When should CT calcium score be used? This simple calculator may help

In primary prevention, CT calcium scoring has been suggested to help decision making surrounding statin use.

Some of the underlying concepts are somewhat complex, but the screening paradigm remains that of matching the intensity of preventive efforts with the individual’s absolute risk.

The appropriateness of CT calcium scoring in an individual patient therefore depends on

-       patient’s pretest probability of atherosclerotic cardiovascular disease

-       potential benefits of preventive therapies

-       negative aspects and risks of preventive therapies

-       patient preference

In many cases, “patient preference” was the influencing factor and determines if CT calcium scoring is useful.

-       On one end of the spectrum, patients may be very risk averse and would prefer to be on preventive therapies despite lowish absolute risk of cardiovascular disease.

-       On the other end of the spectrum, patients may be very medication averse and would prefer NOT to be on preventive therapies despite highish absolute risk of cardiovascular disease

In these cases, this simple calculator may help us. From the MESA cohort data, we can obtain the probability of a non-zero CT calcium score and the predicted calcium score for an individual patient prior to the CT test, based on age, gender, and ethnicity alone.

These probabilities are incredibly useful for clinicians and patients. By considering the probabilities of various scores, including non-zero CT calcium score, it prompts clinicians and patients to carefully consider what they would do with the CT calcium score results. After considering the permutations of test results, one often arrives on a sensible strategy without performing such test. In other situations, one may find the probabilities of needing treatment vs. not needing treatment as toss-up, which reinforces the need for the CT calcium score test.

As case examples, try

(a) 65M, white, who is risk averse, and would like statins unless he has a calcium score of 0;

(b) 45F, Chinese, who is treatment averse, and would not want to be on a statin if at all possible.

The limitation of such calculator is that other risk factors are not taken into account, hence making it necessary for clinicians to adjust these probabilities.

NSAIDs and MI risk

Nonsteroidal anti-inflammatory drugs (NSAIDs) use is associated with a significantly increased risk for myocardial infarction (MI). This includes naproxen, considered by some as one of the safest drugs in this class. This is according to a new patient level meta-analysis from the University of Montreal, studying celecopxib, diclofenac, ibuoprofen, naproxen and rofecoxib.

The increase in MI risk for current NSAID use was 20% to 50% compared with those not using these drugs. This was found for all traditional NSAIDS, including naproxen. The risk for acute MI for celecoxib was not greater than that for traditional NSAIDs and was lower than that for rofecoxib.

Acute MI risk associated with NSAID use

-       Celecoxib: odds ratio 1.24 (0.91-1.82)

-       Ibuprofen:  odds ratio 1.48 (1.00-2.26)

-       Diclofenac: odds ratio 1.50 (1.06-2.04)

-       Naproxen: odds ratio 1.53 (1.07-2.33)

-       Rofecoxib: odds ratio 1.58 (1.07-2.17)

Other important points include

-       The increased MI risk occurred as early as the first week of NSAIDs use.

-       Use of higher doses was associated with increased MI risk.

-       Longer duration of treatment generally did not seem to be associated with greater probability of increased MI risk, i.e. for duration of treatment, risk does not go away but does not increase further

The exact mechanism is unknown, but may be related to the selective COX-2 enzyme inhibition, which may increase blood pressure.

The increased MI risk occurred as early as the first week of NSAIDs use and the risk was greater with higher doses.

Reference:

Bally et al. Risk of acute myocardial infarction with NSAIDs in real world use: Bayesian meta-analysis of individual patient data. BMJ 2017;357;j1909.

Patient centered discussion of primary prevention statin therapy

Statin use in primary prevention of cardiovascular events in the general practice setting has always been a difficult topic, for both patients and physicians.

Decision making depends on various factors, including:

-       individual patient's cardiovascular risk calculation

-       patient perception of and/or aversion towards cardiovascular events

-       patient perception of and/or aversion towards statin medication

-       physician preference

It is often hard to communicate these complex concepts in 5 to 10 minutes.

The Mayo clinic has recently published an electronic tool called “Statin Choice Decision Aid”, which is immensely valuable in helping patients visualize cardiovascular risk, and the benefit of statin medications as applied to them.

