Questions? Call us at 800-810-7790
Feb 14, 2022


Heart Health

StatinsEzetimibePitavastatinCholesterolLowering Cholesterol

Living Heart-Healthy: Understanding How Combination Therapy Benefits You

Statins are the primary medications used to lower high levels of cholesterol. In the United States alone, they are one of the most highly prescribed medications, with over 221 million prescriptions recorded annually and close to 40 million adult Americans reporting their use.

The most recently published guideline on the management of blood cholesterol recommends the routine use of statin therapy in a multitude of patients 40 – 75 years of age with elevated low-density lipoprotein cholesterol (LDL-C), as well as other risk-enhancing factors for cardiovascular disease (e.g. diabetes, prior history of cardiovascular disease).

Benefits of Lower LDL-C

LDL-C is often referred to as the 'bad' cholesterol and can build up along the walls of your arteries and increase your risk of developing cardiovascular disease. In fact, studies have shown that low LDL-C levels are directly correlated with a lower risk of developing a heart attack or stroke. Statins work by blocking one of the enzymes responsible for the manufacture of cholesterol in your liver, reducing the total amount of LDL-C in your blood.

Therefore, in theory, a healthcare provider would want to prescribe a statin that lowers a patient’s LDL-C the most. In reality, these more potent statins can increase the risk of a patient developing severe side effects, such as muscle pain. Therefore, a balance needs to be struck between lowering a patient’s LDL-C effectively, while also minimizing the risk of side effects that they may experience.

Statin Intensity

Cholesterol guidelines categorize statins (and their respective doses) into 3 main categories of intensity, depending on their ability to lower LDL-C.

  • High-intensity statins: The most potent, with very high levels of LDL-C lowering achieved (greater than 50%).
  • Moderate-intensity statins: Associated with medium levels of LDL-C lowering (between 30% and 50%)
  • Low-intensity statins: Associated with lower levels of LDL-C reduction (less than 30%).

If a patient is unable to achieve the desired level of LDL-C reduction, their healthcare provider may increase the dose of their medication or may switch them to a more intense therapy (e.g. move from a moderate-intensity to a high-intensity statin).

Unfortunately, a patient’s risk of muscle pain is directly associated with higher, more intense doses of statin medication. This means that as you increase the dose of your statin, or move to a higher-intensity statin, your risk of muscle pain also increases.

In some cases, a patient is unable to tolerate a higher dose statin but still needs to achieve lower levels of LDL-C. In these situations, what options are available?

Benefits of Ezetimibe (generic Zetia®)

Cholesterol found in the blood comes from 2 primary sources: cholesterol synthesis in the liver (which can be blocked by the use of statins) and cholesterol that has been absorbed by your intestines from the food you eat. By inhibiting cholesterol synthesis and uptake in these 2 areas, you can more effectively decrease the LDL-C level in your blood.

Ezetimibe (generic Zetia®) is a cholesterol absorption inhibitor that interferes with dietary cholesterol by blocking its absorption in the small intestine. On its own, ezetimibe only demonstrates an LDL-C reduction of approximately 15%, which is why it is most commonly used in combination with ongoing statin therapy.

This combination increases the overall LDL-C reduction by effectively blocking the 2 main pathways where LDL-C is added to your blood.

See how you can save 90% on generic Zetia at Marley Drug.

Benefits of Combination Therapy

Combination therapy is most commonly used when a patient is at high risk for heart disease, but statin therapy alone is not effective at lowering LDL-C to its desired level. 

For example, a patient on a high-intensity statin may achieve an LDL-C reduction of 55% but experiences intolerable levels of back pain. Their healthcare provider switches them over to a moderate-intensity statin and the occurrence of back pain is significantly lowered, but the patient is now only able to lower their LDL-C by 44%. As this patient is at a high risk of experiencing a cardiovascular event (due to other existing health conditions), they need to add on an additional therapy to get them back over the 50% level of LDL-C lowering. By adding on ezetimibe, the patient may now be able to obtain an LDL-C reduction of up to 59%, even more than they were receiving on the high-intensity statin alone!

Unlike some combination therapies, the use of statins and ezetimibe together is considered safe, with minimal risk of increased side effects like muscle pain.

Other Lipid-Lowering Options

For patients that are unable to achieve their LDL-C lowering goals, there are a few other options to consider. PCSK9 inhibitors are injectable lipid-lowering drugs that block the activity of PCSK9 proteins. These proteins break down the receptors responsible for cholesterol absorption, so by blocking this action and allowing the body to absorb more cholesterol, LDL-C levels in the blood are effectively lowered.

Another more recent option for LDL-C reduction is through the use of adenosine triphosphate-citrate lyase (ACL) inhibitors. They block the liver’s ability to produce cholesterol similar to statins. Currently, the only ACL inhibitor available on the market is bempedoic acid (Nexletol®). While both of these drug classes do have their advantages, they remain expensive options to many, and importantly, are still meant to be used in combination with statin therapy.

Affordable Combination Therapy

If you need high levels of lipid-lowering but are unable to tolerate the side effects that come along with your medications, talk to your healthcare provider about combination therapy and send your prescription to Marley Drug for massive savings.

Through Marley Drug, you can get many generic statins or ezetimibe from our Wholesale Price List. We also have branded Zypitamag (pitavastatin) tablets available for only $1 per day. Click here to find out why Zypitamag might be the right choice for you!

Click below to see the pricing for some of these medications:

Statin Therapies:

Combination Therapy:

Data was informed by:
(1) Hammersley D, and Signey M. Ezetimibe: an update on its clinical usefulness in specific patient groups. Ther. Adv. Chronic Dis. 2017:8(1):4-11.
(2) Masana et al. Reasons Why Combination Therapy Should Be the New Standard of Care to Achieve the LDL-Cholesterol Target. Curr. Cardiol. Rep. 2020;22(8):66.
(3) Salami JA., et al. National Trends in Statin Use and Expenditures in the US Adult Population From 2002 to 2013: Insights from the Medical Expenditure Panel Survey. JAMA Cardiology. 2017;2(1):56-65.
(4) Grundy SM., et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation; 2019;139:e1082-e1143.

Related posts

Foods that increase your risk of statin side effects

Do Drug Interactions cause Statin Side Effects?

Stopped taking your statin because of muscle pain? We may have a new solution for you!