July 21st, 2014
Selections from Richard Lehman’s Literature Review: July 21st
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint this selection from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
NEJM 17 July 2014 Vol 371
Effects of Extended-Release Niacin with Laropiprant in High-Risk Patients (pg. 203): Niacin is an abundant natural B vitamin, which lowers bad cholesterol and raises good cholesterol. What’s not to like? Well, niacin, unfortunately. In doses that make any difference to lipid levels, it is very likely to make you feel sick, get flushes and/or rashes, and/or feel muscle pains. So Merck decided to market it in combination with laropripant, a prostaglandin antagonist that is meant to combat its unpleasant effects. Even so, a third of people who were recruited to the present trial could not continue past the run-in phase with the active combination. And now that the full results are out, we have confirmation that this dual agent definitely does not offer any cardioprotection despite its “favourable” effect on lipids. Worse still it causes bleeding, raises blood sugar, and shows a tendency to increase mortality in those who can tolerate taking it for three years. The Clinical Trials Support Unit (CTSU) at Oxford did a great job of running this trial with funding from Merck, following its usual rules of independence. In doing so, it provides a great illustration of the fact that lipid fractions are very unreliable surrogates for cardiovascular outcomes. But we knew that already, and it seems a great pity to me that many superb researchers were tied down for so long on a project that has made such a small contribution to clinical knowledge, whatever it may have contributed to the funds of CTSU.
Lancet 19 July 2014 Vol 384
Dual-Antiplatelet Treatment Beyond 1 Year After DES Implantation (ARCTIC-Interruption) (OL): The arrival of drug-eluting stents signalled a bonanza not just for device manufacturers, but for makers of anti-platelet drugs and platelet testing kits too. The small superiority of the new stents over the old bare metal ones depended on using clopidogrel or a similar agent in addition to aspirin for an initial period, now fixed by tradition at 12 months. An extension of the French ARCTIC-Monitoring trial sought to find out whether there might be additional benefit from continuing dual anti-platelet treatment for longer than a year. The answer is no: in fact this just increases the potential for harm from bleeding events.
What if a study treated patients with ROSUVASTATIN 40 mg and the goal/PERFECT/disease-reversing non-HDL cholesterol reached was 90 (HDL 44 & LDL 63 as in HPS2-THRIVE). And then it was decided to add 80 mg of ATORVISTATIN to look for improved atherosclerotic end points. Since disease stabilizing/reversing values had already been obtained before adding the second lipid lowering medication, no doubt only further toxicity would be apparent, as was the case in HPS2-THRIVE. It is disappointing to see such a large study created by such important lipid specialists. Frankly, I consider HPS2-THRIVE unethical and the authors should be appropriately criticized for this pointless undertaking. I felt the same about AIM-HIGH. HRS, MD, FACC