The above example is a hypothetical patient’s graphics, after entering basic demographics, examination and laboratory data. The graphics illustrates the patient’s current heart attack risk over the next 10 years, and contrasts that with this heart attack risk if he takes high dose statins.

In this case example, the patient has "a 16% baseline absolute risk of cardiovascular events over the next 10 years. Statin therapy reduced such risk by 38%, resulting in a residual absolute risk of 10%."

As we can all see, the graphics is way easier to understand than my previous paragraph.

I hope that GPs will find this tool useful in their rooms too.

https://statindecisionaid.mayoclinic.org/index.php/statin/index

Beta-blockers in Hypertension

Case

70-year-old asymptomatic man with hypertension but not cardiovascular disease presented for a routine check. His pulse rate was 40bpm.  His son, aged 45, recently had an MI in Australia.

His medications include

-       Doxazosin 8mg OD

-       Metoprolol 95mg CR OD – since 2006

-       Cilazapril 5mg / Hydrochlorothiazide 12.5mg OD

ECG shows sinus bradycardia, with normal PR interval, QRS duration.

Discussion

Without proven cardiovascular disease, in particular, angina and/or heart failure, the role of beta-blockers for hypertension is debatable.  Even though he is asymptomatic from the sinus bradycardia, it would be useful to adjust his medications with less beta-blockade, and introduce calcium channel blocker.

First line agents for hypertension are one of three classes:

-       ACE inhibitors or Angiotensin receptor blockers

-       Thiazides

-       Calcium channel blockers

There may be some advantage of using ACEi/ARB in the young vs. CCB/thiazides in the older population where isolated systolic hypertension is more prevalent.

β-blocker is generally NOT preferred as first line agent. (JNC8) The exceptions are in the settings of post-myocardial infarction, and heart failure.

Drug preference is mainly influenced by co-morbidities and contraindications, rather than a simple age cut-off. 

Author: Dr Andrew To

Hypertension treatment – how should we choose?

First line agents for hypertension are one of three classes:

-       ACE inhibitors or Angiotensin receptor blockers

-       Thiazides

-       Calcium channel blockers

Drug preference is mainly influenced by co-morbidities and contraindications, rather than a simple age cut-off. 

Co-morbidities & Preferred anti-hypertensive agents

Renal dysfunction,  Microalbuminuria, ESRD, Proteinuria

ACEi/ARB

Prior MI

bB, ACEi/ARB

Angina

bB, CCB

Heart failure

Diuretics, bB, ACEi/ARB, spironolactone

AF, prevention

ARB/ACEi, bB, spironolactone

AF, rate control

bB, Diltiazem

Metabolic syndrome

ACEi/ARB, CCB

Isolated systolic hypertension in elderly

Diuretics, CCB

Pregnancy

Methyldopa (category B); 

bB, CCB (category C)

Diabetes

ACEi/ARB

Aortic aneurysm

bB

Peripheral arterial disease

ACEi, CCB

Anti-hypertensives agents & Contraindications

Thiazides

Gout. Metabolic syndrome. Glucose intolerance, Pregnancy, Hypercalcaemia, Hypokalaemia

Beta-blockers

Asthma. AV block. Metabolic syndrome. Glucose intolerance. Athletes and physically active patients. COPD unless vasodilator bB. 

Dihydropyridines CCB

Tachyarrhythmia. ?Heart failure.

Verapamil, Diltiazem CCB

AV block. Severe LV dysfcuntion. Heart failure.

ACEi / ARB

Pregnancy. Women with child bearing potential. Angioneurotic oedema. 

HyperK. Bilateral renal artery stenosis

Spironolactone

Acute or severe renal failure. HyperK

Author: Dr Andrew To

ECG Case 2016-09

Scenario

32-year-old man presented with cough, breathlessness on exertion and interscapular pain. His ECG was as below.

- Reassure

- CXR, reassure

- CXR, take a more detailed history, then reassure

- CXR, full history, refer for further assessment

Discussion

The patient has Wolff-Parkinson-White ECG with pre-excitation manifested by delta waves and a shortened PR interval. His main symptoms are likely a minor respiratory illness, hence making the ECG findings incidental.

A detailed history needs to be taken to ascertain family history of sudden cardiac death and personal history of palpitations, dizziness/faints or longstanding breathlessness on exertion. Occupational history (e.g. pilot, or heavy machinery operator) is also important.

