Hypercholesterolemia

Hypercholesterolemia remains a significant risk factor for cardiovascular disease. Management of hypercholesterolemia has entailed the use of statins and non-statins, such as omega-3 fatty acid supplements. Common side effects related to fish oil supplements have included reports of gastrointestinal upset and difficulty in swallowing the fish capsules. Common side effects of statin therapy have included reports of muscle aches, abdominal pain, dizziness, leading to non-adherence and termination of therapy.

The debate on the use of omega-3 fatty acids over statins in the management of blood cholesterol continues, calling for more studies.¹  Day 3 of this year’s AHA Scientific Conference highlighted results from recent trials on the use of non-statins and statins in the reduction of cardiovascular events. Here are some takeaways from three studies: the STRENGTH Trial, the OMENI study, and the SAMSON study.

The STRENGTH (Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk Patients With Hypertriglyceridemia) trial – This phase III international study evaluated the use of a medication derived from fish oil, containing the omega-3 fatty acids EPA and DHA, more than 13,000 people who had existing heart disease or who were at high risk of heart disease due to other medical conditions.²

• The medication did not reduce the risk of cardiac events compared to a corn oil-based placebo.
• Atrial fibrillation, an abnormal heart rhythm, occurred more frequently in participants taking the omega-3 CA medication.

The OMENI (OMega-3 fatty acids in Elderly patients with Myocardial Infarction) trial – a study of more than 1,000 patients in Norway investigated whether adding 1.8 grams of omega-3 fatty acids to standard treatment prevented further cardiovascular events among elderly participants with recent heart attacks.

• When compared to placebo, omega-3 fatty acids supplement in addition to statin therapy and/or a blood thinner did not reduce the number of cardiac events in the participants.

The SAMSON (The Self-Assessment Method for Statin Side-effects Or Nocebo) Trial – The study, conducted in London, enrolled adults who had previously taken one or more statins but stopped taking them due to side effects. The participants had self-reported symptoms measured throughout a 12-month period of randomly alternating months of statin use, placebo, and no medications.

• The participants who reported side effects from statins also reported the same side effects when they unknowingly took placebo pills.
• The side effects appeared to be mostly due to psychological rather than pharmacological effects of statins since the reported symptoms were consistent when taking the placebo.

In the discussion led by Dr. Karol E. Watson, statins remain the mainstay in the reduction of Low-Density Lipoprotein (LDL) and Atherosclerotic cardiovascular disease (ASCVD) risk.  As also recommended in the 2018 AHA/ACC/ AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol, non-statin therapies should be considered in high-risk patients with LDL above thresholds.  Heart-healthy lifestyle changes should be also considered as important measures in the reduction of LDL and triglycerides in patients at risk for ASCVD. The heart-healthy lifestyle should include diet, weight control, and physical activity.⁴  It will be important to observe the outcome of future studies including the combined effects of heart-healthy lifestyle interventions and non-statin/statin therapy among those considered to be at high risk for ASCVD. Future discussions should also center on intervention studies to address patients’ perceptions of statin/non-statin therapies.

References

1. Tummala R, Ghosh RK, Jain V, Devanabanda AR, Bandyopadhyay D, Deedwania P, Aronow WS. Fish Oil and Cardiometabolic Diseases: Recent Updates and Controversies. Am J Med. 2019 Oct;132(10):1153-1159. doi: 10.1016/j.amjmed.2019.04.027. Epub 2019 May 8. PMID: 31077653.
2. Nicholls SJ, Lincoff AM, Bash D, Ballantyne CM, Barter PJ, Davidson MH, Kastelein JJP, Koenig W, McGuire DK, Mozaffarian D, Pedersen TR, Ridker PM, Ray K, Karlson BW, Lundström T, Wolski K, Nissen SE. Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: Rationale and design of the STRENGTH trial. Clin Cardiol. 2018 Oct;41(10):1281-1288. doi: 10.1002/clc.23055. Epub 2018 Sep 28. PMID: 30125052; PMCID: PMC6489732.
3. Kalstad AA, Myhre PL, Laake K, Tveit SH, Schmidt EB, Smith P, Trygve Nilsen DW, Tveit A, … Effects of n-3 Fatty Acid Supplements in Elderly Patients after Myocardial Infarction: A Randomized Controlled Trial. Circulation. 2020 Nov. https://doi.org/10.1161/CIRCULATION AHA.120.052209Circulation.
4. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling L, Virani SS, Yeboah J. 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. J Am Coll Cardiol. 2019 Jun 25;73(24):e285-e350. doi: 10.1016/j.jacc.2018.11.003. Epub 2018 Nov 10. Erratum in: J Am Coll Cardiol. 2019 Jun 25;73(24):3237-3241. PMID: 30423393.

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