Statins are the most effective drugs for preventing cardiovascular events.
Other drug classes have limited roles.
Risk reduction for an individual depends on their baseline cardiovascular risk.
NICE recommends assessing this using the QRISK3 tool.
The figures below relate to the use of atorvastatin 20mg, a “high intensity” statin.
Here, “combined cardiovascular events” means: fatal and non-fatal angina, MI, TIA and stroke.
Figures derived from the 2014 NICE guideline (and are current for the 2018 guideline)1.
The figures for the charts above were taken from the decision aid accompanying the 2014 guideline2.
NICE used the section of the evidence analysis looking at high-intensity statins v placebo (6 trials with a mix of primary and secondary prevention patients) and applied a formula to estimate the risk reduction for combined cardiovascular events from high-intensity statins. They then applied it to various thresholds of baseline risk to illustrate the benefits in a primary prevention context3.
1)National Institute for Health and Care Excellence. Cardiovascular disease: Risk Assessment and reduction, including lipid modification 2014 [Internet]. [London]: NICE; 2014 [updated 2016 Sep]. (Clinical guideline [CG181])
2)National Institute for Health and Care Excellence. Cardiovascular disease: Taking a statin to reduce the risk of coronary heart disease and stroke: patient decision aid 2014 [Internet]. [London]: NICE; 2014
3)National Institute for Health and Care Excellence. Patient decision aid: user guide for healthcare professionals. Implementing the NICE guideline on lipid modification(CG181) 2014 [Internet]. [London]: NICE; 2014
| This research provides a very good indication of the treatment effect.
However, it is possible that the true effect is slightly smaller or greater. |
NICE appraised this evidence as HIGH quality1
1)National Institute for Health and Care Excellence. Cardiovascular disease: Risk Assessment and reduction, including lipid modification 2014 [Internet]. [London]: NICE; 2014 [updated 2016 Sep]. (Clinical guideline [CG181])
The population characteristics in statin primary prevention trials1 were:
Data detail
These figures were taken from a Cochrane review because they were not available in the NICE evidence review. However they are broadly representative of the NICE evidence review as they appraise almost the same evidence base.
Reference
1)Taylor F, Ward K, Moore THM et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2013, Issue 1. Art. No.: CD004816
Atorvastatin 20mg, currently recommended by NICE for primary prevention, is a “high intensity” statin1.
Patients on lower intensity statins will improve their risk reduction by switching to this.
Increasing the atorvastatin dose may reduce risk further, but this reduction is likely to be small in absolute terms for most patients in primary prevention.
It is difficult to give absolute numbers for the difference in benefits between statin doses. The information below may help you get an idea:
Understanding statin “intensity”
more
NICE classifies statins according to their ability to lower LDL cholesterol.
Low intensity (pale blue), medium intensity (med blue) and high intensity (dark blue):
| % reduction in LDL Cholesterol | |||||
| Dose per day | 5mg | 10mg | 20mg | 40mg | 80mg |
| Fluvastatin | 21% | 27% | 33% | ||
| Pravastatin | 20% | 24% | 29% | ||
| Simvastatin | 27% | 32% | 37% | 42% | |
| Atorvastatin | 37% | 43% | 49% | 55% | |
| Rosuvastatin | 38% | 43% | 48% | 53% | |
To illustrate with theoretical numbers:
Simvastatin at 10mg a day would reduce a starting LDL cholesterol of 4.0mmol/L to 2.92mmol/L
Atorvastatin at 20mg a day would reduce a starting LDL cholesterol of 4.0mmol/L to 2.28mmol/L
Atorvastatin at 80mg a day would reduce a starting LDL cholesterol of 4.0mmol/L to 1.8mmol/L
How do these changes translate into real benefits?
More
The Cholesterol Treatment Trialists’ Collaboration (CTT) combined individual patient data from multiple trials into a meta-analysis2. Their key finding was:
Increasing to atorvastatin 80mg a day might add another few percent Relative Risk Reduction (NICE estimates at least 2%), but exactly how much is uncertain. The Absolute Risk Reduction difference is likely to be important only in higher risk patients.
Why did NICE settle with atorvastatin 20mg as the recommended dose?
More
This was a committee decision taking into account cost effectiveness, risk of side effects and uncertainty of the evidence.
