Systematic meta-analyses of randomized clinical trials support using an
intensive statin dose such as atorvastatin 80 mg/day over a moderate
intensity statin. He should stay on atorvastatin 80 mg.
CASE 1.
A 63-year-old man is seen in the office 2 weeks after a ST-elevation myocardial
infarction (MI). A former smoker with hypertension, he was discharged on atorvastatin
80mg daily, dual anti-platelet therapy, long-acting metoprolol, and an ACE inhibitor. One
year before the acute MI, he was prescribed simvastatin 40 mg which was then
increased to simvastatin 80 mg. He stopped the simavastatin 80 mg 2 weeks later after
developing muscle cramps in his legs. At that time he was also on a calcium channel
blocker for his hypertension. Although he has no muscle symptoms since he started the
atorvastatin 80 mg, he is concerned about having had muscle cramps in the past on a
statin and would like to decrease the atorvastatin to 20 mg daily.
I. Which of the following statements is the best answer?
a. Randomized trials of high intensity statin therapy versus moderate
intensity statin therapy have not shown a significant difference in
outcomes. He should decrease the atorvastatin to 20 mg to minimize
adverse effects.
b. Systematic meta-analyses of randomized clinical trials support using an
intensive statin dose such as atorvastatin 80 mg/day over a moderate
intensity statin. He should stay on atorvastatin 80 mg.
c. He should be followed with creatine kinase (CK) values when his lipids
are checked at each visit for the first year.
d. Although his liver panel was normal in the hospital, he should have an
alanine aminotransferase (ALT) done at each subsequent visit.
II. The best answer is b.
Individuals with clinical atherosclerotic cardiovascular disease (ASCVD) are in a
statin benefit group, and if ≤75 years of age, they should be treated with a high
intensity statin unless conditions are present that may increase the risk of
adverse effects. An additional reduction in ASCVD events from a high intensity
statin was shown specifically in individuals with acute coronary syndromes in the
PROVE-IT trial where those assigned to atorvastatin 80 mg/day a greater
reduction in ASCVD events than those assigned to pravastatin 40 mg daily after
2 years of treatment. An additional ASCVD risk reduction benefit was also
observed in 2 randomized controlled trials (RCTs) of atorvastatin 80 mg
compared to either atorvastatin 10 mg or simvastatin 20-40 mg in individuals with
chronic coronary heart disease (TNT and IDEAL). In these trials, there was no
lower limit to LDL–C for eligibility; therefore, individuals with clinical ASCVD
should be treated with a statin regardless of the LDL–C level. Although he did
have muscle symptoms on simvastatin 80 mg, he was able to tolerate
simvastatin 40 mg without difficulty. It is therefore reasonable to initiate
atorvastatin 80 mg with patient instructions to monitor for muscle symptoms.
Although CK may be useful at baseline in certain high-risk individuals or in those
with a history of statin myopathy, the CK should not be routinely measured. In the
statin RCTs, CK elevations occurred with similar frequencies in the statin and
placebo/control groups. A CK should be performed if the patient complains of
severe muscle pain or weakness. This patient may have an SLC01B1 deficiency
to explain the interaction between simvastatin 80 mg/day and the calcium
channel blocker that may have caused his muscle symptoms. He was never
rechallenged to determine whether the muscle aches were indeed caused by the
simvastatin 80 mg. On 12/15/11, the FDA indicated that simvastatin 80 mg
should be used only in patients who have been taking this dose for 12 months or
more without evidence of muscle injury. They emphasized that simvastatin 80 mg
should not be started in new patients, including patients already taking lower
doses of the drug.
On 2/28/12, the FDA determined, based on all available data, including the RCT
data reviewed by the Expert Panel, that “all currently marketed statins appear to
be associated with a very low risk of serious liver injury and that routine periodic
monitoring of serum alanine aminotransferase (ALT) does not appear to detect or
prevent serious liver injury in association with statins.”
Thus, neither routine CK nor liver panel tests are required. Nonetheless, some
patients may experience myalgias with statins. If these recur in this patient now
on atorvastatin, after a wash-out period a dose reduction could be contemplated
at that time, or an attempt with another statin, such as rosuvastatin. If symptoms
persist after a reasonable statin-free interval (2 weeks or more) other causes of
myalgia should be considered.
CASE 2.
After 2 years of treatment with atorvastatin 80 mg daily free of muscle symptoms, the
patient developed progressive muscle pains in both lower legs. He stopped the statin 2
Web-posted 11/12/13, Updated 12/12/13 Page 3 of 18
weeks prior to his clinic visit but the muscle pain and weakness did not noticeably
improve. He now wants to know if he can be switched to red yeast Chinese rice. On
examination, he has mild difficulty getting out of a chair and also has weakness after
doing 3 squats. He remembers he felt fine doing squats at the gym about 6 months ago.
