Guidelines for Cardiovascular Disease

November 2019


2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes

The new 2019 guidelines focus on chronic coronary syndrome (CCS) rather than stable coronary artery disease (CAD). They identify six commonly encountered clinical scenarios:

  • Patients with suspected CAD and ‘stable’ angina symptoms, and/or dyspnoea
  • Patients with new onset heart failure [HF] or left ventricular [LV] dysfunction and suspected CAD
  • Asymptomatic and symptomatic patients with stabilized symptoms <1 year after an acute coronary syndrome [ACS] or patients with recent revascularization
  • Asymptomatic and symptomatic patients > 1 year after initial diagnosis or revascularization
  • Patients with angina and suspected vasospastic or microvascular disease
  • Asymptomatic subjects in whom CAD is detected at screening.

A dose of 75-100 mg per day of aspirin is recommended to prevent further events for:

  • Patients with CCS in sinus rhythm who have had a previous MI or revascularisation
  • the prevention of CVD events in patients who have not had an MI or revascularisation but have definitive evidence of CAD on imaging

The guidelines suggest considering dual antithrombotic therapy [aspirin plus another antithrombotic drug] for secondary long- term prevention   in patients with CCS in sinus rhythm who have a high or moderate risk of ischaemic events and who are not at high risk of bleeding events.

Low-dose aspirin [or clopidogrel] can also be considered in addition to long term oral anticoagulant [OAC]  therapy for people with AF, history of MI and at high risk of recurrent ischaemic risks but low risk of a bleeding event.

The guidelines recommended the use of a proton pump inhibitor for people at high risk of gastrointestinal bleeding if they are on aspirin monotherapy, dual antiplatelet therapy [DAPT], or OAC monotherapy to help increase safety.

Life style changes decrease the risk of further CVD events and mortality and should be encouraged by clinicians in addition to secondary prevention therapy at every encounter with the patient.

The guidelines call for further research into the efficacy and safety of aspirin and other antithrombotic therapies in patients with mild atherosclerotic disease that has for example been identified via a coronary computed tomography angiography [CTA]. They recommend that the impact on cancer rates as well as CVD events is studied. Further work to find the optimal long-term antithrombotic therapy is also recommended.

For further information please see:

Knuuti J, Wijns W and Saraste A et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. European Heart Journal 2019 )), 1-71 DOI:10.1093/eurheartj/ehz425

Aspirin summaries:  the role of aspirin in dual and triple antithrombotic therapy for secondary   prevention in cardiovascular disease (CVD)  

Double versus triple antithrombotic therapy in people with atrial fibrillation who undergo percutaneous coronary intervention.

Exploring ways to optimise antithrombotic therapy for the secondary prevention of CVD whilst reducing the risk of bleeding complications is an important and clinically relevant research question.  This article describes a meta-analysis of four non-vitamin K antagonist oral anticoagulant (NOAC) randomised clinical trials in which the safety and efficacy of double versus triple antithrombotic therapy  (DAT vs TAT) are compared in people with atrial fibrillation who require  percutaneous coronary intervention (PCI).

Four trials (AUGUSTUS, ENTRUSTAF-PCI, Pioneer AF-PCI and RE-DUAL  PCI) were included covering 10 234 patients. Major or clinically relevant non-major bleeding was found to be significantly lower for DAT when compared with TAT [risk ratio (RR) 0.66, 95% confidence interval (CI) 0.56-0.78; P<0.0001: I2 =69%] but this was balanced by a significantly increased risk of stent thrombosis [RR 1.59, 95% CI 1.01-2.50: P=0.04: I2 =0%]  and a higher risk of MI in those taking DAT alone. In particular, NOAC based DAT in comparison with vitamin K antagonist TAT showed a significant reduction in intracranial haemorrhage.

One interesting clinically relevant finding from this meta-analysis is the fact that the bleeding benefit from using DAT appears to come with a cost of additional cardiac (but not cerebrovascular) ischaemic events.  The authors state that:

This finding carries relevant clinical and pathophysiological implications and reinforces the notion that the upfront selection between TAT or DAT and/or the optimal timing for aspirin discontinuation after intervention or ACS should be individualized.’

