Risk of Recurrent CV Events

CVD Is a Leading Cause of Morbidity With the
Prevalence Projected to Increase1

Data from the Reduction of Atherothrombosis for Continued Health (REACH) registry showed that patients with established CVD remain at high risk for recurrent ischemic events.1 Cardiovascular disease (CVD) represents one of the leading causes of morbidity worldwide, with heart disease, stroke, and hypertension ranking among the top causes in the USA.2

The REACH Registry Assessed the Risk of Recurrent Ischemic Events in Patients With Prior CV Events

Patients with established CVD in the REACH registry were at the highest risk of experiencing a subsequent cardiovascular (CV) event within the first year of the index event.2 Even patients who are event-free in the year following the index event remain at significant risk for future events, with event rates after MI increasing even years after the index event.3-6

  • The risk for a recurrent ischemic event in patients with history of myocardial infarction (MI) or stroke is ~ 1 in 3. A history of CV events is one of the strongest predictors of future ischemic events.2

REACH Registry: Recurrent CV Event Rates Are Highest in Patients With Prior Event Occurring Within 1 Year.2


Reach Registry: international, observational, prospective cohort of 68,236 patients at risk for atherothrombotic events. 45,227 patients from 29 countries in the REACH registry completed the 4-year analysis. 77% of the patients in this group were on ≥ 1 lipid-lowering drug.
CV, cardiovascular; MI, myocardial infarction; REACH, Reduction of Atherothrombosis for Continued Health.

  • High-risk patients such as those with a recent history of MI experienced significantly higher rates of recurrent CV events than patients with stable atherosclerosis and no prior ischemic events.1,2

Recurrent CV Events Result in Significant Economic Burden7

Healthcare Resource Utilization and Costs at 2-year Follow-up for Patients With a History of CV Event*


Retrospective observational study based on used administrative claims from the HealthCore Integrated Research Database (HIRD). The HIRD contains longitudinal medical and pharmacy claims data for approximately 33 million members from 14 commercial health plans across the USA. The study included patients age 18 to 64 years with a diagnosis of hyperlipidemia or use of lipid-modifying medications from January 1, 2007, to December 31, 2008.
*Patients with a history of a CV event, including MI, stroke, UA, CABG, or PCI.
CABG, coronary artery bypass graft; CV, cardiovascular; MI, myocardial infarction; PCI, percutaneous coronary intervention; UA, unstable angina.

In this retrospective study examining the burden of CV events, 79% of patients who had a prior CV event (n = 7,024) experienced another CV event that required hospitalization during 2-year follow-up.7 In-patient hospitalization was on average 5.8 days and cost $31,320.7

MI is One of the Most Expensive Hospital Principal Discharge Diagnoses

  • 25%
    of the 805,000 MIs per year in the USA are recurrent events.7
  • The total health-care costs of subsequent MIs ranges from
    for patients with one CV event to
    for patients with three CV events over 2 years. 8

Patients With ACS Have a Significant Loss of Work Productivity After CV Event

A U.S. longitudinal registry examining employment status found that 1-in-10 patients reported an adverse change in employment within 1 year following a MI, and nearly half of these patients reported involuntary job loss such as being laid off or no longer working due to their health and disability.9

  1. Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart disease and stroke statistics – 2017 update: a report from the American Heart Association. Circulation. 2017;135(10):e146-e603. doi:10.1161/CIR.0000000000000485.
  2. Bhatt DL, Eagle KA, Ohman EM, et al. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. JAMA. 2010;304(12):1350-1357. doi:10.1001/jama.2010.1322.
  3. Jernberg T, Hasvold P, Henriksson M, Hjelm H, Thuresson M, Janzon M. Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective. Eur Heart J. 2015;36(19):1163-1170. doi:10.1093/eurheartj/ehu505.
  4. Hess CN, Clare RM, Neely ML, et al. Differential occurrence, profile, and impact of first recurrent cardiovascular events after an acute coronary syndrome. Am Heart J. 2017;187:194-203. doi:10.1016/j.ahj.2017.01.016.
  5. Abtan J, Bhatt DL, Elbez Y, et al. Residual ischemic risk and its determinants in patients with previous myocardial infarction and without prior stroke or TIA: insights from the REACH registry. Clin Cardiol. 2016;39(11):670-677. doi:10.1002/clc.22583.
  6. Steg PG, Bhatt DL, Wilson PWF, et al. One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA. 2007;297(11):1197-1206. doi:10.1001/jama.297.11.1197.
  7. Punekar RS, Fox KM, Richhariya A, et al. Burden of first and recurrent cardiovascular events among patients with hyperlipidemia. Clin Cardiol. 2015;38(8):483-491.
  8. Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke statistics–2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56-e528.
  9. Warraich HJ, Kaltenbach LA, Fonarow GC, Peterson ED, and Wang TY. Adverse change in employment status after acute myocardial infarction: analysis from The TRANSLATE-ACS study. Circ Cardiovasc Qual Outcomes. 2018;11(6):e004528. doi: 10.1161/ circoutcomes.117.004528.

Many Patients With Established CVD Remain at Significant Risk for Future Events Despite Treatment With Statins1

Studies show that despite optimal treatment with lipid-lowering agents including statins, niacin and fibrates, significant residual CV risk remains regardless of dose and treatment setting.1

In Clinical Studies, Residual CV Risk Remains Despite Treatment for LDL-C1

risk-remains risk-remains

*Patients who received non-lipid lowering therapy.