If you hear differing opinions about the ideal dose of a statin, this is because the evidence is not black and white!
Evidence details
More
NICE reviewed RCTs comparing statins of different intensity against individual outcomes (such as MI, stroke or mortality considered separately).
The RCTs were at low risk of bias, however, evidence quality was rated as mainly LOW or MODERATE because:
Evidence quality was rated as HIGH for some outcomes which had consistent, statistically significant results, for example:
The CTT analysis generated clearer, statistically significant results by combining data from multiple trials and presenting a composite outcome (major cardiovascular events).
Their review was not included in the NICE analysis, but its key findings are broadly similar and in line with the guideline recommendations.
References
1)National Institute for Health and Care Excellence. Cardiovascular disease: Risk Assessment and reduction, including lipid modification 2014 [Internet]. [London]: NICE; 2014 [updated 2016 Sep]. (Clinical guideline [CG181])
2)Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell J 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
Though there has been controversy about whether statins “save lives” in primary prevention, recent reviews1,2,3 agree:
How does this translate into Absolute Risk Reduction or NNTs?
References
1)National Institute for Health and Care Excellence. Cardiovascular disease: Risk Assessment and reduction, including lipid modification 2014 [Internet]. [London]: NICE; 2014 [updated 2016 Sep]. (Clinical guideline [CG181])
2)Taylor F, Ward K, Moore THM et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2013, Issue 1. Art. No.: CD004816
3)Cholesterol Treatment Trialists’ (CTT) Collaborators, Mihaylova B, Emberson J et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 2012; 380(9841): 581-590
Of the combined cardiovascular events, how many are MIs and how many are strokes or TIAs?
This varies depending on age and sex, the numbers below are intended to be a rough guide only:
Two examples to give you an idea:
Data detail
NICE conducted a health economic analysis which used figures for proportions of first CV events in people of varying ages. These numbers were used to estimate the proportion of CV events in someone at a 40% baseline risk. Then the relative risk reduction of statins on each event was calculated. A similar method was used to develop the NICE statin decision aid1.
Reference
1)Patient decision aid: user guide for healthcare professionals. Implementing the NICE guideline on lipid modification(CG181). [Internet]. [London]: NICE; 2014 Accessed Mar 2021
There is uncertainty about value of statins in people over the age of 75, due to fewer older patients being included in trials.
NICE recommends:
‘For people 85 years or older consider atorvastatin 20 mg as statins may be of benefit in reducing the risk of non-fatal myocardial infarction.’
Two pieces of evidence might inform decisions about treatment in older people:
An RCT1 (included in the NICE review) in older patients showed:
A meta-analysis (not included in the NICE review for technical reasons) combined individual patient data from 28 trials and looked at outcomes in 14,483 people aged over 752. This showed:
A commentary paper3 on this meta-analysis calculated:
The meta-analysis data was presented for an effect with a low intensity statin, so treatment benefits may be higher with a high intensity statin e.g., atorvastatin 20mg (see the “High v low dose” section).
References
1)Shepherd J, Blauw GJ, Murphy MB et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360(9346): 1623-30
2)Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Armitage J et al. Lancet 2019; 393 (10170): 407-415
3)Absolute effects of statins in the elderly.
Muscle pains and general malaise are sometimes reported with statin use. Most of this (roughly 90%) is due to a nocebo* effect.
* an adverse effect experienced because the patient expects it, rather than as a result of the treatment itself
more
This has been controversial over the years with some arguing that they are not genuine side effects because:
Others argued that7:
The question has perhaps been resolved by 2 trials set in the UK, involving patients who had previously reported muscle aches or other side effects with statins10,11. They were given statins, placebo or no tablets for periods of 1-2 months in random order and asked to record their symptoms.
Both trials, which were fully blinded and well conducted, showed that muscle symptoms and other “side effects” (even ones severe enough to stop taking the tablets) were almost as common with placebo tablets. Half to two-thirds of patients were able to restart their statins after receiving feedback.
2-22 excess cases per 10,000 person years for both combined3.
more
The NICE systematic review of RCTs did not find evidence of an increase in these side effects1.
However, RCTs can fail to pick up rare harms. Observational research (LOW quality evidence) has shown the following risks:
Myositis (muscle pain plus elevated CK x 10)
Rhabdomyolysis (severe myopathy with extremely elevated CK, myoglobinaemia and renal impairment)
4 in every 1000 people will develop raised transaminases (ALT >3 x normal) due to taking a statin.
