Guest Blog: Overprescribing the Healthy Elderly: Why Funding Research and Drug Safety Is Paramount

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lderly-2011-06-30

Overprescribing the Healthy Elderly: Why Funding Research and Drug Safety Is

Paramount

By Newman |â  Jun 30, 2011 08:05 AM |â  â 8â 



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My frail, 92-year-old mother was prescribed 80 mgs of the cholesterol-lowering

drug, or statin, simvastatin for years. She fell four times in the last four

years of her life: the last fall was the least forgiving. Doctors diagnosed her

with rhabdomyolysis, a life-threatening condition, and acute kidney failure; she

was dead within 8 weeks.

Source: Newman

The MedlinePlus encyclopedia defines rhabdomyolysis as " the breakdown of muscle

fibers and release of their contents (myoglobin) into the bloodstream. " In

severe case, " the myoglobin breaks down into potentially harmful compounds,

blocking the kidneys, causing damage such as acute tubular necrosis or kidney

failure. Dead muscle tissue may be caused by any condition that results in

damage to skeletal muscle, especially trauma. "

The FDA Safety Alert states that symptoms to watch for are: " muscle pain,

tenderness or weakness, dark or red-colored urine, and unexplained fatigue " and

should be brought to the attention of a health professional. Further, it advises

doctors to inform patients taking that dose that they are at risk for

rhabdomyolysis.

Rhabdomyolysis is a medical emergency. It is not uncommon after crush injuries,

falls, and athletic feats. FDA’s safety warning that 80 mg simvastatin is

linked to myopathy, issued on June 8, 2011, struck a chord in me because the 80

mg dose of simvastatin was the same given my mother.

An article in the Nov. 13, 2010 Lancet sounded an alarm that high-dose

simvastatin could be hazardous. In a blinded randomized trial of more than

12,000 survivors of acute myocardial infarction, investigators found two (0.03%)

cases of myopathy in patients taking 20 mg simvastatin daily, compared with 53

(0.9%) cases in the 80 mg group.

This finding could not be ignored. FDA pressed forward in further analyses. Even

as my mother was in crisis, doctors told me that they were astounded that such a

high-dose statin was given to a low-risk, frail, elderly women. By low-risk, she

had no history of cardiovascular disease and she met the widely used and

time-tested Framingham Risk Factor criteria. She did not smoke, had low-level,

well-controlled hypertension, but a high cholesterol. I sensed deterioration

months before she was diagnosed with rhabdomyolysis. Before she developed

life-threatening rhabdomyolysis, she walked everywhere.

The Author and her mother in Canadian Rockies celebrating her 90th birthday.

Source: Newman

She called me, saying: " All of a sudden I feel exhausted, like my legs won’t

support me, and I keep stopping and sitting down. I just don’t think I can do

it anymore. " Who knew whether it was normal aging? Her doctor did not think much

of these changes.

FDA’s Simvastatin 80 mg Warning

FDA’s Drug Safety Communication: New Restrictions, Contraindications, and

Dose Limitations for Simvastatin to reduce the risk of muscle injury state:

- Simvastatin 80 mg should not be started in new patients, including patients

already taking lower doses of the drugs.

- Patients taking simvastatin 80 mg have an increased risk of myopathy compared

to patients taking lower doses of this drug or other drugs in the same class.

- Muscle problems typically occur in the first year of use.

FDA is taking a major step to improve the public’s health. Whether it is far

enough is debatable.

The consumer health advocacy group, Public Citizen considers 80 mg simvastatin

unsafe and wants it off the market to protect the public. On its Worst Pills,

Best Pills website (subscribers only), it presses for a recall of 80 mg dose and

urges consumers, no matter how long they have been on it, to ask their doctor

for an alternative that is weaker.

According to FDA’s Safety Communication, approximately 2.1 million patients in

the US were prescribed a product containing 80 mg simvastatin in 2010.

