Do nurses have a role in "educating" physicians in new treatments? Consider the story

Nurses General Nursing

Published

below which details four established drugs, that when used together SEEM to cut the risk of death by up to 90% after a heart attack. For instance if you worked in a Cardiac unit and noticed that NONE of the patients that you cared for were benefiting from this new research would any "mechanism" exist for sending a "memo" to the physicians in such a way that it might actually be considered? The implications are profound if the latest treatments are not adopted by physicians. I have what I call the "Integrated health care team theory" of the nursing process which focuses on nurses as patient advocates, and their role as a "check and balance" upon the health care system. In the same way that a "wide receiver" can suggest to the quarterback of a football team that maybe he should consider calling a different play, nurses should when warranted be able to make similar suggestions to doctors without fear of reprimand.

Source: University Of Michigan Health System

Date:

2004-02-17

Inexpensive Four-drug Combo Saves Heart Patients' Lives

ANN ARBOR, Mich. - An inexpensive cocktail of four tiny pills can make a big difference in heart patients' death risk, a new University of Michigan study finds. And the life-saving effect of the four-drug regimen is bigger than the sum of its parts.

In the new paper, U-M Cardiovascular Center researchers report that heart attack and unstable angina patients who were prescribed all four types of proven medications had a 90 percent lower risk of dying in the six months after they left the hospital than those who received none of the drugs. Even patients who got only two or three of the drugs had a much lower death risk than those who got none.

The research is published in the rapid-access online edition of the journal Circulation, and an accompanying editorial notes the clinical importance of the findings.

The four classes of medications are:

* Anti-platelets: Aspirin and other drugs that keep blood clots from forming

* Statins: Cholesterol-lowering drugs

* ACE inhibitors: Blood pressure-lowering drugs that have other beneficial effects

* Beta blockers: Adrenaline-blocking drugs that ease the burden on the heart

Many studies have already shown that individual drugs in each one of the four classes can help prevent problems in patients with previous heart problems and clogged arteries. All four are recommended in national guidelines for doctors. And all four classes of drugs include many individual medications, with at least some available in inexpensive generic form.

The new study is the first to show the power of the four types of drugs together, and it does so in a "real world" setting of 1,264 adult patients treated between 1999 and 2002. All the patients had been admitted to the U-M hospital with an acute coronary syndrome: either myocardial infarction (heart attack) or unstable angina.

The results surprised the researchers, who analyzed the patients' hospital records to see how many of the drugs they had been prescribed and to determine how many would be appropriate for them. Then, they checked in on the patients six months after they left the hospital to determine if they were still living.

"We knew that each of these kinds of drugs works pretty well alone, but we never expected that together they would be this powerful at improving survival," says lead author and U-M cardiologist Debabrata Mukherjee, M.D. "These results clearly show that the effect of combination therapy is synergistic, not just additive: the drugs work together to create a bigger benefit for the patient."

This amplified effect may stem from a beneficial interaction between the ways in which the four types of drugs fight the plaque that builds up in clogged, hardened arteries -- the atherosclerosis that leads to chest pain and reduced blood flow to the heart.

The bottom line for patients, Mukherjee says, is that people who have a history of heart attack or unstable angina should talk with their doctor about making sure they receive prescriptions for as many of the four types of medications as they are eligible for.

And, he notes, they should ask for generic drugs whenever possible. If all four drugs in the cocktail are generic, the total cost may be under $50 a month. "That's a lot of bang for your buck," he says.

The bottom line for physicians is also clear, says U-M CVC clinical director and senior author Kim Eagle, M.D. "Get in line with the guidelines published by the American College of Cardiology and the American Heart Association, and help as many patients as possible benefit from these four proven therapies. There's no reason not to."

Eagle notes that the study's result confirms a known real-world problem: Despite those national guidelines, not all heart attack and unstable angina patients get prescribed all the drugs they should. No drug was prescribed to 100 percent of eligible patients in the study, and 40 percent of patients who could have received ACE inhibitors didn't. About 5 percent lacked an aspirin prescription, almost 18 percent didn't get beta-blockers, and 16 percent weren't prescribed statins.

Since the study ended in 2002, U-M has created a system that reviews each inpatient's eligibility for these agents, and their lifestyle goals, before the patient is discharged, in order to enhance the long-term outcome for every patient. Says Eagle, "We have now created a system to guarantee the best possible treatment at discharge for these at-risk individuals."

