Nonsteroidal anti-inflammatory drugs and cardiovascular safety – translating pharmacological data into clinical readouts

Abstract

The pharmacological management of pain includes the use of nonsteroidal anti-inflammatory drugs(NSAIDs). They comprise traditional(t) NSAIDs and selective cyclooxygenase(COX)-2 inhibitors (named coxibs). The analgesic and anti-inflammatory effects of NSAIDs are dependent on the extent and duration of COX-2 inhibition in the spinal cord and inflammatory sites. However, the simultaneous inhibition of COX-2 in the vasculature translates into a prothrombotic phenotype and promotes hypertension and heart failure. Areas covered: The results of the clinical pharmacology of coxibs and the most used tNSAIDs provide a mechanistic interpretation of the cardiovascular(CV) outcomes found in randomized clinical trials(RCTs), meta-analyses of RCTs and epidemiological studies. A critical analysis of the design and results of the PRECISION trial, which compared the CV risk of celecoxib, ibuprofen, and naproxen in high-risk CV patients, was performed. Expert opinion: tNSAIDs and coxibs may increase the chance of a heart attack or stroke. The reduction of the dose of NSAIDs may mitigate, but not avoid, the risk of CV adverse effects. The development of novel biomarkers which identify susceptibility phenotypes associated with increased risk of CV complications by COX-2 inhibition is an unmet clinical need that once filled will lead to personalized treatments with NSAIDs.

The dorsal skinfold chamber: A valuable model for the in vivo evaluation of topical formulations

“…For instance, Andrioli et al found that ADP‐ and thrombin‐stimulated platelet adhesion is significantly inhibited by high doses of the drug, while low doses show a stimulatory effect. Moreover, Struthmann et al reported that diclofenac accelerates the thrombotic vessel occlusion time of arterioles, which may explain the enhanced risk of acute myocardial infarction observed in diclofenac‐treated patients . Accordingly, the COX inhibitor is meanwhile contraindicated in patients with heart diseases, such as congestive heart failure .…”

Rational Use of Nonsteroidal Anti-Inflammatory Drugs. Clinical Guidelines

“…Существовало мнение, что опасность развития кардиоваскулярных катастроф в большей степени присуща с-НПВП (коксибам). Однако сейчас стало очевидным, что эти осложнения относятся к числу «класс-специфических», они могут возникать при использовании любых НПВП, а вероятность их появления определяется индивидуальными свойствами и дозой конкретного препарата [239][240][241]. В частности, это показывает метаанализ 280 РКИ, где различные НПВП сравнивались с плацебо (n=124 513), и 474 РКИ, где НПВП сравнивались между собой (n=229 296).…”

Association of prestroke medicine use and health outcomes after ischaemic stroke in Sweden: a registry-based cohort study

“…10 Use of non-steroidal anti-inflammatory drugs (NSAIDs), particularly the selective COX-2 inhibitors, has also been associated of a higher risk of stroke. 11 Although studies have evaluated the association of these treatments with stroke incidence, the association with health outcomes after stroke is not as well established. The purpose of this study was therefore to investigate if there is a relationship between preischaemic stroke medicine use and health outcomes after stroke.…”