A case review on cardiac risk stratification in the secondary prevention of cardiovascular diseases
Cardiac risk stratification is an assessment used to evaluate a patient's risk of developing cardiovascular disease (CVD) or the risk of a cardiac event occurring in noncardiac surgeries. CVDs are the number one cause of death globally, taking an estimated 17.9 million lives each year.1 There are 32.4 million myocardial infarctions and strokes worldwide every year. Patients who have had a previous MI are at an increased risk of recurrent infarctions and have an annual death rate of 5% - 6 times higher than people without CVD.2 It is a source of great morbidity and mortality as well as a large portion of economic loss, particularly in low- to middle-income countries.1 Reducing the mortality by both primary and secondary prevention will play a great role. However, it is important to stratify patients according to their CV risk to facilitate a “treat to target” approach that enhances the outcome and maximizes the distribution of resources. Professor Siu, Chung-Wah David, from the Department of Medicine, The University of Hong Kong, shared a case highlighting the importance of risk stratification in the secondary prevention of CVD.
According to the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) 2019 guidelines, a lifetime approach to CV risk should be considered when treating the patients with atherosclerotic cardiovascular disease (ASCVD).3 This implies improving lifestyle habits and reducing risk factor levels in patients with established ASCVD as well as in patients with an increased risk of developing ASCVD.3 All the current guidelines on the prevention of ASCVD in clinical practice recommend the assessment of total CVD risk. Prevention of ASCVD in each person should be related to his or her total CV risk, and the higher the risk, the more intense the action should be. Currently, several comprehensively reviewed CV risk assessment systems for primary prevention are available. Most guidelines utilize at least one of these risk assessment systems in risk classification. Although risk charts should be based on country-specific cohort data ideally, but this is unavailable for most countries.3
However, in clinical decision making, there are fewer tools available to assist on the prevention of secondary CV events or long-term response to treatment among patients in the stable phase of IHD, particularly in patients whose conditions are stabilized after ACSVD or who have established IHD without known previous MI.4
TRS 2oP incorporates risk factors such as older age, diabetes mellitus (DM), hypertension, smoking, peripheral artery disease, previous stroke, previous coronary artery bypass graft (CABG), history of heart failure, and renal dysfunction.4 In addition to predicting long-term outcomes, the TRS 2oP identifies high risk patients who experience the greatest absolute benefit from intensive secondary preventive anti-platelet therapy.4
Prof. Siu explained the use of TRS 2oP in the CV risk assessment with three case scenarios. “In this case sharing what I want to do is to highlight what is missing in the current management. Although we have guidelines and passionate interventional cardiologists, the treatment decisions are still not ideal,” stated Prof. Siu.
He further emphasized the importance of risk stratification in the secondary prevention of ASCVD, commenting, “If we do not realize the risk of the patient, it would affect the overall management of the patient.”
The patient in this case review is a 57-year-old man who was admitted to a hospital with chest pain. He was a smoker and had poorly controlled hypertension. The patient did not have any relevant family history. A thrombotic occlusion of the left anterior descending artery was found during the initial investigation, and the patient was diagnosed with acute MI with ST segment elevation. His initial LDL-C and HDL-C levels were 2.8mmol/L and 0.9mmol/L, respectively. Primary coronary interventions were carried out and the recovery was uneventful. The patient was given standard therapy including, anti-platelet medications, acetylcholine inhibitors, and moderate-to-high intensity statins. At his 3-month follow-up, LDL-C levels dropped to 1.7mmol/L. Prof. Siu mentioned that at this stage, most doctors do not consider their patient’s risk. Although the patient seems stable, it is mandatory to adequately control all risk factors. In order to emphasize optimal control of medical therapy in similar instances, Prof. Siu included more scenarios based on the case (Figure 1).
Scenario 1 is similar to the case presented, but with a renal function of 70%. The patient has an acceptable left ventricular function. Prof. Siu posed a question, “What is the risk of this patient for major adverse cardiovascular events (MACE) in 1 year, 3 years and later?” and remarked, “If we do not know the actual CV risk, we tend to treat either poorly or more aggressively according to the doctor’s perception alone.” Scenario 2 is the same patient with diabetes, slightly poor kidney function and good left ventricular function. In scenario 3, the left ventricular function has deteriorated slightly.