About 70 percent of patients in the study had suffered a heart attack, and 30 percent had unstable angina. Just over 63 percent of the patients in the study were men, and the average age was nearly 64. Two-thirds of the patients included in the study had blood tests positive for biomarkers that indicate damage to the heart muscle, while others were included because of symptoms of acute coronary insufficiency or an electrocardiogram that indicated a blockage in a heart blood vessel.

Patients tended to be obese and many were smokers, with a large percentage having a history of heart attack, angina, high blood pressure and high cholesterol before the acute episode that sent them to the hospital. A sizable minority had a history of stroke, heart failure or diabetes, and many had had angioplasty or bypass surgery in the past.

The researchers reviewed each patient's chart and assigned each a score based on what percentage of the four drug classes they had been prescribed, compared with how many drugs they were eligible to receive based on ACC/AHA guidelines. This score corresponded with an "Appropriateness Level" of 0, I, II, III or IV, with IV being the highest.

Patients who were prescribed none of the four drugs were assigned to Level 0, while those who were prescribed one of the four drugs when they could have been given three or four were grouped into Level I. Patients who received two drugs but could have used three or four, and those who received one when they could have taken two, were classed in Level II. Those who got three medications but could have taken all four were in Level III, and those who were prescribed all four were in Level IV.

In all, Level IV patients had a 90 percent lower risk of dying in the six-month follow-up period than the Level 0 patients. Level III patients and Level II patients also had an advantage over Level 0 patients, of 83 and 82 percent, respectively. And even Level I patients did better with just one drug than those who got none, showing a 64 percent lower risk of dying.

"These very high risk patients received a tremendous benefit from the preventive effects of these drugs, and we need to seize the opportunity to make sure that all patients receive appropriate care," says Mukherjee. "Simple things can make a big difference, if we use them as we know we should."

In addition to Mukherjee and Eagle, the study's authors are Jianming Fang, M.D., Stanley Chetcuti, M.D., Mauro Moscucci, M.D., and Eva Kline-Rogers, RN, all of the U-M Cardiovascular Center.

Editor's Note: The original news release can be found here.

--------------------------------------------------------------------------------

This story has been adapted from a news release issued by University Of Michigan Health System.

Specializes in Nursing Education.

Roland - this information is not new and hopefully post AMI patients on a cardiac unit are receiving these medications unless they are contraindicated for one reason or another. I agree with your analogy of the nursing process and the fact that we need to advocate for our patients. I think ultimately as nurses, we do need to ensure that our patient's needs are met.

While the above statement is true, it is not within our scope of practice to make recommendations to the physician about the types of pharmacological treatments the patient should be taking. Of course, with some physicians or new docs, they may ask us what orders we would like for a patient, but it is really out of our scope to recommend medical treatment modalities for the patient. With that being said, it is certainly appropriate to bring new research to the table and have that research explored for possible patient care benefits. I would think that these types of discussions can be managed within a committee that reviews and validates the research for possible implementation with your establishment.

Over the course of the years that I have been nursing, I have seen many studies that have been published, which would have far reaching positive benefits for the patients under my care. There have been plenty of times I have discussed my research findings with our physicians. This type of dialogue with the physician eccourages a collaborative relationship and also lets the physician know that your practice is research based. Some physicians respect your commitment to exploring research and some do not. Regardless of the what the physician thinks, it is always good to be aware of research, both medical and nursing.

Several years ago, I encouraged our hospital to develop a research committee that reviewed research on several patient care related topics. I was pleased when this committee really took off. Our Medical Services Committee was very involved with the review and validation of research at our hospital and worked very closely with nursing administration and our physicians to ensure that research related practice was a big part of our overall care philosophy.

To this end, it is important for nurses to advocate for their patients and bring current research findings to light in their respective clinical areas. It is also very important to discuss this research with your physicians. As nurses, our ability to advocate for our patients and ensure that they receive care that is validated by research is very important. Our methods of communicating these findings can be just as important and requires us to bring this information to light in a manner which provokes action by nursing leadership.

