will be used. The Cochran’s Q statistic and the I2statistics will be used to analyse statistical heterogeneity between studies. If included studies show high levels of homogeneity, a random effects meta-analysis will be performed using R statistical software.Ethics and disseminationThis will be a review of existing studies and will not require ethical approval. The findings will be disseminated through peer-reviewed publication and presented at local and international conferences. An emerging patient management dilemma is that of the increased incidence of CVD in people living with HIV on HAART. This review may inform treatment and cardiovascular risk stratification of HIV-infected patients at increased risk of developing CVD.PROSPERO registration numberCRD42017062393.


2017 ◽  
Vol 2017 ◽  
pp. 1-19 ◽  
Author(s):  
Konstantinos Makrilakis ◽  
Stavros Liatis

Diabetes mellitus is associated with an increased risk of coronary heart disease (CHD) morbidity and mortality. Although it frequently coexists with other cardiovascular disease (CVD) risk factors, it confers an increased risk for CVD events on its own. Coronary atherosclerosis is generally more aggressive and widespread in people with diabetes (PWD) and is frequently asymptomatic. Screening for silent myocardial ischaemia can be applied in a wide variety of ways. In nearly all asymptomatic PWD, however, the results of screening will generally not change medical therapy, since aggressive preventive measures, such as control of blood pressure and lipids, would have been already indicated, and above all, invasive revascularization procedures (either with percutaneous coronary intervention or coronary artery bypass grafting) have not been shown in randomized clinical trials to confer any benefit on morbidity and mortality. Still, unresolved issues remain regarding the extent of the underlying ischaemia that might affect the risk and the benefit of revascularization (on top of optimal medical therapy) in ameliorating this risk in patients with moderate to severe ischaemia. The issues related to the detection of coronary atherosclerosis and ischaemia, as well as the studies related to management of CHD in asymptomatic PWD, will be reviewed here.


Author(s):  
Gavin Clunie ◽  
Nick Wilkinson ◽  
Elena Nikiphorou ◽  
Deepak R. Jadon

The Oxford Handbook of Rheumatology, 4th edition, emphasizes the importance of evidence-based therapeutics and therefore devotes a whole chapter to medications used to treat rheumatological and bone disease (‘Drugs used in rheumatological disease’). Details about treatments are cross-referenced to specific use of medications for specific diseases and conditions elsewhere in the book. There are chapter sections on analgesics including opiate-based medications, NSAIDs, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, intravenous immunoglobulin, and other immunosuppressants. There is a specific focus in the chapter on drugs used for Raynaud’s disease, osteoporosis (e.g. bisphosphonates), pulmonary hypertension, gout, and hyperuricaemia. Overall there is reference to both adult and paediatric disease treatments in the chapter.


Circulation ◽  
2020 ◽  
Vol 141 (7) ◽  
pp. 592-599 ◽  
Author(s):  
Anandita Agarwala ◽  
Erin D. Michos ◽  
Zainab Samad ◽  
Christie M. Ballantyne ◽  
Salim S. Virani

Cardiovascular disease (CVD) is the leading cause of death among women in the United States. As compared with men, women are less likely to be diagnosed appropriately, receive preventive care, or be treated aggressively for CVD. Sex differences between men and women have allowed for the identification of CVD risk factors and risk markers that are unique to women. The 2018 American Heart Association/American College of Cardiology Multi-Society cholesterol guideline and 2019 American College of Cardiology/American Heart Association guideline on the primary prevention of CVD introduced the concept of risk-enhancing factors that are specific to women and are associated with an increased risk of incident atherosclerotic CVD in women. These factors, if present, would favor more intensified lifestyle interventions and consideration of initiation or intensification of statin therapy for primary prevention to mitigate the increased risk. In this primer, we highlight sex-specific CVD risk factors in women, stress the importance of eliciting a thorough obstetrical and gynecological history during cardiovascular risk assessment, and provide a framework for how to initiate appropriate preventive measures when sex-specific risk factors are present.


