Understanding the NSAID related risk of vascular events

Concern is growing about an increased risk of thrombotic events (including myocardial infarction and stroke) during the use of non-steroidal anti-inflammatory drugs (NSAIDs), in particular the so called selective cyclo-oxygenase-2 (COX 2) inhibitors. Although clinical trials give conflicting results with respect to the incidence of vascular events, increasing evidence shows that a class effect might exist for selective COX 2 inhibitors. Even before the massive introduction of selective COX 2 inhibitors, observational studies showed that the use of NSAIDs causes congestive heart failure in elderly patients.1,2 Conversely, the discontinuation of NSAIDs has also been associated with increased risk of myocardial infarction, especially in the first several weeks after stopping chronic NSAID treatment.3Many different mechanisms could explain the different effects of classic NSAIDs and selective COX 2 inhibitors in relation to thrombotic vascular events. In this review we link biochemical facts concerning NSAIDs and COX inhibitors with data from clinical trials

Construct validity of the interview Time Trade-Off and computer Time Trade-Off in patients with rheumatoid arthritis: A cross-sectional observational pilot study

Background\ud The Time Trade-Off (TTO) is a widely used instrument for valuing preference-based health-related quality of life (HRQoL). The TTO reveals preferences for own current health (‘utilities’) on a scale anchored between death (0) and perfect health (1). Limited information on the external validity of the TTO is available. Aim of this pilot study was to examine the construct validity of both an interview TTO and a computer-based TTO in patients with rheumatoid arthritis (RA).\ud \ud Methods\ud Thirty patients visiting the outpatient rheumatology clinic participated. Construct validity was assessed by measuring convergent and discriminative validity. Convergent validity was assessed by calculating Spearman’s correlations between the utilities obtained from the TTOs and pain, general health (rating scales), health-related quality of life (SF-36 and SF-6D) and functional status (HAQ-DI). Discriminative power of both TTO measures was determined by comparing median utilities between worse and better health outcomes.\ud \ud Results\ud Correlations of both TTO measures with HRQoL, general health, pain and functional status were poor (absolute values ranging from .05 to .26). Both TTOs appeared to have no discriminative value among groups of RA patients who had a worse or better health status defined by six health outcome measures. About one-third of respondents were zero-traders on each of the TTO measures. After excluding zero-traders from analysis, the correlations improved considerably.\ud \ud Conclusions\ud Both the interview TTO and computer TTO showed poor construct validity in RA patients when using measures of HRQol, general health, pain and functional status as reference measures. Possibly, the validity of the TTO improves when using an anchor that is more realistic to RA patients than the anchor ‘death’

Risk management of risk management: Combining proton pump inhibitors with low-dose aspirin

Low-dose aspirin is widely used in the primary and secondary prevention of cardiovascular events, but is associated with a range of upper gastrointestinal side effects. In this review, we summarize the rationale for low-dose aspirin therapy, quantify the risk for upper gastrointestinal side effects, identify the risk factors involved, and provide an overview of preventive strategies, thereby focusing on the rationale and clinical utility of combining proton-pump inhibitors with low-dose aspirin

Limited results of group self-management education for rheumatoid arthritis patients and their partners: explanations from the patient perspective

This study aimed to identify the reasons for limited results of group self-management for RA patients and their partners from the patient perspective. Semi-structured interviews with ten male and ten female patients who had participated in group self-management with or without their partner were content analyzed with respect to motivation to participate and the effects of the program on them. The limited effects of the self-management program appear to be linked with low motivation to participate and to change health behavior. The data show that a decline in health and also stressful life events might be associated with the disappointing effects of the program. Three strategies were proposed for improving the program’s effects: (a) provide information about the program in advance to ensure that patients have appropriate expectations. (b) Enhance intrinsic motivation to change health behavior by counseling techniques. (c) Tailoring with respect to motivation and current concerns could help to form more homogeneous groups or could be the basis for a tailored online intervention

Health-related quality of life in sarcoidosis

Purpose of review: The review presents an overview of the scientific publications in the field of health-related quality of life (HRQL) in sarcoidosis. Recent findings: Literature on HRQL in sarcoidosis is limited. HRQL was mainly used as a primary or secondary endpoint in intervention studies. Moreover, most studies have measured HRQL in sarcoidosis by means of the generic questionnaire 36-Item Short-Form Health Survey. Sarcoidosis-specific questionnaires and computer-adapted testing are innovative approaches to the field. Summary: HRQL as a primary or secondary outcome in sarcoidosis studies is still scarce. In addition to the proper definition of the concept, the mode of measurement of HRQL remains a matter of debate. Because health-economical evaluations require data on gained quality of life, future studies on sarcoidosis should include HRQL as the study endpoin

Hyperuricaemia: a marker of increased cardiovascular risk in rheumatic patients: analysis of the ACT-CVD cohort

