Front-page headlines worldwide announced the “stunning” results of a trial of rosuvastatin (Crestor) in “apparently healthy men and women” with an LDL-cholesterol less than 130 mg/dL (3.4 mmol/L). Serious heart problems were reportedly reduced by about 50%.

“This takes prevention to a whole new level,” said Dr. W. Douglas Weaver, President of the American College of Cardiology (Washington Post 11/10/08).

The trial, called JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) was financially supported by AstraZeneca, the manufacturer of Crestor. It is not stated whether the trial was named before or after data were accumulated. The primary author, Paul Ridker, also is listed as a coinventor on patents for the use of inflammatory biomarkers, including the use of high sensitivity C-reactive protein (HS-CRP) in the evaluation of risk for cardiovascular disease.

The 17,802 subjects in the trial had an elevated HS-CRP of 2.0 mg/L or higher (Ridker PM, et al., N Engl J Med 2008;359:2195-2207).

Until Nov 26, the New England Journal of Medicine is inviting comments on whether this article will change your practice.

As the accompanying editorial noted, the absolute risk reduction was low. The number (percent) of “hard” outcomes (myocardial infarction, stroke, or death from cardiovascular causes) was reduced from 157 (1.8%) in the placebo to 83 (0.9%) in the rosuvastatin group. The number needed to treat was 120. The cost of the drug is $3.45 per day (or nearly $300,000 to prevent one adverse event).

Note that the trial evaluated statins, not HS-CRP testing. It did not compare subjects with and without high HS-CRP, nor compare the usefulness of HS-CRP with other risk factors (ibid.).

On the adverse side of the balance, subjects in the rosuvastatin group had significantly higher glycosylated hemoglobin levels and incidence of diabetes mellitus (3.0% vs. 2.4%) (ibid.) The trial was discontinued three years early, after only 1.9 years, thus cutting off the discovery of potential long-term adverse effects.

While not yet statistically significant, the rosuvastatin group had more muscle weakness and pain and more elevations in laboratory values indicating possible kidney or liver damage. One case of nonfatal rhabdomyolysis was reported in a rosuvastatin recipient after the trial was suspended. During a 4-week run-in period, anyone exhibiting compliance problems or adverse reactions could be screened out; 1,521 subjects were excluded during this period, in addition to the nearly 57,000 eliminated at the outset. Compliance rates during the trial were unusually low, with nearly 15% of the participants stopping their pills during each year, noted Sandy Szwarc, B.S.N., R.N.

What the JUPITER study really shows, remarks Duane Graveline, M.D., M.P.H., is that statins work by reducing inflammation, not by reducing cholesterol. This effect requires much lower doses, which have fewer side effects.

While rates of hospitalization for coronary heart disease have shown decreases since the mid-1980s, the rate for congestive heart failure has increased continually since 1980. From 2002-2006, the relative risk of hospitalization for heart failure was 1.37 times the rate in 1980-1984, according to research presented at the American Heart Association’s 2008 scientific session (Medical News Today 11/12/08).

Additional information:

• “The Failure of Vytorin and Statins to Improve Cardiovascular Health: Bad Cholesterol or Bad Theory?” by Brian Peskin, et al. J Am Phys Surg, Fall 2008.
• “Misleading Recent Papers on Statin Drugs in Peer-Reviewed Journals,” by Joel Kauffman, Ph.D., J Am Phys Surg, Spring 2007.
• “LDL Cholesterol: ‘Bad’ Cholesterol or Bad Science?” Anthony Colpo, J Am Phys Surg, Fall 2005.

A series of articles in the Dallas Morning News focuses on alleged financial conflicts of interest of psychiatrists involved in the Children’s Medication Algorithm Project (CMAP). The CMAP protocol has been “quietly shelved” after objections were raised by Texas Attorney General Greg Abbott.

The state of Texas is suing a pharmaceutical company that allegedly used false advertising and improper influence to get its products on the now-mandatory adult protocol, the Texas Medication Algorithm Project (TMAP).

The newer drugs chosen for the protocol are ten times as expensive than traditional drugs, but have no substantial advantage, according to a report by the National Institute of Mental Health.

Sen. Charles Grassley (R-IA) stated that three Harvard experts whose research contributed to an explosion of antipsychotic drug use in children failed to report a combined $3.2 million in company consulting fees, in violation of Harvard’s rules.

Dr. Graham Emslie of University of Texas Southwestern, on the other hand, said he had never witnessed improper drug company influence in CMAP research.

Without the protocol, CMAP advocates warn that Texas children will be treated by individual doctors who have “their own personal influences” (Emily Ramshaw, Dallas Morning News 8/18/08).

Controversy about promotion of psychotropics in children is breaking out in other states also. New Jersey state assemblyman Michael Coherty wrote to the state department of health on Aug 20, asking about the policy that permited the NJ Medicaid program to spend $73 million between 2000 and 2007 on antipsychotic drugs for children under the age of 18 although the drugs are not FDA approved for pediatric use. Lawsuits are pending in several states (Pharmalot.com 9/3/08).

Issues include improper marketing and failure to disclose serious side effects, which prompted state programs to overpay for olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal).

While slightly fewer people stopped taking atypical antipsychotics Zyprexa and Seroquel because of tremors, compared with older drugs, the new drugs allegedly gave some of them diabetes. (St. Petersburg Times 4/12/08).

Particularly in children, it is not just the drugs prescribed, but the diagnoses that are in question. Six million children have been diagnosed with serious psychiatric disorders warranting drug treatment—1 million with bipolar disorder, long believed to occur only in adults (PBS Frontline, The Medicated Child).

Many children are being identified as potential recipients of psychotropic drugs through government-supported, school-based mental health “screening.” Is this uncovering a vast, previously unrecognized epidemic, as Richard Friedman, M.D., of the Psychopharmacology Clinic at Weill Cornell Medical School, holds (N Engl J Med 2006;355:2717-2719)?

The predictive value of a positive test in the Columbia University TeenScreen program is 16%, although it “demonstrated good sensitivity and reasonable specificity identifying students at risk for suicide,” according to its author (Schaffer D et al., J Am Acad Child Adolesc Psychiatry 2004;43:71-79).

A federal court has given the green light to a civil rights lawsuit filed on behalf of Chelsea Rhoades, who was subjected to TeenScreen without parental consent, and, like a majority of her classmates, was told she suffered from mental health problems.

A BBC All in the Mind radio commentary, which covers the Rhoades case and issues related to screening, is available online.

One ethical concern raised in Texas is the use of psychotropic drugs in children who are in foster care.

Additional information:

• “Psychiatry on the Couch: the Federal Government’s Plan to Transform Mental Health Care in America,” Legislative Alert by Michael Ostrolenk, AAPS News, December 2006.
• “The Dangers of Mental Health Screening,” by Nathaniel S. Lehrman, M.D., J Am Phys Surg, fall 2006.
• “Mandatory Mental Health Screening for Children,” AAPS Action Alert 9/7/04.