Risk of Recurrent CV Events

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

CVD represents one of the leading causes of morbidity worldwide, with heart disease, stroke and hypertension ranking among the top causes of morbidity in the USA.1 Many patients with established CVD remain at risk for subsequent ischemic events.2

  • Risk for a recurrent CV event in patients with history of MI or stroke ~ 1 in 3.2

Risk of Recurrent Events

Patients with a history of prior ischemic events are at higher risk of experiencing subsequent CV events, especially 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

  • A prior history of CV events is one of the strongest predictors of future ischemic events.2

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

cardiovascular

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.

  • Data from the REACH registry showed that high-risk patients, such as those with a recent history of MI, experienced significantly higher rates of recurrent CV events compared to patients with stable atherosclerosis and no prior ischemic events.1,2

Event Rates Continue Increasing Years After the First Event5

event-rates

Events were defined as stroke, cardiovascular death, polyvascular disease, or cardiovascular hospitalization.

  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.

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

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

Landmark statin trials demonstrated that while further reductions in LDL-C, following high-intensity lipid-lowering treatment, are associated with additional reductions in CV risk in patients with established CVD, even those achieving LDL-C levels 62–81 mg/dL remain at risk for future events.1-5

Residual CV Risk Remains Even in Those Receiving Treatment With High-Intensity Statins3-5

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 and that 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 very high-risk patients.1,4

Very Low Achieved LDL-C Levels (< 50 mg/dL) Are Associated With Further Reductions in Risk for Major CV Events1

low-ldlc

*Adjusted for sex, age, smoking, DM, SBP, HDL-C, and trial. > 175– < 200 mg/dL for non-HDL-C.
CV, cardiovascular; DM, diabetes mellitus; HDL-C, high-density lipoprotein cholesterol; HR, hazard ratio; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure.

  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.