We should pay Richard Lehman tuition for the distance-learning he provides

For me, a week isn’t complete without tidbits from Dr. Richard Lehman’s journal review blog for The BMJ.

This week he analyzes widely-reported results of studies on breast cancer and heart disease:

When I see a cancer trial in one of the top journals, I generally scan the abstract to see if there is anything of general interest or importance. I drew a complete blank with this one. “Among women with predominantly stage I HER2-positive breast cancer, treatment with adjuvant paclitaxel plus trastuzumab was associated with a risk of early recurrence of about 2%; 6% of patients withdrew from the study because of protocol-specified adverse events.” Um, compared with what? Well, with what might have happened otherwise, elsewhere, possibly. “We recognize that a prospective, randomized trial would have been the best option. However, we did not believe that such a design would have been feasible given the accumulating evidence from retrospective studies. Patients and their providers may have been unlikely to enroll in a trial that included a group in which patients would not receive trastuzumab. Some clinicians and investigators might have argued for a trial of trastuzumab alone versus trastuzumab plus chemotherapy, but there are limited data indicating that trastuzumab alone is an effective approach.” Aha, but isn’t that exactly why people do RCTs? Why does this trial—which is just a large case series—get space in the New England Journal? Any time your well conducted, randomized, double blind trial gets rejected by the NEJM, you might like to ask them.

And about a paper in The Lancet….

The Cholesterol Treatment Trialists’ Collaboration offer a paper on “Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174?000 participants in 27 randomised trials.” But although there is now some weak evidence LDL-C lowering with ezetimibe may improve cardiovascular outcomes, all the evidence in this review is about statins. These drugs certainly lower LDL-C and “These results indicate that, for each 1 mmol/L reduction in LDL cholesterol, statin therapy reduced major vascular events by about a fifth, major coronary events by a quarter, coronary revascularisations by a quarter, and ischaemic stroke by just under a fifth, and that these proportional reductions were similar in men and women, even though on average women had somewhat lower absolute cardiovascular risk in these trials.” But it’s not just pedantic obstinacy that makes me chary about putting all this down to LDL-C lowering. I’m worried that people will therefore carry on treating cholesterol as some kind of target independent from total cardiovascular risk, whereas we need always to obey the commandment “Treat to level of risk and not to level of risk factor.” And scientifically I still can’t understand how statins can produce marked improvements in acute events before they have had time to reduce LDL-C.

(Note:  The original post at first ended with “HDL-C.”  It has since been corrected to LDL-C, so I have changed the excerpt above accordingly.)

We should be paying Lehman tuition for the distance learning he provides each week.


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