Beyond the prescription: Pharmacists’ pivotal role in cardiovascular prevention

Imagine a world where the leading cause of death is largely preventable. That’s the world we live in, yet cardiovascular disease continues to be the number one killer. New therapies have improved treatment, while imaging and diagnostic testing have advanced to provide earlier and more accurate diagnosis. The gap between the onset of a heart attack and the start of treatment has been reduced. This should ideally lead to a significant decrease in cardiovascular morbidity and mortality. Yet, cardiovascular disease remains the top cause of death. Why is that, you may be asking yourself? From my personal experience as a pharmacist advocating for cardiovascular prevention as well as my own experience as a patient diagnosed with cardiovascular disease I have a few observations. Preventative cardiology just isn’t “sexy.” It’s not exciting or flashy. An acute heart attack gets everyone’s attention and adrenaline flowing. An emergency bypass or stent leaves the surgeon feeling like they have just made a major impact on this patient’s life and they are rightly congratulated for saving a life. With preventative cardiology, if you do everything perfectly, nothing happens. The patient will never know that the soft vulnerable plaque in their coronary artery reduced in size and was secured in place by the formation of a thick fibrous cap or hardened by calcification. They won’t have a near death experience that they live to tell their friends. They will have just lived longer and given the credit to fate. There are obvious ways to reduce your cardiovascular risk, like not smoking, eating healthy, maintaining a good Body Mass Index and exercising regularly. There are risk factors that can’t be changed like genetics, gender, and aging. But there are also simple changes that we as pharmacists can help our patients make by simply taking a few extra minutes to check if their pharmacotherapy is effective and optimized. When I notice a patient refilling a prescription for a maximum dose statin, ezetimibe, and an anti-platelet medication, it signals to me that the patient likely has a compelling story to share. A few simple questions is all it takes to get the patient sharing and remembering a typically dramatic event. This usually allows me to ask some more directed questions about their current efforts of risk reduction: diet, exercise, sleep, stress and of course staying current with lab tests and cardiology follow ups. In the hustle and bustle of the dispensary, time is often scarce. However, when possible, I take a few moments to consult the Ontario provincial database Clinical Viewer, to review their lipid levels. You would be amazed, I certainly was, at the number of patients whose lipids don’t meet the Canadian Cardiovascular Society’s Dyslipidemia thresholds. I don’t like the term targets, because it gives the illusion that if you beat the maximum accepted value that you are good, you are safe with nothing to worry about. In the lipid world the motto is: the lower the better, the sooner the better and the longer the better. The many trials involving proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have shown there is no danger in pushing cholesterol as low as possible. The brain produces its own cholesterol since LDL vesicles are too big to cross the blood brain barrier, so the fears of causing dementia are not causal. The evidence also clearly shows the correlation of lifetime exposure of endothelium to cholesterol as the driver of cardiovascular risk, so the sooner a patient lowers their cholesterol the better. PCSK9is are extremely effective at lowering persistently high cholesterol levels and yet in my pharmacy with over 800 high-dose statin treated patients we only have four patients on a PCSK9i.The evidence is in, and it’s strong. Elevated triglycerides are a clear red flag for cardiovascular risk. Lowering triglycerides has proven ineffective in numerous trials of niacin and fibrates, most recently the PROMINENT trial where pemafibrate lowered triglycerides 25% but had no effect at all on cardiovascular outcomes. Similarly, fish oils or combinations of EPA and DHA have been shown to reduce triglycerides to a similar degree but also showed no benefit in reducing cardiac events. The STRENGTH trial used a pharmaceutical grade combination of Eicosapentaenoic acid (EPA) and docosahexaenoic acid DHA in a large, placebo controlled, double blind randomized controlled trial (RCT) and was stopped earlier for futility. The only triglyceride lowering agent that has proven, with very strong data, to significantly reduce Major Adverse Cardiovascular Events (MACE) is pure EPA when given at high doses in the form of Icosapent Ethyl (IPE). The REDUCE-IT trial using IPE (brand name Vascepa) showed an impressive 25% reduction in MACE with a p value of 0.0000001. That’s seven zeros! It was even