Options for the secondary prevention of coronary heart disease.
In this section, the abbreviation MI (myocardial infarction) includes STEMI and NSTEMI.
Smoking cessation reduces the chance of further heart attacks, strokes and cardiovascular deaths in people with established CHD.
These benefits begin to accrue over the first year of stopping smoking.
The data below is from studies with follow up ranging from 1-10 years, so we have used the approximation “several years”.
Here, “major cardiovascular event” means non-fatal MI or stroke, or cardiovascular death.
Figures derived from a 2022 Cochrane review1.
Reference
1)Wu AD, Lindson N, Hartmann-Boyce J et al. Smoking cessation for secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2022, Issue 8. Art. No.: CD014936
| This research provides a good indication of the treatment effect.There is a moderate possibility that the true effect is smaller or greater. |
The Cochrane reviewers rated this evidence as MODERATE quality1:
Reference
1)Wu AD, Lindson N, Hartmann-Boyce J et al. Smoking cessation for secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2022, Issue 8. Art. No.: CD014936
The population and trial characteristics in the Cochrane review1 were very broad.
Reference
1)Wu AD, Lindson N, Hartmann-Boyce J et al. Smoking cessation for secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2022, Issue 8. Art. No.: CD014936
A Mediterranean-style diet is recommended by NICE for those who have had an MI.
Figures derived from a 2019 Cochrane review1 which found just one trial:
The NICE recommendation on Mediterranean diet has not been updated since 20073.
References
1) Rees K, Takeda A, Martin N et al. Mediterranean‐style diet for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2019, Issue 3. Art. No.: CD009825
2) De Lorgeril M, Salen P, Martin JL et al. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: Final report of the Lyon Diet Heart Study. Circulation 1999; 99(6): 779‐85
3)National Institute for Health and Care Excellence. Acute Coronary Syndromes 2020 [Internet]. [London]: NICE; 2020. (Clinical guideline [CG185])
| This research provides some indication of the treatment effect.
There is a high possibility that the true effect is smaller or greater. |
Cochrane rated this evidence as LOW quality1 due to:
However, the Cochrane authors highlight a large amount of observational research which links Mediterranean Diet with lower rates of cardiovascular disease.
Reference
1) Rees K, Takeda A, Martin N et al. Mediterranean‐style diet for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2019, Issue 3. Art. No.: CD009825
The population characteristics in the Lyon Diet Heart Study1 were:
Reference
1)De Lorgeril M, Salen P, Martin JL et al. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: Final report of the Lyon Diet Heart Study. Circulation 1999; 99(6): 779‐85
The only harms reported in this study were 2 patients with diarrhoea attributed to the margarine supplied as part of the dietary intervention.
NICE recommends an exercise-based cardiac rehabilitation programme for all people with CHD.
The type and amount of exercise is not specified, and ideally is tailored to the individual.
Figures derived from from a 2021 Cochrane review1 :
Reference
Dibben G, Faulkner J, Oldridge N et al. Exercise‐based cardiac rehabilitation for coronary heart disease. Cochrane Database of Systematic Reviews 2021, Issue 11. Art. No.: CD001800
| This research provides a very good indication of the treatment effect.
However, it is possible that the true effect is slightly smaller or greater. |
The Cochrane reviewers rated this evidence as HIGH quality1.
Data detail
The evidence regarding hospital admissions was rated as MODERATE quality due to possible publication bias.
|
This research provides a good indication of the treatment effect. There is a moderate possibility that the true effect is smaller or greater. |
References
1)Dibben G, Faulkner J, Oldridge N et al. Exercise‐based cardiac rehabilitation for coronary heart disease. Cochrane Database of Systematic Reviews 2021, Issue 11. Art. No.: CD001800
The population characteristics in the Cochrane review were very broad. Of the trials analysed:
Neither NICE1 nor Cochrane2 were able to highlight a particular group of patients or mode of rehabilitation which appears to have better or worse outcomes.
References
1)National Institute for Health and Care Excellence. Acute Coronary Syndromes 2020 [Internet]. [London]: NICE; 2020. (Clinical guideline [CG185])
2)Dibben G, Faulkner J, Oldridge N et al. Exercise‐based cardiac rehabilitation for coronary heart disease. Cochrane Database of Systematic Reviews 2021, Issue 11. Art. No.: CD001800
Quality of life scores were measured by some studies:
Reference
Dibben G, Faulkner J, Oldridge N et al. Exercise‐based cardiac rehabilitation for coronary heart disease. Cochrane Database of Systematic Reviews 2021, Issue 11. Art. No.: CD001800
Exercise-based cardiac rehabilitation is very safe. Many studies have shown serious complications to be rare1.
