Statins - to recommend or not?

[Guest guest]

A new Cochrane review has provoked controversy by concluding that there is

not enough evidence to recommend the widespread use of statins in the

primary prevention of heart disease [1].

The authors of the new Cochrane meta-analysis, led by *Dr * *Fiona

*(London

School of Hygiene and Tropical Medicine, UK), issued a press release

questioning the benefit of statins in primary prevention and suggesting that

the previous data showing benefit may have been biased by industry-funded

studies. This has led to headlines in many UK newspapers saying that the

drugs are being overused and that millions of people are needlessly exposing

themselves to potential side effects.

This has angered researchers who have conducted other large statin

meta-analyses, who say the drugs are beneficial, even in the lowest-risk

individuals, and their risk of side effects is negligible. They maintain

that the Cochrane reviewers have misrepresented the data, which they say

could have serious negative consequences for many patients currently taking

these agents.

The Cochrane authors reviewed data from 14 trials involving 34 272 patients.

Outcomes in patients given statins were compared with outcomes in patients

given placebos or usual care. Although results suggested that deaths were

reduced on statins, the researchers say the effect is not large enough to

justify the cost/effort and risk of adverse effects.

Senior author *Dr Shah Ebrahim* (South Asia Network for Chronic Disease, New

Delhi, India) told *heartwire *that their review differed from others done

in primary prevention in that it looked at just those at low risk, limiting

the studies included to just those with populations where *<*10% had a

previous history of CVD.

Ebrahim commented to *heartwire *: " If you look at the hard end points of

all deaths and coronary deaths, the effects are consistent with both benefit

and with the play of chance. But importantly, the absolute benefits are

really rather small--1000 people have to be treated for one year to prevent

one death. It is probably a real effect, but it means a lot of people have

to be treated to gain this small benefit. As we don't know the harms, it

seems wrong-minded to me to treat everyone with a statin. In these

circumstances, lifestyle changes and stopping smoking would be far

preferable. "

*I object to the conclusions they have drawn from their review.*

But *Dr Colin Baigent* (Clinical Trials Service Unit, Oxford, UK) commented

to *heartwire *: " I object to the conclusions they have drawn from their

review. They say there is not good evidence of benefit, but their own data

show significant reductions in deaths and cardiac events. " And Baigent

further objects to the Cochrane authors' suggestion that harms are not known

with statins. " They didn't show any increase in adverse events in their

review, but they then say the benefit is not worth the risk. That doesn't

make sense. "

*Cochrane Results *

The Cochrane review showed that in the eight trials that reported on total

mortality, none of the individual trials showed strong evidence of a

reduction in total mortality, but when the data were pooled, a relative risk

reduction of 17% was observed with statin treatment. On combined fatal and

nonfatal CHD events, nine trials reported on this end point, with four

trials showing evidence of a reduction in this combined outcome, which was

maintained in the pooled analysis, with a 28% relative reduction. Seven

trials reported on fatal and nonfatal stroke, and on pooled analysis, statin

treatment was associated with a 22% relative reduction.

*Cochrane Review: Risk Ratio of Major Events With Statins in Lower-Risk

Primary-Prevention Patients*

*Outcome*

*Risk ratio (95% CI) *

*Total mortality *

0.83 (0.73–0.95)

*Fatal and nonfatal CHD events *

0.72 (0.65–0.79)

*Fatal and nonfatal stroke *

0.78 (0.65–0.94)

No excess in combined adverse events, cancers, or specific biochemical

markers were found.

The authors conclude: " This current systematic review highlights the

shortcomings in the published trials of statins for primary prevention.