Gargiulo et al 2019 Page 3765

For further information please see:

Gargiulo G., Goette A.,  Tijssen J., Eckardt L., Lewalter T., Vranckx P. and Valgimigli M. Safety and efficacy outcomes of double vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic  review and meta-analysis of non-vitamin K antagonist oral anticoagulant-based randomized clinical trials. European Heart Journal (2019) 40, 3757-3767.

Aspirin in people with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI).

The authors in this correspondence article review the evidence for dual antithrombotic therapy  (DAT) versus triple antithrombotic therapy (TAT). They look at some of the limitations in the four randomised clinical trials on which the DAT recommendations are based. These include:

  • Open- label design
  • Lack of power for efficacy outcomes
  • Two of the four trials had efficacy outcomes that included non-thrombotic  events
  • Subsequent meta-analyses  performed on these four trials share these limitations
  • The prognostic impact of a bleeding event is not always equivalent to a non- fatal MI

After a careful discussion of this data the authors conclude:

“It is probably too soon to routinely drop aspirin immediately after PCI in patients with AF.”

Galli M et al 2019

For further information please see:

Galli M., Andreotti F., Savarese G. et al. Dropping aspirin in patients with atrial fibrillation undergoing percutaneous coronary intervention: a jump with a weak parachute? European Heart Journals Cardiovascular Pharmacotherapy (2019) 5, 55-56.

2018 Joint European Consensus document on antithrombotic therapy in people with atrial fibrillation (AF)  presenting with acute coronary syndrome (ACS)  and/or undergoing  percutaneous cardiovascular interventions (PCI)

The Joint European consensus guidelines for antithrombotic therapy discuss recent TAT versus DAT trials for people with AF undergoing PCI and conclude that:

“An initial period of triple therapy should be used in most AF patients undergoing PCI depending on presentation (ACS vs elective), stroke vs bleeding risk, procedural considerations (e.g. disease severity) etc.”

Lip et al 2019

They do however suggest dual therapy with an oral anticoagulant (OAC) plus one P2Y12 inhibitor (e.g. clopidogrel) in people with excessive bleeding risk but a low thrombotic risk.

The authors state that some questions remain over the use of DAT e.g. NOAC plus clopidogrel as opposed to a TAT regimen that includes aspirin.

For further information please see:

Lip G.Y.H., Collet J.P., Haude M. et al.  2018 Joint European consensus document on the management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous cardiovascular interventions: a joint consensus document of EHRA, EAPCI, ACCA, HRS, APHRS, LAHRS, CASSA. Europace (2019) 21 192-193.

Dual versus triple antithrombotic therapy (DAT v TAT) after percutaneous coronary intervention (PCI) in people with atrial fibrillation (AF) – dual therapy brings a lower risk of bleeding events but increases the risk of ischemic events.

This article describes the importance of finding the optimum antithrombotic therapy for people with AF requiring PCI in order to prevent stroke [using an anticoagulant], myocardial infarction (MI) and stent thrombosis [using an anti-platelet].

In reviewing the literature, the authors explain the issue that whilst recent trials, carried out to help find the optimum regimen for this population, have shown that bleeding risk is lower in people taking DAT none of these randomized controlled trials (RCTs) were designed with the power to understand the impact of DAT versus TAT on ischemic events.

Some of the trial work has also indicated that people with other risk factors, such as diabetes and acute coronary syndrome (ACS),  have an increased the risk of having an MI or a stent thrombosis while on DAT, making an individualised approach important.

The authors performed a meta-analysis on five RCTs with data from 9931 patients and this showed that DAT compared with TAT lowers the risk of bleeding events. However, they also found a numerically higher number of ischemic events in the DAT group but this was not statistically significant.

The authors estimate that the currently available trial data does not provide enough patient numbers to perform a meta-analysis that will answer the question as to whether the benefit of less bleeding events comes at a cost of increased ischemic events in this group of people. They estimate that a meta-analysis with 31,290 patients for ischemic events, 39,106 patients for MI and 20,016 patients for stent thrombosis would be required to achieve a study with 80% power and 5% significance.

For further information please see:

Gupta K., Prejean S.P. Vaduganathan M. et al. Does dual vs. triple antithrombotic therapy after percutaneous coronary intervention in patients with atrial fibrillation lower the risk of bleeding at the cost of increased risk of ischemic events? IJC Heart and Vasculature (2019) 24, 100404.

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Prognostic bleeding risk models for aspirin use in the primary prevention of cardiovascular disease. 

