Aggressive new approaches to reduce cholesterol-related heart disease are part of an extensive update of dyslipidemia prevention and treatment guidelines developed by an expert panel of the Canadian Cardiovascular Society (CCS).
“Dyslipidemia is one of the major risk factors in the development and progression of atherosclerotic cardiovascular disease,” says professor of medicine Dr. Glen Pearson of the University of Alberta, who co-chaired the panel that developed the 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults.
The new Guidelines, targeted to physicians, nurses, pharmacists and other allied health professionals, will improve prevention and management of disease, reduce disability, and potentially save thousands of lives.
New recommendations include:
- expanded screening and counselling for women with pregnancy complications, such as gestational diabetes, pre-eclampsia, hypertension and pre-term labour, who may be at higher risk of heart disease;
- in the general population, one-time blood testing for lipoprotein(a) (Lp(a)), a stable blood biomarker that is a genetically determined, causative risk factor for cardiovascular disease;
- use of effective new lipid-lowering medications, including injectables, to treat people who do not achieve adequate lipid control on statin therapy;
- measurement of non-fasting biomarkers apolipoprotein B (ApoB) or non-high density lipoprotein (non-HDL)as an alternative to low-density lipoprotein (LDL), particularly in people with high trigyclerides; and,
- a recommendation against the use of over-the-counter omega-3 fish-oil supplements because they have no cardiovascular benefit.
Reaching out to young women and those with other vascular diseases
For the first time, the Guidelines identify pregnancy complications as red flags. They highlight the need to reach out earlier to women who could be on a path to prematurely developing heart disease risk factors, such as hypertension and diabetes, within 10 years. “The earlier we inform women, the better,” says nursing leader Wendy Wray, a member of the Guidelines panel and director of the Women’s Healthy Heart Initiative at McGill University Health Centre. “Too many young women are not getting this education.”
By knowing the risk, women who experience pregnancy complications can be counselled to get back to their natural weight, and attain and maintain normal blood pressure by limiting alcohol and salt intake, and exercising regularly. “We’ve seen since 2017, there is an uptick in Canada and the United States in heart disease and cardiac events in young women,” Ms. Wray says. “That shouldn’t be happening.”
Similarly, the Guidelines say that people with other diseases such as kidney disease, peripheral arterial disease, abdominal aortic aneurysm and diabetes, need special attention because they are likely to also have heart disease. “That’s another red flag. These are people who should be on a statin,” says University of Ottawa Heart Institute endocrinologist Dr. Ruth McPherson, a member of the expert panel. “These patients need to get their LDLs as low as possible.”
Using different biomarkers – Lp(a), ApoB and non-HDL – to assess risk
Also highlighted in the Guidelines: A new and important primary prevention recommendation to screen people for lipoprotein(a) — a one-time blood test measurement now covered by all provincial health-care plans. A strong risk factor for heart disease, Lp(a) is a genetically determined LDL subset, very stable over time, and an important causative risk factor for cardiovascular disease.
“It binds to the walls of the arteries, promoting cholesterol uptake, and can also impair the breakdown of blood clots,” Dr. McPherson says. “There are two reasons to measure for Lp(a). In an otherwise healthy person, Lp(a) may signal the need to start preventative therapy sooner. For a patient who already has heart disease, there are new treatments in the pipeline that may be of benefit.”
Pharmacist Arden Barry of the University of British Columbia, a member of the expert Guidelines panel, agrees the Lp(a) recommendation is “novel and applicable to all clinicians, including pharmacists.” He also underscores the role of non-fasting biomarkers non-HDL and ApoB as potentially better predictors of cardiovascular disease than LDL alone.
“I think clinicians will become more comfortable with these alternative biomarkers, knowing that LDL, which everyone knows as the bad cholesterol, has been entrenched in practice for many years.” He says it’s important for pharmacists to understand the role of non-HDL and ApoB, and how they relate to drug therapy.
Identifying people who would benefit from non-statin add-on therapies
For patients who do not reach optimal control with statin therapy, the revamped Guidelines recommend the use of new therapies to reduce cardiovascular risk.
“We switched the Guidelines from an approach where we had targeted treatments, where providers were given targets to reach, to a threshold approach,” Dr. Pearson explains. “Under the new Guidelines, if you’re not able with statin therapy to achieve a threshold level, then there are recommendations for newer therapies for intensification.”