JMHO. Patrick

Nurses do not recomend out of their scope of practice. We need to understand that we may learn many things being so closley involved with pt care, but we only have the bare bones compared to what physicians have to know. There have been many occasions where a physician has asked me what my opinion was on a hospice pt and pain tx simply because he was in unfamiliar territory and I had knowledge. I did handle it with respect by stateing protocols and faxing copies of same to physician. There have been other times I have had consults with the pharmacist first and then made recomendations " per pharmacist " and asked pharmacist if it was ok first and give pharmacist opportunity to make the call himself if he wasn't busy. I don't know how many times I have had a CNA try to be a nurse by telling me what a pt needs and that is truly out of her area and extremely irritating.

I am not saying that nurses should have the power to alter a patients treatment outside of their scope of practice. However, I AM saying that there should be "formal" channels in which research, and possibly helpful information can be "made available" to physicians. Consider for instance that the ABOVE information HAS been known for quite awhile and STILL is not utilized by most physicians to the fullest extent (despite being the reccomendation of the American Cardiology Association as stated in the article). I would submit that patients are dying, because information like this IS NOT implemented as soon as it should be under optimal circumstances.

Ironically, my "nurse advisor/input process" might create "pressure" on physicians to better implement the advice of their own organizations! Consider, that at the very least it would create a permanent "record" of "input" by nurses relative to their facility. IF physicians choose not to consider such input they may be creating the foundation for more aggressive malpractice litigation at their facility (an attorney might be able to establish for instance that nurses at a given facility had long brought the above information to the attention of physicians who failed to act upon or even consider the information.). I have long believed that nurses as a profession should be willing to work with attorneys (where appropriate) to bring "pressure" on health care organizations to do the right thing. It can be a BIG hammer and nurses should be willing to utilize it when appropriate. To do less is to fail to be a complete patient advocate and to abandon an important role in the patient care "optimization" process.

Can any of you think of specific examples where nurses "knew" things that could have positively impacted patient care, had their insite been considered? Let me provide one example: At the hospice facility where my mother was taken virtually every patient was placed on Haldol (I know this because I "spoke with" virtually every nurse in the facility during the two weeks she was there). Many of the nurses privately admitted to me that they thought that this amounted to the mass use of "chemical restraints" to lighten the work load on the facility, however they said that it was "the doctor's decision and she really likes Haldol". I called other similar facilities and almost NONE used Haldol (or at least admitted to using) in this manner. Now, THIS would be an example of a situation where were I a nurse that I would use the "built in advisory process" that I am proposing to bring the excessive utilization of Haldol to the attention of the Dr. I have worked at companies where EVERY suggestion receives a responce by upper management. If they didn't like a suggestion or couldn't implement it you still received a reply and generally a specific reason why it couldn't, or wouldn't be implemented.

Much organizational research and experience has time and again confirmed the notion that those "closest to the job being done" often have input that is as or MORE useful than even what the "experts" in "management" can provide. From tragedies such as the Space Shuttle disastors to corporate injustices such as Enron, retrospective analysis has revealed that HAD MANAGEMENT (in this case Dr's and hospital administration) more closely listened to the input of others that major, negative outcomes could have been avoided.

Nurses do not recomend out of their scope of practice. We need to understand that we may learn many things being so closley involved with pt care, but we only have the bare bones compared to what physicians have to know. There have been many occasions where a physician has asked me what my opinion was on a hospice pt and pain tx simply because he was in unfamiliar territory and I had knowledge. I did handle it with respect by stateing protocols and faxing copies of same to physician. There have been other times I have had consults with the pharmacist first and then made recomendations " per pharmacist " and asked pharmacist if it was ok first and give pharmacist opportunity to make the call himself if he wasn't busy. I don't know how many times I have had a CNA try to be a nurse by telling me what a pt needs and that is truly out of her area and extremely irritating.

I agree with this... working in LTC and knowing the pts better than the docs, many of them ask "Whats worked before...What does doc so and so say..." or even "What do you think..What's the pharmacist say.." By no means am I writing an order myself...but sometimes the docs need alittle help or imput so that they can make an informed decision.... Hospice pts and pain control is still not undersood by many of our docs..Another problem is that some docs don't know geriatric pharmacology and often order extremely inappropriate doses or drugs for them... in the end..they are the doctor, I'm the nurse..

Specializes in Nursing Education.

Roland - the long and the short of it is that there are physicians that are great and do wonderful things for their patients. These physicians stay on top of research and work hard to ensure the medical care they provide for their patients is the best it can be. Conversely, there are physicians that could really care less about research and will conduct their practice exactly as they please.

