Review: Analyzing the Latest Data on Recurrent CVD Prevention
Key findings
- In a 30-year follow-up study of patients with coronary artery disease, high-volume physical activity reduced the all-cause mortality risk versus inactivity
- PCSK9 monoclonal antibodies are now available for reduction of low-density lipoprotein cholesterol in very high-risk patients
- According to a phase 3 trial, eicosapentaenoic acid supplementation is associated with a 6% absolute reduction in the risk of major cardiovascular events
- The American College of Cardiology advises that for patients with type 2 diabetes who have cardiovascular disease, clinicians should consider starting a glucagon-like peptide-1 receptor agonist or a sodium–glucose cotransporter-2 inhibitor
- The FDA has approved the combination of rivaroxaban 2.5 mg twice daily and aspirin for secondary prevention of major cardiac events in patients with chronic coronary artery disease or peripheral artery disease
Once a patient experiences a major cardiovascular event, the risk of a recurrent event is high. A combination of tailored lifestyle changes and pharmacological interventions is the most effective strategy for reducing that risk.
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Pradeep Natarajan, MD, MMSc, director of the Cardiovascular Disease Prevention Center at Massachusetts General Hospital, and Maeve Jones-O'Connor, MB, BCh, BAO, resident, recently reviewed the newest data on secondary risk reduction. Their paper appears in Current Treatment Options in Cardiovascular Medicine.
Physical Activity
Physical activity independently confers a survival advantage for patients with coronary artery disease according to a recent study. High-volume physical activity (defined as ≥150 minutes/week of moderate-intensity activity or ≥60 minutes/week of vigorous activity) was linked to a 36% lower all-cause mortality risk versus inactivity. A change from inactive to high physical activity was linked to a 32% lower risk of cardiovascular mortality.
The 2018 US Physical Activity Guidelines recommend that all adults should do 150–300 minutes/week of moderate-intensity activity, 75–150 minutes/week of vigorous-intensity aerobic physical activity or an equivalent combination.
LDL-C Management
Higher levels of low-density lipoprotein cholesterol (LDL-C) continue to be linked to elevated coronary artery disease risk.
- PCSK9 monoclonal antibodies — Alirocumab and evolocumab, both approved by the FDA, are monoclonal antibodies that suppress concentrations of LDL-C. The 2018 American College of Cardiology/American Heart Association (ACC/AHA) Cholesterol Guidelines recommend PCSK9 monoclonal antibodies for achieving LDL-C >50% lowering to <100 mg/dL in patients with very high risk atherosclerotic cardiovascular disease (CVD)
- PCSK9 siRNA — Inclisiran, a small interfering RNA molecule, is an investigational drug for manipulating the PCSK9 pathway. According to a published report on ORION-1, a phase 2 trial, inclisiran was superior to placebo in reducing LDL-C in high-risk patients who had LDL-C above target despite statin therapy. In another analysis of ORION-1, inclisiran lowered LDL-C in patients with diabetes without worsening glycemia
- Bempedoic acid is a first-in-class oral drug that reduces LDL-C by inhibiting cholesterol biosynthesis and increasing LDL receptor expression. The FDA recently announced the acceptance of new drug applications for both bempedoic acid and a combination tablet containing bempedoic acid and ezetimibe. The agency's decisions are expected in February 2020
Pharmacologic Omega-3 Fatty Acids
The large-scale, five-year REDUCE-IT trial examined the benefit of supplementation with 4 g/day of eicosapentaenoic acid. In the secondary prevention cohort, the absolute reduction in the risk of major cardiac events was 6% and the relative risk reduction was 25%.
The ongoing STRENGTH trial is assessing whether a proprietary blend of omega-3 fatty acids reduces the risk of cardiac events in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol.
Hypoglycemic Agents
Ever since the data came out that linked rosiglitazone to increased cardiovascular risk, cardiovascular outcomes trials have been required for all new glucose-lowering agents. To date, the news is good: five trials have demonstrated that the newer classes of hypoglycemic agents help reduce the risk of CVD in patients with diabetes. These agents include:
- Glucagon-like peptide-1 (GLP-1) receptor agonists: semaglutide and liraglutide
- Sodium–glucose cotransporter-2 (SGLT2) inhibitors: empagliflozin, canagliflozin and dapagliflozin
A 2018 ACC expert consensus document recommends that for patients with type 2 diabetes who have established CVD, clinicians should consider starting a GLP-1 receptor agonist or SGLT2 inhibitor. Liraglutide is the preferred GLP-1 receptor agonist and empagliflozin is the preferred SLGT2 inhibitor.
Direct-acting Oral Anticoagulants
Direct-acting oral anticoagulants present less bleeding risk than oral vitamin K antagonists. Based on the COMPASS trial, the FDA has approved the combination of rivaroxaban 2.5 mg twice daily and aspirin for secondary prevention of major CVD events in patients with chronic coronary artery disease or peripheral artery disease. However, this strategy has not yet been incorporated into professional guidelines.
Calculating Recurrent Risk
Dr. Natarajan and his colleague remind readers of the TIMI Risk Score for Secondary Prevention, a clinical calculator for estimating a patient's risk of recurrent CVD. It has been validated in a trial setting, and it has proven to be generalizable to multiple cohorts.
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