New ESC Prevention Guidelines Focus on Tailored, Escalating Therapy

The European Society of Cardiology (ESC) has issued new guidelines for the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), focusing mostly—although not exclusively—on risk factors, risk classification, and the prevention of clinical events. 

The broad guidelines, endorsed by a dozen professional societies and released during the 2021 ESC Congress, are intended to help physicians care for the apparently healthy patient, as well as those with established ASCVD, diabetes, familial hypercholesterolemia (FH), and chronic kidney disease (CKD). The emphasis is on a personalized treatment approach, one that factors in lifetime risk and shared decision-making.

“When we started as a task force over two years ago, we set ourselves several goals,” said Frank L.J. Visseren, MD (University Medical Center Utrecht, the Netherlands), the chair of the ESC’s task force for CVD prevention, who presented them at the meeting. “We wanted to make a single guideline for primary care and hospital care. . . . We also wanted to make a more-personalized cardiovascular disease prevention guideline instead of a one-size-fits-all approach. In clinical practice, patients are very, very different, and we really wanted to have a more-individualized prevention guideline.”

The guidelines also pay particular attention to CVD prevention in older adults, those 70 years and older, and emphasize the importance of intensifying treatment as needed in selected at-risk patients following discussions around the risks and benefits.

“The stepwise intensification approach is to be used as a tool to help patients and physicians pursue these targets in a way that fits patient profiles and preferences,” said David Carballo, MD (Geneva University Hospital, Switzerland), a task force coordinator for the new guidelines. “In a sense, it reflects routine clinical practice, in which treatment strategies are initiated and then intensified as part of a shared decision-making process involving healthcare professionals and patients.”

The ESC recommendations introduce “lifetime risk” into the decision-making process and provide direction for estimating the lifetime risk of CVD in healthy people younger than 50 years old, as well as the lifelong benefits of an intervention.

“It was felt it was time for it to be introduced,” said Konstantinos C. Koskinas, MD (Bern University Hospital, Switzerland), a member of the ESC task force drafting the document. While there is a need for more evidence about the relative benefits of using lifetime risk, “we feel that discussing with the patient the estimated risk, not only for the next 10 years but longer, is critically important, particularly for younger and lower-risk individuals,” he said.

Algorithm, Not a Straitjacket

Outlining the meat and potatoes of the guidelines, Visseren said that one new aspect is the inclusion of the updated risk-prediction algorithms for apparently healthy people, SCORE2 and SCORE2-Older Persons (OP). The SCORE2 and SCORE-OP risk calculators have been calibrated for several geographic regions based on the level of CVD risk as assessed by the World Health Organization. Low-risk countries include Belgium, Denmark, France, Israel, Luxembourg, Norway, Spain, Switzerland, the Netherlands, and the United Kingdom, while the very-high-risk include several Eastern European countries, Russia, and the North African countries Algeria, Egypt, Tunisia, Libya, and Morocco.

Overall, the task force addresses CVD prevention in the different patient groups physicians frequently treat in clinical practice, including those with and without ASCVD, as well as those with diabetes, FH, and CKD. In these clinical scenarios, there is an initial first step with treatment, one that involves the estimation of 10-year ASCVD risk, followed by the consideration of risk modifiers, lifetime risk, treatment benefit, and patient preferences. After the first step, depending on the CVD risk profile, treatment can be further intensified.

Yvo M. Smulders, MD (Amsterdam University Medical Center, the Netherlands), another task force coordinator, outlined the general approach physicians should take when treating healthy adults without ASCVD. The flowcharts for treatment, he stressed, “are not algorithms, [and] they are not a straitjacket.”

Smoking cessation and lifestyle recommendations go for everybody, as does a systolic blood pressure target of less than 160 mm Hg. From there, guidelines provide recommendations for optimal systolic blood pressure and LDL-cholesterol targets based on age (< 50 years, 50-69 years, and ≥ 70 years) and the 10-year risk of ASCVD according to SCORE2.

“Generally, we do not recommend treatment in patients at low-to-moderate CVD risk, and we generally do recommend treatment in very-high CVD risk [patients], with a special note that in patients 70 years and older, the recommendation for starting statins is only a IIb recommendation, or a ‘may consider’ recommendation,” said Smulders.

