A Statin a day...

[Ivor the Engineer]

The results of a trial testing statins in healthy people has been published today, showing a significant risk reduction in cardiac events.

http://content.nejm.org/cgi/content/full/NEJMoa0807646

ABSTRACT
Background Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment.

Methods We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes.

Results The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P=0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P=0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes.

Conclusions In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events.

The editorial in the NEJM comments:

http://content.nejm.org/cgi/content/full/NEJMe0808320

The aphorism "prevention is better than cure" makes perfect sense when applied to healthy habits such as following a sensible diet, maintaining an ideal body weight, exercising regularly, and not smoking. But increasingly, prevention of cardiovascular disease includes drug therapy, particularly statins to lower cholesterol levels. Statins were first tested in subjects at high risk for coronary events, and the limits of treatment have subsequently been expanded to include persons at progressively lower risk.1 The results of the Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER; ClinicalTrials.gov number, NCT00239681 [ClinicalTrials.gov] ), reported by Ridker et al. in this issue of the Journal,2 might push the orbit of statin therapy outward to include even more of the general population. Before pharmacologic treatment for primary prevention is expanded further, however, the evidence should be examined critically.

...

The relative risk reductions achieved with the use of statin therapy in JUPITER were clearly significant. However, absolute differences in risk are more clinically important than relative reductions in risk in deciding whether to recommend drug therapy, since the absolute benefits of treatment must be large enough to justify the associated risks and costs. The proportion of participants with hard cardiac events in JUPITER was reduced from 1.8% (157 of 8901 subjects) in the placebo group to 0.9% (83 of the 8901 subjects) in the rosuvastatin group; thus, 120 participants were treated for 1.9 years to prevent one event.

On the other side of the balance, of concern are the significantly higher glycated hemoglobin levels and incidence of diabetes in the rosuvastatin group in JUPITER (3.0%, vs. 2.4% in the placebo group; P=0.01). There are also no data on the long-term safety of lowering LDL cholesterol to the level of 55 mg per deciliter (1.4 mmol per liter), as was attained with rosuvastatin in JUPITER, which is lower than in previously reported trials. Long-term safety is clearly important in considering committing low-risk subjects without clinical disease to 20 years or more of drug treatment. Finally, the cost of rosuvastatin (roughly $3.45 per day) is much higher than that of generic statins.

The measurement of high-sensitivity C-reactive protein has been shown to improve the estimation of the risk of coronary events.4 An elevated high-sensitivity C-reactive protein level was an entry criterion for JUPITER, but coronary disease is affected by multiple factors, and high-sensitivity C-reactive protein was just one of several indicators of participants' cardiovascular risk. It is unlikely that high-sensitivity C-reactive protein testing is the only way to identify subjects who will benefit from treatment, since statins have reduced the relative risk to a similar extent for every other indicator of cardiovascular risk.1 Ridker et al. suggest, from their meta-regression analysis, that the risk reduction observed in JUPITER was greater than that expected on the basis of previous trials. Meta-regression is not a reliable technique, however, and the early termination of JUPITER owing to the efficacy data probably exaggerated the results to some degree.5

In the near future, will statins be considered standard care once an individual reaches a certain age?

 

[Darat]

I think this will happen more and more as we develop effective and relatively cheap drugs that tackle some of the consequence of growing older. After all a "cure" for old age is something we've been looking for since time immemorial.

 

[Cuddles]

In the near future, will statins be considered standard care once an individual reaches a certain age?

Probably. Asipirin is now used fairly routinely in older people, even though it doesn't have proven benefits for those not diagnosed with heart conditions. From the little I've read, it looks like statins, especially the more recent ones, are much more useful and have less side-effects.

 

[casebro]

That's what I've been saying all along- statins work, but NOT via cholesterol lowering.

Aspirin does too. It does 80% of whatever Statins do.

And apparently Niacin prevents heart disease even better than Statins.

Whereas the Fibrino-things lower cholesterol, but don't help heart disease.

So, the key seems to be lower CRP, ersumpthin...

My latest reading seems to point to auto-immune attacks of arteries. And a genetic link to an auto-immune attack causing hypertension. It ain't the hypertension, it's the attacked arteries? (try googling <o'connor, hypertension, ucsd>)

 

[Soapy Sam]

http://www.cholesterol-and-health.com/Does-Cholesterol-Cause-Heart-Disease-Myth.html
For another view.

 

[kittynh]

well and sadly I was on Crestor. And then my liver started acting up.

It's not uncommon.

Statins are nice, but they do carry other side effects. Even aspirin therapy isn't for everyone.

 

[Dr. Imago]

I tried to start a discussion on this a coupla months ago, but didn't get much interest.

I think this is the future for people who can't/are unwilling to make lifestyle adjustments.

~Dr. Imago

 

[Physiotherapist]

I tried to start a discussion on this a coupla months ago, but didn't get much interest.

I think this is the future for people who can't/are unwilling to make lifestyle adjustments.