2012 ◽  
Vol 46 (11) ◽  
pp. 1491-1505 ◽  
Author(s):  
Rishi J Desai ◽  
Richard A Hansen ◽  
Jaya K Rao ◽  
Tania M Wilkins ◽  
Elizabeth A Harden ◽  
...  

BACKGROUND: Introduction of biologic disease-modifying antirheumatic drugs (DMARDs) has considerably changed treatment options for rheumatoid arthritis (RA) over the past decade. Very little information is available on comparative discontinuation rates of the biologics. OBJECTIVE: To compare treatment discontinuations for 9 biologic DMARDs in adults with RA. METHODS: We searched electronic databases through May 2012 to retrieve randomized controlled trials (RCTs) of patients with RA that compared biologic DMARDs with placebo or another biologic DMARD. The primary outcome was treatment discontinuation during the blinded phase of the trials, measured as overall withdrawals, withdrawals resulting from lack of efficacy, and withdrawals resulting from adverse events. Random-effects meta-analysis estimated the effect size for individual agents, and adjusted indirect comparisons were made between biologics using mixed treatment comparisons (MTC) meta-analysis. RESULTS: Forty-four trials were included in the analysis. In comparison with placebo, biologics were less likely to be withdrawn because of lack of efficacy (OR 0.22, 95% CI 0.17 to 0.27) and more likely to be withdrawn because of an adverse event (OR 1.41, 95% CI 1.16 to 1.70). Based on the MTC, certolizumab had the most favorable overall withdrawal profile, followed by etanercept and rituximab. Certolizumab had lower relative withdrawal rates resulting from lack of efficacy than adalimumab, anakinra, and infliximab. Anakinra had higher relative withdrawal rates resulting from lack of efficacy than most other biologics. Certolizumab and infliximab had more, while etanercept had fewer, withdrawals because of adverse events than most other drugs. CONCLUSIONS: Based on MTC using data from RCTs, differences in discontinuation rates were observed, generally favoring certolizumab, etanercept, and rituximab over other biologic DMARDs. These potential differences need to be further explored in head-to-head trials or well-conducted observational studies.


2021 ◽  
Vol 80 (10) ◽  
pp. 1255-1265 ◽  
Author(s):  
Marcia A Friedman ◽  
Jeffrey R Curtis ◽  
Kevin L Winthrop

Patients with rheumatic diseases are at increased risk of infectious complications; vaccinations are a critical component of their care. Disease-modifying antirheumatic drugs may reduce the immunogenicity of common vaccines. We will review here available data regarding the effect of these medications on influenza, pneumococcal, herpes zoster, SARS-CoV-2, hepatitis B, human papilloma virus and yellow fever vaccines. Rituximab has the most substantial impact on vaccine immunogenicity, which is most profound when vaccinations are given at shorter intervals after rituximab dosing. Methotrexate has less substantial effect but appears to adversely impact most vaccine immunogenicity. Abatacept likely decrease vaccine immunogenicity, although these studies are limited by the lack of adequate control groups. Janus kinase and tumour necrosis factor inhibitors decrease absolute antibody titres for many vaccines, but do not seem to significantly impact the proportions of patients achieving seroprotection. Other biologics (interleukin-6R (IL-6R), IL-12/IL-23 and IL-17 inhibitors) have little observed impact on vaccine immunogenicity. Data regarding the effect of these medications on the SARS-CoV-2 vaccine immunogenicity are just now emerging, and early glimpses appear similar to our experience with other vaccines. In this review, we summarise the most recent data regarding vaccine response and efficacy in this setting, particularly in light of current vaccination recommendations for immunocompromised patients.


2019 ◽  
pp. 089719001986915 ◽  
Author(s):  
Ana Paula M. Gomides ◽  
Cleandro P. Albuquerque ◽  
Ana B.V. Santos ◽  
Rodrigo B. C. Amorim ◽  
Manoel B. Bértolo ◽  
...  