Case in point .... I use to work with a physician that used the old three bottle chest tube system. This system is so old that they do not even make parts for the main suction any longer. I reviewed several different studies and research projects and brought the recommendations of these studies to the attention of this physician and encouraged him to change his practice and begin using the self contained units (in this case it was the PleuroVac System). He refused, stating that he was accustome to working with this system and saw no reason to change. Forget that the research I showed him revealed decreased risks of pneumo and better patient outcomes .... he refused ... end of discussion.

This issue has been a professional and life long issue for most nurses. Physicians do as they please and they probably always will. Is this acceptable? Hell NO! But is it reality? Hell YES! You are right, as nurses, we must continue to advocate for our patients and ensure they get what they need to be well. However, we do not and can not control the practice of a physician. Sure, we can bring in the attorney, case law and many other strong arm ways to provoke the physician to change. When it comes right down to it, the patient has the choice and can and should change physicians if they believe that their care and treatment are not up to date to modern standards and research.

Many people may ask, "well how does the patient know if he/she is getting the most up to date care?" This is where patients need to be in control of their own destiny and get second opinions and remember that their physician is not the end all, be all. I know from personal experience, I have had to call the shots for my care. I was not taking ceratin medications that I knew I should be taking. I approached my physician, who took a real lazy attitude with me (you know the ones ... oh he is a nurse and he is going to tell ME how to care for him). I finally went to another physician and was properly taken care of.

As nurses, we can not change a physician's practice. That is what it all boils down too. :)

I can give an example of nursing promoting standards or whatever you want to call it.

The patient i admitted with an MI was on ARB (type of ace inhibitor) prior to and during her stay. Today i got a note in the progress notes written (not a post it...it was legally written) that said the following..."dear dr. (no...they still can't figure out how to write dear NP!). could you please document in the chart why your patient is not on an ACE post MI?".

Well the long side is it made me double check my orders to make sure. The odd thing is is that the nursing coordinator (discharge planner) didn't know that an ARB was akin /similar and accceptable to an ACE. However, the question is: why was there a note? It came down to something about JCAHO standards and recommendations or some such nonense that would keep our hospital looking good. When i told them that the patient was on a ARB they told me that JCAHO didn't consider that to be okay (probably b/c of cost). So i told the coordinator that the patient was on an ARB b/c we could easily sample the med as opposed to ace which is not as readily available and the patient couldn't afford her meds. I had to document that in the chart.

Regarding promoting standards or suggesting treatments? As a former bedside RN I would welcome another nurse putting something in the chart asking me or suggesting something. While I may have a reason to follow along that recommendation or not it will still provide food for thought and give me an opporunity to think differently.

Specializes in ICU.

Using a big stick is never the way to effect change - it just makes the donkey more stubborn. It is better to dangle a carrot.

So what carrot can we dangle to get the change to happen. Here we are moving towards "evidence based pratice" and whole hospitals have become EBP centres. EBP is where you use recommendations from systematic review centres such as the Cochrane Database for medicine and the Joanna Briggs Institute for nursing. Systematic reviews make sense of the plethora of research on a subject, discount any product bias and identify future avenues for research.

To be honest once I started looking at the JBI's reviews I realised that much of nursing needs to look to itself first and get our own practice right and validated before we heap too much trenchant criticism on others. A bedsore can kill just as effectively as missing one med from the list.

Let me be more specific about how such a system might work. Let's say you were a CT/ICU nurse and you noticed that few of your post MI patients were on anything approaching the above drug combination (maybe you noticed they were getting aspirin, and beta's, but no statins or ACE inhibitors). You would "file" the above article with any relevent personal observations and any additional medical references to support your observations. Once "filed" the reccomendation would go to some sort of "coordinator" who would probably be an MD or NP, their job would be to determine if your advice had even the "slightest" merit (was it essentially scientific with some clinically based evidence to support your thesis). If it met this minimal criteria it would be presented to the head resident of the appropriate unit for consideration at a weekly or monthly meeting (along with other such reccomendations). There it would be discussed and evaluated. In any case it would become a "permanent record" that could be reviewed in the future. Let's say that someone brings litigation because their mother died post MI. Their attorney could present the fact that their were numerous reccomendations on file that this protocol be implemented. This is just one "sample" model that I am sure could be vastly improved upon, just a "starting point". Keep in mind that the above article is nothing more than the EXISTING guidelines published by the American College of Cardiology AND the American Heart Association (the STORY is that despite this being the case this drug combination is STILL seldom utilized in spite of overwhelming evidence supporting its efficacy.) How can nurses be the best possible patient advocates if they ignore this kind of thing?