Prescribing Simvastin in the Elderly

Rodney Hayward, professor of public health and internal medicine at the

University of Michigan, told me that sometimes, fatigue and muscle weakness are

attributed to aging, when the culprit might be excess dosing. He said:

" Unfortunately, people don’t realize that an excessive dose might be causing

loss of appetite, muscle problems, and not eating enough. The most common

adverse event with the high-dose statins are the myopathies, pain in the

muscles. " And if the old are not doing well, the sensible thing is to taper

down. "

Also, of critical importance, " as people age, the risks and benefits of people

being on medicine change, " said Hayward. " Processing through the kidneys

especially is increasingly less effective. You want to be aware of how many

medications, and how many doses people are on, and reconcile that with the

amount of benefit and risk. "

I thought that my mother had an eating disorder. She ate very little; it was all

low fat, low cholesterol, and low salt. She ate like that for decades. She was

5’ 1 " and weighed about 105 pounds. Her refrigerator was pretty empty.

Rita Redberg, MD, director of women’s cardiovascular services, the University

of California San Francisco, points out that many trials of hyperlipidemia have

not included enough women to determine gender-specific benefits and harms.

Therefore, meta-analyses and systematic reviews become imperative. But

particularly glaring is the reality that most studies have never demonstrated a

survival benefit for statins at all for low-risk women like my mother, yet some

doctors go so far as to put them on high-dose statins.

So one could argue that the benefit-risk ratio shifts towards harm in such

women, particularly when they are given high-dose statins. Both Redberg and

Hayward said that they know of no studies showing that low-risk people taken off

statins are at increased risk for cardiac events. Hayward, Redberg, and many

other physicians argue that doctors should be far more cautious in prescribing

medications for the elderly.

" High-dose statins should almost never be used in the elderly, " said Hayward.

" In fact, " he added: " I almost always use low doses of statins in people over 75

unless they have known heart disease, since most of the benefit of statins is

achieved with low doses and there are good reasons to be concerned about the

safety and tolerance of higher doses of statins in the elderly. " People over age

75 are under-represented in clinical trials, leaving physicians in the dark as

to safety.

Moreover, said Hayward: " With stepped-up dosing, the risk for harm escalates

disproportionally. Most of the benefit from the simvastatin is in the initial

dose. "

Factors in Overtreatment

Another issue of concern is whether overtreatment with high-dose statins has

become widespread because of how heavy marketing, according to Hayward.

Marketing of some statins promised achieving very low levels of low-density

lipoprotein (LDL) cholesterol (a.k.a. " bad cholesterol " ). It proved a valuable

selling point. Setting targets this low may be inappropriate for the elderly,

according to numerous pharmacoepidemiologists.

Also adding to the problem of overmedication are pay for performance (P4P)

programs, which set specific targets in cholesterol-lowering to payment. Target

setting is controversial because they may be too low for many individuals, yet

they are widely used for assessing quality of care. One notable exception that

may actually help keep the healthy elderly is that in HEDIS performance

measures, people over age 75 are excluded from lipid-lowering targets.

Differences in the Elderly, in Women

Arguments pressing for treating the elderly differently have been commonplace

for decades because the elderly have been under-represented in clinical trials;

hence, guidance on practice are not science based (Zulman, Sussman, Chen,

Cigalle et al., 2010; McMurd, Witham, Gillespie, 2005; and Guyatt, ).

We are really in new terrain now, with an aging boom and more pills available

for any symptom than could ever have been fathomed America’s shifting

demographics in the United States, as evidenced by the most recent US Census

Bureau report (Table left). The number of people in the oldest age group, namely

age 85 and over, is rising, projected to grow from 5.8 million in 2010, to 8.7

million in 2030, and 19 million by 2050, according to the US Census Bureau. Not

only have people age 75 and over been largely excluded from clinical trials,

subgroup analyses in the aged have barely begun.

These should be compelling reasons for FDA, the Centers for Medicare and

Medicaid Services, and Congress to back drug safety initiatives in the elderly.

Many health researchers are also urging further study of potentially

inappropriate medications (called PIMs) in elderly patients. Archives of

Internal Medicine highlighted the problem in its June 13, 2011 issue, and there

is a growing literature on it.

A recent study of elderly ICU survivors found that 85 percent were discharged

with 1 or more potentially inappropriate medicines, with more than 50 percent in

that group discharged with medications deemed more harmful than beneficial

(Morandi et al, 2011). The authors press for more attention to appropriateness

reviews, with the rationale for starting each therapy in the ICU, and discussion

of when it can be stopped.