WPW risk lies in rapidly conducted pre-excited SVT or AF, which may lead to hemodynamic compromise, VT, VF or even sudden death.

Investigations include

- Exercise tolerance test to assess the maximum rate of antegrade accessory pathway conduction. This is demonstrated by the disappearance of delta waves during exercise. If delta waves disappear at low heart rate, antegrade accessory pathway becomes refractory at a lower heart rate, conducts less rapidly, and hence less risky.

- Echocardiography to exclude structural cardiac abnormalities such as Ebstein’s anomaly and hypertrophic cardiomyopathy

- Holter monitoring if symptoms of palpitations

Treatment

- Radiofrequency ablation is successful in over 95% cases and is the mainstay of therapy.

- Acute pre-excited SVT cannot be treated with AV blocking agents such as betablockers, diltiazem and verapamil.

- Acute pre-excited SVT can be managed with procainamide (class I antiarrhythmic) or amiodarone (class III antiarrhythmic). Flecianide may also be considered.

Author

Dr Seif El-Jack

Individual risk assessment - a common scenario

Scenario

A 40-year-old Maori man came for routine review concerned because his 38-year-old brother, who was a smoker, died suddenly of a heart attack. The patient was athletic, previously played professional rugby, without clinical risk factors.

-      BMI 28

-      LDL 4.9; TC/HDL ratio 4

His calculated cardiovascular risk on these parameters was low. A reasonable approach would include

1)     reinforcing healthy living and reassessing in 5 years

2)     reinforcing healthy lifestyle and starting a statin

3)     reinforcing healthy lifestyle, getting a CTCA, starting a statin

4)     all of the above

Discussion

Being Maori with an immediate first degree relative having proven cardiovascular disease will adjust the calculated cardiovascular risk from low to moderate. However, this adjustment remains arbitrary. Because of his young age, his calculated 5-10 year cardiovascular risk is underestimating his lifetime cardiovascular risk.

Reinforcing lifestyle approach may seem adequate based on risk figures alone, though it is not unreasonable to start a statin on the LDL alone, notwithstanding the significant family history. (ACC/AHA Guidelines 2013)

A more comprehensive approach may be that he gets a statin and a CTCA to delineate his coronary anatomy and may be reinforce compliance. However, evidence for routine CTCA in this situation is currently less robust.

Author

Dr Seif El-Jack

Are cardiologists obsessed with statins?

Scenario

Sam is a 60-year-old male heart attack survivor who had an unremarkable recovery after the successful coronary artery stenting in the middle of the night of his presentation. Now it is 3 months and Sam feels absolutely grand. At follow-up, his cardiologist insists that he should continue all the prescribed medications. He read on the internet some bad press about statin medications and thought, “surely, nothing will happen if I stop taking statins?!”

Discussion

As cardiologists, we all believe that the statin beneficial effects are indisputable.  A lot of the evidence has been based on randomised controlled trials based on highly selected trial patients.  And for this reason, the lack of real-life data is sometimes suggested as a weakness in such argument.

A Danish nationwide prospective cohort study was recently published in the European Heart Journal.  This study is unique in that it followed the entire Danish population from 1995 to 2010.  This is real-life data, including everyone over 40 years of age who were initiated on statin therapy, totalling 674 900 individuals. 

Two important take home messages from the study (and therefore applicable for Sam in the above scnaerio) were:

1.     Early statin discontinuation was associated with myocardial infarction and death, with a hazard ratio of 1.26 and 1.18 respectively.  In plain English, those who stopped taking a statin early early on were 26% more likely to have an MI and 18% more likely to die, during follow-up.

2.     Early statin discontinuation was quite significantly influenced by negative news stories. Many of these negative news stories were based on hearsay criticisms of poor-quality reports. Clinicians continue to have a central role of debunking the “statin myth”.

