Anti-inflammatory therapy in ischaemic heart disease: from canakinumab to colchicine

Abstract Four large trials have recently evaluated the effects of anti-inflammatory drugs in the secondary prevention of major cardiovascular events (MACE) in over 25 000 patients followed for 1.9–3.7 years. CANTOS tested subcutaneous canakinumab [an anti-interleukin (IL) 1β antibody] 300 mg every 3 months against placebo in patients with a history of myocardial infarction (MI) and serum C-reactive protein (CRP) >2 mg/L, demonstrating efficacy in preventing MACE but increased rates of fatal infections. COLCOT (in patients with recent MI) and LoDoCo2 (in patients with chronic coronary syndromes) tested oral colchicine (an NLRP3 inflammasome inhibitor) 0.5 mg daily vs. placebo, demonstrating prevention of MACE with a slightly increased risk of pneumonia in COLCOT (0.9 vs. 0.4%) but not in LoDoCo2. CIRT tested oral methotrexate (an anti-rheumatic anti-nuclear factor-kB) 15–20 mg per week against placebo in ischaemic heart disease patients with diabetes or metabolic syndrome, without significant reduction in MACE rates or in circulating IL6 or CRP levels, and with increased risk of skin cancers. In summary, canakinumab and colchicine have shown efficacy in preventing MACE in ischaemic heart disease patients, but only colchicine has acceptable safety (and cost) for use in secondary cardiovascular prevention. Clinical results are expected with the anti-IL6 ziltivekimab.

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Incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes

Cardiovascular Diabetology ◽

10.1186/s12933-021-01313-7 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Amy Groenewegen ◽

Victor W. Zwartkruis ◽

Betül Cekic ◽

Rudolf. A. de Boer ◽

Michiel Rienstra ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Heart Disease ◽

Ischaemic Heart Disease ◽

Incidence Rate ◽

Diabetes Status ◽

Increased Risk ◽

Patients With Diabetes ◽

Rate Ratios ◽

Age And Sex

Abstract Background Diabetes has strongly been linked to atrial fibrillation, ischaemic heart disease and heart failure. The epidemiology of these cardiovascular diseases is changing, however, due to changes in prevalence of obesity-related conditions and preventive measures. Recent population studies on incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes are needed. Methods A dynamic longitudinal cohort study was performed using primary care databases of the Julius General Practitioners’ Network. Diabetes status was determined at baseline (1 January 2014 or upon entering the cohort) and participants were followed-up for atrial fibrillation, ischaemic heart disease and heart failure until 1 February 2019. Age and sex-specific incidence and incidence rate ratios were calculated. Results Mean follow-up was 4.2 years, 12,168 patients were included in the diabetes group, and 130,143 individuals in the background group. Incidence rate ratios, adjusted for age and sex, were 1.17 (95% confidence interval 1.06–1.30) for atrial fibrillation, 1.66 (1.55–1.83) for ischaemic heart disease, and 2.36 (2.10–2.64) for heart failure. Overall, incidence rate ratios were highest in the younger age categories, converging thereafter. Conclusion There is a clear association between diabetes and incidence of the major chronic progressive heart diseases, notably with heart failure with a more than twice increased risk.

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Increased risk of myocardial infarction as first manifestation of ischaemic heart disease and nonselective nonsteroidal anti-inflammatory drugs

British Journal of Clinical Pharmacology ◽

10.1111/j.1365-2125.2006.02644.x ◽

2006 ◽

Vol 61 (6) ◽

pp. 730-737 ◽

Cited By ~ 18

Author(s):

C. J. Hawkey ◽

G. M. Hawkey ◽

S. Everitt ◽

M. M. Skelly ◽

W. A. Stack ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Disease ◽

Ischaemic Heart Disease ◽

Increased Risk ◽

Inflammatory Drugs ◽

Anti Inflammatory

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Role of depressive symptoms in cardiometabolic diseases and subsequent transitions to all-cause mortality: an application of multistate models in a prospective cohort study

Stroke and Vascular Neurology ◽

10.1136/svn-2020-000693 ◽

2021 ◽

pp. svn-2020-000693

Author(s):

Yanan Qiao ◽

Siyuan Liu ◽

Guochen Li ◽

Yanqiang Lu ◽

Ying Wu ◽

...

