Читать книгу Interventional Cardiology - Группа авторов - Страница 146

In a well‐conducted clinical trial, particularly with double‐blind randomized trials, the possibility of bias is minimal and therefore the observed outcome difference between treatment groups is either a genuine effect or due to chance variation. Significance tests enable one to assess the strength of evidence that a real effect is present rather than a chance finding. There are three main types of outcome data analyzed in contemporary studies, with different measures and tests of association, as shown in Table 6.1.

Table 6.1 Three main types of outcome data are analyzed in contemporary studies with different measures and tests of association.

Type of data	Example	Measure of association	Test of association
Binary	In‐stent restenosis	Odds ratio	Chi‐square test
Time to event	Time to death	Hazard ratio	Log‐rank test
Quantitative	Late loss (mm)	Mean	t‐test

While the calculations differ, the underlying principle is the same for all significance tests. For example, in the Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug‐Coated Stent versus the Gazelle Bare‐Metal Stent in Patients at High Bleeding Risk (LEADERS FREE) trial [1], 2432 patients at high bleeding risk (HBR) and coronary artery disease (CAD) with a clinical indication for percutaneous coronary intervention (PCI) were randomly allocated to undergo PCI either with the BioFreedom polymer‐free biolimus A9‐coated stent (n = 1221) or a similar bare‐metal stent (BMS, n = 1211) and followed for at least one year. The primary safety outcome was the composite of cardiac death, myocardial infarction, or definite or probable stent thrombosis. At one year, the number (%) of patients with a primary outcome event in the BioFreedom and BMS groups was 112 (9.4%) and 154 (12.9%), respectively, with a log‐rank p‐value < 0.001.

The interpretation of the p‐value is predicated on the formulation of the null hypothesis, which in the case of the LEADERS FREE trial assumed that both BioFreedom stent and BMS were equally effective in patients at HBR and CAD with clinical indication for revascularization. Then the p‐value is defined as the probability p of detecting a difference of 9.4% vs 12.9% or larger under the assumption that no true difference exists (i.e. the null hypothesis is true).

The answer from the log‐rank test is a probability < 0.1% (p‐value < 0.001).

The smaller the probability p, the more convincing the evidence to contradict the null hypothesis. In the case of the LEADERS FREE trial, we have strong evidence that BioFreedom biolimus A9 coated stent reduces the risk of the primary safety endpoint compared to BMS.