For example, a 1-year prospective study of 65 cardiac rehabilitation centres in France2 showed:
*CV events were: Chest pain/weakness/heart failure/non-sustained VT
MODERATE quality evidence, because:
| This research provides a good indication of the treatment effect.
There is a moderate possibility that the true effect is smaller or greater. |
References
1)Dibben G, Faulkner J, Oldridge N et al. Exercise‐based cardiac rehabilitation for coronary heart disease. Cochrane Database of Systematic Reviews 2021, Issue 11. Art. No.: CD001800
2)Pavy B, Iliou MC, Meurin P et al. Functional Evaluation and Cardiac Rehabilitation Working Group of the French Society of Cardiology. Safety of Exercise Training for Cardiac Patients: Results of the French Registry of Complications During Cardiac Rehabilitation. Arch Intern Med 2006; 166(21): 2329–2334
NICE recommends aspirin as indefinite therapy following Acute Coronary Syndrome1
Dual antiplatelet therapy
A P2Y12 inhibitor, in addition to aspirin, is recommended for 1 year post-MI.
Aspirin v placebo
Figures derived from a 2009 systematic review1:
Clopidogrel+aspirin v aspirin alone
Figures derived from the 2001 CURE study2:
Ticagrelor and prasugrel
The evidence review for the 2020 NICE guideline4 explored the complex evidence base for these drugs.
included 28 studies comparing these two drugs to clopidogrel or each other in combination with aspirin following acute coronary syndrome (ACS)
The studies were highly varied in terms of type of ACS and other treatments (e.g., revascularisation or no revascularisation), so there is no single data set which provides an overall estimate of their benefits and harms.
References
1)Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. The Lancet 2009; 373(9678): 1849-1860
2)CURE Investigators. Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes without ST-Segment Elevation. N Engl J Med 2001; 345: 494-502
3) Squizzato A, Bellesini M, Takeda A et al. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events. Cochrane Database of Systematic Reviews 2017, Issue 12. Art. No.: CD005158
4)National Institute for Health and Care Excellence. Acute Coronary Syndromes 2020 [Internet]. [London]: NICE; 2020 (Clinical guideline [CG185]).
|
The evidence for both aspirin and clopidogrel is MODERATE quality:
However,
NICE rates the evidence for ticagrelor and prasugrel as LOW quality for a variety of reasons.
| This research provides some indication of the treatment effect.
There is a high possibility that the true effect is smaller or greater. |
References
1)Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373(9678): 1849-1860
2)CURE Investigators. Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes without ST-Segment Elevation. N Engl J Med 2001; 345:494-502
3) Squizzato A, Bellesini M, Takeda A et al. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events. Cochrane Database of Systematic Reviews 2017, Issue 12. Art. No.: CD005158
4)National Institute for Health and Care Excellence. Acute Coronary Syndromes 2020 [Internet]. [London]: NICE; 2020 (Clinical guideline [CG185])
The population characteristics in the aspirin vs placebo analyses were not reported1.
The population characteristics in the CURE study2 (clopidogrel+aspirin vs aspirin alone) were:
References
1)Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373(9678): 1849-1860
2)CURE Investigators. Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes without ST-Segment Elevation. N Engl J Med 2001; 345: 494-502
Many patients have a dual indication for antiplatelets and oral anticoagulants.
Current evidence is not clear enough to provide good estimates of benefit or bleeding risk for the variety of situations we may encounter.
For patients with atrial fibrillation and stable ischaemic heart disease (say, an MI more than one year ago):
For patients with more complex needs (e.g., after coronary artery stent insertion, who may need dual antiplatelet therapy in addition to an oral anticoagulant) the evidence is complex:
References
1)2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. European Heart Journal 2021 Feb 1; 42(5): 373-498
2)Lemesle G. Aspirin on Top of Anticoagulation in Patients With Concomitant Stable Coronary Artery Disease and Atrial Fibrillation. Circulation 2019; 139: 617–619
3)National Institute for Health and Care Excellence. Acute Coronary Syndromes 2020 [Internet]. [London]: NICE; 2020 (Clinical guideline [CG185])
4)MASTER DAPT Investigators. Abbreviated Antiplatelet Therapy in Patients at High Bleeding Risk With or Without Oral Anticoagulant Therapy After Coronary Stenting: An Open-Label, Randomized, Controlled Trial. Circulation 2021 Oct 12; 144(15): 1196-1211
Bleeding risk with aspirin
1 in 200 people will experience a major bleed due to aspirin therapy over the course of 5 years treatment1
Extra bleeding risk with P2Y12 inhibitors
1 in 100 extra people will experience a major bleed from clopidogrel therapy in addition to aspirin over 1 year.
3 in 100 extra people will experience a minor bleed from clopidogrel therapy in addition to aspirin over 1 year.
