Should I take a cholesterol tablet? If so, which one?

[TLKeymaster]

Here’s a discussion for comment. When a consensus is reached, more evidence is added, and the language is improved, this may become a POQ.

There is no evidence that taking medications to lower your cholesterol per se is worthwhile.

However, there is good evidence through many studies that statins can be beneficial in the secondary prevention of heart disease ie in people who have already had a cardiovasualar event.

NNT calculates that in secondary prevention, by taking statins for 5 years, 96% receive no benefit. 1 in 83 avoid death, 1 in 39 avoid non-fatal heart attack, 1 in 125 avoid stroke.

There is also some evidence that in selected high risk individuals without a history of cardiovascular disease the benefits of statins may outweigh the ‘disbenefits’. Cochrane says that of ’1000 people treated with a statin for five years, 18 would avoid a major CVD event. They add the caveat that ‘selective reporting of outcomes, adverse events and inclusion of people with cardiovascular disease in many of the trials included in previous reviews of the role of statins in primary prevention make the evidence impossible to disentangle without individual patient data’

http://summaries.cochrane.org/CD004816/statins-for-the-primary-prevention-of-cardiovascular-disease

A systematic review in the Archives of Internal Medicine found no reduction in all-cause mortality over 5 years in primary prevention
Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants.

http://www.ncbi.nlm.nih.gov/pubmed/20585067

NNT calculates that in primary prevention taking a statin for 5 years, 98% receive no benefit. 0 lives are saved, 1 in 60 benefit by preventing a heart attack, 1 in 268 by preventing a stroke. On the flip side, 1 in 10 develop muscle damage.

The WOSCOPS trial demonstrated some benefits for statins in people with a Total Chol > 7

http://mystudies.org/studies.php#studies/2e2d7d45-61e0-4d25-b07d-a79211bc8896/paper

There is good evidence for benefit from Statins in patients with diabetes.
CARDS http://mystudies.org/studies.php#studies/5fbe3273-093f-405b-9097-b1b59470b018/outcome

There is mixed evidence for the use of Statins in patients with hypertension
ASCOT-LLA http://mystudies.org/studies.php#studies/8af5e9e1-df68-453e-b2ff-b3686da471dc/paper
ALLHAT-LLA http://mystudies.org/studies.php#studies/0bd678c9-0d7a-4705-a7ee-1099722ea5af/paper

Although statins do decrease total Cholesterol and LDL levels, there is no evidence that this is the mechanism by which they improve cardiac outcomes.

The benefits of statins are greater at higher doses.
PROVE-IT http://mystudies.org/studies.php#studies/0786bf46-f0ae-4548-a504-9b593d9c4516/paper

There is however no evidence that treating to a target lipid level is worthwhile.

There is no evidence that any class of medications (other than statins) that is aimed at improving lipid level cause a decrease in death or stroke.

In fact, some medications that reduce LDL and increase HDL have shown an increase in mortality. The RADIANCE 2 trail for Torcetrapib was terminated in 2006 and the HPS2-THRIVE trial of niacin were terminated earlier this year when both medications were shown to increase mortality despite favourable outcomes in lipid profiles.

RADIANCE 2 http://www.ncbi.nlm.nih.gov/pubmed/17630038
HPS2-THRIVE http://www.thrivestudy.org

Fibrates added to Statins are of no benefit (why is the combination drug Vytorin still on the market?)
ACCORD http://mystudies.org/studies.php#studies/373d507e-32d6-4d45-8d88-fb54011fdc9b/paper

Fibrates used alone probably have a 10% relative risk reduction in non fatal coronary events in both primary and secondary prevention
(The FIELD study showed a not statistically significant increase in cardiovascualar mortality and all cause mortality but a significant decrease in non fatal MI)
Tools for Practice http://www.acfp.ca/Portals/0/docs/TFP/20131007_090323.pdf
FIELD http://mystudies.org/studies.php#studies/77e3fb39-f1e4-434c-a880-54508db4dc2a/paper

The Person Orientated Questions are:

Should I take a cholesterol tablet?