Selective reporting and inclusion of people with cardiovascular disease in

many of the trials . . . in previous reviews of [statins'] role in primary

prevention make the evidence impossible to disentangle without individual

patient data. "

They say that in people at high risk of cardiovascular events (*>*20%

10-year risk), " it is likely that the benefits of statins are greater than

potential short-term harms, although long-term effects (over decades) remain

unknown. " They conclude: " Any decision to use statins for primary prevention

should be made cautiously and in the light of an assessment of the patient's

overall cardiovascular risk profile. Widespread use of statins in people at

low risk of cardiovascular events--below a 1% annual all-cause mortality

risk or an annual CVD event rate of below 2% observed in the control groups

in the trials considered here--is not supported by the existing evidence. "

*Latest Oxford Meta-Analysis Not Included *

The Cochrane review did not include the recent meta-analysis from the Oxford

group, published late last year, which showed a clear reduction in events

with statin therapy in primary-prevention patients. Baigent noted that this

meta-analysis was more reliable than the Cochrane review, as the Oxford

researchers used individual patient data from all the trials. " Our 2010

meta-analysis in primary prevention is substantially more complete than the

Cochrane review and provides direct and overwhelmingly statistically

convincing evidence of a clear reduction in events in all patient groups,

right down to those at the lowest risk. "

On the possible hazards of taking these drugs, Baigent says: " Statin therapy

is very safe. The most serious hazard, rhabdomyolysis, is very rare, and

most often seen at high doses. There is a possibility that reducing LDL

cholesterol might increase the risk of hemorrhagic stroke, but even in

primary prevention these hazards would be much smaller than the benefits,

and there is no reliable evidence for other hazards mentioned by the

Cochrane authors, such as depression and cognitive impairment. "

*It All Comes Down to Economics *

Baigent says the only argument against using statins in low-risk people is

economic. " The absolute benefits of statin therapy become very small when

used among people at low absolute risk, so it is important that the costs of

such treatment are considered when weighing how widely statins should be

used. That is a government decision. "

In the UK, the *National Institute for Clinical Excellence* [NICE] currently

recommends that statins not be used for people with a CHD risk below 20%

over 10 years. Ebrahim says the Cochrane conclusions are in line with this.

But Baigent argues that the benefits of statins are clear at levels far

below this threshold. " Whether or not it is economic to use them in the

lowest-risk individuals is not for me to say, but generic statins are now

very cheap, and there is clear evidence of benefit and safety based on

substantial numbers of individuals studied in large-scale trials. So, when

all the relevant randomized evidence is considered, there does not seem to

me to be any justification at all for the Cochrane authors' claim that the

evidence is unclear on this issue. "

*Educational Programs Also of Little Benefit*

In a separate Cochrane review [2], the same group looked at the use of

" healthy heart programs " that use counseling and educational methods to

encourage people to reduce their risks for developing heart disease. These

risk factors include high cholesterol, excessive salt intake, high blood

pressure, excess weight, a high-fat diet, smoking, diabetes, and a sedentary

lifestyle. They reviewed 55 trials that aimed to reduce more than one risk

factor in people without evidence of cardiovascular disease. Results showed

that after a median duration of 12 months of follow-up, multiple risk-factor

intervention was associated with small reductions in risk factors, including

blood pressure, cholesterol, and smoking, but had little or no impact on the

risk of coronary heart disease mortality or morbidity. They conclude: " The

methods of attempting behavior change in the general population are limited

and do not appear to be effective. Different approaches to behavior change

are needed and should be tested empirically before being widely promoted,

particularly in developing countries where cardiovascular disease rates are

rising. "

In an accompanying editorial [3], *Dr Carl Heneghan *(University of Oxford,

UK) suggests an alternative approach for policy is to focus on

populationwide prevention. He reports that " legislating for smoke-free

public spaces, redesigning public spaces to improve exercise, or reducing

daily dietary salt intake prove generally effective and can be cost-saving

interventions. Given the scale of the worldwide CVD problem, large-scale

commissioned studies of multiple risk-factor interventions are urgently

required. "

www.medscape.com

--

Ortiz, MS, RD

*The FRUGAL Dietitian* <http://www.thefrugaldietitian.com>

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