Ticagrelor and prasugrel have similar bleeding risks to clopidogrel3.
References
1)Selak V, Jackson R, Poppe K et al. Predicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease. A cohort study. Annals of Internal Medicine 2019; 170(6): 357-368
2) CURE investigators. Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes without ST-Segment Elevation. N Engl J Med 2001; 345: 494-502
3)National Institute for Health and Care Excellence. Acute Coronary Syndromes 2020 [Internet]. [London]: NICE; 2020 (Clinical guideline [CG185])
NICE recommends atorvastatin 80mg in those with a previous MI to reduce the risk of further cardiovascular events.
NICE recommends a range of second-line treatments to consider if the following cholesterol targets are not met:
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.
Summary of second-line treatments
more
NICE recommends considering ezetimibe, inclisiran or PCSK9 inhibitors (evolocumab and alirocumab) as additional treatments if cholesterol targets are not met.
Ezetimibe may be consdiered as an additional option for further risk reduction even if targets are met.
Follow these links for evidence summaries for ezetimibe, PCSK9 inhibitors and incliseran.
The figure of a 40% RRR (relative risk reduction) for atorvastatin 80mg was estimated from the evidence review for the 2014 NICE guideline on lipid modification1.
The figures for cardiovascular event rates with “No treatment” are from a meta-analysis which pooled data from 5 trials of statin v placebo in patients with established CHD.2
The recommendations for second-line lipid lowering agents were made in an update to the NICE guideline in December 2023.
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) 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
| 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 the body of evidence on statins as HIGH quality1:
However, this estimate of effect of atorvastatin 80mg in post-MI patients may be less accurate because:
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 statin secondary prevention trials were:
Reference
1)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
An increasing benefit from higher intensity statins was found in the overall NICE evidence review for cardiovascular risk reduction1.
However, there is no direct trial comparison of atorvastatin 80mg v (say) atorvastatin 20mg in post-MI patients.
The recommendation for atorvastatin 80mg was a NICE committee decision1.
Reference
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])
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
MoreThis 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.
MoreThe 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)
Rhabdomyolisis (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.
MoreThis 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.
MoreRCT 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.
MoreThis 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
More1)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) Should people at low risk of cardiovascular disease take a statin?
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) Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials
|
**This section applies to those patients with normal left-ventricular systolic function post-MI. For patients with impaired LV function, see the HF-REF section (link below)** |
NICE guidelines from 2020 include a change from the previous practice of continuing beta-blockers indefinitely. They now say:
Discuss the potential benefits and risks of stopping or continuing beta-blockers beyond 12 months after an MI for people without reduced left ventricular ejection fraction. Include in the discussion:
The guidelines are slightly ambiguous because the evidence to support the use of beta-blockers post-MI is not straightforward.
The figures below are from the original trials of beta-blockers post-MI.
For a summary of evidence behind the new recommendations, see here:
More
How long should someone continue a beta-blocker?
What does this mean for patients?
There are a number of clinical trials which should clarify these questions due to report in 2023-2025.
Figures derived from a 2021 Cochrane review1 which included
Reference
1)Safi S, Sethi NJ, Korang SK et al. Beta‐blockers in patients without heart failure after myocardial infarction. Cochrane Database of Systematic Reviews 2021, Issue 11. Art. No.: CD012565
| This research does not provide a reliable indication of the treatment effect.
There is a very high possibility that the true effect is greater, smaller or absent. |
Cochrane rated this evidence as LOW – VERY LOW quality1 because:
Reference
1)Safi S, Sethi NJ, Korang SK et al. Beta‐blockers in patients without heart failure after myocardial infarction. Cochrane Database of Systematic Reviews 2021, Issue 11. Art. No.: CD012565
Note: the Cochrane reviewers rated the evidence as MODERATE – LOW quality but did not account for the poor applicability of the evidence to the modern era, so the quality rating has been downgraded one step further here.
The Cochrane review1 selected trials where:
Limited information is available on the participants’ characteristics:
Reference
1)Safi S, Sethi NJ, Korang SK et al. Beta‐blockers in patients without heart failure after myocardial infarction. Cochrane Database of Systematic Reviews 2021, Issue 11. Art. No.: CD012565
Beta-blockers can control anginal symptoms but do not have a prognostic benefit in stable angina in the way they may do post-MI.
NICE recommends considering either a beta-blocker or calcium channel blocker as first-line treatment1.
References
1)National Institute for Health and Care Excellence. Management of Stable Angina [Internet]. [London]: NICE; 2016 (Clinical guideline [CG126])
2)Huang HL, Fox KA. The impact of beta-blockers on mortality in stable angina: a meta-analysis. Scottish Medical Journal 2012; 57: 69–75
Beta-blockers are safe to use for CHD with these co-morbidities1:
Caution is needed in asthma (or reversible airways disease) as beta-blockers can induce bronchospasm.