Specializes in Nursing Education.
Using a big stick is never the way to effect change - it just makes the donkey more stubborn. It is better to dangle a carrot.

So what carrot can we dangle to get the change to happen. Here we are moving towards "evidence based pratice" and whole hospitals have become EBP centres. EBP is where you use recommendations from systematic review centres such as the Cochrane Database for medicine and the Joanna Briggs Institute for nursing. Systematic reviews make sense of the plethora of research on a subject, discount any product bias and identify future avenues for research.

To be honest once I started looking at the JBI's reviews I realised that much of nursing needs to look to itself first and get our own practice right and validated before we heap too much trenchant criticism on others. A bedsore can kill just as effectively as missing one med from the list.

Bravo to your hospital for this type of philosophy! Wonderful to hear, I wish my hospital was doing something like this. :uhoh21:

Specializes in ICU.

Roland - you are still advocating a system running by negative feedback whereas an EBP system runs by positive input. We are finding out here the real cost of litigation and our approach is to cut out the lawyers as much as possible by having good systems in place in the first place.

This sounds like a nice system but there are at least 3 major flaws which will prevent implimentation.

1) Who decides?? Research outcomes even when systematically reviewed are not cut and dried

2)Pt individuality - you might decide that the pt should be on beta blockers but the pt might be asthmatic - conraindicated!!! OR and I have seen this the cardiologist choose not to prescribe because the patient is known to be non-compliant in the extreme and will ignore tablets for days only to take 5 at once - not good with Beta blockers - and this was a Pt we had TRIED to educate

3) Cost - your system is costly

4) You are assuming the nurse IS as knowledgable as the MO what if the latest research proves what is now suspected - that statins can interfere with memory - it is still a recommendation by the heart association but MO are now reluctant to prescribe because it becomes a matter of which system is most important - mind or heart??? Comes back to the saying - if you want entertainment watch a neurosurgeon and a cardiologist argue over a patients' BP

There is evidence to indicate that many of the complications from long term statin therapy can be ameliorated by the concurrent administration of coenzyme Q-10 (available OTC see references below about coenzyme Q10). In addition, there is mounting scientific evidence that alpha lipoic acid in combination with acetyl-l-carnitine can have a powerful effect in counteracting non dementia related memory loss. Of course there will always be situations where a particular drug is not appropriate for a given patient. However, my scenario goes to a situation where the four drug combination is CONSISTENTLY not being utilized (as the study indicates that it is not).

While I don't believe nurses to be nearly as knowledable as M.D.'s it doesn't change the fact that they often have valuble, relevent, input that can be germaine to optimal patient care and outcomes. My concern is that currently there exists no formal system by which nurses can consistently share this input (indeed, nursing schools do not often stress the role of nurses as "guardians of patient care"). My approach to emphasizing a permanent record that might aid future litigation exists because I believe it to be the ONLY way that M.D.'s and administration will be persuaded to consistently consider such input (there must be a potential monetary cost to NOT doing so or a potential economic benefit for DOING so).

My model emphasizes an interconnected, integrated "health care team" where each segment nurses, doctors, and allied health care personnel act as a "check and balence" upon the other with the goal of providing the best patient care possible. I believe that this can only occur in an environment with recognized, formal channels of communication for the exchange of pertinent information. I would be willing to consider other mechanisms that might accomplish the same objective.

Coenzyme Q-10 References (note references 1, 22, and 23 are especially relevent)

1. Ellis CJ, Scott R. Statins and coenzyme Q10. Lancet. 2003 Mar 29;361(9363):1134-5.

2. Singh RB, Neki NS, Kartikey K, et al. Effect of coenzyme Q10 on risk of athero- sclerosis in patients with recent myocardial infarction. Mol Cell Biochem. 2003 Apr;246(1-2):75-82.

3. Ohmoto N, Fujiwara Y, Kibira S, Kobayashi M, Saito T, Miura M. Cardiomyopathy showing progression from diffuse left ventricular hypertrophy to dilated phase associated with mitochondrial DNA point mutation A3243G: A case report. J Cardiol. 2003 Jan;41(1):21-7.