statistically significant at reducing CV death 20%, something the JUPITER trial failed to do using rosuvastatin. Many people question why REDUCE-IT was so successful while every other omega 3-related trial was not and the answer is simple, yet complicated. REDUCE-IT was not the first, nor the last, trial showing high doses of pure EPA causes a significant reduction in cardiovascular events. Earlier trials included JELIS and CHERRY while later trials included EVAPORATE and most recently RESPECT-EPA. They all consistently showed a 19-25% reduction in first events and up to 30% of total events. The reason for the consistent benefits appears to be the result of 2 key factors: achieving high serum EPA levels (which STRENGTH did not) and the absence of DHA competing at the COX enzyme, something all the fish oil mixtures contain. EPA is metabolized via the Cyclooxygenase (COX) and 5-Lipoxygenase (5-LOX) enzymes into anti-inflammatory E-Series RESOLVINS. These RESOLVINS, as the name implies, work as cytokines that resolve inflammation, like the inflammation going on with foam cells in the vulnerable plaque of coronary arteries. Simply put, EPA is an anti-inflammatory or more accurately an inflammation resolving molecule. DHA competes with EPA at the COX binding site and is metabolized into D-Series RESOLVINS and PROTECTINS that do not appear to be beneficial to reducing cardiovascular disease. Read: New screening tool available to asssess CVD risk for Alberta patientsArachidonic Acid is an Omega 6 fatty acid that produces inflammatory cytokines like prostaglandins, thromboxanes and leukotrienes. They function as the “attack and destroy” part of the immune response while the Omega 3 EPA functions as the “clean up and repair” part of the immune system. Historically, for thousands of years, humans had a ratio of Omega 6: Omega 3 of about 1:1 to 3:1. With the radical change of the industrialized food industry that revolves around soybeans and corn (both high in Omega 6s) that ratio is now closer to 20:1. This has led to the exponential growth of inflammatory conditions like cardiovascular disease, diabetes, obesity, autoimmune disorders etc. Very high doses of EPA without DHA restores the natural ratio and returns balance to the immune system. And that is the simple, yet complicated way in which Icosapent Ethyl (IPE) is so effective. The pharmacist’s perspectiveLooking back at that statin/ezetimibe/anti-platelet patient, I would be checking to see if their ApoB (otherwise nonHDL, or lastly LDLc) could be improved with a PCSK9i or if their triglyceride level qualified them for IPE. So why aren’t you seeing any prescriptions for PCSK9i or IPE? I have several opinions on why that is the case. Government and private insurance policies have been created which obstruct access, such as the Ontario government’s new EXCEPTIONAL ACCESS PROGRAM form specifically for IPE requiring a FASTING TG within the past three months instead of the standard Limited Use Code written on the Rx. Also partially because the drug Vascepa was launched in February 2020—a month before COVID-19 changed the world. Drug reps couldn’t get in to see doctors. In part because doctors don’t understand the mechanism of action which, in addition to the above, causes membrane stabilization with reduction in cholesterol crystals, anti-platelet activity, antioxidant and other biochemical functions. And partly because IPE is mistakenly lumped in with “fish oils.” But mostly because, as mentioned above, cardiovascular prevention just isn’t “sexy” and attracts no attention. The two main cardiologists in my town both have a default line at the end of their consults that states: “I will leave the patient’s blood pressure and lipid control to you with a goal of keeping LDLc under 1.8[MOU1] mmol/L” for their patients with known cardiovascular disease. Family doctors, already burdened with managing acute care, often assume that if their patients with cardiovascular issues are under the care of a cardiologist, then decisions about adding cardiovascular medications should fall to the specialist. However, this often results in a stalemate, with neither party taking the initiative to add life-saving medications like PCSK9 inhibitors or Icosapent Ethyl (IPE), both of which have been shown to significantly reduce risk.It’s time for us, as pharmacists, to take the lead in cardiovascular prevention. We are the healthcare professionals who interact with patients most frequently, and we have the knowledge and tools to make a real difference. Let’s not just dispense medication, but dispense knowledge, encouragement, and hope. Do not just treat diseases, but prevent them. Let’s not just extend lives, but enhance them. This is our calling, our responsibility, and our opportunity. Let’s seize it.

Beyond the prescription: Pharmacists’ pivotal role in cardiovascular prevention

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