Wednesday, July 8, 2009

Conflicts galore: Statin study authors on the take from statin makers

Just yesterday, Senators Charles Grassley and Herbert Kohl announced that language requiring the public disclosure of payments to doctors from drug and medical device companies has been included in the draft bills for health care reform now being debated in the House and Senate. In case you haven't been convinced by the parade of doctors on the take (who in some cases were found to have skewed scientific data as a result of their conflicts of interest), here's one more reason why public disclosure of such conflicts is so important.

On June 30, the British Medical Journal published a meta-analysis purporting to show that cholesterol-lowering statins reduce the risk of heart attacks and improve survival rates in people without established heart disease. Up till now, evidence that statins like Lipitor, Crestor, Zocor and Pravachol prevent heart attacks in people without known heart risks remains ambiguous at best. And there is little evidence that statins reduce the risk of heart attacks in women, since most of the clinical trials have been in men. Now comes a meta-analysis that examines 10 previous clinical trials and concludes that lo and behold, statins do improve survival rates for men and women and other groups not previously shown to be helped by these drugs.

But before you break out the champagne, please consider these caveats. First off, as Gary Schwitzer pointed out in his health news blog, not everyone is convinced this meta-analysis shows what its authors claim it does. As one online commentator noted, if you look carefully at the data in the study, there is no evidence that the benefits of statins are significant for all 4 end points listed in women, people over the age of 65 and patients with diabetes. And as other commentators noted, the study also doesn't pay much attention to the serious side effects of statins or the fact that there are safer ways to reduce cardiovascular risk, such as exercise and dietary changes.

But what bothers me most about this meta-analysis are the substantial conflicts of interest among six of its 12 authors, most of whom are doctors. According to the fine print at the end of the BMJ study itself, six of the authors are consultants for one or more of the drug companies that make statins, which, by the way, are among the top five classes of drugs sold in the US today. For example, two of the authors are consultants for Merck, which makes Zocor; another researcher, a professor at Cornell University, consults for Bristol-Myers Squibb, which makes Pravachol, another statin; a third has received speaking fees from Pfizer, which makes Lipitor, and a fourth researcher has consulted for Astra-Zeneca, which makes Crestor, as well as Merck. One of the authors (who like six of his colleagues hails from the Netherlands) also sits on the board of two biotech-pharm companies (Aegerion and Arisaph), which are developing cholesterol-lowering drugs. Still another co-author (the one who consults for both Merck and Astra-Zeneca) has developed cardiovascular biomarkers that have been licensed to Siemens and Astra-Zeneca.

In sum, what we have here is a study rife with conflicts of interest. But what we don't know from the fine print is how much these fine fellows are making from their ties to the statin industry; is it $10,000 a year, $100,000 or a $1 million? As I've reported in previous blogs and Side Effects, even a little money can affect the outcome of clinical research and a lot of money can affect it a lot.

That's why we so badly need public disclosure of the financial ties between specific health professionals and health product companies. So consumers can see for themselves just how conflicted the researchers of a particular study are and decide for themselves how much weight they want to give the study's results. In the absence of such key information, I'd have to agree with one of the online commentators on the BMJ study: that the jury is still out when it comes to the benefit of statins in reducing the risk of heart attacks in folks without known heart problems.


Dan said...

Treating Dyslipidemia: What Is Believed To Be Qualities Of All Statin Medications:

Statins are a class of medications specifically prescribed to lower LDL, primarily, which is one of five lipid parameters of a person’s lipid profile, which is alto the name of the blood test to measure these parameters.

They are beneficial for those patients with dyslipidemia and cardiovascular disease, as several studies have concluded. Lipitor is known to have the greatest efficacy of the available statins for prescription.

There are about 6 available statins to choose for lipid management as needed- with three that are combination drugs that have a statin included as a component in these particular drugs.

There are other classes of medications for lipid management, such as bile acid sequestrants and nicotinic acid, which is known as niacin. Yet the side effect profile is more unfavorable of these classes of medications compared with the statin class of drugs.

One’s cholesterol level is primarily due to how they produce cholesterol in their liver, which is overall genetically determined.

This level is also determined by one’s lifestyle and diet as well.

If a person has too much cholesterol in their blood, it can lead to hardening and narrowing of their arteries as well as the formation of coronary plaques in the coronary arteries.

If these plaques break off of the arterial wall, this leads to a myocardial infarction, or heart attack. Statins are believed to stabilize coronary plaques so this does not occur.

To measure one’s cholesterol, a blood test called a lipid profile is obtained from a person after they have fasted for at least 12 hours.

The test should also be performed only if the person is free of any acute illness, as this may affect true lipid measures.

If the results prove to be abnormal, lipid altering medicinal therapy may be initiated- according to the discretion of the person’s health care provider. This therapy usually involves a statin medication.

Adverse events associated with the statin class of pharmaceuticals are thought to occur more often than they are reported- with high doses of statins prescribed to patients in particular at times that may not be necessary to control their dyslipidemia based on their lipid profile.

Side effects may include muscle pain, or possible damage to the patient’s liver, if not their muscle as well.

However, since this class of statin drugs has existed for use for over 20 years, statins are considered to be overall safe and effective for enhancing the clearance of LDL noted to be elevated in the lipid profiles of patients.

Also, they have proven to reduce cardiovascular mortality with one who is treated with a statin that has dyslipidemia.

In addition to lowering LDL by up to about 60 percent- depending on the choice of the statin prescribed for the patient, and how high the LDL cholesterol is in a patient.