Prof. Siu highlighted that patients have been frequently followed up without a change in their drug regimen. He further stated, “For a long time, LDL-C was used as the only target, but with LDL-C alone we cannot determine the actual risk for secondary events.” Therefore, Prof. Siu suggested TRS 2oP to assess the CV risk in the given case scenarios. It is a simple 9-point risk stratification tool, previously developed in a large population with atherothrombosis to predict CV death, MI, and ischemic cerebrovascular accident in the IMPROVE-IT trial (Figure 2).4
All parameters present in an individual patient are given a point and the cumulative value gives an estimate for CV risk in 7 years, from which the annual risk can be calculated. Thus, the 7-year CV risk for the 3 case scenarios presented are 3%, 7%, and 9%, respectively. Risk is categorized as low when the cumulative risk index is 0-1, 2 as moderate risk and ≥3 as high risk. “In patients with scenario 2 and 3, more potent drugs such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can be considered. The patient at scenario 1 could be managed with less potent drugs,” said Prof. Siu.
The current ESC/EAS 2019 guidelines for secondary prevention of ASCVD, recommend a dual goal of a LDL-C reduction of ≥50% from baseline and a LDL-C target of <1.4mmol/L in very-high risk patients.3 Prof. Siu mentioned that patients who have not reached previous target of 1.8mmol/L should focus on reducing LDL-C levels further with available potent drugs, while patients who have already reached previous target should have additional risk assessment arranged to determine the treatment regimen.
Compared to very-high-risk category, in the high-risk category, there could be a risk variation within the group from low to high. In these situations, it is necessary to be selective to identify these specific subgroups. In fact, patients with a high burden of ASCVD benefit from greater relative and/or absolute risk reductions with PCSK9 inhibition.5 Moreover, the addition of PCSK9 inhibitors in the treatment of dyslipidemia has contributed to a reduction in plasma LDL-C levels by approximately 60%, significantly, reducing the risk of major vascular events and with no adverse effects.5
Evolocumab, a potent PCSK9 inhibitor, has been beneficial in patients with high atherosclerotic burden who are receiving optimized lipid-lowering therapy with statins. In a sub-analysis of the FOURIER trial, the efficacy of evolocumab was assessed in high-risk patients with recent MI, number of prior MI, and presence of residual multivessel coronary artery disease.6 Evolocumab reduced CV events by 20% in those with a recent MI (HR=0.80; 95% CI: 0.71-0.91), 18% in those with multiple prior MI (HR=0.82; 95% CI: 0.72-0.93), and 21% in those with multivessel disease (HR=0.79; 95% CI: 0.69-0.91).6 Given the higher baseline risk in patients with high risk features, the absolute risk reductions tended to be greater in those with high risk features compared to patients at low risk. Additionally, evolocumab reduced the relative risk for MACE by 19% over the first year in patients with at least one high risk feature (Figure 3).6 Furthermore, evolocumab significantly reduced CV outcomes in DM patients with 17% risk reduction (95% CI: 0.75–0.93; p=0.0008).7
Additionally, according to ESC/EAS 2019 guidelines, patients with ASCVD who experience a second vascular event within 2 years while taking maximally tolerated statin therapy should consider an LDL-C goal of <1.0mmol/L. However, some patients may still experience secondary ASCVD events even after LDL-C levels are lowered to below the recommended threshold. Prof. Siu mentioned, “If they are on potent anti-lipid therapy and still have an event, there must be an unidentified risk factor,” and remarked, “When the full profile of drugs, including PCSK9 inhibitors, are already implemented, additional medical interventions and further risk stratification should be considered in this cohort of patients.” Moreover, recent ESC/EAS 2019 guidelines have also recommended CV imaging such as arterial ultrasonography and lipoprotein a [Lp(a)] measurement for risk stratification.
CV risk stratification offers clinicians a practical strategy to identify those patients with the greatest potential to benefit from intensive secondary preventive therapy. TRS 2oP has been shown to effectively identify the risk of recurrent major CV events across low, medium, and high risk categories in patients in stable condition who have established IHD and previous MI. Patients at high risk, reflecting greater atherosclerotic burden, are more likely to benefit from the PCSK9 inhibitors. They have demonstrated greater clinical benefit in patients with high CV burden, particularly, evolocumab has reduced the CV risk significantly in this cohort of patients.
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