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. 

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

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"

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