Niacin Added to Statin Therapy Improves Cardiovascular Outcomes Compared to Ezetimibe

Statins are a class of drugs that block de novo synthesis of cholesterol. They are prescribed to patients to with high LDL cholesterol, a classic marker for increased risk of adverse cardiovascular events. LDL is thought to contribute to atherosclerotic plaques, which can ultimately lead to heart attack or stroke. Statin therapy alone for some patients is insufficient to lower LDL levels into an acceptable range associated with a lower risk of cardiovascular events and requires the addition of another lipid lowering drug. Combination therapy may also be necessary for patients tolerant to low dose, but intolerant to high dose therapy to optimally lower LDL.

Which drug to add on to statins that provides both optimal LDL lowering and positive cardiovascular outcomes has been debatable. However, a new study in the New England Journal of Medicine suggests that niacin, also known as vitamin-B3, is more beneficial than ezetimibe not for LDL lowering, but for overall prevention of adverse cardiovascular events. Ezetimibe is marketed under the name Zetia and decreases LDL by blocking the uptake of cholesterol in the intestine.

The studies primary endpoint of the trial was the change in thickness of the carotid intima-media after 14 months with statin therapy in conjunction with either ezetimibe for niacin. The thickness of this artery is a marker of atherosclerotic disease severity. The secondary endpoints included changes in the lipid profile, adverse cardiovascular events, and overall wellness.

In the study, co-treatment with ezetimibe led to a decrease in total cholesterol and LDL levels greater than that niacin. However, niacin increased HDL, also referred to as good cholesterol, to a greater extent than ezetimibe. Niacin also decreased triglyceride levels more extensively than ezetimibe. Measurements were taken every 2 months up to month 14.

The change in thickness of the carotid intima-media was monitored at baseline, month 8, and month 14 using B-mode ultrasonography. Statin treatment with ezetimibe did not lead to a significant decrease in artery thickness at month 14 from baseline. However, niacin co-treatment led to a statistically significant decrease. Suggesting that niacin is superior to ezetimibe in reducing atherosclerotic plaque.

Most importantly, major adverse cardiovascular events were higher in the group co-treated with ezetimibe compared with niacin, 5% and 1% respectively. Major adverse events included heart attack, revascularization, hospitalization from acute coronary syndrome, and death related to heart disease. This suggests that although ezetimibe lowers LDL better than niacin, niacin improves artery narrowing from atherosclerosis and reduces the risk of an adverse cardiovascular event.

Although vitamin-B3 is available over the counter as a supplement and in multivitamins, the dose in prescription niacin is higher than what is found in these products. Hence, patients currently on a statin should not try to augment their therapy with vitamin-B3 using these products. Niacin should only be initiated under the direct supervision of a physician using current cholesterol lowering treatment guidelines that are designed for patient specific clinical scenarios.

References:

Katzung B, Masters S, Trevor A. Basic and Clinical Pharmacology. 2009. McGraw-Hill Medical; 11 edition

Taylor EJ et, al. Extended-Release Niacin or Ezetimibe and Carotid Intima-Media Thickness. ­NEJM. 2009; 361.