Importantly, the latest guidelines lower the thresholds for considering young individuals at low-to-moderate risk of CVD. Using SCORE2 and SCORE2-OP, individuals younger than 50 years with a 10-year risk below 2.5% are considered low-to-moderate risk, while those aged 50-60 years and 70 years and older with scores of < 5% and < 7.5%, respectively, fall into the low-to-moderate risk category. Conversely, in those younger than 50, 50-69, and 70 years and older with a 10-year risk of CVD ≥ 7.5%, ≥ 10%, and ≥ 15%, are now considered very high risk for CVD. This differs from the previous guidelines where classification wasn’t stratified by age (the 2016 thresholds were < 5%, ≥ 5 to 10%, and ≥ 10% for low-to-moderate, high, and very-high risk).

“One of the reasons to have a lower risk threshold in younger people is to avoid undertreatment,” said Visseren. “With a younger age, people don’t reach conventional risk thresholds and so you wouldn’t treat these younger patients. But we all know if you start young, your lifetime benefit is way higher.”

Depending on the patient’s age, risk score, CVD risk modifiers, and lifetime risk, a systolic blood pressure target of 130 to 140 mm Hg is recommended. For those younger than 70 years, a lower target of less than 130 mm Hg is an option. An LDL cholesterol of less than 100 mg/dL is recommended broadly, but physicians should aim for lower if the patient is at high risk or very high risk for ASCVD. In primary prevention, ezetimibe can be added to a statin if the goal is not achieved (class I, level of evidence B), and a PCSK9 inhibitor can be added after that if the patient is still not at goal (class IIb, level of evidence C). 

Aspirin in not recommended for the primary prevention of ASCVD events in low-to-moderate-risk patients because of the increased risk of bleeding (class III, level of evidence A).

Smulders noted that coronary artery calcium (CAC) scores may be used to improve risk classification for treatment decisions in primary prevention (class IIb, level of evidence C), but the routine collection of potential modifiers, like genetic risk scores, circulating or urinary biomarkers, or vascular tests (aside from CAC, or carotid ultrasound if CAC testing is unavailable), is not recommended.

Patients With ASCVD

For the patients with established ASCVD, the treatment targets and goals for LDL cholesterol and systolic blood pressure are unchanged from the last iteration of the clinical guidelines. As always, smoking cessation and lifestyle changes are recommended, followed by a systolic blood pressure target 130 to 140 mm Hg (class I, evidence varies depending on age) and intensive lipid lowering aiming for a 50% or more reduction in LDL cholesterol and a target of less than 70 mg/dL (class I, evidence varies depending on age). After that initial first step, based on clinical risk factors and risk modifiers, a systolic blood pressure target of less than 130 mm Hg and LDL cholesterol of less than 55 mg/dL is recommended.

The ESC prevention guidelines make no mention of treating to a target of less than 40 mg/dL, a threshold broached in the 2019 ESC/European Atherosclerosis Society (EAS) guidelines for the treatment of dyslipidemias. While the overall target in the two guidelines is the same—less than 55 mg/dL in very-high-risk ASCVD patients—the ESC/EAS guidelines state that a target of 40 mg/dL or lower “may be considered” in the very-high-risk ASCVD patient who has had a second cardiovascular event within 2 years despite taking optimal statin therapy.

In terms of new other new ESC recommendations for high-risk ASCVD patients, physicians might consider colchicine 0.5 mg per day in secondary prevention if other risk factors insufficiently controlled (class IIb, level of evidence A) based on the results of the COLCOT and LoDoCo2 trials. In high-risk patients with triglycerides > 135 mg/dL despite treatment and lifestyle changes, icosapent ethyl 2 g twice per day may be considered in combination with a statin (class IIb, level of evidence B). 

The updated guidelines also address for the first time the impact of environment factors on CVD risk. These include air and soil pollution, above-threshold noise levels, and the effect of climate change. Patients at very high risk for CVD are encouraged to avoid long-term exposure to regions with high air pollution (class IIb, level of evidence C), and in these regions, more opportunistic CVD risk screening can be considered (class IIb, level of evidence C).

Finally, the guidelines also take a 30,000-foot view, addressing CVD prevention at the population level, and include sections on public health policy. These address not only pollution and climate change, but also interventions aimed at altering the environment to encourage physical activity, better dietary habits, the cessation of smoking, and moderation of alcohol use.