Yes, if you have had a heart attack, bypass surgery, stents, or are otherwise known to have coronary artery disease.
Yes, if you have a high risk of heart disease.This requires further examination of the evidence. It may be that a cholesterol measurement above a certain level is enough of a risk factor.
Otherwise, no, even if your cholesterol level is above normal.

What tablet should I take?

You should take a statin, starting at a low dose and titrating to a higher dose if you have no problems.
There is no evidence that any one brand of statin has better person-orientated benefits than another.

What if my cholesterol does not come down to a normal level?

There is no evidence that taking another class of medication adds any benefit.

What if I get side effects from a statin and can’t take one?

There is a possible small benefit in taking a fibrate. Fibrates do not decrease your risk of death or stroke, but may decrease your risk of a non-fatal heart attack (by about 10%). That means if your current risk over 5 years of having a heart attack is 10%, Fibrates may reduce the risk to 9%.

What else can I do
Monitor and manage your blood pressure.
Stop smoking.
Go for a walk.
Eat healthily.

[Dr Dan EwaldParticipant]

here is a summary that Ben Ewald did for discussion in the RACGP Red Book editorial committee. Unfortunately the graphs do not copy and paste and I cant see how to upload the word doc.

What evidence supports screening for lipids in general practice patients without CVD?

The kinds of evidence that would support this practice:
• That finding elevated LDL leads to treatment that reduces the risk of death.
• Finding elevated LDL leads to treatment that reduces the risk of non fatal CVD.
• That treatment of elevated LDL with statins reduces the risk of fatal and non fatal CVD.
• That elevated LDL denotes CVD risk beyond what is available from history and physical examination.

• Frequency of testing: What is the pre test probability that normal lipids one year may be followed by elevated lipids in a subsequent year?

The previous editions of the RedBook and much literature supports the concept of addressing overall CV risk rather than a single factor. The predominant risk factor for CV death in Australia is waist hip ratio, as shown by Welborn in the analysis of the 1989 Aust Risk Factor Prevalance study 11 year follow up. Waist:Hip ratio is not included in the Framingham equations, but has a much more powerful effect than cholesterol levels.

(graphs showing the predictive power of waist hip ratio, diastolic BP, trigs, and total chol decline in that order).

Waist:Hip ratio can be easily measured in the clinic, is quicker and cheaper than measuring cholesterol, and denotes risk more strongly so why dont we use it?

Does primary prevention with statins reduce mortality, and is any benefit related to baseline lipid levels?
This question is the topic of many trials and several systematic reviews and meta analyses. The main methodological problem is that many prevention trials have been done on samples that include patients with existing CHD. Here I have summarised 2 reviews:

1) Statins and all cause mortality in high-risk primary prevention. K.Ray Arch Int Med 2010; 170 (12):1024-1031 11 trials, cut date May 09.

A 2010 meta analysis by Ray, has solved this problem by obtaining the data from original trials stratified by prior CHD status. Re analysis shows that primary prevention with statins gave RR 0.91 (ci 0.83-1.01) so a non significant result, based on 65 229 participants and 244000 person years of follow up. One large trial that favoured treatment with statins “Jupiter” specifically recruited people with normal lipids but elevated CRP. [Authors of this trial also have extensive conflicts of interest, such as holding patents on a method for high sensitivity CRP testing]

The paper by Ray also examined the effect of baseline lipids on risk reduction. Figure 4, p 1029. This convincingly shows that the degree of benefit has no relationship to the baseline cholesterol level.

Ray did not report the effect on CVD mortality but this was later calculated by Dentali showing RR 0.89 (0.80-0.99). Now statistically significant but a small effect.

In summary there was no statistically significant effect despite the huge sample size. If we accept the observed RR and apply this to a 60 year person with mortality of 10/1000 person years as observed in these studies, NNT is 1110 for 1 year to prevent one death, or 990 using the number for CVD deaths only.