The technical details of the paper are as below:

Early statin discontinuation was positively associated with these factors:

1.09 (1.06–1.12) for negative statin-related news stories,

1.04 (1.02 – 1.07) per increasing calendar year,

1.04 (1.02 – 1.06) per increasing defined daily dose of statin,

1.05 (1.03 – 1.06) for male sex,

1.13 (1.11 – 1.15) for living in cities,

1.67 (1.63 – 1.71) for other ethnicity than Danish,

Early statin discontinuation was positively associated with these factors:

0.92 (0.90–0.94) for positive statin-related news stories,

0.73 (0.72–0.74) for baseline cardiovascular disease,

0.91 (0.90–0.93) for baseline diabetes

(odds ratio; 95% confidence interval)

Reference

Nielsen SF, Nordestgaard BG. Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: a nationwide prospective cohort study. Eur Heart J. 2015 Dec 1.  PMID: 26643266

Author

Dr Andrew To

Atrial Fibrillation and Coronary Artery Disease: Aspirin and Oral Anticoagulants

Scenario

A normally well 76-year-old lady had an NSTEMI 2 years ago and had successful stenting with a drug eluting stent (DES) for a severe left anterior descending artery narrowing. She had residual mild diffuse disease elsewhere.

After 12 months of dual antiplatelet therapy with Aspirin and Ticagrelor, she is now on Aspirin, in addition to Atorvastatin 40mg and Cilazapril 2.5mg for hypertension.

When seen in clinic, she reported no angina but was found to have new incidental asymptomatic atrial fibrillation.  She had no history of stroke or TIA.

The best strategy for managing her stroke risk is

1)  Aspirin alone

2)  Aspirin plus Warfarin

3)  Aspirin plus Dabigatran

4)  Warfarin alone

5)  Dabigatran alone

Discussion

Her CHA2DS2VASC score is high at 5 indicating an annual stroke risk of 6.7%. She will require anticoagulation.

The more conclusive evidence of Aspirin is after an ACS and certainly in the first 6-12 months after a DES.

The combination of Aspirin and oral anticoagulation (Warfarin or newer novel oral anticoagulant) increases the risk of bleeding (especially gastrointestinal) without additional vascular benefit.

The aspirin could be stopped and oral anticoagulation started. If a novel oral anticoagulant is chosen, one needs to be cautious with the usual contraindications, including advanced age and renal function.

Author

Dr Seif El-Jack

Dual anti-platelet therapy and non-cardiac surgery

Scenario:

A 75-year-old male is now 7-month post anterior myocardial infarction. He had successful proximal LAD drug eluting stent, currently on Aspirin and Ticagrelor. He is awaiting total hip joint replacement, and the orthopaedic surgeon would like to know whether he could stop his anti-platelets.

Thinopyridines in combination with Aspirin should in general continue for:

• At least 12 months after ACS – Stent (DES or BMS) or No Stent
• 1 month after BMS (Bare Metal Stent) in stable CAD
• 6 – 12 months after DES (Drug Eluting Stent) in stable CAD – some recent evidence that the duration can be shortened to 3 months in special circumstances with modern stents (after discussion with cardiologist)

Dual antiplatelet therapy interruption

Whether to discontinue depends on: type of surgery, comfort level of the surgeon, time from the index stent procedure, type of stent used and vessel treated.

General guide for stopping dual anti-platelet prior to non-cardiac surgery:

• Aspirin not to be stopped
• Clopidogrel 5 days prior to surgery
• Ticagrelor 5 days prior to surgery
• Prasugrel 7 days prior to surgery

The key point here is that there is much variation between individual patients, depending on both the cardiac and non-cardiac issues. Cardiologists should be consulted before stopping such therapy so that we could come up with the best solution for the individual patient.

In the scenario above, how we deal with the Ticagrelor around the time of hip surgery would most likely depend on the technical aspects of the STEMI and stent implantation, as well as the urgency of the hip surgery. 

Author:

Dr Ali Khan

CT coronary angiography - Cases

Scenario 1:

A 45-year-old man with no prior cardiac history, but with cardiovascular risk factors including a 10-pack-year smoking history stopped last year, 5-year history of Type II diabetes on Metformin, obesity with BMI of 37, without a family history of premature coronary artery disease, now presented with exertional but inconsistent central chest tightness.

He was investigated extensively, including a negative exercise tolerance ECG at 13 minutes without symptom or ECG change.  Despite reassurance, his chest pain continued at random, and has not resolved with a course of Omeprazole for presumed non-cardiac (possibly gastrointestinal reflux) chest pain.

What should we do?

