Reducing ASCVD risk by optimizing risk factor management

Unexploited potential of risk factor treatment in patients with atherosclerotic cardiovascular disease

Literature - Van Trier TJ, Snaterse M, Hageman SHJ, et al. - Eur J Prev Cardiol. 2023 Feb 9;zwad038. doi: 10.1093/eurjpc/zwad038

Introduction and methods


Most patients with established ASCVD remain at (very) high risk of recurrent CV events, because they maintain their unhealthy lifestyles and show decreasing adherence to preventive medications [1-7]. With initial lifestyle changes and pharmacological treatment, some patients do achieve risk factor targets, but they retain a residual risk. In ASCVD risk management, it is therefore important to identify patients who require treatment intensification and at which level (lifestyle changes, increasing adherence to conventional medication, or selective use of novel medication).

Aim of the study

The study aim was to quantify 10-year and lifetime risk of recurrent ASCVD events under current risk factor management and under maximal preventive strategies in patients with recent ACS or coronary revascularization.


In this multistudy analysis, data from 6 large, contemporary studies conducted in the Netherlands were pooled (i.e., RESPONSE (Randomized Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists) 1 and 2, OPTICARE (OPTImal CArdiac Rehabilitation), Dutch participants of EUROASPIRE (European Action on Secondary and Primary Prevention by Intervention to Reduce Events) IV and V, and HELIUS (HEalthy Life in an Urban Setting)). Of these 6 studies, 3 were RCTs, 2 were cross-sectional surveys, and 1 was a prospective cohort study. A total of 3230 patients aged ≥45 years with a first or recurrent ACS event (acute MI or unstable angina pectoris) or coronary revascularization (percutaneous or coronary artery bypass graft surgery) were included, at a median time after the index event of 1.1 years (IQR: 1.0–1.8). The authors modelled a scenario in which all patients received maximal ASCVD treatment, defined as non-smoking, achievement of risk factor targets irrespective of whether this was accomplished with drug therapy or lifestyle adjustments (SBD ≤120 mmHg, LDL-c < 1.8 mmol/L, and HbA1c ≤53 mmol/mol), and additional use of DAPT, colchicine, and –if diagnosed with DM– GLP-1RA and SGLT2i.


Primary endpoints were 10-year and lifetime (i.e., until 90 years of age) risk of recurrent MI, stroke, or vascular death with current treatment, which were estimated using the SMART-REACH risk score. Secondary endpoints included current risk factor management, current use of conventional ASCVD preventive medication, and estimated individual benefit from maximal preventive therapy (i.e., optimization of both lifestyle and pharmacological therapy, including additional use of novel drug strategies).

Main results

Current risk factor management and medication use

  • In the study population, 98% had ≥1 lifestyle-related or drug-modifiable risk factor; 91% had an unhealthy lifestyle (including persistent smoking, being overweight, or insufficient physical activity), and 82% were not on target for ≥1 drug-modifiable risk factor (including abnormal LDL-c, HbA1c, or glucose level, or increased systolic blood pressure).
  • In total, 70% of the patients were on standard ESC Guidelines–based cardioprotective combination therapy (i.e., antiplatelet or anticoagulation, lipid-lowering, blood pressure–lowering, and, if diagnosed with DM, glucose-lowering medications).

10-year and lifetime risk of recurrent ASCVD events under current treatment

  • The median 10-year risk of recurrent ASCVD events with current treatments was 20% (IQR: 15%–27%), while the median lifetime risk of these events was 54% (IQR: 47%–63%).
  • The 10-year risk was relatively low in younger and middle-aged patients but increased when estimated for lifetime exposure.
  • The ratio between lifetime and 10-year risks decreased with increasing age and reversed in patients aged >80 years.

Potential benefit from additional treatment

  • If ASCVD therapy were to be maximized, the median 10-year risk of recurrent events decreased to 6% (IQR: 4%–8%) and the median lifetime risk to 20% (IQR: 15%–27%).
  • At the same time, the proportion of patients with a residual 10-year risk <10% increased from 2% to 85%.
  • This risk reduction resulted in a median gain of 7.3 ASCVD event–free years (IQR: 5.4–10.4), with greater estimated overall treatment benefit in younger patients.


In a pooled analysis of 3230 patients with established ASCVD, current suboptimal risk factor management resulted in a 10-year risk of recurrent ASCVD events of 20% and a lifetime risk of 54%. However, 98% of the patients had ≥1 lifestyle-related or drug-modifiable risk factor, and only 70% were taking standard ESC Guidelines–based cardioprotective medications. Maximizing ASCVD therapy by optimizing lifestyle and drug therapy could theoretically reduce the 10-year risk to 6% and the lifetime risk to 20%, which corresponded to a lifetime benefit of 7.3 event-free years.

The authors note that the “present findings may slightly underestimate the potential gain with maximal risk factor control for non-trial patients or patients in moderate- to high-risk countries but possibly overestimate the achievable gain in practice.”


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2. Minneboo M, Lachman S, Snaterse M, Jorstad HT, Ter Riet G, Boekholdt SM, et al. Community-based lifestyle intervention in patients with coronary artery disease: the RESPONSE-2 trial. J Am Coll Cardiol. 2017;70:318–327.

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5. Ray KK, Molemans B, Schoonen WM, Giovas P, Bray S, Kiru G, et al. EU-wide cross-sectional observational study of lipid-modifying therapy use in secondary and primary care: the DA VINCI study. Eur J Prev Cardiol. 2021;28:1279–1289.

6. Naderi SH, Bestwick JP, Wald DS. Adherence to drugs that prevent cardiovascular disease: meta-analysis on 376,162 patients. Am J Med. 2012;125:882–887 e881.

7. Bjorklund E, Nielsen SJ, Hansson EC, Karlsson M, Wallinder A, Martinsson A, et al. Secondary prevention medications after coronary artery bypass grafting and long-term survival: a population-based longitudinal study from the SWEDEHEART registry. Eur Heart J. 2020;41:1653–1661.

Find this article online at Eur J Prev Cardiol.

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