References
1)Chronic Heart Failure: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care: Partial Update [Internet]. London: Royal College of Physicians (UK); 2010 Aug. (NICE Clinical Guidelines, No. 108.) 4, Diagnosing heart failure
2)Salpeter SR, Ormiston TM, Salpeter EE. Cardioselective beta‐blockers for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD003566
3)Radack K, Deck C. Beta-adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease. A meta-analysis of randomized controlled trials. Arch Intern Med 1991 Sep; 151(9): 1769-76
4)Hirst JA, Farmer AJ, Feakins BG et al. Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus – a systematic review and meta-analysis. British Journal of Clinical Pharmacology 2015; 79(5): 733–743
5)Salpeter SR, Ormiston TM, Salpeter EE, Wood‐Baker R. Cardioselective beta‐blockers for reversible airway disease. Cochrane Database of Systematic Reviews 2002, Issue 4. Art. No.: CD002992
6). The safety of cardioselective β1-blockers in asthma: literature review and search of global pharmacovigilance safety reports.
The data on side-effect rates with beta-blockers in the post-MI population is uncertain.
NICE reported the following rates in their evidence review1:
| Placebo | Beta-blocker | Absolute Risk Increase | Number Needed to Harm | |
| Dizziness | 1% | 15% | 14% | 7 |
| Fatigue | 5.9% | 13.5% | 7.6% | 13 |
| Bradycardia | 2.6% | 6.6% | 4% | 25 |
Another systematic review2 found no difference in the rates of depression, fatigue and sexual dysfunction in clinical trials comparing beta-blocker to placebo, though this was not fully exhaustive.
References
1)National Institute for Health and Care Excellence. MI – secondary prevention. Secondary prevention in primary and secondary care for patients following a myocardial infarction 2013 [Internet]. [London]: NICE; 2013 (Clinical guideline [CG48])
2)Ko DT, Hebert PR, Coffey CS et al. β-Blocker Therapy and Symptoms of Depression, Fatigue, and Sexual Dysfunction. JAMA 2002; 288(3): 351–357
|
**This section applies to those patients with normal left-ventricular systolic function post-MI. For patients with impaired LV function, see the HF-REF section (link below)** |
ACE inhibitors and ARBs can improve outcomes when used as treatment for secondary prevention post-MI.
Part of this effect may be due to blood pressure lowering, but it is unclear how much.
Figures derived from a key trial (EUROPA)1 which formed part of the 2013 NICE evidence review2.
The NICE review drew mainly on 2 very similar trials with similar results (the other study was HOPE3).
We have presented the EUROPA results as they are slightly more applicable to current practice (see Study Population for more details).
References
1)National Institute for Health and Care Excellence. MI – Secondary Prevention Partial Update[Internet]. [London]: NICE; 2013. (Clinical guideline [CG48])
2)The EUROPA Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003; 362(9386): 782-788
3)The HOPE Investigators. Effects of an Angiotensin-Converting–Enzyme Inhibitor, Ramipril, on Cardiovascular Events in High-Risk Patients. N Engl J Med 2000; 342: 145-153
| 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:
However,
Reference
1)National Institute for Health and Care Excellence. MI – Secondary Prevention [Internet]. [London]: NICE; 2013 (Clinical guideline [CG48])
The characteristics of participants in the EUROPA trial were1:
Reference
1)The EUROPA Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003; 362(9386): 782-788
Angiotensin Receptor Blockers (ARBs) appear to be as effective as ACE inhibitors in preventing future vascular events and mortality in a post-MI population.
The NICE evidence review in 20131 found 1 trial2 involving:
LOW-MODERATE quality evidence:
| This research provides a good indication of the treatment effect.
There is a moderate possibility that the true effect is smaller or greater. |
References
1)National Institute for Health and Care Excellence. MI – Secondary Prevention [Internet]. [London]: NICE; 2013 (Clinical guideline [CG48])
2)The ONTARGET Investigators. Telmisartan, Ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547-1559
Side effect rates in the EUROPA trial1 :
| Placebo | Perindopril 8mg | Absolute risk increase | Number Needed to Harm | |
| Cough | 0.5% | 2.7% | 2.2% | 45 |
| Hypotension | 0.3% | 1.0% | 0.7% | 143 |
| Kidney Failure | 0.3% | 0.3% | none | none |
| Intolerance (non specific) | 1.3% | 2.4% | 1.1% | 91 |
Note: these rates are reported as those severe enough to result in withdrawal from treatment
Evidence quality: MODERATE
|
Reference
1)The EUROPA Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). The Lancet 2003; 362(9386): 782-788
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.