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1 December 2014
Hypertriglyceridaemia: the clinical and economic burden of undertreatment

This report shows that not only are elevated triglycerides (TG) undertreated, but this failure impacts the residual risk of vascular complications and pancreatitis, as well as healthcare costs, depending on the extent of hypertriglyceridaemia.

Toth PP, Grabner M, Ramey N, Higuchi K. Clinical and economic outcomes in a real-world population of patients with elevated triglyceride levels. Atherosclerosis 2014; 10.1016/j.atherosclerosis.2014.09.029.
Summary
Comments & References
STUDY SUMMARY
Objective: To investigate real-world treatment patterns, healthcare utilisation, and costs of hypertriglyceridaemia in a large commercially insured US population
Study design:  Retrospective US observational claims study.
Study population:  Adults with elevated TG (>500 mg/dL or 5.6 mmol/L) between 1 January 2007 and 30 April 2013. Patients were stratified based on their first available TG measurement: TG≥1,500 mg/dL or 16.9 mg/dL (Cohort A, n=1,964); 750≤TG<1,500 [8.5 to 16.9 mmol/L] (Cohort B, n=7,432), and 500<TG<750 [5.6 to 8.5 mmol/L] (Cohort C, n=17,500). All subjects had baseline and follow-up TG levels. Across the cohorts, patients were mainly young (mean age 46-48 years) and predominantly male (75%-80%). 
Primary variable: •  Healthcare utilisation and costs derived from medical and pharmacy administrative claims and electronic laboratory results taken from the HealthCore Integrated Research Database 
Methods:  Disease-related healthcare utilisation included all medical claims with an International Classification of Disease (ICD-9-CM)-code for dyslipidaemia or pancreatitis and all pharmacy claims for TG-related medications. Costs were computed as the total of plan paid plus patient paid amounts, and presented at constant 2013 US dollars. Multivariable logistic regression analyses, adjusted for baseline demographic, clinical, and economic characteristics, were used to investigate the impact of pancreatitis on healthcare utilisation and costs. 
Main results:

  • Hypertriglyceridemia was underdiagnosed; the diagnosis was made in 4-8% of patients at baseline, and 12-23% at follow-up, despite laboratory evidence.

• Hypertriglyceridaemia was undertreated. For treatment-naïve patients, 23-40% did not receive pharmacotherapy within 4 months of the first elevated TG value. Among patients who received treatment, about 50% received statins, 30% fibrates and 8% omega-3 fatty acids as first-line therapy.

• Mean all-cause costs/patient increased with the severity of elevated TG ($10,683 in Coho$11,504 in Cohort B, and $12,642 in Cohort A). The proportion of costs that were dyslipidaemia-related also increased correspondly (from 19% [$2,055] in Cohort C, 21% [$2,401] in Cohort B, and 30% [$3,730] in Cohort A). 

Authors’ conclusion: The findings of this study suggest that hypertriglyceridaemia is severely undertreated and healthcare utilisation and costs increase with the magnitude of TG elevation. There is a clear unmet need for additional disease education targeting both providers and the patient population as well as for the development of new treatments for hypertriglyceridaemia.

COMMENT

About one-third of adults in developed countries have elevated TG (defined according to the Joint European guidelines as fasting TG >150 mg/dL or 1.7 mmol/L).1-3    This has important implications, given that elevated TG (either fasting or nonfasting), a marker for TG-rich lipoproteins and their remnants, has been strongly associated with increased risk of myocardial infarction, ischaemic heart disease and stroke.4-7 Indeed, the R3i and other expert consensus groups have drawn attention to the need to treat elevated TG as a risk factor for residual cardiovascular risk.8.9 Additionally, severely elevated TG (defined as >10 mmol/L according to a recent consensus statement) warrant action because of pancreatitis risk.10 Given this rationale, it is therefore pertinent to consider the socioeconomic impact of undertreatment of TG, especially in the current restrained economic climate.

The results of this US analysis based on real-world data highlight the cost of failure to adequately manage hypertriglyceridaemia. Increasing levels of TG were associated with increasing healthcare utilisation and costs, which was especially notable in individuals with very high TG. Mean all-cause costs/patient increased by 19% in patients with TG levels of 500-750 mg/dL (5.6 to 8.5 mmol/L, consistent with mild to moderate hypertriglyceridaemia as defined by a recent consensus statement10) but were 30% higher in those with markedly elevated levels (severe hypertriglyceridaemia10). These findings are in agreement with previous reports, which showed that medical costs per annum, independent of resource-intensive conditions such as cardiovascular disease and diabetes, were increased in patients with elevated TG and up to one-third higher in those with markedly elevated levels.1,11

These findings reinforce the need to target and manage elevated TG in the clinic. Indeed, a separate report highlights the socioeconomic benefit of effective management of hypertriglyceridaemia. In patient in whom TG levels were reduced by more than 60%, there were cost savings compared with individuals in whom TG levels increased over a 5-year period.11  Thus, there is a clear impetus to manage elevated TG, to reduce the societal and economic burden of residual cardiovascular and pancreatitis risk. Education to improve awareness of the need to diagnose and treat hypertriglyceridaemia is clearly warranted; a role which can be addressed by the R3i as part of its mission to educate and inform about residual vascular risk.

References  

1. Nichols GA, Arondekar B, Garrison LP Jr. Patient characteristics and medical care costs associated with hypertriglyceridemia. Am J Cardiol 2011;107:225-9.

2. Laforest L, Souchet T, Moulin P et al. Prevalence of low high-density lipoprotein cholesterol and hypertriglyceridaemia in patients treated with hypolipidaemic drugs. Arch Cardiovasc Dis 2009;102:43-50.

3. Reiner Z, Catapano AL, De Backer G et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769-818.

4. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 2007; 298: 299–308.

5. Freiberg JJ, Tybjaerg-Hansen A, Jensen JS, Nordestgaard BG. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA 2008; 300: 2142–52.

6. Varbo A, Benn M, Tybjærg-Hansen A, Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol 2013; 61: 427–36.

7. Jørgensen AB, Frikke-Schmidt R, West AS, Grande P, Nordestgaard BG, Tybjærg-Hansen A. Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur Heart J 2013;34: 1826–33.

8. Fruchart JC, Davignon J, Hermans MP et al. Residual macrovascular risk in 2013: what have we learned? Cardiovasc Diabetol 2014;13:26.

9. Chapman MJ, Ginsberg HN, Amarenco P et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 2011 ;32:1345-61.

10. Hegele RA, Ginsberg HN, Chapman MJ et al. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol 2014;2:655-66.

11. Nichols GA, Arondekar B, Jacobson TA.  Hospital use and medical care costs up to 5 years after triglyceride lowering among patients with severe hypertriglyceridemia. J Clin Lipidol 2012;6:443-9. 

Key words  triglycerides; healthcare utilisation; costs; undertreatment, unmet need