Statin-related raised transaminases up to 3 x the upper limit of normal are thought to be harmless and do not require statin therapy to be stopped if stable1.
more
This approximate figure is found by both the NICE systematic review of RCTs (who rated it MODERATE quality evidence)1 and a Cochrane review of observational studies2.
Acute hepatitis and liver failure associated with statins are so rare it is uncertain whether there is a causal effect.
more
RCT data has not shown an increase in these harms compared to placebo. A 2007 review paper5 said:
‘Although hepatitis and liver failure have been reported spontaneously and from trials of statins, it is not clear whether they are causally related or that the risk is over and above the background risk of sporadic liver failure.’
1 excess case per 200 people over a 5-year period due to taking a statin.
However, the cardiovascular benefits of statins outweigh risks associated with glycaemic changes5.
Statins do not need to be stopped in response to increases in blood glucose or HbA1c1.
more
This number comes from the NICE evidence review of RCTs and was rated as HIGH quality evidence1. A similar figure was produced in another large systematic review of RCTs2.
Larger risks have been reported in observational studies (up to 2% per annum), though this was described as weak evidence by the Cochrane review group undertaking the analysis3.
Larger risks (up to a few percent over 5 years) have been shown in RCTs using atorvastatin 80mg. This was in subgroups with 2 or more risk factors for diabetes. Not all findings were statistically significant so there is uncertainty about the size of the effect4.
References
more
1)National Institute for Health and Care Excellence. Cardiovascular disease: Risk Assessment and reduction, including lipid modification 2014 [Internet]. [London]: NICE; 2014 [updated 2016 Sep]. (Clinical guideline [CG181])
2)Sattar N, Preiss D, Murray HM et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010; 375(9716): 735-742
3)Macedo AF, Taylor FC, Casas JP et al. Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis. BMC Med 2014; 12: 51
4)Waters DD, Ho JE, DeMicco D et al. Predictors of New-Onset Diabetes in Patients Treated With Atorvastatin: Results From 3 Large Randomized Clinical Trials. J Am Coll Cardiol 2011; 14: 1535-1545
5)Armitage J. The safety of statins in clinical practice. Lancet 2010; 370(9601): 1781-1790
6)Collins R, Reith C, Emberson J et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet 2016; 388(10059): 2532-2561
7)Abramson JD, Rosenberg HG, Jewell N, Wright JM. Should people at low risk of cardiovascular disease take a statin? BMJ 2013; 347 :f6123
8)Buettner C, Davis RB, Leveille SG et al. Prevalence of musculoskeletal pain and statin use. J Gen Intern Med 2008 Aug; 23(8): 1182-1186
9)Mansi I, Frei CR, Pugh MJ et al. Statins and Musculoskeletal Conditions, Arthropathies, and Injuries. JAMA Intern Med 2013; 173(14): 1318–1326
10)Wood FA, Howard JP, Finegold JA et al. N-of-1 Trial of a Statin, Placebo, or No Treatment to Assess Side Effects. N Engl J Med 2020; 383: 2182-2184
11)Herrett E, Williamson E, Brack K et al. Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials BMJ 2021; 372 :n135
No longer recommended as first-line treatment for cardiovascular prevention, but may be an option for those unable to take statins.
Fibrates slightly reduce the risk of non-fatal MI compared to placebo.
There is no evidence of additional benefit from adding a fibrate to a statin for most primary prevention patients.
They may have a role in those with hypertriglyceridaemia or familial hyperlipidaemia, usually under specialist supervision.
Figures derived from the 2014 NICE guideline (and are current for the 2018 guideline)1.
One trial in primary prevention:
One trial in patients with diabetes in (mainly) primary prevention:
Data detail
Figures for the second study3 are rounded to the nearest integer. There were small differences between treatment arms but these did not reach statistical significance.
1)National Institute for Health and Care Excellence. Cardiovascular disease: Risk Assessment and reduction, including lipid modification 2014 [Internet]. [London]: NICE; 2014 [updated 2016 Sep]. (Clinical guideline [CG181]).
