Differences in cardiovascular safety with non‐steroidal anti‐inflammatory drug therapy—A nationwide study in patients with osteoarthritis

Osteoarthritis (OA) and the non‐steroidal anti‐inflammatory drugs (NSAIDs) used to relieve OA‐associated pain have been linked independently to increased cardiovascular risk. We examined the risk of cardiovascular events associated with NSAID use in patients with OA. We employed linked nationwide administrative registers to examine NSAID use between 1996 and 2015 by Danish patients with OA aged ≥18 years. Using adjusted Cox proportional hazard analyses, we calculated the risk of the composite outcome of cardiovascular death, non‐fatal myocardial infarction and non‐fatal ischaemic stroke/TIA, and of each outcome separately, up to 5 years after OA diagnosis. Of 533 502 patients included, 64.3% received NSAIDs and 38 226 (7.2%) experienced a cardiovascular event during follow‐up. Compared with non‐use, all NSAIDs were associated with increased risk of the composite outcome: hazard ratio (HR) for rofecoxib, 1.90 (95% confidence interval, 1.74‐2.08); celecoxib, 1.47 (1.34‐1.62); diclofenac, 1.44 (1.36‐1.54); ibuprofen, 1.20 (1.15‐1.25); and naproxen, 1.20 (1.04‐1.39). Similar results were seen for each outcome separately. When celecoxib was used as reference, ibuprofen (HRs: 0.81 [CI: 0.74‐0.90]) and naproxen (HRs: 0.81 [0.68‐0.97]) exhibited a lower cardiovascular risk, even when low doses were compared. Low‐dose naproxen and ibuprofen were associated with the lowest risks of the composite outcome compared to no NSAID use: HRs: 1.12 (1.07‐1.19) and 1.16 (0.92‐1.42), respectively. In patients with OA, we found significant differences in cardiovascular risk among NSAIDs. Naproxen and ibuprofen appeared to be safer compared to celecoxib, also when we examined equivalent low doses. In terms of cardiovascular safety, naproxen and ibuprofen, at the lowest effective doses, may be the preferred first choices among patients with OA needing pain relief.     

Renal cell carcinoma metastases to gallbladder

A 74-year old man underwent a radical cholecystectomy for presumed gallbladder cancer. The histology of the resected specimen in fact revealed the lesion to be metastatic renal cell carcinoma from his resected right nephrectomy performed 14 years previously.     

Spontaneous,self-limited,non-atherosclerotic dissection of the superior mesenteric artery

A case of spontaneous, non-atherosclerotic dissection of the superior mesenteric artery is described. The patient presented with severe abdominal pain. An initial computed tomography scan did not disclose any pathology, namely the major mesenteric arteries were perfused. The patient's initial symptoms resolved during the first 48 h under conservative treatment. Sagittal reconstruction from a follow-up computed tomography scan disclosed a 7 cm long dissection of the proximal superior mesenteric artery with thrombosis of the false lumen and residual blood flow through the true lumen. There were no signs of transmural infarction of the bowel. Anticoagulation with heparin and later with phenprocoumon was initiated and the patient is well after 6 months. Together with several other cases reported recently, and in contrast to previous experience, this case adds evidence that conservative treatment of spontaneous, non-atherosclerotic dissection of the superior mesenteric artery may be an alternative to surgery if residual blood flow is maintained.     

Hyperprolactinemia exerts a negative effect on the beta-endorphin content of the rat neurointermediate pituitary lobe

Implantation of the PRL, ACTH, beta-endorphin (beta-EP), and beta-lipotropin (beta-LPH)-secreting transplantable rat pituitary tumor 7315a resulted in a suppression of the PRL and the ACTH content of the anterior pituitary gland and also of the beta-EP/beta-LPH content of the neurointermediate (NI) lobe. Treatment with bromocriptine further diminished the anterior lobe PRL content, whereas haloperidol partially inhibited this tumor-mediated diminution. The administration of these drugs did not influence the suppressed ACTH content of the anterior pituitary lobe. The diminished beta-EP/beta-LPH content of the NI lobe of tumor-bearing rats became completely normal after treatment with haloperidol, whereas bromocriptine administration further diminished the NI lobe beta-EP/beta-LPH content. There was a close correlation between the anterior pituitary lobe PRL content and the beta-EP/beta-LPH content of the NI lobe in all four groups of rats taken together (including nontumor-bearing controls, control tumor rats, and tumor rats treated with bromocriptine or haloperidol; P less than 0.01). Implantation of the pure PRL-secreting pituitary tumor 7315b resulted in hyperprolactinemia and a suppression of the PRL content of the anterior lobe and the beta-EP/beta-LPH content of the NI lobe, without affecting the ACTH content of the anterior pituitary lobe. There was a negative correlation between the level of the circulating PRL concentration and the beta-EP/beta-LPH content of the NI lobe. These results suggest a possible relationship between the synthesis of PRL by the anterior pituitary lactotroph and of the hormones of the NI lobe. The level of the circulating PRL concentration may play, directly or indirectly, a role in the regulation of both systems.     

Triple Therapy for Atrial Fibrillation and Percutaneous Coronary Intervention : A Contemporary Review

Chronic oral anticoagulant therapy is recommended (class I) in patients with mechanical heart valves and in patients with atrial fibrillation with a CHA₂DS₂-VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or transient ischemic attack or thromboembolism, Vascular disease, Age 65 to 74 years, Sex category) score ≥1. When these patients undergo percutaneous coronary intervention with stenting, treatment with aspirin and a P2Y₁₂ receptor inhibitor also becomes indicated. Before 2014, guidelines recommended the use of triple therapy (vitamin K antagonists, aspirin, and clopidogrel) for these patients. However, major bleeding is increasingly recognized as the Achilles’ heel of the triple therapy regimen. Lately, various studies have investigated this topic, including a prospective randomized trial, and the evidence for adding aspirin to the regimen of vitamin K antagonists and clopidogrel seems to be weakened. In this group of patients, the challenge is finding the optimal equilibrium to prevent thromboembolic events, such as stent thrombosis and thromboembolic stroke, without increasing bleeding risk.