ShortCuts-This Week in the Journals

November 13, 2007

roadworks_germany_a9.jpgCommentary by Judith Brenner MD, Associate Program Director, NYU Internal Medicine Residency Program

Published early online in NEJM comes the CORONA study “Rosuvastatin in Older Patients with Systolic Heart Failure”. In this trial, 5000 patients with class II, III and IV ischemic, systolic heart failure were randomized to receive placebo or rosuvastatin 10 mg. In prior statin trials, patients with reduced ejection fractions were not included, so this trial is important for that reason. The results surprisingly revealed no significant differences between the groups in any of the primary outcomes: death from cardiovascular cause, nonfatal MI or nonfatal stroke. The only difference found was a decrease in cardiovascular admissions in the rosuvastatin group. The explanation for this result is likely multifactorial, as suggested by the accompanying editorial by Massoudi. Ischemic events in this population may occur less frequently. Furthermore, because this is an older population with multiple medical problems in addition to heart failure, the medical regimen that these patients are on is quite complex. The bottom line- the results are not understood completely. It’s still prudent to treat your patients with ischemic CAD and heart failure with statins.

And moving from the world of LDL to the world of HDL, also from NEJM comes the ILLUMINATE trial, a study initially reported by the media back in December 2006.  The publication of this trial details why the much anticipated drug torcetrapib, a CETP inhibitor, was pulled from further development. Torcetrapib, a cholesterol ester transport inhibitor, was the drug that the medical community was waiting for as a drug to elevate HDL levels.  In this trial, 15,000 patients at high risk for CAD were treated with atorvastatin to an LDL goal of <100 and then randomized to placebo or torcetrapib.  The effect on HDL was dramatic, with a 72% increase over a 6 month period, along with a further reduction in LDL concentration.  The problem, however, was the increase in cardiovascular events (25%) and death from cardiovascular causes (40%) that was observed over just a 6 month period.  Most interesting was the 2 fold increase in non-cardiovascular death, mostly related to an increase in death from malignancy as well as infection.  This begs the question of whether HDL may have some role in the immune system (with the answer being most likely YES).  The drug was also associated with an increase in BP and changes in electrolytes consistent with increased mineralocorticoid excess. The questions that remain are: Why did this happen?  Is this a class effect of CETP inhibition or particular to this CETP inhibitor?  And, perhaps most important, is the HDL hypothesis one still worth pursuing?

Also from the NEJM was the TRITON-TIMI 38 (hope you know the preceding 37!) investigating the platelet inhibitor Prasugrel and comparing it to Clopidogrel in nearly 14,000 patients with ACS scheduled for PCI. Prasugrel is similar to Clopidogrel in its action, but more potent at inhibiting platelet aggregation. Patients were already on aspirin and randomized to Prasugrel or Clopidogrel for a median of 14.5 months. Follow up was outstanding with only 0.1% lost. I’ll make the findings short and sweet: there was a decrease in the primary endpoints of death from CVD, nonfatal MI and nonfatal stroke in the prasugrel group, but an increase in bleeding, including fatal bleeding. In fact, for each death from cardiovascular causes prevented by the use of Prasugrel, approximately one additional episode of fatal bleeding was caused by it. So, clearly, greater platelet inhibition comes at a price. The questions of the future: Are there subgroups who would benefit? Will we be able to identify those individuals with targeted anti-platelet therapy?

From the BMJ, “Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study” was published on November 6th.  1.2 million women aged 50-64 were followed for cancer incidence (5.4 years) and mortality (7 years).  The main outcomes waere relative risks of incidence and mortality for all cancers, and for 17 specific types of cancer, according to body mass index, adjusted for a variety of variables.  Over 45,000 cancers and 17,000 deaths from cancer occurred during the period of study.  The incidence of many types of cancers, including esophageal adenocarcinoma, renal cell carcinoma, leukemia, pancreatic carcinoma, ovarian cancer, and breast cancer in postmenopausal women was related to BMI. Mortality was largely similar. One of the most interesting statistics to be reported was the percentage of each cancers that were attributable to excess weight.  This was most dramatic for endometrial and esophageal, where it was estimated that 51% and 48 % of each of these cancers was attributable to BMI’s >25. This makes weight loss a potentially reversible risk factor for these particular cancers.

And lastly, as a stark reminder of the care of our veterans on this Veterans Day 2007, in an article published online from the American Journal of Public Health, Himmelstein et al. report that in 2004, nearly 4 million veterans and their household dependents were without health care.  While the system prioritizes recent combat vets, those with service connections or disabilities and the poorest among them, a growing number of those too poor to afford private health insurance and too well off to qualify through the VA system are left without access to care.  A small minority simply live too far from a facility.  For this uninsured population, which comprises 12% of total Americans without health insurance, the solution is unclear.

Image courtesy of Wikimedia Commons; A9 Autobahn, Germany