CV, cardiovascular; LDL-C, low-density lipoprotein cholesterol.

Reductions in low-density lipoprotein cholesterol (LDL-C) following high-intensity lipid-lowering treatment are associated with additional reductions in CV risk in patients with established cardiovascular disease (CVD). However, landmark statin trials demonstrated that even patients who achieve lower LDL-C levels (62-81 mg/dL) remain at risk for future CV events.1-5

Residual CV Risk Remains Even in Those Receiving Treatment With High-Intensity Statins At 2-Year Folllow-up3-5

risk-remain-high risk-remain-high

*Mean or median LDL-C after treatment.
CV, cardiovascular; CVD, cardiovascular disease; LDL-C, low-density lipoprotein cholesterol.

  1. Sampson UK, Fazio S, Linton MF. Residual cardiovascular risk despite optimal LDL cholesterol reduction with statins: the evidence, etiology, and therapeutic challenges. Curr Atheroscler Rep. 2012;14(1):1-10. doi:10.1007/s11883-011-0219-7.
  2. Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681. doi:10.1016/S0140-6736(10)61350-5.
  3. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387-2397. doi:10.1056/NEJMoa1410489.
  4. Pedersen TR, Faergeman O, Kastelein JJP, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005;294(19):2437-2445. doi:10.1001/jama.294.19.2437.
  5. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425-1435. doi:10.1056/NEJMoa050461.

Lowest Achieved LDL-C Levels Translate Into Lower Risk for Major CV Events With the Benefit Accumulating With Every Subsequent Year of Treatment1

Meta-analyses of Studies Evaluating the Effects of Lipid-Lowering Treatments on CV Outcomes, Including the Cholesterol Treatment Trialists' Collaboration Analyses Have Shown That:

  • More intensive LDL-C lowering is associated with further reductions in CV event rates.2

  • These reductions are safe and beneficial even for individuals with low baseline LDL levels (70 mg/dL).2

  • The linear relationship between LDL-C reduction and CV event reduction is independent of baseline LDL-C levels and dependent on the absolute reduction in LDL-C.1-3

  • The clinical benefits of LDL-C lowering on CV risk reduction extend to patients with very low baseline LDL-C levels and are greatest in those with the lowest achieved LDL-C levels.1,2

  • The beneficial effect of LDL-C lowering on CV risk reduction increases with time, with maximum risk reduction occurring over 4 years of treatment.1,3

The lack of a documented lower threshold at which LDL lowering is no longer beneficial, as suggested by epidemiological, genetic, and clinical studies, has led to the hypothesis that intensive LDL-C lowering, beyond recommended thresholds, could provide additional benefits, especially for patients with very high-risk atherosclerotic cardiovascular disease.1,4,5

Very Low Achieved LDL-C Levels (< 50 mg/dL) With Statins Are Associated With Further Reductions in Risk for Major CV Events6,7


CTTC meta-analysis of major lipid secondary prevention statin trials conducted in 2010: median follow-up ~ 5 years, N = 169,138.
CTTC, Cholesterol Treatment Trialists' Collaboration; CV, cardiovascular; LDL-C, low-density lipoprotein cholesterol.

The SWEDEHEART Registry Showed that MI Patients With > 50% Reduction in LDL-C Demonstrate the Lowest Rates of Additional Cardiovascular Events5

During a 10-year period, the SWEDEHEART registry study followed approximately 40,000 Swedish patients who were admitted for myocardial infarction (MI), looking for changes in LDL-C levels and incidence of CV events. LDL-C reduction after the index MI event was associated with a reduced incidence of major adverse CV events, CV-related mortality, and coronary revascularization.5

*Percent change in LDL-C levels from the index event to the follow-up cardiac rehabilitation visit (6–10 weeks after hospital discharge).2

Meta-analysis used individual patient data (n = 38,153) from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. MACE was defined as the composite outcome of cardiovascular mortality, MI, ischemic stroke. Major vascular event: composite outcome of cardiovascular mortality, MI, ischemic stroke, and coronary revascularization (CABG/PCI).

CABG, coronary artery bypass graft; LDL-C, low-density lipoprotein cholesterol; MACE, major adverse cardiovascular events; MI, myocardial infarction; PCI, percutaneous coronary intervention; PY, person-year.

  1. Boekholdt SM, Hovingh GK, Mora S, et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol. 2014;64(5):485-494. doi:10.1016/j.jacc.2014.02.615.
  2. Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681. doi:10.1016/S0140-6736(10)61350-5.
  3. Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267-1278. doi:10.1016/S0140-6736(05)67394-1.
  4. Soran H, Dent R, Durrington P. Evidence-based goals in LDL-C reduction. Clin Res Cardiol. 2017;106(4):237-248. doi:10.1007/s00392-016-1069-7.
  5. Schubert J, Lindhal B, Melhus H, et al. Low-density lipoprotein cholesterol reduction and station intensity in myocardial infarction patients and major adverse outcomes: a Swedish nationwide cohort study. Eur Heart J. 2021;42(3):243-252. doi:10.1093/eurheartj/ehaa1011.
  6. Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681. doi:10.1016/ S0140-6736(10)61350-5.
  7. Raymond C, Cho L, Rocco M, Hazen SL. New guidelines for reduction of blood cholesterol: was it worth the wait?Cleve Clin J Med. 2014;81(1):11-19. doi:10.3949/ccjm.81a.13161.