Background: Rheumatoid arthritis (RA) is associated with high frequency of comorbidities and increased risk of polypharmacy. Although there is a great potential for complications, there is a gap in literature on polypharmacy in patients with rheumatic arthritis. Objective: To evaluate the prevalence and factors associated with polypharmacy in a population in a real-life setting. Methods: A cross-sectional multicenter study was conducted in Brazil. Patients underwent clinical evaluation and medical records analysis. Polypharmacy was considered as a dependent variable. To test independent variables, we used Poisson regression. Results: We evaluated 792 patients (89% female, median age 56.6 years). Median duration of disease was 12.7 years, 78.73% had a positive rheumatoid factor. The median of disease activity score-28 was 3.5 (disease with mild activity), median of the clinical disease activity index score was 9, and median of health assessment questionnaire-disability index was 0.875; 47% used corticosteroids, 9.1% used nonsteroidal anti-inflammatory drugs, 90.9% used synthetic disease-modifying antirheumatic drugs, 35.7% used biologic disease-modifying antirheumatic drugs (DMARDs). In total, 537 (67.9%) patients used 5 or more drugs. Polypharmacy showed a relationship with a number of comorbidities and use of specific drugs (corticosteroids, methotrexate, and biological DMARDs). Conclusion: We found a high prevalence of polypharmacy (67.9%) in RA. Solutions to management this problem should be stimulated.


2015 ◽  
Vol 2015 ◽  
pp. 1-2 ◽  
Author(s):  
Ian Chang ◽  
Carla Guggenheim ◽  
Heather Laird-Fick

Background. Disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX), are associated with gastrointestinal toxicity. MTX inhibits dihydrofolate reductase, but it is unclear if polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene predict toxicity.Case. We describe a 33-year-old male with polyarticular rheumatoid arthritis who developed sigmoid diverticular perforation while receiving methotrexate, folic acid, prednisone, and naproxen. He tested heterozygous for the C677T alleleMTHFRgene.Discussion. Rheumatoid arthritis and its treatments are associated with increased risk of gastrointestinal disease. In one study, perforation was highest among individuals with concomitant exposure to NSAIDs, nonbiologic DMARDs, and glucocorticoids. Multiple mutations of theMTHFRgene have been identified, but their association with MTX toxicity is unclear. This case adds to a growing body of literature that could help inform the treatment of others in the future.


2016 ◽  
Vol 19 (18) ◽  
pp. 3369-3377 ◽  
Author(s):  
Caroline J Bull ◽  
Kate Northstone

AbstractObjectiveTo investigate the prospective associations between dietary patterns in childhood and CVD risk in adolescence.DesignProspective cohort study. Exposures were dietary patterns at age 7, 10 and 13 years derived by cluster analysis. Outcomes were physiological and biochemical cardiovascular risk markers.SettingAvon Longitudinal Study of Parents and Children (ALSPAC), UK.SubjectsChildren (n2311, 44.1 % male) with complete data available.ResultsAfter adjustment for known confounders, we observed an association between being in the ‘Processed’ and ‘Packed lunch’ dietary pattern clusters at age 7 and BMI at age 17. Compared with the ‘healthy’ cluster, the OR (95 % CI) for being in the top 10 % for BMI was 1·60 (1·01, 2·55;P=0·05) for the ‘Processed’ cluster and 1·96 (1·22, 3·13;P=0·005) for the ‘Packed lunch’ cluster. However, no association was observed between BMI and dietary patterns at age 10 and 13. Longitudinal analyses showed that being in either the ‘Processed’ or ‘Packed lunch’ cluster at age 7 was associated with increased risk of being in the top 10 % for BMI regardless of subsequent cluster membership. No associations between other cardiovascular risk measures and dietary patterns were robust to adjustment for confounders.ConclusionsWe did not find any consistent evidence to support an association between dietary patterns in childhood and cardiovascular risk factors in adolescence, with the exception of BMI and dietary pattern at age 7 only. However, the importance of dietary intake in childhood upon health later in life requires further investigation and we would encourage the adoption of a healthy diet as early in life as possible.


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