Medical Perspectives | Cardio-Metabolic, Others

June 19, 2021

Wilmark N. Gular, M.D.

Cardiovascular disease (CVD) remains to be the leading cause of mortality worldwide. Its management is not exclusive to cardiologists but extends to primary care physicians. In this article, we take a look at the recent developments in the field and shed light on its importance in primary care.


Aspirations for Aspirin: Amiss for Primary Prevention


Owing to its antithrombotic effect, low-dose aspirin has been recommended for the primary prevention of CVD by the American Heart Association and the United States Preventive Services Task Force. However, recent findings of three large scale trials have showed little to no benefit in this regard.


Aspirin to Reduce Risk of Initial Vascular Events (ARRIVE), ASCEND or A Study of Cardiovascular Events iN Diabetes, and Aspirin in Reducing Events in the Elderly (ASPREE) are randomized controlled trials that compared the daily use of 100 mg aspirin versus placebo.


ARRIVE revealed no overall reduction in primary endpoints of major CVD events (myocardial infarction, stroke, and death). ASCEND showed significant reduction in vascular events however, these were counterbalanced by the risk of major bleeding. The ASPREE trial did not show benefit in terms of disability-free survival (death, dementia, physical disability).


The Atherosclerotic CVD (ASCVD) risk calculator estimates 10 year and lifetime risk of CVD. It risk-stratifies patients and recommends dietary, lifestyle, and therapeutic interventions. Aspirin use is identified and recommended depending on the calculated risk. ASCVD risk calculators are available as mobile applications that can be used by primary care physicians.


Primary care physicians should exercise prudence in recommending use of aspirin. In light of the recent findings, aspirin should not be recommended for primary prevention of CVD in low risk patients. It may be considered among diabetics and those with moderate ASCVD risk but one should be cautious of its use among the elderly and those with risks of bleeding.


The Future of Fish Oil

Findings from two recently concluded trials on the use of omega-3 from fish oil were conflicting. REDUCE-IT used the high-grade prescription fish oil Vascepa 2 g twice daily and it showed superiority over placebo in lowering triglycerides and preventing CV events. The VITAL trial used 1 g daily of omega-3 fatty acid but did not show benefit over placebo.


The Japan Eicosapentaenoic Acid (EPA) Lipid Intervention Study (JELIS) used 1800 mg EPA daily along with statin versus control. The combination showed extension of the benefit of statins in patients with known CAD.


When recommending omega-3 fatty acid from fish oil, the primary care physician should know first if the patient is hypersensitive to fish or shellfish as supplementation in this case is avoided. A patient’s fish consumption must also be taken into account since those who have low fish intake benefit the most from supplementation as evidenced by findings of the VITAL study.


Currently, fish oil has no clear role in the primary prevention of CVD. However, high-grade fish oil may be considered by primary care physicians for those with CAD, hypercholesterolemia or hypertriglyceridemia as secondary prevention of CVD.


Low Density Lipoprotein Cholesterol (LDL-C): How Low Should One Go?


LDL-C or best known as bad cholesterol becomes a component of atherosclerotic plaques when oxidized. This can block the coronary arteries and reduce blood flow resulting to coronary artery disease (CAD). Lowering LDL thus became a priority among cardiologists.


The advent of proprotein convertase subtilisin kexin 9 or PCSK9 inhibitor use has been substantiated by results of two randomized trials namely FOURIER and ODYSSEY. PCSK9 inhibitors like evolocumab and alirocumab prevent the degradation of the LDL receptors that bind LDL and eliminate them. PCSK9 inhbitors are currently indicated for patients with familial hypercholesterolemia but their use is limited by the cost and availability11.


The cholesterol absorption inhibitor ezetimibe can be added to simvastatin. The trial IMPROVE-IT showed that the combination is better than statin alone in terms of decreasing LDL cholesterol among high-risk patients (post-acute coronary syndrome: myocardial infarction and unstable angina)12.