Keyword(s):

Heart Disease ◽

Depressive Symptoms ◽

Depression Scale ◽

European Population ◽

Multistate Models ◽

Cardiometabolic Diseases ◽

Increased Risk ◽

All Cause Mortality ◽

Patients With Diabetes

Background and purposeThe role of depression in the development and outcome of cardiometabolic diseases remains to be clarified. We aimed to examine the extent to which depressive symptoms affect the transitions from healthy to diabetes, stroke, heart disease and subsequent all-cause mortality in a middle-aged and elderly European population.MethodsA total of 78 212 individuals aged ≥50 years from the Survey of Health Ageing and Retirement in Europe were included. Participants with any baseline cardiometabolic diseases including diabetes, stroke and heart disease were excluded. Depressive symptoms were measured by the Euro-Depression scale at baseline. Participants were followed up to determine the occurrence of cardiometabolic diseases and all-cause mortality. We used multistate models to estimate the transition-specific HRs and 95% CIs after adjustment of confounders.ResultsDuring 500 711 person-years of follow-up, 4742 participants developed diabetes, 2173 had stroke, 5487 developed heart disease and 7182 died. Depressive symptoms were significantly associated with transitions from healthy to diabetes (HR: 1.12, 95% CI: 1.05 to 1.20), stroke (HR: 1.31, 95% CI: 1.18 to 1.44), heart disease (HR: 1.26, 95% CI: 1.18 to 1.34) and all-cause mortality (HR: 1.41, 95% CI: 1.34 to 1.49). After cardiometabolic diseases, depressive symptoms were associated with the increased risk of all-cause mortality in patients with diabetes (HR: 1.54, 95% CI: 1.25 to 1.89), patients who had stroke (HR: 1.29, 95% CI: 1.03 to 1.61) and patients with heart disease (HR: 1.21, 95% CI: 1.02 to 1.44).ConclusionsDepressive symptoms increase the risk of diabetes, stroke and heart disease, and affect the risk of mortality after the onset of these cardiometabolic conditions. Screening and treatment of depressive symptoms may have profound implications for the prevention and prognosis of cardiometabolic diseases.

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Electronic Record Linkage cohort study of evidence-based management and outcomes in patients with ischaemic heart disease and atrial fibrillation

10.23889/suthesis.58169 ◽

2021 ◽

Author(s):

◽

Edward Daniel Harris

Keyword(s):

Atrial Fibrillation ◽

Heart Disease ◽

Ischaemic Heart Disease ◽

Evidence Based Medicine ◽

Lipid Lowering ◽

Evidence Based ◽

Lipid Lowering Therapy ◽

Lipid Levels ◽

Increased Risk ◽

Based Medicine

BACKGROUND Implementation of evidence-based medicine is often suboptimal. The objectives of this thesis are to explore the delivery of evidence-based medicine and outcomes in patients with ischaemic heart disease (IHD) and atrial fibrillation (AF). METHODS Retrospective observational cohort studies were conducted using linked anonymised data from the secure anonymised information linkage (SAIL) databank. Patients included (i) those undergoing percutaneous coronary intervention, (ii) patients prescribed vitamin K antagonist (VKA) for AF, and (iii) patients with AF who had undergone successful PCI. RESULTS Amongst patients directed to take clopidogrel for one-year post-PCI, discontinuation was far lower (~6%) than in previous studies where the treatment duration was not known. Despite this, early discontinuation and/or bleeding was associated with an increased risk of adverse events. In a national cohort of PCI patients, we observed a low rate of achievement of international guideline target lipid levels (<25%) and low prescribing of intensive lipid lowering therapy amongst those not at target. Females and patients who had undergone elective PCI were least likely to have their lipid levels documented and be at target. In patients prescribed VKA for AF guideline defined poor anticoagulation control was common and associated with significantly higher bleeding event rates, independent of common comorbidities that are recognised as risk factors for stroke and bleeding. In patients with AF who had undergone PCI outcomes were poor: approximately 1 in 5 had either a stroke, acute coronary syndrome (ACS) or died in the year follow-up. Bleeding events were also common and associated with a five, three and four-fold increased risk of stroke, ACS, and death. CONCLUSION This thesis has characterised the nature of multiple therapeutic gaps and associated adverse outcomes with common clinical conditions. Thus, identifying opportunities to improve outcomes in individual patients and at population level.