~Dr. Imago

Yes and therein lies the problem. People expect to be given a pill to cure all when they are unwilling to make lifestyle adjustments and take any responsibility for their health at all.

Simple lifestyle adjustments such as not smoking, drinking less, including more fruit and veg in your diet, cutting down on red meat, eating more chicken and fish and taking more exercise for at least 30 mins three times weekly to increase your heart rate can go a long way to improving your overall fitness and health.

 

[Ivor the Engineer]

What data are there on the long-term harm (if any) of lowering serum cholesterol levels using statins?

The editorial mentions there is no data for the very low levels (LDL: 1.4mmol/L) achieved during this study.

A related question is what is the strength of the correlations between serum cholesterol levels and ratios and all-cause mortality in the general population?

 

[tusenfem]

Simple lifestyle adjustments such as not smoking, drinking less, including more fruit and veg in your diet, cutting down on red meat, eating more chicken and fish and taking more exercise for at least 30 mins three times weekly to increase your heart rate can go a long way to improving your overall fitness and health.

Actually, I did all that after the doctor found very high cholestrol levels in my blood. I ate almost fat and cholestrol free, I biked to work every day, did tae bo twice a week and basic training twice a week and I love fruit and drank vegetable juice. After a month of doing that my numbers went down from 320 to 310.

 

[Rolfe]

That's from 8.32 to 8.06 mmol/l, for those using SI units. Since we would usually only consider the assay accurate to one digit after the decimal point, at best, then the change has been from 8.3 to 8.1 mmol/l.

Not a lot, and still significantly elevated.

Rolfe.

 

[Ivor the Engineer]

That's from 8.32 to 8.06 mmol/l, for those using SI units. Since we would usually only consider the assay accurate to one digit after the decimal point, at best, then the change has been from 8.3 to 8.1 mmol/l.

Not a lot, and still significantly elevated.

Rolfe.

While still a high TC compared to the average, it's important to know the breakdown of LDL, HDL and Transglycerides to be able to put such a number in context.

http://www.webmd.com/cholesterol-management/guide/understanding-numbers

E.g., if the drop from 320 to 310 after a month consisted of a significant boost in HDL and drop in LDL and Transglycerides, such a total cholesterol value may not be too much to worry about.

 

[Cuddles]

Yes and therein lies the problem. People expect to be given a pill to cure all when they are unwilling to make lifestyle adjustments and take any responsibility for their health at all.

Simple lifestyle adjustments such as not smoking, drinking less, including more fruit and veg in your diet, cutting down on red meat, eating more chicken and fish and taking more exercise for at least 30 mins three times weekly to increase your heart rate can go a long way to improving your overall fitness and health.

While this is a fair point, there is also the all important question - so what? If a pill can be found that allows for a healthy body despite various indulgences, why is that a problem? If the goal is a more healthy population then surely such a pill would be a very good thing, given that rising obesity, cardiovascular disease and so on clearly show the current approaches aren't working.

The problem isn't that people expect a cure-all pill, it's that they will act the same way whether one is available or not. Unless someone comes up with a pill to change human nature, I don't see that changing any time soon.

 

[Soapy Sam]

One problem of reading this forum and columns like Ben Goldacre's "Bad Science" is that one builds up an automatic sceptical response to any heavily advertised (or pushed) medical development, particularly when it's a pill that seems to have multiple positive effects with hardly any downside. If it sounds too good to be true...

So, when my GP prescribed a statin for my congenitally high cholesterol, I was sceptical. I remain so.
I eat a sane diet (though I have little control of diet at work). I never use salt in cooking. I have not owned a frying pan in 30 years. I drink in moderation. I don't smoke. At 53, my BP is typically 125:80 or close to it. 5 ft 11", 182lbs.

I have been on 40mg a day of Simvastatin for several months. Cholesterol decreased from 7.3 to 5.2 , but is now drifting back up- currently at 6.0 No dietary change I'm aware of.

I think I'm seeing a system which has been nudged away from equilibrium and is now returning to it, via gods know what mechanism.
The doc's response is to double the dose.
I'm balking.
First, I suspect we will see a repeat- a dip, followed by a return to previous norms, but now with a high dose of cholesterol suppressant added to the hellacious complexity of the cholesterol / lipid system. If I then go off the stuff, will my levels skyrocket before returning to my norm?

Second, frankly I don't feel any better on the stuff than not. I have noted a significant memory hit in the last few months- I'm having hell doing crosswords for example. This may be coincidence, but I don't think it's imagination.

Third, I'm not biochemist enough to know whether the whole "cholesterol is bad" idea is actually true or not. The link I gave in my earlier post is just one that suggests the story is far from as clear as the pharmas would have us believe- but I have no more reason to believe that argument than it's opposite.

I'm also concerned that these drugs are being pushed so aggressively by GPs. This is (one supposes) because they are honestly convinced statins are a good thing.
But are they right? Or are they just accepting the latest fad?

