Inger L. Meek

Interference of NSAIDs with the thrombocyte inhibitory effect of aspirin: A placebo-controlled, ex vivo, serial placebo-controlled serial crossover study

PurposeNonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) are often prescribed concurrently in patients with nociceptive pain and cardiovascular comorbidity. NSAIDs and ASA inhibit the same COX-enzymes, and thus may interact. ASA’s cardioprotective antiplatelet effect is entirely COX-1 dependent. NSAIDs can be either non-COX-1 and COX-2 selective or COX-2 selective. The aim of this study was to examine the interaction between ASA and different selective and nonselective NSAIDs on thrombocyte function.MethodsSingle-blind, prospective, placebo-controlled, ex vivo, serial crossover trial of 3-day cycles separated by washout periods of at least 12xa0days in 30 healthy volunteers, evaluating interaction on ASA’s antithrombocyte effect by naproxen, ibuprofen, meloxicam, or etoricoxib taken 2xa0h before ASA. Ex vivo thrombocyte function, closure time (CT) in seconds, was measured using the Platelet Function Analyzer 100 (PFA-100). CT prolongation during a cycle reflects thrombocyte inhibitory effect. ASA nonresponse was defined as CT prolongation <40xa0% in the placebo cycle. ASA nonresponders were excluded. Wilcoxon signed-rank was used to evaluate NSAID effect on ASA-induced CT prolongation.ResultsIbuprofen and naproxen inhibit ASA’s antithrombocyte effect below the nonresponse threshold. Etoricoxib and meloxicam do not cause relevant change in ASA thrombocyte inhibition. Naproxen has an inherent weak thrombocyte inhibitory action below the ASA response threshold.ConclusionsCOX-1 affinity determines the interaction between NSAIDs and ASA on thrombocyte adhesion and aggregation. Ibuprofen and naproxen, but not etoricoxib or meloxicam, taken 2xa0h before ASA, significantly inhibit ASA’s antithrombocyte effect.

Non-Steroidal Anti-Inflammatory Drugs: An Overview of Cardiovascular Risks

While aspirin may offer protection, other non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) can cause serious cardiovascular side effects and complications. This has led to a general black box warning for cardiovascular adverse events for NSAIDs. This review explores the different mechanisms underlying the protective effects of aspirin, the NSAID associated renovascular effects causing hypertension, edema and heart failure, the cardiovascular effects causing myocardial infarction and stroke, and the possible deleterious interaction between NSAIDs and aspirin.

Stopping Tumor Necrosis Factor Inhibitor Treatment in Patients With Established Rheumatoid Arthritis in Remission or With Stable Low Disease Activity: A Pragmatic Multicenter, Open‐Label Randomized Controlled Trial

Tumor necrosis factor inhibitor (TNFi) biologic agents are an effective treatment for rheumatoid arthritis (RA). It is unclear whether patients whose disease is in remission or who have stable low disease activity need to continue use of TNFi or can stop this treatment. This study was undertaken to assess whether patients with established RA who are in remission or have stable low disease activity can effectively and safely stop their TNFi therapy.

Increased cardiovascular risk factors in different rheumatic diseases compared with the general population

OBJECTIVESnTo study the prevalence of cardiovascular risk factors among patients attending a rheumatology outpatient clinic in comparison with the general population.nnnMETHODSnCross-sectional comparison between a rheumatic outpatient cohort of consecutive patients (nu2009=u20091233) between 36 and 75 years of age attending the Arthritis Center Twente (ACT) in the year 2009: RA (nu2009=u2009546), gout (nu2009=u2009129), OA (nu2009=u2009168), CTD (nu2009=u200985), PMR (nu2009=u200991) and chronic localized or generalized pain syndromes (CPSs; nu2009=u2009214) and a random sample from a long-lasting population-based health study in the Netherlands (nu2009=u20094523). The main outcome measures were hypertension (systolic blood pressureu2009≥u2009140u2009mmHg and/or a diastolic blood pressureu2009≥u200990u2009mmHg and/or the use of antihypertensive medication), abnormal cholesterol profile (total cholesterolu2009≥u20096.5u2009mmol/l, and/or high-density lipoproteinu2009<u20090.9u2009mmol/l and/or use of lipid lowering medication), overweight (BMIu2009≥u200925u2009kg/m(2)), obesity (BMIu2009≥u200930u2009kg/m(2)) and cigarette smoking habits (self-reported current smoking).nnnRESULTSnCompared with the general population, patients with rheumatic diseases have a significantly higher prevalence of hypertension (P(ACT)u2009=u200968%, P(general)u2009=u200957%), being overweight (P(ACT)u2009=u200972%, P(general)u2009=u200962%), obesity (P(ACT)u2009=u200930%, P(general)u2009=u200917%) and cigarette smoking (P(ACT)u2009=u200926%, P(general)u2009=u200921%). The worst risk profile was found in gout patients, with higher prevalence of all cardiovascular risk factors studied.nnnCONCLUSIONnLifestyle-associated potentially modifiable cardiovascular risk factors are over-represented along the whole spectrum of chronic rheumatic diseases, and not only in RA, as suggested by preceding studies.

Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis

Objectives Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA. Methods In 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions. Results 5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics). Conclusions In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.

Choosing Wisely in daily practice: An intervention study on Antinuclear Antibody testing by rheumatologists

To assess the effect of a simple intervention on antinuclear antibody (ANA) test overuse by rheumatologists.

Stopping Tumor Necrosis Factor-inhibitors in Patients with Established Rheumatoid Arthritis in Remission or Stable Low Disease Activity: A Pragmatic Randomized Multicenter Open-Label Controlled Trial

Tumor necrosis factor inhibitor (TNFi) biologic agents are an effective treatment for rheumatoid arthritis (RA). It is unclear whether patients whose disease is in remission or who have stable low disease activity need to continue use of TNFi or can stop this treatment. This study was undertaken to assess whether patients with established RA who are in remission or have stable low disease activity can effectively and safely stop their TNFi therapy.

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

BackgroundGout 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.Methodscross-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.ResultsIndividual 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.ConclusionsGA 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 inflammation.

Stopping Tumor Necrosis Factor Inhibitor Treatment in Patients With Established Rheumatoid Arthritis in Remission or With Stable Low Disease Activity

Tumor necrosis factor inhibitor (TNFi) biologic agents are an effective treatment for rheumatoid arthritis (RA). It is unclear whether patients whose disease is in remission or who have stable low disease activity need to continue use of TNFi or can stop this treatment. This study was undertaken to assess whether patients with established RA who are in remission or have stable low disease activity can effectively and safely stop their TNFi therapy.

Stopping Tumor Necrosis Factor Inhibitor Treatment in Patients With Established Rheumatoid Arthritis in Remission or With Stable Low Disease Activity : A Pragmatic Randomized Multicenter Open-Label Controlled Trial

Tumor necrosis factor inhibitor (TNFi) biologic agents are an effective treatment for rheumatoid arthritis (RA). It is unclear whether patients whose disease is in remission or who have stable low disease activity need to continue use of TNFi or can stop this treatment. This study was undertaken to assess whether patients with established RA who are in remission or have stable low disease activity can effectively and safely stop their TNFi therapy.