2) F. Taylor , Cochrane review, Statins for the primary prevention of cardiovascular disease. 14 trials, cut date march 07

Taylor accepted trails with up to 10% secondary prevention patients. This set includes neither JUPITER or ALLHAT, the two biggest contributors to Ray. They wanted to examine the effect by baseline LDL level but the information was missing from many reports.
Effects seen:
All cause mortality RR 0.83 (0.73-0.95) NNT as above, 588-1 yr.
Fatal + non fatal CHD events RR 0.72 (.65-.79)
Fatal + non fatal stroke RR 0.78 (.65-.94)
Revascularisation RR 0.66 (.53-.83)

In summary, the effects of statins on all cause mortality are small, if present, and are not related to baseline LDL level. The effects on non fatal CHD, stroke, and revascularisation are larger. While we could accept that statins have a small benefit in primary prevention it is not based on the baseline LDL level.

The Redbook 7th edition lists testing for lipids in those aged 45 as level A evidence, referencing a NHF position statement, however the position statement does not examine screening, only treatment.

Should lipids be re-measured?
Evidence from child-to adult cohort studies such as the Bogalusa heart study shows considerable tracking of lipid levels. People tend to stay in their quartiles. I could not find any reports of the natural variation in untreated lipid levels over time but the evidence must exist.

Proposed changes to guidance
Measure lipid levels once at age 35, to detect those with familial hypercholesterolaemia, (prevalence about 0.2%) then not again unless people are high risk on other grounds.

BMI, Waist,or Waist:Hip ratio?
Welborn examined the predictive values of various ways to measure obesity, as shown in the figure below, showing that Waist:Hip ratio is much more predictive than BMI, or Waist circumference.

[TLKeymaster]

Thanks Dan,

The studies quoted by Ben confirm that the benefits of statins are unrelated to the baseline LDL level, but they do have some benefit in primary prevention. The extent of that benefit is dependent on absolute cardiac risk.

Measuring lipids once to determine absolute cardiac risk (at age 35-55) seems like a valid recommendation.
Improve the factors that can be improved (smoking, blood pressure).
If risk remains > X %, Statins may be indicated in primary prevention. (is X = 15%?)

[TLKeymaster]

This week, the American College of Cardiology and American Heart Association (ACC/AHA) released new guidelines for the management of Lipids.

The new guidelines are a major shift in thinking. They are far closer to the proposed POQ in the discussion above than to the previous guidelines. Spooky. This is clearly cause and effect. Who would have thought we had that much influence?

Key points in new guidelines.
Treating to LDL cholesterol targets is no longer recommended.

Patients should receive Statins if they fall into one of these four groups.

• Patients with clinical atherosclerotic cardiovascular disease (ASCVD) should receive high-intensity (age, <75) or moderate-intensity (age, ≥75) statin therapy.
• Patients with LDL cholesterol levels ≥ 4.9 mmol/L should receive high-intensity statin therapy.
• Diabetic patients aged 40–75 with LDL cholesterol levels of 1.8–4.9 mmol/L and without clinical ASCVD should receive at least moderate-intensity statin therapy (and possibly high-intensity statin therapy when estimated 10-year ASCVD risk is ≥7.5%).
• Patients without clinical ASCVD or diabetes but with LDL cholesterol levels of 1.8-4.9 mg/dL and estimated 10-year ASCVD risk ≥7.5% should receive moderate- or high-intensity statin therapy.

High-intensity statin therapies are atorvastatin (40–80 mg) or rosuvastatin (Crestor; 20–40 mg). Moderate-intensity statin therapies include atorvastatin (10–20 mg), rosuvastatin (5–10 mg), simvastatin (20–40 mg), pravastatin (40–80 mg), and several others.

With few exceptions, use of lipid-modifying drugs other than statins is discouraged.

Lifestyle modification is recommended for all patients, regardless of cholesterol-lowering drug therapy.

These guidelines use a new ten year risk calculator which includes both coronary events and stroke, and is only available as an Excel spreadsheet currently.
This is different to the calculators used in Australia, as per another discussion on this site.

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