A 54 year old type 2 diabetic presents to the ER with substernal chest pain consistent with angina. An EKG demonstrated 2 mm ST elevation in the V!, V2, V3 leads. He underwent an emergent cardiac catherizaton which demonstrated 98% occlusion of the LAD and prior complete occlusion of his Rt coronary artery. He had a emergent stent done which was successful. His A1c was 7.3%, his prior lipid studies were total cholesterol 214 , total triglycerides were 677, HDL of 26 and LDL of 129. The lipid studies were done while the patient was on simvastatin 40 mg /day. His diabetes therapy consists of metformin 1000 mg bid, Lantus 50 units 2 times per day.
What would you recommend regarding his diabetes therapy?
As the patient now has vascular disease, they would benefit from medications with proven benefit for secondary prevention of Major Adverse Cardiac Events. If readers are unfamiliar I really like the full diagram from page S166 of Part 9 (Pharmacologic Approaches to Glycemic Treatment) of the 2024 ADA guidelines. Wordy I know but the diagram itself is easy to read and I often refer primary care docs or residents to it if they need a handy guide. I’ve included an excerpt of the full chart here:
I would start with a GLP-1 agonist as in the trials the biggest improvement in the composite MACE outcomes was in reduction of vascular disease. SGLT-2s are great as well but had the biggest improvement in the heart failure component, likely because of their effectiveness as diuretics. With his relatively good A1c adding one class would definitely be enough to achieve goal. With both it might be possible to even get the patient off insulin. Since hypoglycemia is associated with heart events I ideally would reduce or eliminate glargine.
Excellent review of the data. Unfortunately his insurer’s copay was markedly higher for the GLP-1 agent and so the patient was started on empagliflozin at 10 mg/day. His A1c was 6.8% 4 months after starting the medication.
What do you think about his cardiovascular therapy?
As goal is now secondary prevention I would treat this patient aggressively. While AHA guidelines usually risk stratify patients to therapy based on risks (an understandable approach), as an endocrinologist I would take this further and shoot for specific LDL cutoffs. For secondary prevention goal is LDL <70. In Europe they shoot for an even more aggressive goal of <55. I would start by switching to a high intensity statin like atorvastatin or rosuvastatin. I expect he will also need at least ezetimibe to reach that LDL goal, and possibly might need a PCSK9 inhibition to reach the goal. These are injectible medications that potentiate LDL receptors by acting on PCSK9. Since that enzyme breaks down LDL receptors, inhibiting it causes them to last longer, lowering LDL levels tremendously.
Finally I think his triglycerides should be addressed as well. While we often focus on LDL levels triglycerides are a major risk as well. I am hopeful improved glycemic control will assist with this. However with a value of 677 he will likely also need targeted treatment such as fish oil and fibrates alongside diet modifications. Vascepa (icosapent ethyl) is a fortified fish oil with only one of the isomers rather than a racemic mixture. It was shown in trials to be effective for secondary prevention for patients with triglyceride values <180 (Bhatt et al NEJM Jan 2019)
The patient was switched to rosuvastatin at 40 mg /day with 10 mg of ezetimibe also added. His repeat LDL was 67. Given his previously known high triglycerides we can assume he has a very high level of small dense LDL particles which are more atherogenic. Therefore we elected to switch him to PCSk9 therapy. His insurance plan rejected his prescription as he was at target LDL. We then chose to attack his triglycerides aggressively with Vascepa. His triglycerides are now down to 85 but his LDL rose to 75. We are appealing the PCSK9 rejection.
What do you think you about his long term condition given the aborted MI?
I think the stenting was the correct approach given his acute coronary syndrome. However post procedure I still think he is very high risk, hence the aggressive treatment plan above. However pharmacologic treatment remains the mainstay for secondary prevention.
Citations:
American Diabetes Association Professional Practice Committee. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2024. Diabetes Care. 2024 Jan 1;47(Suppl 1):S158-S178. doi: 10.2337/dc24-S009. PMID: 38078590; PMCID: PMC10725810.
Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM; REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019 Jan 3;380(1):11-22. doi: 10.1056/NEJMoa1812792. Epub 2018 Nov 10. PMID: 30415628.