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Signaling mediators modulated by cardioprotective interventions in healthy and diabetic myocardium with ischaemia–reperfusion injury

European Journal of Preventive Cardiology ◽

10.1177/2047487318756420 ◽

2018 ◽

Vol 25 (14) ◽

pp. 1463-1481 ◽

Cited By ~ 7

Author(s):

Feyzizadeh Saeid ◽

Javadi Aniseh ◽

Badalzadeh Reza ◽

Vafaee S Manouchehr

Keyword(s):

Heart Disease ◽

Reperfusion Injury ◽

Ischaemic Heart Disease ◽

Signaling Pathways ◽

Intracellular Signaling ◽

Heart Diseases ◽

Ischaemia Reperfusion Injury ◽

Ischaemia Reperfusion ◽

Diabetic Myocardium ◽

Patients With Diabetes

Ischaemic heart diseases are one of the major causes of death in the world. In most patients, ischaemic heart disease is coincident with other risk factors such as diabetes. Patients with diabetes are more prone to cardiac ischaemic dysfunctions including ischaemia–reperfusion injury. Ischaemic preconditioning, postconditioning and remote conditionings are reliable interventions to protect the myocardium against ischaemia–reperfusion injuries through activating various signaling pathways and intracellular mediators. Diabetes can disrupt the intracellular signaling cascades involved in these myocardial protections, and studies have revealed that cardioprotective effects of the conditioning interventions are diminished in the diabetic condition. The complex pathophysiology and poor prognosis of ischaemic heart disease among people with diabetes necessitate the investigation of the interaction of diabetes with ischaemia–reperfusion injury and cardioprotective mechanisms. Reducing the outcomes of ischaemia–reperfusion injury using targeted strategies would be particularly helpful in this population. In this study, we review the protective interventional signaling pathways and mediators which are activated by ischaemic conditioning strategies in healthy and diabetic myocardium with ischaemia–reperfusion injury.

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Abstract P372: U.S. National Estimates of Prescription Nonsteroidal Anti-inflammatory Drugs Among Patients With Cardiovascular Disease

Circulation ◽

10.1161/circ.141.suppl_1.p372 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Andrew Y Hwang ◽

Steven M Smith

Keyword(s):

