Cost-effectiveness of Adding Prolonged-Release Nicotinic Acid
Cost-effectiveness of Adding Prolonged-Release Nicotinic Acid
Clinical guidelines focus on statins for dyslipidaemia management for prevention of cardiovascular disease. It is clear, however, that there remains an unacceptably high residual risk of further events among patients who achieve target low-density lipoprotein (LDL) cholesterol levels. Low high-density lipoprotein (HDL) cholesterol levels, an independent predictive factor, is likely to be an important contributor to this excess risk, and is also common among dyslipidaemic patients. The ARBITER 2 study (ARterial Biology for the Investigation of the Treatment Effects of Reducing cholesterol) showed that raising HDL cholesterol with prolonged-release (PR) nicotinic acid in addition to lowering LDL cholesterol with a statin slows progression of atherosclerosis, and would therefore be expected to improve cardiovascular risk reduction in this setting. This economic analysis evaluated the cost-effectiveness of this strategy using computer simulation economic modelling incorporating two decision analytic sub-models.
In the first sub-model, a cohort of 2,000 patients was generated using baseline characteristics and statin effect from the Heart Protection Study. Treatment effects observed with PR nicotinic acid (1,000 mg/day) in the ARBITER 2 study were then applied. The second model evaluated long-term clinical and economic outcomes using Framingham risk estimates. Direct medical costs were accounted from a National Health Service (NHS) perspective and discounted by 3.5%. In the UK setting, the addition of PR nicotinic acid to statin therapy resulted in long-term reduction in CHD events and increased life expectancy in patients who had achieved target LDL cholesterol levels but had persistently low HDL cholesterol, and this was achieved at a cost well within the threshold (< £30,000 per life years gained) considered good value for money in the UK. This strategy was highly cost-effective in patients with diabetes. Thus, adding PR nicotinic acid to statin therapy in these patients is both clinically and cost-effective and could be recommended for routine use in this setting in the UK.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the UK. In 2004, CVD accounted for just over 216,000 deaths, more than one in three of all cases. Coronary heart disease (CHD) was the primary cause in nearly half of these deaths -- about one in five in men and one in six in women. CVD also imposes a major economic burden. Overall, CHD is estimated to cost the UK economy over £7.9 billion per year, over 50% of total healthcare system costs.
National and international guidelines emphasise the importance of risk factor modification for prevention of CVD. In particular, dyslipidaemia is identified as a prominent factor that warrants aggressive intervention. Treatment guidelines focus on lowering low-density lipoprotein (LDL) cholesterol levels with a statin (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) as the primary lipid-modifying therapy. A recent meta-analysis including 90,056 subjects in 14 randomised prospective trials has demonstrated that statin therapy improves clinical outcome in all patient subgroups, resulting in a 21% proportional reduction in the incidence of major vascular events per mmol/L reduction in LDL cholesterol during a mean of five years of treatment. Statins are also considered highly cost-effective in the treatment of CVD. They even have incremental benefits. Yet among those patients on statin therapy who achieve target LDL cholesterol levels, more than one in six experience further events in the following five years.
Dyslipidaemia is not a single defect. Evidence from population-based studies such as AMORIS (Apolipoprotein-related Mortality Risk Study) and INTERHEART indicate that the balance between atherogenic lipoproteins (mainly apolipoprotein B-containing particles, indicative of LDL cholesterol levels) and anti-atherogenic lipoproteins (mainly apolipoprotein A-I-containing particles, indicative of high-density lipoprotein [HDL] cholesterol levels) is the most important risk factor for myocardial infarction (MI). In INTERHEART, a case-control study involving 52 countries, this ratio accounted for up to 60% of the population attributable risk for MI.
A low HDL cholesterol level is established as an independent predictive factor for CVD, supported by a wealth of evidence from epidemiological studies. The recently updated Joint British Societies guidelines has highlighted the importance of low HDL cholesterol (< 1.0 mmol/L in men and < 1.2 mmol/L in women) and recommended its inclusion in lipid assessment, especially in patients at target LDL cholesterol levels. Low HDL cholesterol makes a significant independent contribution to CHD risk among patients with type 2 diabetes, as demonstrated in the UK Prospective Diabetes Study, as well as in statin-treated patients who achieve LDL cholesterol goals but have low HDL cholesterol levels.
Nicotinic acid is the most effective therapeutic agent currently available to clinicians for raising HDL cholesterol. A prolonged-release (PR) formulation has been developed that effectively raises HDL cholesterol levels by up to 26% at clinically recommended doses of 1,000--2,000 mg/day, and offers improved tolerability compared with previous formulations. The addition of PR nicotinic acid to statin therapy in patients with pre-existing CHD, as in the ARBITER 2 study, raised HDL cholesterol levels and reduced progression of atherosclerosis, as assessed by carotid intima-media thickness (CIMT), over 12 months. In contrast, patients treated with statin alone had no change in HDL cholesterol and a significant increase in CIMT, indicative of progression of atherosclerosis. Moreover, continuation of PR nicotinic acid combination treatment for a further 12 months induced regression of atherosclerosis. These data therefore indicate that a strategy aimed at raising HDL cholesterol with PR nicotinic acid in statin-treated patients who have achieved target LDL cholesterol levels but have persistently low HDL cholesterol levels (< 1.0 mmol/L), is likely to be important for improving cardiovascular risk reduction. The aim of this economic analysis was to evaluate the cost-effectiveness of this strategy from a UK NHS perspective.