2)Frick MH, Elo O, Haapa K et al. Helsinki Heart Study: Primary-Prevention Trial with Gemfibrozil in Middle-Aged Men with Dyslipidemia. N Engl J Med 1987; 317(20): 1237-1245
3)ACCORD Study Group. Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus. N Engl J Med 2010; 362(17): 1563-1574
| This research provides a good indication of the treatment effect.
There is a moderate possibility that the true effect is smaller or greater. |
NICE rated this evidence as MODERATE quality1:
but size of the treatment effect is uncertain due to:
1) National Institute for Health and Care Excellence. Cardiovascular disease: Risk Assessment and reduction, including lipid modification 2014 [Internet]. [London]: NICE; 2014 [updated 2016 Sep]. (Clinical guideline [CG181])
The population characteristics in the study testing fibrate v placebo1 were:
The population characteristics in the study testing fibrate plus statin v statin alone2 were:
References
1)Frick MH, Elo O, Haapa K et al. Helsinki Heart Study: Primary-Prevention Trial with Gemfibrozil in Middle-Aged Men with Dyslipidemia. N Engl J Med 1987; 317(20): 1237-1245
2)ACCORD Study Group. Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus. N Engl J Med 2010; 362(17): 1563-1574
Gastrointestinal side effects
1 in 10-100
Source: BNF
More
A Cochrane review1 of fibrate v placebo trials reported discontinuation due to side effects in 29% of fibrate users compared to 26% of those on placebo.
Rise in serum creatinine
11% of fibrate users (approximately), not thought to be clinically significant.
It is thought that fibrates increase creatinine production rather than impair renal excretion.
More
A Cochrane review1 of fibrate v placebo trials reported raised creatinine in 24% of fibrate users compared to 13% of those on placebo.
An American fibrate safety review2 reported a 12% average increase in serum creatinine, though formal eGFR testing showed no reduction in renal function.
Myopathy and rhabdomyolysis
6 per 10,000 person years of treatment (approximately).
More
Two observational studies provide the estimate above4,5.
The second study5 reports a higher (but still very low) rate of hospitalisation with rhabdomyolysis of 14 per 10,000 years with the combination of fenofibrate and atorvastatin.
These have not been detected in systematic reviews of RCTs of fibrates1,3 .
The BNF warns of the potential interaction between statins and fibrates and provides specific recommendations.
References
1)Jakob T, Nordmann AJ, Schandelmaier S et al. Fibrates for primary prevention of cardiovascular disease events. Cochrane Database of Systematic Reviews 2016, Issue 11. Art. No.: CD009753
2)Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety considerations with fibrate therapy. Am J Cardiol 2007; 99(6A): 3C-18C
3)National Institute for Health and Care Excellence. Cardiovascular disease: Risk Assessment and reduction, including lipid modification 2014 [Internet]. [London]: NICE; 2014 [updated 2016 Sep]. (Clinical guideline [CG181])
4)Gaist D, Rodríguez LA, Huerta C et al. Lipid-Lowering Drugs and Risk of Myopathy: A Population-Based Follow-Up Study. Epidemiology 2001; 12(5): 565-569
5)Graham DJ, Staffa JA, Shatin D et al. Incidence of Hospitalized Rhabdomyolysis in Patients Treated With Lipid-Lowering Drugs. JAMA 2004; 292(21): 2585-2590
NICE recommends ezetimibe as an option for the primary prevention of cardiovascular disease:
and for secondary prevention:
Cholesterol targets for secondary prevention are
non-HDL cholesterol ≤ 2.6 mmol/L OR
LDL cholesterol ≤ 2.0 mmol/L
The NICE guideline emphasises that decisions about escalting treatment should be made taking into account patient preferences about the potential benefits of extra medication balanced against issues such as co-morbdities, multiple medications and life expectancy.
Figures derived from a single study (the only study to examine cardiovascular outcomes for ezetemibe)1:
NICE reviewed the evidence for ezetimibe in a 2023 update to their lipid guideline2. Other, small, short term trials with ezetimibe had been conducted but this was the only one of enough size and duration to show an effect on cardiovascular outcomes.
Reference
1)Cannon CP, Blazing MA, Guigliano RP et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med 2015; 372: 2387-2397
2)National Institute for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification – Escalation of Therapy update [Internet]. [London]: NICE; 2023 (Clinical guideline [CG181])
| This research provides a good indication of the treatment effect.