Primary care physicians order lipid profiles for CVD screening. CVD Patients with LDL-C levels more than 70 mg/dL despite maximal statin, may benefit from the addition of ezetimibe and PCSK9 inhibitor. LDL-C can be lowered to less than 50 mg/dL or, as some cardiologists would recommend, to as low as the patient can tolerate without the adverse events13.


A More Personalized Approach for Cholesterol Management


The American College of Cardiology and the American Heart Association released a new cholesterol guideline in November 201814. Family history, ethnicity, metabolic syndrome, chronic kidney disease, chronic inflammatory conditions, premature menopause, preeclampsia, and high lipid biomarkers were added to traditional risk factors for individualized risk estimation.


Non-statin drugs such as ezetimibe and PCSK9 inhibitors are recommended for patients at very high risk of ASCVD. These drugs can be added to statins in patients who have high LDL-C levels despite maximal statin therapy.


The new guideline promotes a heart-healthy lifestyle across all ages. This includes diet high in vegetables, fruits, whole grains, legumes, low-fat dairy, low-fat poultry (without the skin), fish/seafood, and nuts. Intake of sweets, sugar-sweetened beverages, and red meat should be kept to a minimum. Moderate to vigorous-intensity aerobic physical activity for forty minutes is recommended 3 to 4 times a week.


The Need to be Updated


A Hong Kong university professor once said, “Fifty percent of what we know about medicine five years ago, may not be true in the present. The sad news is we do not know which fifty percent.” Therefore, a primary care physician must be up-to-date with advancements in medicine, more so with the fast-paced field of cardiology.




  • World Health Organization. (2018, May 24). The top 10 causes of death. Retrieved from:
  • Goldstein, L. et al. American Heart Association Stroke Council. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011; 42:517-84
  • United States Preventive Services Task Force. (2017, September). Final Recommendation Statement: Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Preventive Medication. Retrieved from: https://www.uspreventiveservic...
  • Gaziano, J. et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomized, double-blind, placebo-controlled trial. Lancet. September 2018.
  • Bowman, L. et al. ASCEND: or A Study of Cardiovascular Events iN Diabetes: Characteristics of a randomized trial of aspirin and of omega-3 fatty acid supplementation in 15,480 people with diabetes. American Heart Journal. April 2018.
  • McNeil JJ, Woods RL, Nelson MR, et al., on behalf of the ASPREE Investigator Group. Effect of Aspirin on Disability-free Survival in the Healthy Elderly. N Engl J Med 2018;379:1499-1508.
  • American College of Cardiology. (2018, November) ASCVD Risk Estimator Plus.
  • Bhatt, D. et al. Cardiovascular Risk Reduction with Icosapent-Ethyl for Hypertriglyceridemia. New England Journal of Medicine. January 2019.
  • Manson JE, Cook NR, Lee IM, et al., on behalf of the VITAL Research Group. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. New England Journal of Medicine. January 3, 2019;380:33-44.
  • Yokoyama M. Effects of eicosapentaenoic acid (EPA) on major cardiovascular events in hypercholesterolemic patients: the Japan EPA Lipid Intervention Study (JELIS). American Heart Association Scientific Sessions 2005; November 13-16, 2005; Dallas, Texas. Late Breaking Clinical Trials II.
  • Robert S. RosensonRobert A. HegeleSergio Fazio and Christopher P. Cannon. The Evolving Future of PCSK9 Inhibitors. Journal of the American College of Cardiology. July 2018.
  • Giugliano RP, Cannon CP, Blazing MA, et al., on behalf of the IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) Investigators. Benefit of Adding Ezetimibe to Statin Therapy on Cardiovascular Outcomes and Safety in Patients With vs. Without Diabetes: Results from IMPROVE-IT. Circulation 2017;Dec 20
  • Harrington, R. and Gibson, M. The Top 10 Cardiology Trials of 2018 in Review. Medscape. February 12, 2019.
  • 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 Jr SC, 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, Journal of the American College of Cardiology (2018), doi:

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