I. Which of the following is the best answer?
a. He should be switched from the atorvastatin 80 mg daily to red yeast
Chinese rice based on evidence in U.S. studies.
b. He should stay off the statin until he is evaluated for possible causes of
his muscle problems. A useful approach is to look for exogenous causes
(e.g., medications, alcohol), systemic causes (examples include
hypothyroidism, rheumatologic disorders such as polymyalgia
rheumatica), and primary muscle disorders. He should be questioned
about a family history of primary muscle disorders or others in the family
with muscle problems taking a statin.
c. He should be switched to rosuvastatin 40 mg daily and given CoQ10.
d. He should be rechallenged with atorvastatin 80 mg daily.
e. If he is African-American, CK levels are not useful in evaluating muscle
symptoms.
II. The best answer is b.
The history is consistent with statin-associated muscle symptoms, but muscle
symptoms on a statin can be mimicked by a variety of other conditions, including
polymyalgia rheumatica in older adults. Because his muscle symptoms had not
shown any improvement within 2 weeks and the muscle weakness persisted
after discontinuing the atorvastatin 80 mg, he was evaluated for systemic causes
of myopathy. His CK was normal but his sedimentation rate was over 100 mm/hr
and he was treated for his polymyalgia rheumatica. In general, statin-related
muscle symptoms begin resolving within 1-2 weeks after statin discontinuation
and muscle symptoms have completely resolved within 2 months. Failure of
muscle symptoms to resolve within this time frame suggests another cause for
the muscle symptoms.
Switching to another statin without determining the underlying etiology for the
muscle symptoms denies the patient the opportunity to have a correct diagnosis.
If his symptoms had instead resolved within two weeks, the cholesterol
guidelines suggest he should be re-challenged with a lower dose of the same
statin or switched to a comparable lower dose of another statin. The statin dose
should then be increased as tolerated.
CoQ10 would not be useful in this case of polymyalgia rheumatica. The data
supporting the use of CoQ10 for statin-associated muscle symptoms is
inconsistent.
African Americans have higher CK levels on average than non African Americans.
However, CK elevation above baseline can still be useful for monitoring statin-associated
muscle symptoms.
Finally, a Chinese formulation containing red yeast rice was shown to reduce
ASCVD events more than placebo in a randomized trial performed in China.
There are no ASCVD outcomes data from U.S. RCTs trials available for red yeast Chinese rice.
intensive statin dose such as atorvastatin 80 mg/day over a moderate
intensity statin. He should stay on atorvastatin 80 mg.
CASE 1.
A 63-year-old man is seen in the office 2 weeks after a ST-elevation myocardial
infarction (MI). A former smoker with hypertension, he was discharged on atorvastatin
80mg daily, dual anti-platelet therapy, long-acting metoprolol, and an ACE inhibitor. One
year before the acute MI, he was prescribed simvastatin 40 mg which was then
increased to simvastatin 80 mg. He stopped the simavastatin 80 mg 2 weeks later after
developing muscle cramps in his legs. At that time he was also on a calcium channel
blocker for his hypertension. Although he has no muscle symptoms since he started the
atorvastatin 80 mg, he is concerned about having had muscle cramps in the past on a
statin and would like to decrease the atorvastatin to 20 mg daily.
I. Which of the following statements is the best answer?
a. Randomized trials of high intensity statin therapy versus moderate
intensity statin therapy have not shown a significant difference in
outcomes. He should decrease the atorvastatin to 20 mg to minimize
adverse effects.
b. Systematic meta-analyses of randomized clinical trials support using an
intensive statin dose such as atorvastatin 80 mg/day over a moderate
intensity statin. He should stay on atorvastatin 80 mg.
c. He should be followed with creatine kinase (CK) values when his lipids
are checked at each visit for the first year.
d. Although his liver panel was normal in the hospital, he should have an
alanine aminotransferase (ALT) done at each subsequent visit.
II. The best answer is b.
Individuals with clinical atherosclerotic cardiovascular disease (ASCVD) are in a
statin benefit group, and if ≤75 years of age, they should be treated with a high
intensity statin unless conditions are present that may increase the risk of
adverse effects. An additional reduction in ASCVD events from a high intensity
statin was shown specifically in individuals with acute coronary syndromes in the
PROVE-IT trial where those assigned to atorvastatin 80 mg/day a greater
reduction in ASCVD events than those assigned to pravastatin 40 mg daily after
2 years of treatment. An additional ASCVD risk reduction benefit was also
observed in 2 randomized controlled trials (RCTs) of atorvastatin 80 mg
compared to either atorvastatin 10 mg or simvastatin 20-40 mg in individuals with
chronic coronary heart disease (TNT and IDEAL). In these trials, there was no
lower limit to LDL–C for eligibility; therefore, individuals with clinical ASCVD
should be treated with a statin regardless of the LDL–C level. Although he did
have muscle symptoms on simvastatin 80 mg, he was able to tolerate
simvastatin 40 mg without difficulty. It is therefore reasonable to initiate
atorvastatin 80 mg with patient instructions to monitor for muscle symptoms.