Abstract and Introduction
Abstract
Clinical guidelines focus on statins for dyslipidaemia management for prevention of cardiovascular disease. It is clear, however, that there remains an unacceptably high residual risk of further events among patients who achieve target low-density lipoprotein (LDL) cholesterol levels. Low high-density lipoprotein (HDL) cholesterol levels, an independent predictive factor, is likely to be an important contributor to this excess risk, and is also common among dyslipidaemic patients. The ARBITER 2 study (ARterial Biology for the Investigation of the Treatment Effects of Reducing cholesterol) showed that raising HDL cholesterol with prolonged-release (PR) nicotinic acid in addition to lowering LDL cholesterol with a statin slows progression of atherosclerosis, and would therefore be expected to improve cardiovascular risk reduction in this setting. This economic analysis evaluated the cost-effectiveness of this strategy using computer simulation economic modelling incorporating two decision analytic sub-models.
In the first sub-model, a cohort of 2,000 patients was generated using baseline characteristics and statin effect from the Heart Protection Study. Treatment effects observed with PR nicotinic acid (1,000 mg/day) in the ARBITER 2 study were then applied. The second model evaluated long-term clinical and economic outcomes using Framingham risk estimates. Direct medical costs were accounted from a National Health Service (NHS) perspective and discounted by 3.5%. In the UK setting, the addition of PR nicotinic acid to statin therapy resulted in long-term reduction in CHD events and increased life expectancy in patients who had achieved target LDL cholesterol levels but had persistently low HDL cholesterol, and this was achieved at a cost well within the threshold (< £30,000 per life years gained) considered good value for money in the UK. This strategy was highly cost-effective in patients with diabetes. Thus, adding PR nicotinic acid to statin therapy in these patients is both clinically and cost-effective and could be recommended for routine use in this setting in the UK.
Introduction
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the UK. In 2004, CVD accounted for just over 216,000 deaths, more than one in three of all cases. Coronary heart disease (CHD) was the primary cause in nearly half of these deaths -- about one in five in men and one in six in women. CVD also imposes a major economic burden. Overall, CHD is estimated to cost the UK economy over £7.9 billion per year, over 50% of total healthcare system costs.
National and international guidelines emphasise the importance of risk factor modification for prevention of CVD. In particular, dyslipidaemia is identified as a prominent factor that warrants aggressive intervention. Treatment guidelines focus on lowering low-density lipoprotein (LDL) cholesterol levels with a statin (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) as the primary lipid-modifying therapy. A recent meta-analysis including 90,056 subjects in 14 randomised prospective trials has demonstrated that statin therapy improves clinical outcome in all patient subgroups, resulting in a 21% proportional reduction in the incidence of major vascular events per mmol/L reduction in LDL cholesterol during a mean of five years of treatment. Statins are also considered highly cost-effective in the treatment of CVD. They even have incremental benefits. Yet among those patients on statin therapy who achieve target LDL cholesterol levels, more than one in six experience further events in the following five years.
Dyslipidaemia is not a single defect. Evidence from population-based studies such as AMORIS (Apolipoprotein-related Mortality Risk Study) and INTERHEART indicate that the balance between atherogenic lipoproteins (mainly apolipoprotein B-containing particles, indicative of LDL cholesterol levels) and anti-atherogenic lipoproteins (mainly apolipoprotein A-I-containing particles, indicative of high-density lipoprotein [HDL] cholesterol levels) is the most important risk factor for myocardial infarction (MI). In INTERHEART, a case-control study involving 52 countries, this ratio accounted for up to 60% of the population attributable risk for MI.
A low HDL cholesterol level is established as an independent predictive factor for CVD, supported by a wealth of evidence from epidemiological studies. The recently updated Joint British Societies guidelines has highlighted the importance of low HDL cholesterol (< 1.0 mmol/L in men and < 1.2 mmol/L in women) and recommended its inclusion in lipid assessment, especially in patients at target LDL cholesterol levels. Low HDL cholesterol makes a significant independent contribution to CHD risk among patients with type 2 diabetes, as demonstrated in the UK Prospective Diabetes Study, as well as in statin-treated patients who achieve LDL cholesterol goals but have low HDL cholesterol levels.
Nicotinic acid is the most effective therapeutic agent currently available to clinicians for raising HDL cholesterol. A prolonged-release (PR) formulation has been developed that effectively raises HDL cholesterol levels by up to 26% at clinically recommended doses of 1,000--2,000 mg/day, and offers improved tolerability compared with previous formulations. The addition of PR nicotinic acid to statin therapy in patients with pre-existing CHD, as in the ARBITER 2 study, raised HDL cholesterol levels and reduced progression of atherosclerosis, as assessed by carotid intima-media thickness (CIMT), over 12 months. In contrast, patients treated with statin alone had no change in HDL cholesterol and a significant increase in CIMT, indicative of progression of atherosclerosis. Moreover, continuation of PR nicotinic acid combination treatment for a further 12 months induced regression of atherosclerosis. These data therefore indicate that a strategy aimed at raising HDL cholesterol with PR nicotinic acid in statin-treated patients who have achieved target LDL cholesterol levels but have persistently low HDL cholesterol levels (< 1.0 mmol/L), is likely to be important for improving cardiovascular risk reduction. The aim of this economic analysis was to evaluate the cost-effectiveness of this strategy from a UK NHS perspective.