Health Briefs

March 29, 2004

ANTI-INFLAMMATORY DRUGS MAY HELP FAILING HEARTS

A great deal of research is underway using the class of drugs known as COX-2 (cyclooxygenase-2) inhibitors.  These drugs belong to a larger group of anti-inflammatory drugs known as COX inhibitors, which includes aspirin, ibuprofen, naproxen, and piroxicam, among others.  The COX-2 inhibitors block the pro-inflammatory effects of one form of the COX enzyme (COX-2), and are thought to have fewer side-effects than nonspecific COX inhibitors.  Celebrex and Vioxx are the two most frequently prescribed COX-2 inhibitors in the US.

Previous research has shown that the COX-2 enzyme plays an important role in the development of several cancers, as well as in cardiovascular disease; and so it is not surprising that COX-2 inhibitors are being evaluated in clinical trials as potential preventive agents for these diseases.  A new study in the current volume of the journal Circulation looked at the effects of COX-2 inhibitors in mice with heart failure.  The mice were treated with doxorubicin (a common chemotherapy drug with known cardiac toxicity side effects) for 6 weeks, and the presence of significant congestive heart failure (CHF) was subsequently confirmed in all of the animals using ultrasound.  After 6 weeks of doxorubicin treatment, left ventricular function was assessed in 100 mice (the left ventricle pumps blood throughout the body, and becomes weakened and less effective after the onset of CHF).  Half of the mice were then placed on a diet that included a COX-2 inhibitor, and the remaining 50 mice were fed standard mice chow without a COX-2 inhibitor.  Repeat cardiac ultrasound examinations were performed on the mice every 2 weeks.  At 70 days into the study, the left ventricular pumping efficiency (left ventricular ejection fraction) in the mice fed only standard mice chow had declined by 29%, while the mice fed chow containing a COX-2 inhibitor experienced only a 9% decline in ventricular function.  Moreover, while 38% of the mice consuming standard mice chow died during the course of this study, only 18% of the mice treated with a COX-2 inhibitor died. 

This is a fascinating study with potentially significant implications.  An estimated 4 to 5 million Americans live with failing hearts, and the incidence of CHF appears to be rising in proportion to our increasing lifespans.  Indeed, the two greatest risk factors for CHF are preexisting coronary artery disease and advanced age.  More than 90% of patients with CHF have a history of coronary artery disease or/and chronic high blood pressure.  Diabetes is also associated with a higher incidence of CHF, as well as elevated rates of coronary artery disease and high blood pressure. 

In view of the enormous impact of CHF on the health of our aging population, the findings of this study may prove to be very important indeed.  The results of this study suggest that the development of CHF after an acute injury to the heart may be markedly attenuated by COX-2 inhibitors.  As a corollary to this finding, the ability of a COX-2 inhibitor to markedly reduce the incidence of CHF 6 weeks after the initiation of cardiotoxic treatment with doxorubicin suggests that there is a substantial interval between the initial cardiac injury and the onset of clinically significant CHF.  I also find the reduction in CHF risk following doxorubicin therapy to be interesting as a cancer physician, as this drug is commonly used to treat cancers of the breast, as well as other types of cancers.  While the judicious dosing of doxorubicin rarely results in significant cardiac injury in patients with healthy hearts, the use of this chemotherapeutic agent is generally contraindicated in cancer patients with preexisting heart disease.  Thus, this study suggests that the concomitant use of a COX-2 inhibitor with doxorubicin and related chemotherapy drugs might enable patients with preexisting heart disease to receive standard chemotherapy regimens.  Of course, this study was performed in mice, and its findings will have to be confirmed in humans before the routine use of COX-2 inhibitors for CHF prevention can be recommended.  Still, this is a very exciting study, and the implications of its findings may be very profound, indeed.

IRAQI PHYSICIAN COMPLICITY IN HUMAN RIGHTS ABUSES

On a somewhat darker note, a report in the current Volume of the Journal of the American Medical Association (JAMA) assesses the extent of physician involvement in human rights abuses in Iraq during the regime of Saddam Hussein.  In June and July of 2003, the study’s authors surveyed 98 Iraqi physicians at 3 major hospitals in southern Iraq.  These Iraqi doctors independently completed research surveys, while another group of hospital directors and physicians underwent more structured interviews.  It should be noted that 88% of the participating physicians were male, and 97% were Shi’a Muslims (approximately 60% of the Iraqi populace are thought to be Shi’a Muslims, and this segment of the population was brutally repressed by the Saddam Hussein regime). 