Dr. Barry says that moving away from a specific lipid target is “progressive and more in line with current evidence” but it will take time to shift practice because “this concept of LDL and a specific target is very ingrained.” On the plus side, the new approach eliminates the need for serial lipid monitoring to achieve a certain number.
Three drug classes are identified as add-on therapies. One is ezetimibe, which has been around for years. It is the only medication within this class that is a cholesterol-absorption inhibitor. The second class is PCSK9 inhibitors, which are the injectable drugs. “There is good evidence that these are beneficial,” Dr. McPherson says. The third is icosapent ethyl, a novel purified formulation of EPA, which is an omega-3 fatty acid.
However, complicating the recommendation to intensify therapy is the fact that some of the newer medications are not covered by all drug plans, so the CCS is pushing for expanded coverage. “If people have coverage they should be using these agents but it’s limited by access issues,” Dr. Pearson adds.
Advocating a combo approach – medication plus lifestyle counselling
Guidelines continue to emphasize the impact of lifestyle changes to improve cholesterol levels, but acknowledge these changes need to be done hand-in-hand with drug therapy. It’s no longer a case of trying to get a patient to first try to lose weight and exercise before determining if statins need to be introduced.
“If you become a vegan and you train for a marathon for the rest of your life, you may not get your cholesterol down to an ideal level,” Dr. Pearson says. Neither is a quick pill the answer if a patient unable to stop smoking or get active. Medication optimizes behavior modification and vice versa. It’s not a stepped approach, it’s a combination one that is most effective.
In terms of dietary fat intake, “we certainly don’t recommend ketogenic diets because they are high in fat, high in cholesterol, and high in saturated fats,” Dr. McPherson says. “We recommend a Mediterranean-type diet or DASH diet – nuts, fish, liquid vegetable oil. And, if you live in Canada, the best liquid vegetable oil is canola oil because it’s got a nice balance of mono- and poly-unsaturated fatty acids. Maybe even better for you than olive oil and less expensive.”
She also tells her patients to get 8,000-10,000 steps a day and reduce the size of their food portions. “People have to learn they can’t eat the way they did when they were teenagers, and they can’t eat the way their grandfather did when he was working on the farm.”
Dr. McPherson likes to point family doctors to the HOPE-3 study, a global trial involving thousands of patients and run out of McMaster University. “That trial enrolled men over the age of 55, and women over the age of 65, with no history of heart disease.” To qualify, participants had to have one cardiovascular risk factor – such as overweight, high blood pressure, family history of heart disease, low level HDL cholesterol. “Most middle-aged people have at least one risk factor.” Of the study participants put on a low-dose statin compared to placebo, there was a significant decrease in heart attacks and strokes over a five-year period and the curve continued to diverge over time.
“Based on this large, well-controlled clinical trial, most middle-aged individuals would benefit from statin therapy,” Dr. McPherson says.
Telling patients to stop over-the-counter Omega-3 supplements
What clearly doesn’t work? Omega-3 fatty acid supplements. “We have a lot of evidence with recently published clinical trials to suggest they are not effective in lowering cardiovascular disease risk,” Dr. Barry says. “One thing I have tried to highlight with my colleagues, especially ones who work in pharmacies, is to recommend against the use of over-the-counter omega-3 fatty acid supplements specifically for cardiovascular disease.” They are not benign. “There is potential risk associated with them. They do have a blood-thinning effect and they do interact with some other medications.”
Dr. Pearson says people have been taking omega-3 for years “so this is the culmination of all that data showing there is no benefit from anything sourced over-the-counter.”
Applying the best research evidence to save lives
“If all of this is applied to the right patients, we should see further reductions in morbidity and mortality from atherosclerotic cardiovascular disease,” Dr. Pearson says.
“Guidelines are important but, to me, what’s equally important is how you apply them,” Ms. Wray says. “My concern is that health-care professionals need to really use these Guidelines. We know our health-care system is overburdened. In heart disease, a lot of it is prevention and you’ve got the evidence-based research in front of you. Now, let’s get it out there.”
Pocket guides are one tool the CCS produces that supports health care professionals in applying the Guideline recommendations. The quick reference tools feature essential diagnostic and treatment recommendations for the most recent Dyslipidemia Guidelines. The 2022 edition of the Dyslipidemia Guidelines pocket guide is now available as a downloadable PDF.
Want a summary of what the new Dyslipidemia Guidelines recommend? See our Top 10 Takeaways and share them with your colleagues.
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