-       Reassure him that this pain is almost certainly non-cardiac

-       Perform a stress echocardiogram as it has a higher sensitivity than an exercise ECG

-       Perform an invasive angiography

Scenario 2:

A 50-year-old woman with no prior cardiac history, but with her only cardiovascular risk factor being essential hypertension on thiazides for last 5 years, now presented with atypical chest pain at rest and never on exertion.

She was again investigated extensively, with a positive exercise tolerance ECG at 9 minutes, with 1-2 mm inferolateral ST depression at peak exercise and early recovery.

What should we do?

-       Reassure her that this pain is almost certainly non-cardiac.  The exercise tolerance test must have been falsely positive.

-       Perform a stress echocardiogram as it has a higher specificity than an exercise ECG

-       Perform an invasive angiography

Scenarios explained

Both scenarios are classic dilemmas that cardiologists face. One cannot assert that one particular option is always right or wrong.  The pre-test probability of obstructive coronary artery disease in both cases is reasonably small, but not absolutely zero. 

Performing invasive angiogram will almost certainly lead to a significant probability of normal or near-normal coronary angiograms, arguing that risks associated with the invasive procedure might have been unnecessary.  Reassurance will almost certainly be fine most of the time, except the infrequent cases where obstructive coronary artery disease is missed.  

CT coronary angiography could therefore be considered for both these scenarios, and in more general terms, cases with intermediate probability of finding of obstructive coronary artery disease.

Because of intrinsic limitations of CTCA, interpretation could be difficult, and should be in the context of the clinical picture, as well as the scan quality. A collaborative team approach between imaging and interventional cardiologists is essential.

Author:

Dr Andrew To

CT coronary angiography - How good is it?

CT coronary angiography

CT coronary angiography has now been routinely performed, at least in the Waitemata area since 2011, where we were the first to implement CTCA in the workup of acute chest pain in New Zealand.

There has been significant improvement in image quality and radiation dose reduction. Depending on body habitus, most scans with prospective ECG gating can be done with 1mSv (background radiation = 3mSv/year).

CTCA provides anatomical information on coronary artery stenosis, similar to invasive angiography. 

This is different to to routine functional testing such as exercise treadmill ECG (ETT), exercise stress echocardiogram (ESE), nuclear stress test or even adenosine stress MRI.

Compared to invasive angiography,

CTCA has a high negative predictive value. i.e. normal CTCA with good image quality means that the patient does not have coronary artery disease. This can be said with a high degree of confidence.

However, CTCA has moderate positive predictive value. When plaques are seen, we may not be able to quantify the exact severity. This depends entirely on image quality.

CTCA has changed how we should deploy the various tests for troponin-negative chest pain.

- Suitable patients may proceed directly to CTCA rather than exercise treadmill testing to rule out coronary artery stenosis.

- In others, CTCA should be used instead of invasive angiography. This minimises risks and complications!

Author:

Dr Andrew To

Treatment of hypertriglyceridemia

Scenario

-       45M with no other cardiovascular risk factor, presented with HDL 0.6, LDL 2.6, triglyceride 4.5; no prior ischaemic heart disease; failed lifestyle modifications

Issue

-       What to do with a high triglyceride, low HDL, but reasonably normal LDL?

Lovely dessert @ Meredith's 2015. 

Clinical points

-       Epidemiology

o   Prevalence of hyperlipiaemia is high. Its incidence is highest in patients with premature coronary artery disease

o   Disturbances in lipoprotein metabolism are often familial, and may include lipoprotein(a) excess, hypertriglyceridemia with hypoalphalipoproteinemia, and combined hyperlipidemia

-       Associated abnormalities

o   Elevated triglyceride; Low HDL; Elevated small, dense LDL particles

o   Atherogenic triglyceride-rich lipoprotein remnants

o   Insulin resistance

o   Increases in coagulability and viscosity

-       Needs to exclude

o   Poorly controlled diabetes

o   Nephrotic syndrome

o   Hypothyroidism

o   Obesity

-       Non-drug therapy

o   Weight loss via hypocaloric diet

o   Aerobic exercise

o   Strict glycemic control in diabetics

o   Other lifestyle interventions for cardiovascular health

-       Drug therapy

o   STATINS!

