# How a Cholesterol Medication That Bypasses Statin Side Effects Shrunk Dangerous Heart Plaque: A Patient's Success Story This case report describes a 66-year-old woman with coronary artery disease who could not take statins or ezetimibe due to severe side effects, but achieved remarkable success with a newer medication called bempedoic acid. Her LDL cholesterol (the "bad" cholesterol) dropped from an initial level of 162 mg/dl to just 34–38 mg/dl, and follow-up CT scans showed that dangerous soft plaque in her coronary arteries actually shrank and stabilized over 20 months. This is the first reported case showing favorable plaque changes from bempedoic acid monotherapy using serial coronary CT angiography (CCTA), offering hope for patients who are intolerant to standard cholesterol medications. # How a Cholesterol Medication That Bypasses Statin Side Effects Shrunk Dangerous Heart Plaque: A Patient's Success Story ## Table of Contents - Key Points - Why This Research Matters - The Patient's Journey: A 66-Year-Old Woman with Heart Disease and Medication Intolerance - What the CT Scans Revealed: Plaque Shrinkage Over 20 Months - Understanding Bempedoic Acid: How It Works and What Studies Show - What This Means for Patients - Study Limitations: What This Case Couldn't Prove - Recommendations for Patients - Frequently Asked Questions - Source Information ## Key Points - A 66-year-old woman with coronary disease and statin/ezeitimibe intolerance achieved LDL drop from 162 to 34–38 mg/dl on bempedoic acid alone. - Follow-up CT scans after 20 months showed shrinkage of soft, dangerous coronary plaque and stabilization of a moderate blockage. - Bempedoic acid works differently from statins, reducing cholesterol synthesis upstream and causing fewer muscle side effects. - In statin-intolerant patients, bempedoic acid lowers LDL by about 23% alone, and over 40% with ezetimibe; this patient was a 'hyper-responder' receiving over 80% reduction. - This is a single case report; individual responses vary, and a large trial called LOCATE is ongoing to further investigate plaque changes. ## Why This Research Matters Cholesterol-lowering therapy is the cornerstone of treatment for atherosclerotic cardiovascular disease — a condition where fatty deposits build up inside artery walls, restricting blood flow and increasing the risk of heart attacks and strokes. Extensive clinical and experimental evidence has shown that low-density lipoprotein (LDL), often called the "bad cholesterol," plays a central role in this process of atherosclerosis (hardening and narrowing of the arteries). Current guidelines from the European Society of Cardiology recommend that patients at very high risk for atherosclerotic cardiovascular disease achieve an LDL cholesterol reduction of **more than 50% from baseline** and reach an LDL goal of **below 55 mg/dl**, both in primary prevention (before heart disease develops) and secondary prevention (after heart disease is already diagnosed). Until recently, statins have been the primary medications used to achieve these goals. However, a significant number of patients cannot tolerate statins due to muscle pain and other side effects, leaving them without adequate treatment. This case report focuses on an alternative — a newer drug called **bempedoic acid** — and provides visual evidence of its benefits using advanced heart imaging. The imaging technology used here, **coronary computed tomography angiography (CCTA)**, has emerged as the central non-invasive imaging technique not only for detecting significant coronary artery disease but also for evaluating the composition of atherosclerotic plaque within the arterial wall. This is important because total **low-attenuation plaque burden** (soft, dangerous plaque that is more prone to rupture) was reported as the most robust predictor of death and myocardial infarction (heart attack), beyond stenosis severity (how narrowed the artery is) in patients with coronary artery disease. ## The Patient's Journey: A 66-Year-Old Woman with Heart Disease and Medication Intolerance ### Initial Presentation in March 2017 A 66-year-old woman was initially referred to an outpatient cardiology center in March 2017 with suspected coronary artery disease (CAD). She was experiencing **exertional angina** (chest pain triggered by physical activity) classified as CCS class II, along with shortness of breath. Her medical history included: - **Arterial hypertension** (high blood pressure), treated with 5 mg of ramipril per day - **Hyperlipidemia** (high cholesterol), treated for 2 years with 10 mg of simvastatin, with an initial LDL cholesterol level of **162 mg/dl** Her electrocardiogram (ECG) showed normal findings. An echocardiogram revealed mild myocardial hypertrophy (thickening of the heart muscle) but normal ventricular diameters and function, with a **left ventricular ejection fraction of 62%** (meaning her heart was pumping blood effectively). Because of her symptoms and an intermediate pre-test probability of **16%** for coronary artery disease, doctors performed a **vasodilator stress cardiac magnetic resonance (CMR)** scan. This test showed myocardial perfusion abnormalities (reduced blood flow) in the septal and inferior walls of the heart. Fortunately, no myocardial scars were detected through late gadolinium enhancement imaging. Due to inducible myocardial ischemia (reduced blood flow triggered by stress) in two heart segments, along