STICH Trial: Um Estudo Negativo (por Anis Rassi Jr)

O STICH trial foi comentado neste Blog como um estudo negativo, ou seja, indica que cirurgia de revascularização não traz benefício além do tratamento clínico em pacientes com miocardiopatia isquêmica.

Percebe-se ao longo do estudo uma tendência a não aceitar plenamente sua negatividade. Isso fica demonstrado na dúbia conclusão do autor:

In this randomized trial, there was no significant difference between medical therapy alone and medical therapy plus CABG with respect to the primary end point of death from any cause. Patients assigned to CABG, as compared with those assigned to medical therapy alone, had lower rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes.

As colocações informais do autor vão ainda mais longe na valorização de análises secundários, em detrimento da análise primária, colocando o estudo como pró-cirúrgico: 

No trial is “negative” if patients and physicians win by having access to truly new data to inform complex decision making. The totality of the information — i.e., the adjusted analyses of the as-randomized (intention-to-treat population) for the all-cause mortality endpoint, the unadjusted and adjusted analyses of the important secondary endpoints, and the treatment-received and per-protocol analyses of all the endpoints — clearly supports the clinical efficacy of CABG plus medical therapy over that of medical therapy alone. My fellow investigators and I hypothesized that CABG plus medical therapy would reduce unadjusted all-cause mortality by 25%; instead, the hazard ratio in the CABG group was 0.86 (relative risk reduction, 14%; P=0.12). So from a purely statistical perspective, our finding did not prove our hypothesis; what we may infer clinically from the data is a different thing.

Em resposta, Anis Rassi Jr enviou a correspondência abaixo ao New England Journal of Medicine, nos cedida pelo autor para postagem neste Blog. Um bom exemplo de interpretação correta de evidências científicas:

Findings of the STICH Trial do not support preferential indication of CABG above medical therapy alone for patients with left ventricular dysfunction. All-cause mortality (primary outcome) did not differ between treatment groups. The decrease in cardiovascular mortality (secondary outcome) was marginal (p=0.05), unadjusted for multiple outcome comparisons, and clinically irrelevant since overall mortality was unaffected. Death from any cause or hospitalization for cardiovascular causes (another major secondary outcome), although lower in the CABG group, was not prespecified and was newly introduced in the published report.

Also, whether subsequent CABG was counted as a hospitalization event is not clear, but doing so could have biased the results against the medically-treated group. Finally, there is no justifiable reason for secondary as-treated and per-protocol analyses, particularly when treatment crossovers of up to 20% were anticipated and included in the sample size and power calculations (2). With recent evidence that in different subgroups of patients with chronic CAD, surgical or percutaneous coronary revascularization is not superior to optimal medical therapy (1,3,4) a randomized trial of left main disease is now justified.