4. Fosslien E. Review: Mitochondrial medicine--cardiomyopathy caused by defective oxidative phosphorylation. Ann Clin Lab Sci. 2003 Fall;33(4):371-95.

5. Engelsen J, Nielsen JD, Hansen KF. Effect of coenzyme Q10 and ginkgo biloba on war- farin dosage in patients on long-term war- farin treatment. A randomized, double- blind, placebo-controlled cross-over trial. Ugeskr Laeger. 2003 Apr 28;165(18):1868-71.

6. Singh RB, Kartik C, Otsuka K, Pella D, Pella J. Brain-heart connection and the risk of heart attack. Biomed Pharmacother. 2002;56 Suppl 2:257s-265s.

7. Sarter B. Coenzyme Q10 and cardiovascu- lar disease: a review. J Cardiovasc Nurs. 2002 Jul;16(4):9-20.

8. Piotrowska D, Dlugosz A, Pajak J. Antioxidative properties of coenzyme Q10 and vitamin E in exposure to xylene and gasoline and their mixture with methanol. Acta Pol Pharm. 2002 Nov-Dec;59(6):427-32.

9. Tran MT, Mitchell TM, Kennedy DT, Giles JT. Role of coenzyme Q10 in chronic heart failure, angina, and hypertension. Pharmacotherapy. 2001 Jul;21(7):797-806.

10. Shults CW, Oakes D, Kieburtz K, et al. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the function al decline. Arch Neurol. 2002 Oct;59(10):1541-50.

11. Kishimoto C, Tomioka N, Nakayama Y, Miyamoto M. Anti-oxidant effects of coen- zyme Q10 on experimental viral myocarditis in mice. J Cardiovasc Pharmacol. 2003 Nov;42(5):588-92.

12. Sandhu JK, Pandey S, Ribecco-Lutkiewicz M, et al. Molecular mechanisms of gluta- mate neurotoxicity in mixed cultures of NT2-derived neurons and astrocytes: pro- tective effects of coenzyme Q10. J Neurosci Res. 2003 Jun 15;72(6):691-703.

13. Chuang YC, Chan JY, Chang AY, et al. Neuroprotective effects of coenzyme Q10 at rostral ventrolateral medulla against fatality during experimental endotoxemia in the rat. Shock. 2003 May;19(5):427-32.

14. Shults CW. Coenzyme Q10 in neurodegen- erative diseases. Curr Med Chem. 2003 Oct;10(19):1917-21.

15. Kishimoto C, Tamaki S, Matsumori A, Tomioka N, Kawai C. The protection of coenzyme Q10 against experimental viral myocarditis in mice. Jpn Circ J. 1984 Dec;48(12):1358-61.

16. Lamperti C, Naini A, Hirano M, et al. Cerebellar ataxia and coenzyme Q10 defi- ciency. Neurology. 2003 Apr 8;60(7):1206-8.

17. Langsjoen PH, Langsjoen A, Willis R, Folkers K. Treatment of hypertrophic car- diomyopathy with coenzyme Q10. Mol Aspects Med. 1997;18 Suppl:S145-51.

18. Langsjoen P, Langsjoen P, Willis R, Folkers K. Treatment of essential hypertension with coenzyme Q10. Mol Aspects Med. 1994;15 Suppl:S265-72.

19. Langsjoen H, Langsjoen P, Langsjoen P, Willis R, Folkers K. Usefulness of coen- zyme Q10 in clinical cardiology: a long-term study. Mol Aspects Med. 1994;15 Suppl:s165-75.

20. Langsjoen PH, Langsjoen PH, Folkers K. Isolated diastolic dysfunction of the myocardium and its response to CoQ10 treatment. Clin Investig. 1993;71(8 Suppl):S140-4.

21. Folkers K, Langsjoen P, Langsjoen PH. Therapy with coenzyme Q10 of patients in heart failure who are eligible or ineligible for a transplant. Biochem Biophys Res Commun. 1992 Jan 15;182(1):247-53.

22. Folkers K, Langsjoen P, Willis R, et al. Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8931-4.

23. Langsjoen PH, Langsjoen PH, Folkers K. A six-year clinical study of therapy of car- diomyopathy with coenzyme Q10. Int J Tissue React. 1990;12(3):169-71

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