Jorge Francisco Gomez Cerezo

Outcome trials of COX-2 selective inhibitors: global safety evaluation does not promise benefits

BackgroundGastrointestinal toxicity is the most frequent adverse effect associated with nonsteroidal anti-inflammatory drug use. The most clinically relevant side effects of this toxicity are ulcer complications, including perforation, obstruction, or bleeding. Selective cyclooxygenase (COX-2) inhibitors (coxibs) have been proposed as a safer alternative to traditional, nonsteroidal anti-inflammatory drugs and they are currently widely used in clinical practice. The aim of this review was to analyze the available evidence and then critically evaluate the outcome trials supporting the use of coxibs in terms of their clinical gastrointestinal benefits and global safety.MethodsAll published clinical trials on selective COX-2 inhibitors were identified by searching Medline, the World Wide Web (WWW), and abstracts in Congress proceedings. From these, we selected randomized trials that clinically evaluated relevant safety outcome measures. Papers only describing endoscopic evaluation were excluded.ResultsOur search yielded three outcome trials and two pooled safety analyses. The outcome studies supporting the gastrointestinal and global safety of coxibs were found to be biased in their design, analysis, and dissemination, and interpretation of a clinical benefit. Cost considerations would make the use of coxibs acceptable only in patients at high gastrointestinal risk.ConclusionsThe association of the reduced gastroerosive potential of coxibs with improved meaningful outcomes is debatable. Bias in the design of the trials, selection of outcome measures, post-hoc changes in analysis and the variables used, as well as flaws in the publication and reporting of trial results cast serious doubts on the gastrointestinal and global safety profile of coxibs. In addition, their high cost and the lack of clear identification of patients that would benefit most from treatment means the effectiveness of these drugs is uncertain at the moment. Background. Gastrointestinal toxicity is the most frequent adverse effect associated with nonsteroidal anti-inflammatory drug use. The most clinically relevant side effects of this toxicity are ulcer complications, including perforation, obstruction, or bleeding. Selective cyclooxygenase (COX-2) inhibitors (coxibs) have been proposed as a safer alternative to traditional, nonsteroidal anti-inflammatory drugs and they are currently widely used in clinical practice. The aim of this review was to analyze the available evidence and then critically evaluate the outcome trials supporting the use of coxibs in terms of their clinical gastrointestinal benefits and global safety. Methods. All published clinical trials on selective COX-2 inhibitors were identified by searching Medline, the World Wide Web (WWW), and abstracts in Congress proceedings. From these, we selected randomized trials that clinically evaluated relevant safety outcome measures. Papers only describing endoscopic evaluation were excluded. Results. Our search yielded three outcome trials and two pooled safety analyses. The outcome studies supporting the gastrointestinal and global safety of coxibs were found to be biased in their design, analysis, and dissemination, and interpretation of a clinical benefit. Cost considerations would make the use of coxibs acceptable only in patients at high gastrointestinal risk. Conclusions. The association of the reduced gastroerosive potential of coxibs with improved meaningful outcomes is debatable. Bias in the design of the trials, selection of outcome measures, post-hoc changes in analysis and the variables used, as well as flaws in the publication and reporting of trial results cast serious doubts on the gastrointestinal and global safety profile of coxibs. In addition, their high cost and the lack of clear identification of patients that would benefit most from treatment means the effectiveness of these drugs is uncertain at the moment.

Utilización de fármacos en el registro REACH: desde las guías a la práctica clínica

: The REACH registry allows the degree of control of risk factors associated with atherothrombosis to be evaluated. Although 90% were taking at least one antihypertensive agent, hypertension was controlled in only 42.9% of the patients with vascular disease. This inadequate control may have multiple causes but the main factors are probably clinical inertia, lack of treatment adherence and the absence of combination therapies. Among patients with vascular disease, the percentage of those with good diabetes mellitus control was acceptable. The proportion of subjects with healthy cholesterol levels was suboptimal, even though 71.3% were receiving statins. The percentage of active smokers was 12% in the group of patients with vascular disease. More than 80% of the total population was taking at least one antiplatelet agent. Although the use of these agents is widespread in secondary prevention and that of lipid-lowering drugs is increasing, blood pressure and cholesterol goals are not being achieved in most patients with established vascular disease. In the REACH study, a substantial percentage of patients are not achieving adequate control of cardiovascular risk factors and are not receiving the treatments recommended in clinical practice guidelines.Resumen El registro REACH (REduction of Atherothrombosis for Continued Health) permite evaluar el grado de control de los factores de riesgo asociados a la aterotrombosis. Aunque el 90% de los pacientes con enfermedad vascular (EV) tomaba al menos un farmaco hipotensor, unicamente en el 42,9% se obtuvo el control de la hipertension arterial (HTA). El origen de este control inadecuado puede ser multifactorial pero probablemente la inercia clinica, el incumplimiento terapeutico y la ausencia de terapias combinadas sean los factores responsables. El porcentaje de control de la diabetes mellitus fue aceptable en el grupo de pacientes con EV. La proporcion de sujetos con valores adecuados de colesterol fue suboptima a pesar de que el 71,3% estaba en tratamiento con estatinas. El porcentaje de pacientes con tabaquismo activo fue del 12% en el grupo de pacientes con EV. Mas del 80% de la poblacion total tomaba al menos un antiagregante. Aunque el empleo de antiagregantes en prevencion secundaria es generalizado y se va ampliando el uso de hipolipemiantes, en la mayoria de los pacientes con EV establecida no se alcanzan los objetivos de presion arterial y colesterol. En el estudio REACH un porcentaje relevante de pacientes no consigue el control adecuado de los factores de riesgo cardiovascular y no recibe los tratamientos recomendados en las guias clinicas.