Is there a scenario in our future where refusal to take these drugs will be seen as akin to smoking- a refusal to play one's part in one's own healthcare, with the suggestion perhaps that unless we take these drugs from childhood on , we may be refused other forms of care?
Certainly I get the imprssion my GP thinks I'm being foolishly perverse, whereas I feel I'm not ill and have no more reason to take this drug than to take -say Vitamin E or Omega-3 oil supplements.

Prevention is better than intervention after the event- but to me, taking exercise and eating sensibly, as I feel I do, are very different from taking a drug because my GP thinks I should, even though I have no symptoms of illness.

Am I just being stubborn? Am I taking scepticism too far? Is the case for statins really so clear cut?
Or is this the biggest pharma-scam of all time?

 

[casebro]

Do you folks know that the Total Cholesterol (TC) number includes 23% of your triglycerides? That a triglyceride number of 400 means an excess (and false) addition of 88 to your TC ? So a low-fat, high carb diet can raise your triglycerides and your TC. You need to view the whole of the lipid panel to judge your problems and 'cures'. I went low-carb last year, my TC is lower than ever. And my insulin usage dropped 90%. It's the carbs that are killing us, not the fats.

 

[Ivor the Engineer]

http://www.guardian.co.uk/society/2008/sep/29/health.medicalresearch

Tests start on pill that could lengthen millions of lives

Tablet aims to cut heart attack and stroke risk
Four-in-one drug could be sold for just $1 a month

Monday September 29 2008

A drug that combines four different medicines and could halve deaths from heart attacks and stroke around the globe will enter human trials this week in London.

The once-a-day polypill has been the dream of doctors for many years, but because the drugs it contains, including aspirin, are cheap, there has been no financial incentive for the pharmaceutical industry to get involved.

Now, however, international teams of researchers, with the backing in the UK of the Wellcome Trust and the British Heart Foundation, are just a few years away from making the polypill an accessible reality.

...

The polypill combines aspirin, a statin to lower cholesterol and an ACE inhibitor and a thiazide to counter high blood pressure in one tablet.

More info. on the polypill at Wiki:

http://en.wikipedia.org/wiki/Polypill

And for those who like their drugs to be "natural":

http://en.wikipedia.org/wiki/Polymeal

 

[Dr. Imago]

Simple lifestyle adjustments such as not smoking, drinking less, including more fruit and veg in your diet, cutting down on red meat, eating more chicken and fish and taking more exercise for at least 30 mins three times weekly to increase your heart rate can go a long way to improving your overall fitness and health.

I'm not disagreeing with you, and clearly this is what I advocate for all patients (and have always said on this forum if you search my posting history). But, surely you've heard the expression: "You can lead a horse to water, but you can't make him drink." My realization, working in a tertiary referral center, is that people will often pick the path of least resistance.

Or, as one of my ex-resident colleagues (who lost roughly 150 lbs the hard way... exercise, dieting, counting calories, etc.) once said, "Food tastes good, exercise hurts." He was motivated. Most people aren't.

At this point, I've all but given up expecting people to quit their bad habits. My new mindset is damage control.

~Dr. Imago

 

[Dr. Imago]

The once-a-day polypill has been the dream of doctors for many years, but because the drugs it contains, including aspirin, are cheap, there has been no financial incentive for the pharmaceutical industry to get involved.

This has also been a huge obstacle in producing an AIDS treatment that is easy to take (i.e., one or two pills a day vs. a handful at various times). Some "rogue" pharmaceutical companies have produced these medications, in combination form, "illegally" to market to African countries and the like. They are met with stalwart and aggressive anti-patent attorneys at various Big Pharma companies.

Taking care of people is a business, folks. We can argue whether or not that is right or wrong on a separate thread.

~Dr. Imago

 

[Skeptic Ginger]

....



In the near future, will statins be considered standard care once an individual reaches a certain age?

In some circles, they already are unless one has a naturally low cardiac risk profile.

 

[Physiotherapist]

While this is a fair point, there is also the all important question - so what? If a pill can be found that allows for a healthy body despite various indulgences, why is that a problem? If the goal is a more healthy population then surely such a pill would be a very good thing, given that rising obesity, cardiovascular disease and so on clearly show the current approaches aren't working.

The problem isn't that people expect a cure-all pill, it's that they will act the same way whether one is available or not. Unless someone comes up with a pill to change human nature, I don't see that changing any time soon.

The problem is that this is totally unrealistic. There will never be one pill that any one person can take for a healthy body or one that will prevent obesity.

To prevent obesity people need some dietary and exercise re-education. Eat less - take in fewer calories of better quality foods, being fruit and veg, chicken, fish and complex carbs rather than sugar and do some exercise. It does not need to be anything fantastic, but some simple walking three times a week and it needs to be something that will increase your pulse rate so that you derive cardiovascular benefit.

The fact is that we have muscles for a reason - we were designed for movement and being a Physical Therapist, I know this better than most.