This class of drugs also has the ability to raise their HDL lipid parameter as well as lower to their benefit their triglyceride parameter of their lipid profile.

Both of these additional effects in addition to lowering the LDL parameter from taking a statin drug is ultimately beneficial for the patient on a statin drug for lipid management.

Dan said...

Statins 2:

Statin therapy is also recommended for those patients who have a greater than twenty percent risk of developing cardiovascular disease, or those patients that have clinical evidence of this disease.

Additionally, there appears to be no comparable reduction in cardiovascular morbidity or mortality, as well as a difference in the increase of one’s lifespan, if one is on any particular statin medication for their lipid management over another, others have concluded.

So caution should perhaps be considered if one chooses to prescribe a statin for a patient if they are absent of, or have only mild dyslipidemia to a significant degree.

Furthermore, research should be done by the health care provider if they are under the belief that one statin medication provides a greater cardiovascular benefit over another.

In other words, the health care provider should be assured that any choice of statin therapy for their patients should be considered reasonable and necessary if the LDL in their patients need to be reduced.

Furthermore, the statin selection should be determined by the results that have been shown with a particular statin.

There exist abstract etiologies for health care providers at times to choose to prescribe statin drugs on occasion for reasons not indicated with the medicinal treatment of these statin drugs.

Examples include the speculated benefits associated with statins- such as reducing CRP levels, or for Alzheimer’s treatment, or other reasons not directly related to cholesterol management.

Statin therapy for such patients may not be considered appropriate, reasonable, or necessary prophylaxis at this point for any patient who does not have the indications for which statins are approved for to treat patients with dyslipidemia.

All other benefits that appear to have favorable effects in such areas not involved with a patient's cholesterol are suggested at this point due to minimal research in these other variables aside from lipid management.

Other reasons for placing a patient on a statin drug at this time require further research for these disease states and dysfunctions that may exist with a patient aside from dyslipidemia.

Statins as a class of drugs repeatedly seem to in fact decrease the risk of cardiovascular events significantly, it has been proven. Statins also decrease thrombus formation as well as modulate inflammatory responses (CRP) as additional benefits of the medication.

For those patients with dyslipidemia who are placed on a statin, the effects of that statin on reducing a patient’s LDL level can be measured after about five weeks of therapy on a particular statin drug.

Liver Function blood tests are recommended for those patients on continued statin therapy, and most are chronically taking statins for the rest of their lives to manage their lipid profile in regards to maintaining the suitable LDL level for a particular patient presently.

Patients should be made aware of potential additional side effects as well, such as myopathy and muscular dysfunctions that occur on occasion when one is on statin therapy.

Yet some have said that about half of all strokes and heart attacks that do occur are not because of increased cholesterol levels of these patients. So it appears clear that high cholesterol may not be an absolute for cardiovascular events for them to occur.

Others believe that it is oxidized cholesterol that causes vulnerable plaques to form on coronary arterial walls, which is the catalyst for a heart attack, and that there is no medicinal treatment for the formation or stabilization of these plaques to prevent heart attacks or strokes.

Some who support statin medicinal therapy for their clinically appropriate patients claim that these drugs, do, in fact, stabilize these plaques as an added benefit, and therefore are beneficial.

Dan said...

Statins 3:

As stated previously, in regards to other uses of statins besides just primarily LDL reduction, there is some evidence to suggest that statins have other benefits besides lowering LDL, but not enough evidence yet to prescribe statins for alternative medical conditions, according to some medical experts.

These other disease states include aside from what has been stated already, such as those patients with neurological disease, as well as statins being beneficial for certain cancer patients.

Some have suggested that statins interfere with cancer treatment with bladder cancer patients as well. Yet again, these other roles for statin therapy have only been minimally explored and researched, comparatively speaking.

Because of the limited evidence regarding additional benefits of statin medications, the drug should again be prescribed for those with dyslipidemia only at this time involving elevated LDL levels as detected in the patient’s bloodstream.

Yet overall, the existing cholesterol lowering recommendations or guidelines should possibly be re-evaluated. The cholesterol guidelines that presently exist may be over-exaggerated possibly due to tacit suggestions from the makers of statins to those who create these current lipid lowering guidelines.

This is notable if one chooses to compare these cholesterol guidelines with the other guidelines that have existed in the past.

The cholesterol guidelines that exist now are considered by many health care providers and experts to be rather unreasonable and unnecessary, as well as possibly have the potential to be detrimental to a patient’s health.

Yet statins are beneficial medications for those many people that exist with elevated LDL levels that can cause cardiovascular events to occur because of this abnormality.

What that ideal LDL level is may have yet to be empirically determined.

Finally, a focus on children and their lifestyles should be amplified so their arteries do not become those of one who is middle-aged, and this may prevent them from being candidates for statin therapy now and in the future, regarding the high cholesterol issue.

Treating children with a statin drug for dyslipidemia is controversial presently. Dietary management should be the first consideration in regards to correcting lipid dysfunctions that may exist in patients.

Dan Abshear

Roy M. Poses MD said...

Sadly, I think that this level of conflicts affecting authors of major clinical papers in well-known medical journals is becoming the rule, rather than the exception. The journals may be getting slightly better at getting the authors to disclose minimal details about the conflicts. But we are not making progress reducing the severity or number of conflicts.

Mickeh1962 said...

Hi !

Here is a link to a horrible scandal in Sweden

Regards Michael

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