There is a moderate possibility that the true effect is smaller or greater. |
A Cochrane review rated this evidence as MODERATE quality:
However,
Reference
1)Zhan S, Tang M, Liu F et al. Ezetimibe for the prevention of cardiovascular disease and all‐cause mortality events. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD012502
The population characteristics in this study were1:
Reference
1)Zhan S, Tang M, Liu F et al. Ezetimibe for the prevention of cardiovascular disease and all‐cause mortality events. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD012502
In this trial1 involving 18,144 patients followed up for 7 years, there were no increases in rates of
associated with the addition of ezetemibe to simvastatin.
A systematic review of 48 trials involving 28,444 participants2, found that
References
1)Cannon CP, Blazing MA, Guigliano RP et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med 2015; 372: 2387-2397
2) et al. Safety of ezetimibe in lipid-lowering treatment: systematic review and meta-analysis of randomised controlled trials and cohort studies.
NICE recommends these drugs as additional options to consider for the secondary prevention of cardiovascular disease when cholesterol targets have not been met with optimal statin therapy.
Cholesterol targets for secondary prevention are
The NICE guideline emphasises that decisions about escalting treatment should be made taking into account patient preferences about the potential benefits of extra medication balanced against issues such as co-morbdities, multiple medications and life expectancy.
NICE also recommends these as an option for primary prevention in those with familial hypercholesterolaemia where LDL cholesterol levels are ≥ 5.0 mmol/L on maximally tolerated standard treatment.
evidence shows a reduction in cardiovascular events in high-risk patients when given in addition to a statin
although they are less effective than statins at reducing cardiovascular endpoints in direct comparisons
They are monoclonal antibodies which protect LDL receptors in the liver, reducing circulating LDL.
administered by injection every 2-4 weeks
Figures derived from the 2023 NICE guideline update evidence review1
References
1)National Institute for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification – Escalation of Therapy update [Internet]. [London]: NICE; 2023 (Clinical guideline [CG181])
2)ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med 2018; 379:2097-2107
3)FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med 2017; 376:1713-1722
| This research provides a good indication of the treatment effect.
There is a moderate possibility that the true effect is smaller or greater. |
NICE rated this evidence as MODERATE quality:
Reference
1) National Institute for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification – Escalation of Therapy update [Internet]. [London]: NICE; 2023 (Clinical guideline [CG181])
The population characteristics in these two trials were, roughly:
Reference
1) National Institute for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification – Escalation of Therapy update [Internet]. [London]: NICE; 2023 (Clinical guideline [CG181])
Local injection site reaction
2.9% of people developed a local reaction to PCSK9i injections compared to 1.8% with placebo injections in the clinical trial1,2.
Otherwise there were no excess adverse events reported compared to placebo in these trial involving 46,488 people over 3 years.
Nasal complaints and itching
1 in 10 – 1 in 100
Source: BNF
Reference
1)ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med 2018; 379:2097-2107
2)FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med 2017; 376:1713-1722
Inclisiran is a small interfering RNA which limits production of PCSK9, increasing uptake of LDL-cholesterol and thereby lowering levels in blood (BNF).
NICE recommends this as additional option to consider for the secondary prevention of cardiovascular disease when cholesterol targets have not been met with optimal statin therapy.
Cholesterol targets for secondary prevention are
The NICE guideline emphasises that decisions about escalting treatment should be made taking into account patient preferences about the potential benefits of extra medication balanced against issues such as co-morbdities, multiple medications and life expectancy
Figures derived from the 2023 NICE guideline update evidence review1
References
1)National Institute for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification – Escalation of Therapy update [Internet]. [London]: NICE; 2023 (Clinical guideline [CG181])
2)ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med 2020; 382:1507-1519
| This research provides a good indication of the treatment effect.
There is a moderate possibility that the true effect is smaller or greater. |
NICE rated this evidence as MODERATE quality:
Reference
1) National Institute for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification – Escalation of Therapy update [Internet]. [London]: NICE; 2023 (Clinical guideline [CG181])
The population characteristics in these two trials1 were, roughly:
Reference
1)ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med 2020; 382:1507-1519
Local injection site reactions occurred in approximately:
No other side effects are reported by the BNF.
No other side effects or harms due to incliseran were detected in a systematic review of 5 RCTs of incliseran involving 4226 patients over 1 1/2 years2.
