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A 48-Year-Old Man With Familial Hypertension
Editor's Note: Based on the 2013 Blood Cholesterol, Lifestyle Management, Obesity, and Risk Assessment Guidelines.
A 48-year-old man with FH and history of 3-vessel coronary artery bypass surgery 7 years ago sees you now for statin intolerance. The maximum dose of statin that he can tolerate is rosuvastatin 10 mg twice a week. On more frequent dosing he developed shoulder, low back, and thigh aching without weakness and a normal CK level. He had similar symptoms on low doses of simvastatin, atorvastatin and pravastatin. On rosuvastatin 10 mg twice a week, his most recent LDL–C was 168 mg/dL, triglycerides were 138 mg/dL, and HDL–C was 46 mg/dL.
Which of the following statements is the most correct answer?
Show Answer
The correct answer is: c. Bile acid sequestrants have been shown to reduce ASCVD events when used as monotherapy in men with primary hypercholesterolemia.. He should continue the rosuvastatin and cholestyramine 4 g packet twice daily should be added.
This patient has FH, placing him in a statin benefit group. In patients with untreated primary LDL–C ≥190 mg/dL, a high-intensity statin should be used if tolerated and he would be expected to achieve a >50% LDL–C reduction. With an untreated baseline LDL–C of about 240 mg/dL, this patient has experienced about a 30% reduction in LDL–C. Although this percent reduction in LDL–C is suboptimal it still is providing substantial ASCVD risk reduction benefit. According to the CTT 2010 meta-analysis, each 39 mg/dL reduction in LDL–C is associated with a 22% reduction in ASCVD events. Therefore this patient's 72 mg/dL reduction is LDL–C from rosuvastatin 10 mg twice a week might be expected to reduce his relative risk ASCVD by about 40%.
LDL–C lowering nonstatin drugs that have been shown to reduce ASCVD events when used as monotherapy include niacin and the bile acid sequestrant cholestyramine. However, the incremental ASCVD event reduction benefit of these drugs added to statin therapy has yet to be established. No ASCVD outcomes trials of bile acid sequestrants added to statins have been performed or are planned. A trial of extended-release (ER) niacin coadministered with laropriprant, a drug to block flushing, did not find an ASCVD event reduction benefit from niacin/laropriprant compared to placebo in statin-treated patients. The AIM-HIGH trial found 2 strategies that lowered LDL–C to 40-80 mg/dL had similar ASCVD event rates (simvastatin/ER niacin + ezetimibe versus simvastatin + ezetimibe). The incremental benefit of ezetimibe added to simvastatin is undergoing evaluation in the IMPROVE-IT trial. However, a trial of ezetimibe coadministered with simvastatin in individuals with chronic kidney disease did reduce ASCVD events compared to placebo.
Thus, due to the lack of ASCVD outcomes data to determine the incremental benefit of a non-statin added to statin therapy at this time, there is no best LDL–C lowering therapy to recommend when the maximal tolerated statin dose is suboptimal. Use of a nonstatin is therefore a matter of clinical judgment. Considerations include results in clinical trials as monotherapy and in combination with a statin, tolerability, potential for drug-drug interactions, cost, and patient preference.
Gemfibrozil has been shown to reduce ASCVD events in men with coronary heart disease, low HDL–C and low LDL–C when compared to placebo. However, gemfibrozil does not lower LDL–C and it should not be combined with statin due to an unacceptable potential for myopathy and rhabdomyolysis. Fenofibrate is safer to administer with a statin, but does not appear to provide additional ASCVD event reduction benefits when used with a statin.
Although he might tolerate lovastatin 40 mg daily, given his prior history of intolerance to 3 other statins at low doses, this seems less likely. Moreover, less than daily doses of lovastatin are unlikely to result in a reduction in in LDL–C comparable to the 30% reduction in LDL–C he is experiencing with rosuvastatin 10 mg twice a week. Rosuvastatin results in the greatest percent reduction in LDL–C per milligram. An alternative is pitavastatin. At the maximum dose of 4 mg daily, pitavastatin has comparable LDL–C lowering efficacy to simvastatin 40 mg daily.
A rule of thumb for comparing statin doses that lower LDL–C approximately 30% to 35% is:
-
Fluvastatin 80 mg
Lovastatin 40 mg
Pravastatin 40 mg
Simvastatin 20 mg
Atorvastatin 10 mg
Rosuvastatin 5 mg
Pitavastatin 1 mg
References
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- Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA. 1984; 251:365-374.
- The AIM-HIGH Investigators. Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy. N Engl J Med. 2011; 365:2255-2267.
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- Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial). Am J Cardiol. 2003; 92:152-160.
- Novartis Pharmaceuticals. Lescol (fluvastatin sodium) [prescribing information]. 2012; http://www.pharma.us.novartis.com/product/pi/pdf/Lescol.pdf, accessed November 2013.
- Kowa Pharmaceuticals. Livalo (pitivastatin) prescribing information. 2013; http://www.livalorx.com/Pages/, accessed November 2013.
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