Heart Disease ◽

Boxed Warning ◽

Self Report ◽

Cross Sectional ◽

Increased Risk ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Cv Disease ◽

Prescription Nsaid

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain, fever, and inflammation, but their ubiquitous use has led to concerns over increased risk of adverse cardiovascular (CV) events, particularly in patients with established CV disease (CVD). In 2005, the FDA revised labels for all NSAIDs to include a boxed warning highlighting the potential for increased CV risk. However, little is known regarding real-world prescribing of NSAIDs among patients with CVD. Our objective was to characterize the use of prescription NSAIDs among patients with CVD from 1988-2016 in the U.S. Methods: Using cross-sectional National Health and Nutrition Examination Survey (NHANES) data from 1988-1994 and 1999-2016, we included participants aged ≥18 years with hypertension (defined by self-report, mean blood pressure ≥140/90, or use of an antihypertensive medication), or aged ≥20 years with ≥1 of the following self-reported heart disease conditions: congestive heart failure (CHF), coronary heart disease (CHD), angina, myocardial infarction (MI), or stroke. Survey-weighted data were analyzed to assess prevalence and trends of prescription NSAID use within each CVD population in 6-year examination periods. Results: Overall, prescription NSAID use declined among all U.S. CVD populations over the study period. Prevalence of prescription NSAID use was highest during the 1999-2004 examination years, but thereafter, declined during the 2005-2010 examination years for those with hypertension (13.9% to 8.8%), CHF (14.6% to 8.5%), CHD (16.3% to 7.0%), angina (17.6% to 9.73%), MI (16.1% to 8.2%), and stroke (15.7% to 8.8%). Use of prescription NSAIDs since the 2005-2010 examination years has remained consistent in all CVD populations. These decreases were driven in part by reduced use of COX-2-selective NSAIDs, whereas non-selective NSAID use among all CVD populations was relatively steady from 1999 to 2016. Conclusions: Prescription NSAID use among patients with CVD appears to have declined from 1988 to 2016, primarily because of less COX-2 NSAID use following removal of 2 approved agents. Otherwise, the prevalence of prescription NSAIDs has remained somewhat stable and relatively high among these high-risk CV populations. Our results suggest additional efforts may be needed to limit the use of NSAIDs among patients with CVD, given that these agents are known to be associated with adverse CVD outcomes.

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INCREASED RISK OF ISCHAEMIC HEART DISEASE IN SHIFT WORKERS

The Lancet ◽

10.1016/s0140-6736(86)91619-3 ◽

1986 ◽

Vol 328 (8498) ◽

pp. 89-92 ◽

Cited By ~ 224

Author(s):

Anders Knutsson ◽

BjornG. Jonsson ◽

Torbjorn Akerstedt ◽

Kristina Orth-Gomer

Keyword(s):

Heart Disease ◽

Ischaemic Heart Disease ◽

Shift Workers ◽

Increased Risk

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Epidemiology, morbidity and mortality in Behçet’s disease: a cohort study using The Health Improvement Network (THIN)

Rheumatology ◽

10.1093/rheumatology/keaa010 ◽

2020 ◽

Vol 59 (10) ◽

pp. 2785-2795 ◽

Cited By ~ 1

Author(s):

Tom Thomas ◽

Joht Singh Chandan ◽

Anuradhaa Subramanian ◽

Krishna Gokhale ◽

George Gkoutos ◽

...

Keyword(s):

Pulmonary Embolism ◽

Cohort Study ◽

Heart Disease ◽

General Population ◽

Venous Thrombosis ◽

Ischaemic Heart Disease ◽

Thromboembolic Disease ◽

Age And Gender ◽

Increased Risk ◽

And Gender

Abstract Objectives The epidemiology of Behçet’s disease (BD) has not been well characterized in the UK. Evidence on the risk of cardiovascular disease, thromboembolic disease and mortality in patients with BD compared with the general population is scarce. Methods We used a large UK primary care database to investigate the epidemiology of BD. A retrospective matched cohort study was used to assess the following outcomes: risk of cardiovascular, thromboembolic disease and mortality. Controls were selected at a 1:4 ratio (age and gender matched). Cox proportional hazard models were used to derive adjusted hazard ratios (aHR). Results The prevalence of BD was 14.61 (95% CI 13.35–15.88) per 100 000 population in 2017. A total of 1281 patients with BD were compared with 5124 age- and gender-matched controls. There was significantly increased risk of ischaemic heart disease [aHR 3.09 (1.28–7.44)], venous thrombosis [aHR 4.80 (2.42–9.54)] and mortality [aHR 1.40 (1.07–1.84)] in patients with BD compared with corresponding controls. Patients with BD were at higher risk of pulmonary embolism compared with corresponding controls at baseline [adjusted odds ratio 4.64 (2.66–8.09), P < 0.0001]. The majority of patients with pulmonary embolism and a diagnosis of BD had pulmonary embolism preceding the diagnosis of BD, not after (87.5%; n = 28/32). Conclusion BD has a higher prevalence than previously thought. Physicians should be aware of the increased risk of developing ischaemic heart disease, stroke/transient ischaemic attack and deep venous thrombosis in patients with BD at an earlier age compared with the general population. Risk of embolism in patients with BD might vary across the disease course.

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