TABLE 2.
Effects of currently used medication for chronic inflammatory diseases on cardiac manifestations
| Inflammatory disease | Drug | Effect on CV outcome | |
|---|---|---|---|
| Clinical studies | Experimental studies and underlying mechanisms | ||
| Rheumatoid arthritis (RA) | Anti‐IL‐1 (Anakinra) |
Improvement of vascular and left ventricular function in RA patients (Ikonomidis et al., 2008) Improvement of myocardial deformation in RA patients (Ikonomidis et al., 2009) Improvement of vascular function, myocardial deformation, and twisting in CAD patients with RA (Ikonomidis et al., 2014) |
|
| Anti‐IL‐6 (Tocilizumab) |
Improvement of vascular function in RA patients (Ikonomidis, Pavlidis, et al., 2019) Decreased risk of major adverse CV events (non‐fatal MI, need for coronary revascularization, cardiovascular death with or without angina, CHF, peripheral artery disease, or abdominal aortic aneurysm) in RA patients (Singh et al., 2019) |
||
| Anti‐TNF‐α |
Reduced risk of CV events including MI in RA patients (Barnabe, Martin, & Ghali, 2011) Reduced risk of major CV events (defined as angina, MI, coronary artery bypass graft, PCI, other heart disease, stroke/transient ischaemic attack, or death from cardiovascular causes) in patients with inflammatory arthritis including RA (Lee et al., 2018) |
||
| Auranofin | Reduction of infarct size and improved cardiac function after I/R likely via PTP‐PEST‐ErbB‐2 signalling axis in an in vivo model of AMI in mice (Yang et al., 2019) | ||
| Methotrexate | Reduction of CV events in RA patients (Micha et al., 2011; Roubile et al., 2015) | ||
| Systemic Lupus Erythematosus (SLE) | Antimalarials (chloroquine and hydroxychloroquine) | Antimalarial‐induced cardiomyopathy in SLE patients (Tselios et al., 2016; Tselios et al., 2019) |
Conferred atheroprotection through a p53‐dependent mechanism in atherosclerosis‐prone ApoE‐null mice (Razani, Feng, & Semenkovich, 2010) Improved NO‐mediated vasorelaxation of mesenteric arteries in a murine model of SLE (Virdis et al., 2015) Reduced heart rate and LV pressure in Langendorff perfused rat hearts and exerted cardiotoxic effects in isolated cardiomyocytes (Blignaut, Espach, van Vuuren, Dhanabalan, & Huisamen, 2019) Reduce pressure overload‐induced cardiac hypertrophy but impaired cardiac relaxation and contractility in rats (Chaanine et al., 2015) |
| Glucocorticoids | Deleterious effects in heart and vessels in patients with SLE (Wu et al., 2016) | ||
| Immunosuppressants (mycophenolate mofetil) | Attenuation of atherosclerosis in lupus‐prone mice (van Leuven et al., 2012) | ||
| Methotrexate | Reduction of cardiac vasculopathy via activation of AMPK‐CREB in murine model of inflammatory vasculopathy (Thornton et al., 2016) | ||
| Systemic sclerosis (SS; lacks a specific therapy) | Nintedanib (inhibitor of GF‐RTKs) | Antifibrotic effects and amelioration of histological features of pulmonary arterial hypertension, microangiopathy and pulmonary fibrosis in Fra2 mouse model of SS (Huang et al., 2017) | |
| Psoriasis | Anti‐IL‐12/23 (ustekinumab) |
Improvement of coronary microcirculatoy function, arterial stiffness, and myocardial function in psoriasis patients—greater improvement than Anti‐TNF‐α or cyclosporine treatment (Ikonomidis et al., 2017) Reduction of aortic vascular inflammation with reduction in inflammatory cytokines associated with CV disease in psoriasis patients (Gelfand et al., 2019) |
|
| Anti‐IL‐17A (secukinumab) |
Improvement of vascular and myocardial function in psoriasis patients—greater improvement than methotrexate or cyclosporine treatment (Makavos et al., 2019) Improvement of arterial flow‐mediated dilation in psoriasis patients suggesting beneficial effects on CV risk by improving endothelial function (von Stebut et al., 2019) |
||
| Anti‐TNF‐α (etanercept), | Improvement of cardiac function in psoriasis patients (Ikonomidis et al., 2017) | ||
| Anti‐TNF‐α | Reduced risk of major CV events (angina, MI, coronary artery bypass graft, PCI, other heart disease, stroke/transient ischaemic attack, or death from cardiovascular causes) in patients with inflammatory arthritis including psoriasis (Lee et al., 2018) | ||
| Cyclosporine | Improvement of cardiac function in psoriasis patients (Ikonomidis et al., 2017) | ||
| Diverse biological therapies (anti‐TNF‐α, anti‐IL‐12/23, or anti‐IL‐17) |
Reduction of coronary inflammation (indicated by reduction of perivascular fat attenuation index) in psoriasis patients (Elnabawi, Oikonomou, et al., 2019) Reduction of non‐calcified plaque burden in psoriasis patients suggesting beneficial modulation of coronary plaque composition (Elnabawi, Dey, et al., 2019) |
||
| Methotrexate | Improvement of vascular and myocardial function in psoriasis patients (Makavos et al., 2019) | ||
| NF‐κB inhibitor (dimethyl fumarate) | Reduction of myocardial infarct size after I/R in rats in vivo likely through inhibition of NF‐κB in cardiac endothelial cells (Meili‐Butz et al., 2008) | ||
| Inflammatory bowel disease (IBD) | 5‐Aminosalicylic acids | Decreased risk of IHD in IBD patients (Rungoe et al., 2013) | |
| 6‐Mercaptopurine | Induction of calcium deposition in in vitro cultured vascular smooth muscle cells and in ex vivo media layer of rat aorta rings which might accelerate the evolution of arteriosclerosis and CVD (Prüfer et al., 2014) | ||
| Anti‐TNF‐α | Non‐significant decrease of IHD in IBD patients (Rungoe et al., 2013) | ||
| Azathioprine + aminosalicylates | Lower risk of CVD (calculated by Framingham Risk Score, a gender‐specific algorithm for estimating the 10‐year CV risk) in comparison to aminosalicilates only, and increased anti‐inflammatory cytokines in women with ulcerative colitis (UC; dos Santos et al., 2015) | ||
Abbreviations: AMI, acute myocardial infarction; AMPK, AMP‐activated protein kinase; ApoE, apolipoprotein E; CREB, cAMP response element‐binding protein; CHF, congestive heart failure; CV, cardiovascular; Fra2, fos‐related antigen‐2; GF, growth factor; IHD, ischaemic heart disease; PTP‐PEST, tyrosine‐protein phosphatase non‐receptor type 12; RTK, receptor tyrosine‐kinases.