Bacon will kill you,
But damn is it delicious!
Here’s to more Statins!
How do statins work?
HMG-CoA Reductase Inhibitor
Behold – the power of the statin
Statin Use
• Clinically, statins are prescribed to people who fail
to have meaningful reduction of lipid panel
values after attempting the following
interventions:
– Lifestyle Modification
– Healthier Diet
– Increased Physical Exercise
• How many people succeed with these
interventions?
• Who benefits from statins?
Lipid-lowering guidelines EBM?
• 2001, Americans on statins ↑ from 13M to
36M based on NCEP ATP III guidelines
– Most of these people in “moderate” risk group
• No clinical evidence of occlusive disease
• ? What percentage of people on statins are in:
– High risk group:
– Moderate risk group:
– Low risk group:
Statin Usefulness
• Primary prevention?
– Elevated lipids w/o history of heart disease
Why statins fail in primary prevention
• Current guidelines are based on the assumption
that cardiovascular risk is a continuum
• ASSUMES that evidence of benefit in people with
occlusive vascular disease (secondary prevention)
can be extrapolated to primary prevention
populations
• This assumption, plus the assumption that
cardiovascular risk can be accurately predicted,
leads to the recommendation that a substantial
proportion of the healthy population should be
placed on statin therapy
Statin Usefulness
• Secondary prevention?
– Decreasing mortality in people with pre-existing
CVD
Statin Usefulness
• Secondary prevention?
– Decreasing mortality in people with pre-existing
CVD
BULLSHIT
What you see as a practicing physician
ACP Internist Newsletter, 03/03/2014
Statin challenges may allow some with
myalgia to continue their regimen
November 2013
Pooled Cohort Eq. Predicts 10-year Risk
2013 ACC/AHA Guideline on the
Treatment of Blood Cholesterol
2013 ACC/AHA Guideline on the
Treatment of Blood Cholesterol
• High-intensity therapy for ♂ and ♀ < 75 with
clinical ASCVD
• LDL-c > 190 mg/dL or TG > 500 mg/dL
evaluate for secondary causes of
hyperlipidemia
• Moderate-intensity therapy for 40-75 yo IDDM
• LDL-c 70-189mg/dL, w/o clinical ASCVD OR
DM should be treated w/ moderate-to-highintensity therapy
Lower cholesterol as much as
possible?
• Recently, Getz et al calculated that in Norway,
one of the healthiest nations in the world,
about 85% of men and more than 20% of the
women over age 40 would be classified as
high risk using the new criterion. If followed,
the new recommendations might therefore
put most of the Western world’s adult
population on statin therapy.
Are high statin doses safe?
• In the Treating to New Targets (TNT) trial, the only
study comparing a low and high dose of the same
statin, not even 80 mg atorvastatin was able to lower
mean low density lipoprotein cholesterol below 1.81
mmol/l.
• Clinical experience has taught us that a dose increase
of that size of any drug will inevitably increase both the
number and the seriousness of side effects. This
apparently did not concern the authors, who
concluded, “Intensive lipid lowering therapy with 80
mg of atorvastatin per day in patients with stable CHD
[coronary heart disease] provides significant clinical
benefit.”
Are high statin doses safe?
• In the Incremental Decrease in End points through
Aggressive Lipid lowering (IDEAL) trial, which compared
usual dose simvastatin with 80 mg atorvastatin, no
significant difference was seen on the major end points.
• 90% of participants in both groups had side effects, and in
almost half of them they were recorded as serious.
• The authors of the IDEAL trial did not comment on this
except that, “there was no difference between the groups
in the frequency of adverse events that were rated as
serious”; neither did they inform readers about the nature
of these events.
Adverse effects of statins
• Heart failure:
– Inhibit the synthesis of hydroxymethylglutaryl coenzyme A
reductase, an enzyme involved in synthesis of the precursor of
cholesterol and other important molecules such as coenzyme
Q10, vital for mitochondrial energy production.
– Thus statins lowerplasma Q10 concentrations and worsen
cardiac function in patients with heart failure, and oral
coenzyme Q10 can improve or prevent this serious
complication.
– Heart failure has not been reported with statins, possibly
because it has been seen to be the result of the primary disease
rather than an adverse effect but also because patients with
imminent or manifest congestive failure are routinely excluded
from statin trials.
Adverse effects of statins
• Myalgia and rhabdomyolysis:
– Claimed to occur in less than 1% of patients taking
statins
– 22 professional athletes with familial
hypercholesterolaemia who were treatedwith
various statins, sixteen discontinued the
treatment because of muscle side effects
• 4.2 cases of rhabdomyolysis per 100 000
patient years after atorvastatin treatment
– Relative risk increase of 100% in untreated
Adverse effects of statins
• Mental and neurological symptoms:
– Cholesterol is required for your brain to work
– Severe irritability, aggressive behaviour, suicidal
impulses, cognitive impairment, memory loss,
global amnesia, polyneuropathy, and erectile
dysfunction.
– In many cases the symptoms were reversible and
re-occurred after re-challenge.
• Cancer:
Adverse effects of statins
– Problem with followup
• Significant increase in breast cancer was seen in the cholesterol and
recurrent events trial (CARE), with most cases being recurrences.
– Since then patients with a history of cancer have been excluded from statin
trials
• To my knowledge, no trial has analyzed cancer incidence separately for
smokers and nonsmokers.
• In the trial of pravastatin in elderly individuals at risk of vascular disease
(PROSPER), the only statin trial exclusively in elderly people, the significant
increase in cancer mortality neutralized the benefit from fewer
cardiovascular deaths.
– Finding dismissed by referring to a meta-analysis of all statin trials that failed
to find an association with cancer, but the authors ignored mentioning that
the mean age of participants in these trials was about 25 years lower than in
PROSPER.
Simvastatin impairs exercise training
adaptations J Am Coll Cardiol. 2013 Aug 20;62(8):70914. doi: 10.1016/j.jacc.2013.02.074. Epub 2013 Apr 10
• 37 participants (exercise plus statins: n = 18; exercise only: n = 19)
completed the study. Cardiorespiratory fitness increased by 10% (p <
0.05) in response to exercise training alone, but was blunted by the
addition of simvastatin resulting in only a 1.5% increase (p < 0.005).
Similarly, skeletal muscle citrate synthase activity increased by 13% in
the exercise-only group (p < 0.05), but decreased by 4.5% in the
simvastatin-plus-exercise group (p < 0.05)
• Simvastatin attenuates increases in cardiorespiratory fitness and
skeletal muscle mitochondrial content when combined with exercise
training in overweight or obese patients at risk of the metabolic
syndrome.