with persistent symptoms, a coronary angiography (invasive X-ray imaging of the heart's arteries) was performed, confirming **high-grade lesions (severe blockages) in the left anterior descending artery (LAD)** and the **right coronary artery (RCA)**. Percutaneous coronary intervention (PCI) — a procedure to open blocked arteries, typically with stents — was performed in both arteries, resulting in complete resolution of her angina symptoms. ### Statin Troubles Begin After the procedure, her lipid-lowering treatment was changed to **20 mg of atorvastatin per day**. This resulted in an LDL cholesterol of **101 mg/dl in July 2017** and **118 mg/dl in October 2017**. Since the target value of **below 70 mg/dl** recommended by the 2016 guidelines could not be achieved, doctors added **10 mg of ezetimibe** — another cholesterol-lowering medication that works by blocking cholesterol absorption in the gut — to her regimen. This did not significantly affect her LDL cholesterol, which was measured at **113 mg/dl in April 2018**. ### A Diagnosis of Statin-Associated Muscle Symptoms In June 2018, the patient began experiencing **unsteadiness, weakness, hypoesthesia (reduced sensation), and muscle pain in both legs**. An electrophysiology examination of her peripheral muscles revealed no detectable neurologic abnormalities, so doctors suspected **statin-associated muscle symptoms (SAMS)** — a well-recognized side effect of statin medications. Atorvastatin (20 mg per day) was changed to **pravastatin (10 mg per day)**, which led to clinical improvement of her muscle symptoms. However, her LDL cholesterol remained high, measuring **143 mg/dl in October 2018**. In March 2019, the patient was referred to rheumatologists due to a recurrence of her muscle symptoms. Here, doctors diagnosed **small fiber neuropathy (SFN)** associated with **anti-Mi-2 autoantibody-positive myositis** (a type of inflammatory muscle disease). Since SFN can have several causes — including diabetes, anti-retroviral medications, hypothyroidism, and hyperlipidemia — and has also been associated with statin therapy, her pravastatin was discontinued. Her muscle symptoms further improved, and she was continued on ezetimibe (10 mg per day) alone. During the period from March 2019 to December 2020, her LDL cholesterol remained above the desired target, ranging between **102 and 124 mg/dl**. ### A New Medication and New Imaging In March 2021, the patient reported new onset of **atypical angina** (chest pain not clearly related to exertion) accompanied by exertional shortness of breath. Additionally, ezetimibe intolerance was suspected due to nausea. A CCTA was performed using a third-generation dual-source CT scanner (SOMATOM Force, Siemens Healthineers). This scan showed: - Patent (open) stents in the LAD and RCA - No other high-grade blockages - A **moderate stenosis (narrowing) in the distal RCA**, composed of both non-calcified and calcified components The plaque was located directly at the crux of the RCA (where the artery bends around the bottom of the heart), resulting in a moderate **50–70% diameter stenosis**, classified as a **coronary artery disease reporting and data system (CAD-RADS) 2.0 score of 3** (meaning moderate blockage). A repeated stress CMR showed normal perfusion, so invasive angiography was deferred. ## What the CT Scans Revealed: Plaque Shrinkage Over 20 Months Because of the patient's recurrent atypical symptoms, doctors discontinued ezetimibe due to recurrent nausea and started treatment with **bempedoic acid**. The results were dramatic: - In **November 2021**, after treatment with bempedoic acid alone, her LDL cholesterol dropped to **34 mg/dl** - In **December 2022**, her LDL remained low at **38 mg/dl** Since the LDL target from current guidelines was now achieved, treatment with bempedoic acid was continued, and treatment with **PCSK9 inhibitors** (a more expensive injectable cholesterol medication) was deferred. A follow-up CCTA examination was performed in **December 2022 — 20 months after the initial CCTA** — using the same third-generation dual-source CT scanner. The results were remarkable: - The stents in the LAD and proximal RCA remained patent (open) - The moderate lesion in the distal RCA showed signs of **plaque stabilization** - The **calcified plaque component remained similar** (visible on follow-up scans) - The **low-attenuation (soft, dangerous) plaque component was now barely detectable** — a sign of plaque shrinkage - The resultant lumen narrowing (blockage) was now considered only mild, causing about **25–50% diameter stenosis**, downgraded to a **CAD-RADS 2.0 score of 2** The patient continued on treatment with **180 mg of bempedoic acid daily**, and her clinical course over the next 4 months was uneventful. ## Understanding Bempedoic Acid: How It Works and What Studies Show This case is, to the authors' knowledge, **the first in the current literature to report favorable plaque component modification** using serial CCTA studies in a patient where bempedoic acid monotherapy achieved substantial LDL reduction — a result that could not be achieved with multiple statins and ezetimibe due to intolerance. ### The Mechanism of Action Bempedoic acid is a **non-statin lipid-lowering drug** that prevents cholesterol synthesis by inhibiting the action of **adenosine triphosphate (ATP) citrate lyase** — a cytosolic enzyme that works upstream of the enzyme targeted by statins (HMG-CoA reductase). Because it works at a different point in the cholesterol production pathway, it is associated with a **low incidence of muscle-related adverse events**, making it an attractive option for patients who cannot tolerate statins. ### What Prior Studies Have Shown The authors cite several important studies that provide context for this case: - In monotherapy for patients with statin intolerance, bempedoic acid reduces LDL levels by **23%** - LDL reduction may exceed **40%** when bempedoic acid is combined with ezetimibe - The recent **CLEAR Outcomes study** showed that treatment with bempedoic acid in statin-intolerant patients was associated with a **lower risk of major adverse cardiovascular events** — specifically the composite endpoint of death from cardiovascular causes, non-fatal myocardial infarction (heart attack), non-fatal stroke, and coronary revascularization - Previous studies reported the ability of bempedoic acid to reduce **high-sensitive C-reactive protein (hs-CRP)**, a biomarker of low-grade inflammation involved in atherosclerotic disease progression. This suggests the drug may offer **anti-inflammatory benefits** in addition to its lipid-lowering effects ### A Remarkable Response In this patient, bempedoic acid reduced LDL cholesterol by **over 80% compared to her initial LDL values** (from 162 mg/dl down to 34 mg/dl). This is particularly notable because relatively high inter-individual variation in LDL lowering — ranging from **0% to over 80%** — has been described in previous studies. Similar variability has been reported with statins, which may result from genetic polymorphisms that modulate cholesterol homeostasis. In this context, the patient appears to be a **"hyper-responder" to bempedoic acid**, achieving both highly effective LDL reduction and favorable plaque modification. The authors note that future studies, like the ongoing **LOCATE trial** (available at https://drks.de/search/de/trial/DRKS00031954), are warranted to investigate the potential of bempedoic acid and other lipid-lowering or anti-inflammatory drugs on plaque modification through multicenter serial CCTA studies. ## What This Means for Patients This case report carries several important messages for patients and their doctors: 1. **Statin intolerance is real and manageable.** Patients who experience muscle pain, weakness, or other side effects from statins should not simply stop treatment without discussing alternatives with their doctor. There are effective non-statin options available. 1. **Bempedoic acid is a viable alternative.** For patients who cannot tolerate multiple statins or ezetimibe, bempedoic acid can dramatically lower LDL cholesterol — in some cases, as this report shows, by more than 80%. 1. **Lower LDL can translate into visible plaque changes.** This case provides visual evidence that aggressive LDL lowering with bempedoic acid was accompanied by shrinkage of the dangerous, soft (low-attenuation) plaque component in the coronary arteries — the type of plaque most likely to rupture and cause heart attacks. 1. **CT imaging can track treatment success.** Serial CCTA scans allow doctors to see not just whether a blockage is present, but whether plaque composition is changing in response to treatment — moving from dangerous soft plaque toward more stable calcified plaque. 1. **Individual responses vary.** Not every patient will respond as dramatically as this patient did. LDL lowering with bempedoic acid can range from 0% to over 80%, and genetic factors may play a role. Regular monitoring is essential. ## Study Limitations: What This Case Couldn't Prove As a case report — a detailed description of a single patient — this study has important limitations that patients should understand: - **Single patient experience:** Results from one patient cannot be generalized to all patients. What worked spectacularly for this individual may not work the same way for others. - **Confounding prior treatments:** The patient had been on statins and ezetimibe for a considerable time before starting bempedoic acid. These earlier treatments may have contributed to some of the plaque changes observed, although they were not sufficient to achieve LDL targets on their own. - **Treatment sequencing:** Bempedoic acid was tried before PCSK9 inhibitors due to the patient's preference for oral (pill) over subcutaneous (injection) therapy and due to cost issues. In Germany's reimbursement system, proof of administration of all possible oral lipid-lowering treatments — including statins, ezetimibe, and bempedoic acid — is required before approval of PCSK9 inhibitor coverage. - **No control group:** There is no comparison patient or group to determine how much of the plaque change was due specifically to bempedoic acid versus other factors. ## Recommendations for Patients Based on this case and the research it builds upon, patients with coronary artery disease and cholesterol management challenges should consider the following: 1. **Know your numbers.** The current guideline recommends an LDL goal of **below 55 mg/dl** for patients at very high risk, and a reduction of **more than 50% from baseline**. Ask your doctor what your target is and track your progress. 1. **Don't suffer in silence.** If you experience muscle pain, weakness, unsteadiness, or other symptoms while taking statins, report them to your healthcare provider. There are alternatives — including bempedoic acid, ezetimibe, and PCSK9 inhibitors — that may work without the same side effects. 