References
1)National Institute for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification – Escalation of Therapy update [Internet]. [London]: NICE; 2023 (Clinical guideline [CG181])
2)Cicero A,Fogacci F, Zambon A et al.Efficacy and safety of inclisiran a newly approved FDA drug: a systematic review and pooled analysis of available clinical studies. American Heart Journal Plus: Cardiology Research and Practice Volume 13, 2022, 100127.
Bempedoic acid has a restricted recommendation from NICE1
It is an adenosine triphosphate citrate lyase (ACL) inhibitor which inhibits cholesterol synthesis in the liver, thereby lowering LDL-cholesterol (BNF).
Criteria for prescription in England (NICE):
| Bempedoic acid | Patients with or without established CHD, in whom statins are contraindicated or not tolerated and where LDL-C is not “controlled well enough” with ezetemibe. To be given in combination with ezetemibe1 |
Bempedoic acid harms:
Uric acid levels are increased on average, by 49umol/l by bempedoic acid.
Incidence of gout attacks is increased depending on history and uric acid level:
| Rates of gout attacks per person per year | ||
| Previous gout history | Placebo | Bempedoic acid |
| History of gout, urate >ULN* | 9.5% | 23% |
| History of gout, urate normal | 0% | 5.7% |
| No history of gout, urate >ULN | 0.4% | 3.1% |
| No history of gout, urate normal | 0.2% | 0.3% |
* Upper limit of normal. Not defined in this study, suggest use local laboratory recommendation
Anaemia
Data source: safety analysis of 4 randomised controlled trials involving 3621 patients2.
References
1)National Institute for Health and Care Excellence. Bempedoic acid with ezetimibe for treating primary hypercholesterolaemia or mixed dyslipidaemia. Technology Appraisal Guidance. (TA694) April 2021
2)Bays HE, Banach M, Catapano AL et al. Bempedoic acid safety analysis: Pooled data from four phase 3 clinical trials. Journal of Clinical Lipidology 2020; 14(5): 649-659
3)CLEAR Outcomes Investigators. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients.N Engl J Med 2023; 388:1353-1364
People who have an adverse event
People whose adverse event is prevented by treatment
People who were never going to have an adverse event anyway
Graphics and NNTs are rounded to the nearest integer
These three statistical terms offer three different ways of looking at the results of trial data.
Absolute Risk Reduction
This tells you how many people out of 100 who take a treatment have an adverse event prevented.
MoreThe value of the ARR changes with the baseline risk of the person (or population) taking the treatment. The higher the starting risk, the greater the absolute chance of benefit.
You need to think about over what time the trial data show this benefit, as it is usually assumed that more absolute risk reduction is gained over time.
Your patient might be taking the treatment for much longer than the length of a clinical trial (or, if life expectancy is limited, perhaps for less time).
Number Needed to Treat
This tells you how many people need to take the treatment in order for one person to avoid an adverse event.
The lower the number, the more effective the treatment.
MoreThe value of the NNT changes with the baseline risk of the person (or population) taking the treatment. The higher the starting risk, the smaller the NNT.
You need to think about over what time the trial data show benefit, as it is usually assumed that more benefit is gained over time and therefore the NNT will drop over time.
Your patient might be taking the treatment for much longer than the length of a clinical trial (or, if life expectancy is limited, perhaps for less time).
Relative Risk Reduction
This tells you the proportion of adverse events that are avoided if the entire population at risk is treated.
MoreThe value of the RRR is usually constant in people (or populations) at varying degrees of risk.
It is also usually assumed to stay constant over time.
This can be helpful, especially when thinking about population outcomes, but can be misleading for an individual person:
For example, a RRR of 25% in someone with a baseline risk of 40% would give them an ARR of 10% and an NNT of 10.
A RRR of 25% in someone with a baseline risk of 4% would give them an ARR or 1% and an NNT of 100.
This website is designed for use by General Practitioners and other healthcare professionals. The content is not exhaustive and assumes a standard level of GP professional knowledge. The information here is intended to support clinical judgement and shared decision making alongside clinical guidelines and standard practice.
If you are a patient/member of the public, do feel free to look around, but please don’t make any changes to your treatments based on information here. If you find something which seems relevant to you, you could show this website to your healthcare professional to help a discussion.