Strom, MD, professor of public health and pharmacology, University of

Pennsylvania, describes the issues this way: " The problem is Congress and our

research agencies. They fund so little work on the pharmacology of the aged and

other demographic subgroups, and their risk of drug interactions. And, there is

phenomenally small, and shrinking by 60% (down to $5.1 million/year), amount of

money being spent supporting the Centers for Education and Research and

Therapeutics, who are charged with doing studies that industry would not fund,

and with changing prescribing to be more rational. "

Caregiver Remorse

The entire experience of trying to find quality care for my mother was made

especially difficult because of the dearth of good clinical practice guidelines

and science guiding chronic care for the elderly. I think it is way too much to

ask family and caregivers to take this on. Now both my parents are dead. I see

friends and family struggle under impossible odds, yet physicians who care for

the elderly have little science to guide them.

This is where Congress, the Centers for Medicare and Medicaid Services, and the

FDA must step up, expand funding, and beef up post-marketing drug surveillance.

FDA has a treasure trove of safety data that has been deemed proprietary, some

of it preferentially published, that could improve the public’s health. " No

one has the right to inspect this data except the FDA, " said Hayward. " Most of

the trials data is industry-supported and the industry can hide safety data, " he

said, " but with public pressure, ineffectiveness and harm may be detected. "

Without well-funded research and analyses of subgroups of the aged (age 85-100),

and postmarketing surveillance, the US is operating in too much darkness and

uncertainty for the public’s health. Many generations of Americans will

continue to suffer.

The aged take disproportionally more drugs than every group, and as a result are

more at risk for drug-drug interactions. It will take a significant commitment

from the federal government to marshall science and surveillance of drugs in

this population.

References:

Rhabdomyolysis. Accessed on June 27, 2011.

FDA Simvastatin 80 mg drug safety. Accessed on June 27, 2011.

Armitage et al. (2010) Intensive lowering of LDL cholesterol with 80 mg versus

20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a

double-blind randomised trial, Lancet: 376(9753):1658-69. Epub 2010 Nov 8.

Morandi et al. Inappropriate Medications in Elderly ICU Survivors: Where to

Intervene? Arch Intern Med.2011; 171: 1032-1034.

Risk Assessment Tool for Estimating Your 10-year Risk of Having a Heart Attack

Ten-Year Cardiovascular Disease Risk Calculator. Third report from the Expert

Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol.

Downloaded on June 27, 2011.

Walsh JME, Pignone M. Drug treatment of hyperlipidemia in women. JAMA 2004;

291(18):2243-2252. Abstract

IA, Guyatt GH. Cautionary tales in the interpretation of clinical studies

involving older persons.Arch Intern Med. 2010 Jun 14;170(11):927.

Jerry H. Gurwitz; J. Goldberg. Age-Based Exclusions From Cardiovascular

Clinical Trials: Implications for Elderly Individuals (and for All of Us):

Comment on " The Persistent Exclusion of Older Patients From Ongoing Clinical

Trials Regarding Heart Failure " Arch Intern Med, Mar 2011; 171: 557 - 558.

doi:10.1001/archinternmed.2011.33

Cho S, Lau SWJ, ; Tandon,V; Kumi K, Pfuma A, Abernethy DR Geriatric Drug

Evaluation. Where Are We Now and Where Should We Be in the Future? Arch Intern

Med. 2011;171(10):937-940. doi:10.1001/archinternmed.2011.152

, Grayson K. and A. Velkoff, 2010, THE NEXT FOUR DECADES, The

Older Population in the United States: 2010 to 2050, Current Population Reports,

P25-1138, U.S. Census Bureau, Washington, DC.

Hamilton H, Gallagher P, C, Byrne S, O'Mahony D. Potentially Inappropriate

Medications Defined by STOPP Criteria and the Risk of Adverse Drug Events in

Older Hospitalized Patients. Arch Intern Med. 2011 Jun 13;171(11):1013-9

Schnipper J. Medication Safety: Are We There Yet?: Comment on " Potentially

Inappropriate Medications Defined by STOPP Criteria and the Risk of Adverse Drug

Events in Older Hospitalized Patients " . Arch Int Med 2011 Jun 13;171(11):1019

 

About the Author: Newman writes about medicine, health policy, and

clinical outcomes research. She has a long-term interest in healthcare reform

and what matters to patients. She has written news in health and medicine in

peer-review journals, on the web, and for newsletters. blogs at Patient

POV, is active on twitter at @lauranewmanny, and she is especially interested in

integrating patients into health reform efforts.

The views expressed are those of the author and are not necessarily those of

Scientific American.

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