Although CK may be useful at baseline in certain high-risk individuals or in those
with a history of statin myopathy, the CK should not be routinely measured. In the
statin RCTs, CK elevations occurred with similar frequencies in the statin and
placebo/control groups. A CK should be performed if the patient complains of
severe muscle pain or weakness. This patient may have an SLC01B1 deficiency
to explain the interaction between simvastatin 80 mg/day and the calcium
channel blocker that may have caused his muscle symptoms. He was never
rechallenged to determine whether the muscle aches were indeed caused by the
simvastatin 80 mg. On 12/15/11, the FDA indicated that simvastatin 80 mg
should be used only in patients who have been taking this dose for 12 months or
more without evidence of muscle injury. They emphasized that simvastatin 80 mg
should not be started in new patients, including patients already taking lower
doses of the drug.
On 2/28/12, the FDA determined, based on all available data, including the RCT
data reviewed by the Expert Panel, that “all currently marketed statins appear to
be associated with a very low risk of serious liver injury and that routine periodic
monitoring of serum alanine aminotransferase (ALT) does not appear to detect or
prevent serious liver injury in association with statins.”
Thus, neither routine CK nor liver panel tests are required. Nonetheless, some
patients may experience myalgias with statins. If these recur in this patient now
on atorvastatin, after a wash-out period a dose reduction could be contemplated
at that time, or an attempt with another statin, such as rosuvastatin. If symptoms
persist after a reasonable statin-free interval (2 weeks or more) other causes of
myalgia should be considered.
CASE 2.
After 2 years of treatment with atorvastatin 80 mg daily free of muscle symptoms, the
patient developed progressive muscle pains in both lower legs. He stopped the statin 2
Web-posted 11/12/13, Updated 12/12/13 Page 3 of 18
weeks prior to his clinic visit but the muscle pain and weakness did not noticeably
improve. He now wants to know if he can be switched to red yeast Chinese rice. On
examination, he has mild difficulty getting out of a chair and also has weakness after
doing 3 squats. He remembers he felt fine doing squats at the gym about 6 months ago.
I. Which of the following is the best answer?
a. He should be switched from the atorvastatin 80 mg daily to red yeast
Chinese rice based on evidence in U.S. studies.
b. He should stay off the statin until he is evaluated for possible causes of
his muscle problems. A useful approach is to look for exogenous causes
(e.g., medications, alcohol), systemic causes (examples include
hypothyroidism, rheumatologic disorders such as polymyalgia
rheumatica), and primary muscle disorders. He should be questioned
about a family history of primary muscle disorders or others in the family
with muscle problems taking a statin.
c. He should be switched to rosuvastatin 40 mg daily and given CoQ10.
d. He should be rechallenged with atorvastatin 80 mg daily.
e. If he is African-American, CK levels are not useful in evaluating muscle
symptoms.
II. The best answer is b.
The history is consistent with statin-associated muscle symptoms, but muscle
symptoms on a statin can be mimicked by a variety of other conditions, including
polymyalgia rheumatica in older adults. Because his muscle symptoms had not
shown any improvement within 2 weeks and the muscle weakness persisted
after discontinuing the atorvastatin 80 mg, he was evaluated for systemic causes
of myopathy. His CK was normal but his sedimentation rate was over 100 mm/hr
and he was treated for his polymyalgia rheumatica. In general, statin-related
muscle symptoms begin resolving within 1-2 weeks after statin discontinuation
and muscle symptoms have completely resolved within 2 months. Failure of
muscle symptoms to resolve within this time frame suggests another cause for
the muscle symptoms.
Switching to another statin without determining the underlying etiology for the
muscle symptoms denies the patient the opportunity to have a correct diagnosis.
If his symptoms had instead resolved within two weeks, the cholesterol
guidelines suggest he should be re-challenged with a lower dose of the same
statin or switched to a comparable lower dose of another statin. The statin dose
should then be increased as tolerated.
CoQ10 would not be useful in this case of polymyalgia rheumatica. The data
supporting the use of CoQ10 for statin-associated muscle symptoms is
inconsistent.
African Americans have higher CK levels on average than non African Americans.
However, CK elevation above baseline can still be useful for monitoring statin-associated
muscle symptoms.
Finally, a Chinese formulation containing red yeast rice was shown to reduce
ASCVD events more than placebo in a randomized trial performed in China.
There are no ASCVD outcomes data from U.S. RCTs trials available for red yeast Chinese rice.
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