With the ever-increasing public concern about drug safety, and the profusion of wave-making research into clinical endpoints, occasional very public collisions are inevitable. And so opens this week’s Shortcuts…
Two recent seemingly opposing results were published in the past few weeks concerning the effects of statin therapy on patients with low LDL. Circulation featured a study looking at the safety and clinical outcomes associated with statin therapy in patients with very low LDL levels (defined as less than 60mg/dL). This non-randomized, prospective observational study followed patients for a mean of 2 years and the primary endpoint was mortality – which was found to be significantly lower in patients prescribed statins (Hazard Ratio .65). In this one study of 4295 patients, there were no observed increases in the risks of cancer, rhabdomyolysis, or LFT abnormalities. There WAS a slight increase in the risk of cerebrovascular accidents – which disappeared after adjustment for observed risk factors (no distinction between hemorrhagic and ischemic events was detailed).
Interestingly, the week prior to this article’s publication, the Journal of the American College of Cardiology published an analysis of controlled trials of statins published through November 2005. There was an increase in LFT abnormalities with increased dose of statin, but no significant change in the incidence of rhabdomyolysis. There WAS a trend toward increasing cancer rate among patients with higher statin doses and with lower LDL levels achieved. The data in either case are far from definitive – and the data that was used to compile the JACC analysis suffers from important constraints (notably a lack of reporting cancer rates in many of the statin trials); but they make for good stories and odds are these stories are going to make their way into wide press. Accompanying editorials provide a nice perspective.
(A big by-the-way to this is a retrospective case-controlled study published in CHEST in May – suggesting that statin therapy PROTECTS individuals from lung cancer. Go figure.)
The Annals has published an early-release on-line rebuttal, of sorts, to the Nissen article concerning the safety of Rosiglitizone that contends that the meta-analytic approach that was used possibly exaggerated the effect of rosiglitazone on cardiovascular endpoints. For specific and detailed discussion of the number-crunching hijinks involved, I refer you directly to the article.
With everyone still up in arms about rosiglitazone, the FDA issued a public notice about its ongoing probe of the use of omeprazole and esomeprazole – stating that it has NOT found reason to believe that these drugs are associated with an increased risk of heart disease. Concern was originally raised because two long term studies documented an increase risk of heart disease in patients who were treated with these agents as opposed to patients who were referred for surgical correction of their GERD. It appears, however, that this risk is likely to be related to discrepant patient variables such that determine a patient’s fitness for surgery.
These early alerts and increasing FDA transparency are certain to have an effect on doctor-patient conversations. Given the extent and effect of the media coverage on this issue of drug safety, congressional legislation this past year has been a hot button issue. As Congress is now poised to vote on the final version of the Prescription Drug User Fee Act, new and highly significant drug safety legislation is being put up for consideration. For an ultra-quick editorial, see this week’s NEJM.
And on a slightly different note, the International AIDS Society was all about the CCR -5 receptor blockers and the integrase inhibitors. Both represent entirely new classes of medicines and are associated with rapid and impressive reductions in viral loads as well as increases in CD4 counts. The CCR-5 inhibitor maraviroc was approved by the FDA for patients with resistant HIV who have CCR-5 tropic virus. The introduction of these agents will prompt wider spread “tropism-testing” to discern whether patients have CCR-5 or CXCR-4 tropic virus. Interestingly, and in keeping with the above, the CCR-5 inhibitor vicriviroc has been associated with a non-specific increase in risk for malignancy. We will have to see what becomes of this…
Image of Kapan-Goris road courtesy of Wikipedia Commons