Sadly, 71% of the physician respondents reported physician involvement in torture was a very common occurrence in Saddam Hussein’s Iraq.  According to the physicians’ surveys, 50% of their physician peers directly participated in physician-assisted or physician-conducted “nontherapeutic” amputations of ears, 49% falsified medical records to conceal acts of torture, and 32% falsified the death certificates of people who died following torture.  Not surprisingly, only a handful of the study’s volunteers reported participation in such activities….  At the same time, 52% of the surveyed doctors indicated that physicians taking part in torture-related activities did so involuntarily, and 93% of the respondents stated that the Iraqi paramilitary force Fedayeen Saddam was primarily responsible for compelling physician participation in such activities.  Complicit physicians explained their coerced participation in torture-related activities in terms of fear for their families’ safety, as well as fear of harm to themselves.  Physicians who refused to participate in human rights abuses reported the subsequent loss of their jobs, imprisonment, or torture, while other noncompliant physicians simply “disappeared.”   When asked what could be done to reduce the potential for future physician involvement in human rights abuses, 99% of the respondents recommended increased human rights and ethics training for Iraqi physicians, 97% recommended a tightening of laws regulating physician behavior, 96% advised that punitive sanctions against physicians participating in such abuses should be enhanced, and 95% of the respondents suggested that a mechanism be devised to ensure independence of physician from state authorities.

While the veracity of these disturbing allegations cannot be independently verified, they nonetheless suggest at least some significant level of physician involvement in state-sanctioned torture and other human rights abuses in Saddam Hussein’s Iraq.  Previous instances of physician complicity in human rights abuses are hardly unknown, including large-scale human experimentation and mass-murder by Nazi and Japanese physicians during World War II, and the more recent tortures and genocidal actions committed by Taliban physicians in Afghanistan, and by the Bosnian-Serbian psychiatrist Radovan Karadzic, all of whom remain at large still.  Of course, physician-murderers are not always involved in state-sanctioned thuggery.  In 2000, British physician Harold Shipman was sentenced to 15 concurrent life sentences after being convicted of murdering an estimated 260 patients over a period of at least 20 years, making him the most prolific mass-murderer in British history.  (He later committed suicide in his cell in January of this year.)

Primum non nocerum, or, first do no harm, is a fundamental precept for the vast majority of physicians throughout the world.  However, in the setting of totalitarian states bent on terrorizing its citizens, history has shown that some physicians will violate this precept, either willingly or unwillingly, and sometimes in egregious ways.  As a physician, I cannot think of a more tragic and reprehensible abuse of medical knowledge and training than to use them to intentionally inflict harm on another human being.

BRIEFLY…

Lancet:  A prospective study (1993 to 2000) of 2,298 men presenting to sexually transmitted disease (STD) clinics in India with non-HIV venereal diseases evaluated the impact of circumcision on the risk of developing HIV/AIDS.  All of these men were tested for HIV/AIDS, as well as other non-HIV STDs, on a quarterly basis, and all were free of HIV/AIDS infection when they entered the study.  The men in both groups were closely matched in terms of sexual behaviors and related risk factors, irrespective of their circumcision or religious history.  Over the duration of the study, the 191 circumcised men were 85% less likely to develop positive blood tests for HIV when compared to the 2,107 uncircumcised men.  However, circumcision appeared to offer no protection against syphilis, gonorrhea, or genital herpes.

British Medical Journal:  A year-long randomized prospective study of 401 chronic and/or migraine headache sufferers in the UK was undertaken to assess the efficacy of acupuncture as an alternative to standard medical therapy.  The patients who received acupuncture reported fewer and less-severe headaches than did the patients who received standard medical therapy.  Moreover, the acupuncture-treated patients experienced 22 fewer days of headaches per year and used 15% less headache medications.  Although not statistically significant, there was also a trend towards fewer visits to primary care doctors and fewer days of sick-leave taken by the group receiving acupuncture.