1. **Understand your options.** Bempedoic acid is taken as a pill (180 mg daily in this case), while PCSK9 inhibitors are injections. Cost, insurance coverage, and personal preference all play a role in choosing the right treatment. Ask your doctor about what is covered and what makes sense for your situation. 1. **Ask about imaging.** If you have known coronary artery disease and are starting or changing lipid-lowering therapy, ask whether follow-up CCTA imaging might be appropriate to monitor plaque changes over time. This is especially relevant if you have recurrent or new symptoms. 1. **Take inflammation seriously.** The ability of bempedoic acid to reduce hs-CRP (a marker of inflammation) suggests that managing inflammation — not just cholesterol — may be an important part of protecting your heart. Ask your doctor about inflammatory markers and what they mean for your risk. 1. **Stay patient and persistent.** Achieving LDL targets may require trying multiple medications or combinations. This patient's journey spanned nearly 6 years (from March 2017 to December 2022) before her cholesterol reached the recommended target. Don't get discouraged — effective options exist. The authors note that this research was conducted in accordance with ethical guidelines. Ethical review and approval were not required for the study on human participants in accordance with local legislation and institutional requirements, and the patient provided written informed consent to participate and for publication of potentially identifiable images or data, in line with COPE guidelines. ## Frequently Asked Questions ### I can't take statins because of muscle pain. Is there another cholesterol medication that might work for me? Yes. Bempedoic acid is a non-statin pill that works differently from statins and has a low risk of muscle side effects. In this case report, it lowered LDL cholesterol from 162 to 34–38 mg/dl in a statin-intolerant patient. Talk to your doctor about whether it may be an option for you. ### My LDL cholesterol is high despite taking statins and ezetimibe. What can I do? In this report, a patient who could not tolerate statins or ezetimibe was switched to bempedoic acid. Her LDL dropped from over 160 to below 40 mg/dl, and her dangerous soft plaque shrank on CT scans. Ask your doctor if bempedoic acid might help you reach your LDL target. ### What is bempedoic acid and how does it lower cholesterol? Bempedoic acid is a pill that blocks an enzyme upstream of the one statins target, reducing cholesterol production in the liver. It is associated with fewer muscle side effects than statins. In studies, it lowers LDL by about 23% when used alone, and by over 40% when combined with ezetimibe. ### Will taking bempedoic acid shrink the dangerous plaque in my heart arteries? This case report showed that in one patient, bempedoic acid dramatically lowered LDL and, on follow-up CT scans after 20 months, the soft, dangerous plaque in a coronary artery was barely detectable. However, this is a single case, so similar results are not guaranteed for everyone. ### How quickly did the patient's cholesterol improve with bempedoic acid? In this case, the patient started bempedoic acid in 2021. By November 2021, her LDL had dropped to 34 mg/dl. In December 2022, it was still low at 38 mg/dl. Her follow-up CT scan showed plaque stabilization. But response varies widely between individuals. ### What is low-attenuation plaque on a coronary CT scan and why does it matter? Low-attenuation plaque is the soft, dangerous type of plaque in artery walls that is more prone to rupture and cause heart attacks. It is a stronger predictor of death or heart attack than the degree of narrowing. This case showed that aggressive LDL lowering reduced that soft plaque component. ### Are there limitations to this case report about bempedoic acid and plaque shrinkage? Yes. This is a single patient's experience, so it cannot be generalized. The patient had previously taken statins and ezetimibe, and there was no control group. Also, bempedoic acid was tried before PCSK9 inhibitors. These factors make it impossible to prove exactly what caused the plaque changes. ## Source Information This patient-friendly article is based on the following peer-reviewed research: - **Original Title:** Case report: Strong low-density-cholesterol reduction accompanied by shrinkage of low-attenuation coronary plaque during lipid-lowering treatment with bempedoic acid — serial evaluation by coronary computed tomography angiography - **Authors:** Grigorios Korosoglou, Alexander Giesen, Eva Geiss, and Ksenija Stach - **Journal:** Frontiers in Cardiovascular Medicine, Volume 10, Article 1203832 - **Publication Date:** August 4, 2023 - **DOI:** 10.3389/fcvm.2023.1203832 This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and does not constitute medical advice. Patients should consult their healthcare providers about their individual treatment options. --- Publisher: Diagnostic Detectives Network (https://diagnosticdetectives.com) — independent multi-expert medical second opinions, worldwide, private-pay. Author byline: Anton Titov, MD, PhD. Contact: https://diagnosticdetectives.com/pages/contact Canonical page: https://diagnosticdetectives.com/products/how-a-cholesterol-medication-that-bypasses-statin-side-effects-shrunk-dangerous-heart-plaque-a-patients-success-story