Benefits and Risks of Nonsteroidal Anti-inflammatory Drugs: Methodologic Limitations Lead to Clinical Uncertainties

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) include traditional (tNSAIDs), such as ibuprofen, naproxen, and diclofenac, as well as selective cyclooxygenase-2 inhibitors (COXIBs), principally celecoxib. COXIBs were developed to decrease gastrointestinal side effects. Recently, the US Food and Drug Administration strengthened its warning about the risks of non-aspirin NSAIDs on myocardial infarction and stroke. The Cyclooxygenase 2 and Non-Steroidal Anti-Inflammatory Drug Trialist collaboration conducted a comprehensive worldwide meta-analysis using individual patient data exploring the risks of various COXIBs and NSAIDs on cardiovascular disease (CVD). Recently, the results of the Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) trial were published that tested risks of COXIBs and NSAIDs on CVD. Generally, data from meta-analyses of trials not designed a priori to test hypotheses are less reliable than large-scale randomized trials to test small to moderate benefits or harm. When the sample size is large, randomization provides control of confounding not possible to achieve in any observational study. Further, observational studies, and especially claims data, have inherent confounding by indication larger than the effects being sought. Nonetheless, trials must be of sufficient size and duration and achieve high compliance and follow-up to avoid bias and confounding. In this regard, PRECISION has high rates of nonadherence and losses to follow-up that may have introduced bias and confounding. At present, therefore, it may be most prudent for clinicians to remain uncertain about benefits and risks of these drugs and make individual clinical judgments for each of their patients.

Gastroprotective effect of the root extract of Alpinia officinarum Hance (Zingiberoside) against acute indomethacin-induced gastric injuries in rats: Involvement of H+/K+-ATPase and prostaglandin E receptors

“…The worldwide use of nonsteroidal antiinflammatory drugs (NSAIDs) has increased the incidence of gastric injury [1,2]. It is generally known that reinforcing gastric mucosal barrier and inhibiting excessive gastric acid secretion are crucial strategies in ameliorating gastric ulcer induced by NSAIDs [3].…”

Risks of Cardiovascular Disease and Beyond in Prescription of Nonsteroidal Anti-Inflammatory Drugs

“…Recently, the US Food and Drug Administration strengthened its warning about the risks of nonaspirin NSAIDs on myocardial infarction (MI) and stroke. 2,3 Clinicians prescribing NSAIDs should be aware of the complexities of the decision-making. Specifically, clinical decision-making should include but not limited to protective and deleterious effects on cardiovascular disease (CVD).…”

“…Traditional NSAIDs reversibly and nonspecifically inhibit both isoforms of the enzyme cyclooxygenase (COX-1 and COX-2), thereby blocking prostaglandin release which in turn mitigates downstream inflammation and pain, which in turn suggests a plausible explanation for their observed increased risks of CVD. 2,3 Cyclooxygenase 2 inhibitors were developed primarily because of their favorable GI side effect profile relative to traditional NSAIDs. The Cyclooxygenase 2 and Non-Steroidal Anti-Inflammatory Drug Trialists (CNT) collaboration conducted a comprehensive meta-analysis exploring the risks of COXIBs and NSAIDs on CVD.…”

Антиексудативні властивості рідкого спиртово-водного екстракту листя аїру звичайного (Acorus calamus L.)

“…Лікарськими засобами першої лінії для фармакологічної корекції запальних процесів є нестероїдні протизапальні засоби (НПЗЗ), але коротко та/ або довгострокові системні побічні ефекти цієї групи препаратів [2,3] обмежують їхнє застосування в ряді випадків [4].…”