§  No direct trials of statins at patients with normal LDL but elevated triglycerides

§  However, the cardiovascular event reduction with statins were equally observed in those with high triglyceride levels

o   Targeted HDL/triglyceride drug therapy

§  Fibrates – raises HDL, lowers triglyceride

§  Nicotinic acid – raises HDL

§  BUT, no strong evidence that these medications reduce cardiovascular events

§  Combining these non-statin agents to statins may increase adverse effects

In the scenario above

-       Emphasis on lifestyle changes!!!

-       May consider drug therapy if lifestyle changes fail

-       Drug of choice – low dose statin (e.g. Atorvastatin 20mg)

-       May consider further risk stratification with CT coronary angiography (if patient is reluctant to start statin for primary prevention)

Author:

Dr Andrew To

Vitamin D and stain myalgia

Scenario

-       55M IHD with prior stents; prior myalgia with Simvastatin and Atorvastatin; but yet still more myalgia with Pravastatin. The treating physician decided to check his vitamin D level and his coenzyme Q10 level.

Issue

- Which one, vitamin D level or coenzyme Q10 level, is relevant in statin myalgia?

Sunrise @ Pukehina Beach 2015

Discussion

A recent study on vitamin D and statins is intriguing.  A meta-analysis of seven observational studies with 2400 patients showed that patients with statin associated myalgia has significantly lower plasma vitamin D levels and those without muscle ache. (1)

A small study further demonstrated that in statin intolerant patients who had a low vitamin D level of <32ng/mL, weekly 50,000 to 100,000 units of vitamin D supplementation resulted in an improvement in statin tolerance.  In fact, at 24 months, 95% of those who had normalised vitamin D levels remain on the statin. (2)

Certainly, this will need further study due to the small number of patients in these trials. However, it may be another useful strategy to try.

On the other hand, coenzyme Q10 does not appear to be effective in the treatment of statin related myalgia, according to a recent meta analysis of randomised controlled trials demonstrating the lack of effectiveness of coenzyme Q10 supplementation on either muscle pain or plasma creatine kinase (CK) level. (3)

References 

Michalska-Kasiczak M, Sahebkar A, Mikhailidis DP, et al; Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group. Analysis of vitamin D levels in patients with and without statin-associated myalgia—a systematic review and meta-analysis of 7 studies with 2420 patients. Int J Cardiol. 2015;178:111-116.

Khayznikov M, Hemachrandra K, Pandit R, Kumar A, Wang P, Glueck CJ. Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci. 2015;7:86-93.

Banach M, Serban C, Sahebkar A, et al; Lipid and Blood Pressure Meta-analysis Collaboration Group. Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials. Mayo Clin Proc. 2015;90:24-34

Author:

Dr Andrew To

Statin Intolerance - the 2015 Approach

Scenario = 55M IHD with stents, trialed simvastatin, atorvastatin and pravastatin, all causing myalgia, without CK rise

Question = what to do?

Atorvastatin - cardiologist's "friend"

Statin intolerance - consider these:

• Vitamin D level - low vitamin D level has been associated with statin induced myalgia
• Drug interactions
  • amiodarone - increases statin toxicity, especially for simvastatin lovastatin
  • erythromycin and clarithromycin, but not azithromycin
  • verapamil and diltiazem, but less likely with amlodipine
  • protease inhibitors, especially ritonavir
  • fibrates - significantly increases the risk of statin toxicity, more frequently with gemfibrozil
• Other statins
  • Twice-weekly or every-other-day schedule Rosuvastatin (or Atorvastatin)
    • Retrospective studies in lipid clinics have had some success in using twice-weekly or every other day dosing of rosuvastatin. (Ref)  The dosage is usually 5 mg twice weekly 5 mg every other day.  In the two studies, 80% and 72% of patients managed to stay on statin. 
    • It is of note that there is no outcome study examining such dosing regimen.
  • Pravastatin is metabolised differently from other statins.  Most statins are metabolised by the cytochrome P-450 isoenzyme.  Instead, pravastatin is significantly renally excreted.

References:

Gadarla M, Kearns AK, Thompson PD. Efficacy of rosuvastatin (5 mg and 10 mg) twice a week in patients intolerant to daily statins. Am J Cardiol. 2008;101:1747-1748.

Backes JM, Venero CV, Gibson CA, et al. Effectiveness and tolerability of every-other-day rosuvastatin dosing in patients with prior statin intolerance. Ann Pharmacother. 2008;42:341-346. 

Author:

Dr Andrew To