Background Gout and hyperuricaemia may be associated with increased cardiovascular risk, but analyses in different populations show conflicting results. This study investigates the impact of serum uric acid, inflammation and traditional CV risk parameters on CV event risk in patients with gouty arthritis and patients with non-gouty rheumatic disease. Methods cross-sectional and prospective multivariate analysis of the relation between tertiles of serum uric acid and individual traditional CV risk factors in a cohort of gouty arthritis (GA, n=172), rheumatoid arthritis (RA, n=480) and osteoarthritis (OA, n=206) patients. Main outcome measures: systolic blood pressure, TC/HDL ratio, GlyHb, BMI and first CV events. Results Individual CV risk factors were significantly less favourable in GA (systolic blood pressure, TC/HDL ratio, BMI, p<0.05). In RA and OA, but not in GA, individual cardiometabolic parameters correlated with serum uric acid values (OA: RA: systolic blood pressure, TC/HDL ratio, BMI; systolic blood pressure, TC/HDL ratio, GlyHb, BMI; p<0.05). In non-GA individuals the highest tertile of serum uric acid (>0.34 mmol/L) and NT proBNP level were independent predictors of first CV events, against age and GlyHb level in GA (p<0.05). The hazard of first CV events was equally significantly increased in GA patients (HR 3.169, 95% CI 1.287-7.806) and non-GA individuals with a serum uric acid ≥ 0.34 mmol/L (HR 3.721, 95% CI 1.603-8.634) compared to non-GA individuals with a serum uric acid < 0.27. Conclusions GA is associated with a 3.1-fold hazard of first CV events. In non-GA rheumatic patients increasing serum uric acid is associated with increased CV risk, whereas CV risk in GA is independent of serum uric acid values. The presence of GA or a baseline serum uric acid in the upper range are possibly stronger predictors of first CV events than some traditional CV risk factors or parameters of inflammatio

Patient education and disease activity: A study among rheumatoid arthritis patients

Objective: To determine whether patients experiencing high disease activity derive more benefit from patient education than those experiencing low disease activity. - \ud Methods: Data from a randomized study on the effects of a program of patient education were analyzed retrospectively. Four subgroups were studied: the high disease activity subgroup of patients who had participated in the educational program, the complementary low disease activity subgroup, the high disease activity subgroup of controls, and its low disease activity complement. Patients with erythrocyte sedimentation rate >28 mm/first hour were classified as having high disease activity. Effects on frequency of physical exercises, endurance exercises, and relaxation exercises and effects on health status (Modified Health Assessment Questionnaire, Dutch Arthritis Impact Measurement Scales [AIMS]) were measured. - \ud Results: There were no significant differences between the adherence parameters of the various pairs of groups. Four months after the educational program began, anxiety and depression scores on the Dutch-AIMS had increased among participating patients who were experiencing high disease activity and decreased among those who were experiencing low disease activity. - \ud Conclusions: Patients experiencing high disease activity did not derive more benefit from patient education than those experiencing low disease activity. On the contrary, an increase of anxiety and depression is found in these patients. Further study is needed to confirm our findings

Cardiovascular case fatality in rheumatoid arthritis is decreasing; first prospective analysis of a current low disease activity rheumatoid arthritis cohort and review of the literature

Background Previous studies found increased case fatality after myocardial infarction and more frequent sudden death in RA patients compared to non-RA subjects. The RA associated CV risk might be explained by the combined effects of chronic systemic inflammation and increased lifestyle associated cardiovascular risk factors, and modified by the use of medication such as non steroidal anti-inflammatory drugs, corticosteroids and disease modifying anti-rheumatic drugs. Trends in case fatality rate in RA after the introduction of potent anti-inflammatory biologic therapies and treat-to-target treatment strategies aiming at remission are not known. This study was performed to examine the cardiovascular fatality rate in current low disease activity RA, and to evaluate trends in RA associated CV case fatality over time. Methods Prospective study to determine the incidence of fatal and nonfatal CV events in 480 RA patients included in the ACT-CVD cohort between February 2009 and December 2011. Patients with prior CV disease were excluded. Cox regression analysis was performed to determine CV event risk and contributing risk factors over time. The results of the cohort analysis were put into the context of a review of the literature to evaluate trends in RA associated CV fatality rate over time. Results The study included 480 RA patients, 72.3% female with median disease duration of 4.2 years, 72.1% being in clinical remission (Disease Activity Score in 28 joints). During a mean follow up of 2.9 years 29 patients (6%) experienced a first CV event, 2 fatal and 27 non-fatal, corresponding to a 6.9% case fatality rate. Comparison with previous studies in cohorts with successive enrolment periods shows a trend towards a decrease in CV case fatality in RA from 52.9% in 1998 to 6.9% in our study. Conclusion CV case fatality in current low disease activity RA is importantly lower than in previous studies, and a trend towards decreasing CV fatality in RA is suggeste

Predictive value of gastrointestinal symptoms and patient risk factors for NSAID-associated gastrointestinal ulcers defined by endoscopy? Insights from a pooled analysis of two naproxen clinical trials

Objective: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat pain and rheumatic conditions. To facilitate patient management, we determined the predictive value of gastrointestinal (GI) symptoms and risk factors for the development of NSAID-associated GI injuries.Methods: Post-hoc analysis of pooled data from naproxen treatment arms of two identical, randomized, double-blind, controlled phase 3 trials in arthritis patients at risk of GI adverse events. Endoscopic incidence of GI ulcers at baseline, and 1, 3, and 6 months was employed as a surrogate parameter for GI injury. For GI symptom analysis, Severity of Dyspepsia Assessment questionnaire was used. For GI risk factor analysis, the high risk factors: previous GI injury, concomitant selective serotonin reuptake inhibitors or corticosteroids, ulcer history, concomitant low-dose aspirin, and age &gt;65 years were employed.Results: Data of 426 naproxen patients were analyzed. Distribution of GI symptoms between patients with and without ulcer was similar; about one third of patients developing an ulcer reported no GI pain symptoms. GI symptoms experienced under naproxen treatment were thus not indicative of GI injury. The proportion of patients developing an ulcer increased with the number of risk factors present, however, about a quarter of patients without any of the analyzed risk factors still developed an ulcer.Conclusion: GI symptoms and the number of risk factors are not reliable predictors of NSAID-induced GI injury to decide which patients need gastroprotection and will lead to a large group of patients with GI injuries. A preventive rather than reactive approach should be taken.</p