Post Hoc Q: Did IMPROVE-IT Only Show Meaningful CV Benefits — For Diabetics?

As ever, CardioBrief — with Larry Husten on the keyboard — does an excellent job of pointing out just how “fuzzy” the ultimate learnings may be — from even large studies (with 18,000 patients) — upon careful, closer (post hoc) data analysis.

In a sub-set post-hoc study, it would seem that the vast bulk of the CV outcomes benefit appeared in about only one quarter of the study’s population: those who already had diabetes. Of course, correlation is not causation, and perhaps the diabetics were sicker, as a group, but it is. . . intriguing, nonetheless. Can we (as a finite resource/constrained payer-based system) justify these premium prices, for any non-diabetic cholesterol management patient in the US, where the outcome benefit seen in a very large group, over several years, was almost. . . non-existent? This is a very fair question — and do go read it all, for some other competing theories to explain the subset data — but here’s a bit:

. . . .The beneficial effects of ezetimibe are found almost exclusively in patients with diabetes. . . .

The main IMPROVE-IT trial randomized 18,144 patients with acute coronary syndrome to the combination of ezetimibe and simvastatin or simvastatin alone. The primary endpoint of the trial– CV death, MI, documented unstable angina requiring rehospitalization, coronary revascularization after one month of treatment, or stroke– was significantly reduced in the ezetimibe group (32.7% vs. 34.7%, p = 0.016).

The ESC presentation focused on the 27% of patients in the trial (n= 4,933) who had diabetes. “We did see a quantitative, statistically significant interaction between diabetics and non diabetics,” said Giugliano. . . .

Giugliano concluded that diabetic patients were at higher risk than non-diabetic patients and that they had a greater relative and absolute benefit from the addition of ezetimibe. The greater benefit in diabetics was driven by reductions of MI and ischemic stroke. . . .

Almost a year ago, we had asked whether one fewer CV event, in 50 patients, over seven years, was worth almost an additional $750,000 in spending. [That’s what the legacy Schering-Plough combo-pill Vytorin® costs, compared to a generic statin.] I think the answer now will be. . . no, unless the patient is ALSO diabetic. Harlan Krumholz (the world renown expert, at Yale University) has all but said as much, previously. And so. . . onward. . . with a lovely end to a short week approaching. . . .


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