This prospective cohort study looked at 385 191 people (aged 30-79) from the PREDICT cohort in New Zealand who had a cardiovascular disease (CVD) risk assessment in primary care between 2007 and 2016. Anyone who already had indications for or contraindications against aspirin use were excluded along with those already receiving antiplatelet and anticoagulant therapy.

The study had 1 619 846 person years of follow up during which 4442 of the people had a major bleeding event (including 313 fatal events).

Sex-specific prognostic bleeding risk models were developed to help predict the absolute bleeding harms of aspirin in primary CVD prevention. Predictors used included demographics (age, ethnicity and socioeconomic deprivation), clinical measures (BP, cholesterol ratio), family history of premature CVD, medical history (smoking, diabetes, bleeding, peptic ulcer disease, cancer, chronic liver disease, chronic pancreatitis or alcohol related problems) and medication use (NSAIDs, corticosteroids and SSRIs).

The study confirmed established risk factors that are already known to increase bleeding risk in men and women. These are:

  • Age
  • Smoking
  • Diabetes
  • Clinical history
  • Use of SSRIs, NSAIDSs or corticosteroid medications

In addition the study identifies the use of antihypertensives as a risk factor.

The study also identified the bleeding risks associated with socioeconomic deprivation and non-European/non-Indian ethnicity. In total the risk calculator required 19 patient characteristics to be collected.  This could be simplified by making adjustments for the population the score is being used for and by utilising autoscoring  with electronic records.

The study found that there was good calibration between predicted and observed events. This appears to be the first published model for predicting bleeding risk among people considering aspirin for primary CVD prevention. External validation in populations outside of New Zealand will be needed before broader use can be made of this new model.

For further information please see:
Selak V, Jackson R and 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.

Whitlock EP and Johnson ES. Are we there yet? Another milepost in the journey to identify appropriate candidates for aspirin primary prevention.  Annals of Internal Medicine 2019 170:411-413.

Primary prevention

This review article seeks to put the results of new aspirin trials published in 2018 into the context of the previous evidence for aspirin in the primary prevention of cardiovascular disease [CVD] and seek to identify a more targeted approach to low-dose aspirin use by identifying individuals where the reduction in vascular events outweighs the risk of bleeding. One of the key issues with using aspirin for primary CVD prevention is that those who appear at highest risk of having a vascular event are also at highest risk of having a bleed.  

The paper explores the mechanism of action of aspirin and its pharmacology before conducting an in depth analysis of the randomized trials of aspirin versus placebo for the primary prevention of CVD.A detailed analysis of the safety of aspirin is also carried out in which the authors look not only at bleeding risk but also co-therapy with gastroprotectant and interactions with other cardiovascular drugs.

The paper identifies the following research gaps:

  • Improved risk stratification scores
  • Safer antithrombotic drugs
  • Tailored aspirin dosing
  • Further work on non-cardiovascular benefits of aspirin e.g. cancer prevention

The authors conclude that the results of three new randomised controlled trials; ASPREE, ARRIVE and ASCEND are consistent with previous trial results in primary prevention which show that in this setting aspirin use yields small benefits and small hazards. The challenge is to identify people at high risk of CVD but low risk of a bleeding event. The authors suggest:

‘Future work to explore this dilemma requires a new approach, perhaps combining the use of coronary imaging, to identify a group of apparently healthy people at substantially increased risk of vascular events, with the use of gastroprotectant therapy to reduce the risk of bleeding. Tailoring the aspirin regimen according to body mass and platelet turnover is an additional strategy worth investigating to optimize effectiveness.’

For further information please see:

Patrono C and Baigent C. Role of aspirin in primary prevention of cardiovascular disease. Nature Reviews Cardiology June 2019

NICE CKS Antiplatelet treatment: Primary prevention of CVD Last revised October 2015 “Do not routinely prescribe antiplatelet treatment for the primary prevention of cardiovascular disease (CVD).” It does however discuss the pros and cons and cautions for prescribing antiplatelet therapy for those with high blood pressure.

SIGN 149 Risk estimation and the prevention of cardiovascular disease does not recommend aspirin for primary prevention of CVD (Published 2017).

JBS 3 2014 does not recommend aspirin for those at higher risk of CVD e.g. diabetics to use aspirin for primary prevention of CVD.


NICE CKS Antiplatelet treatment: secondary prevention of CVD guidelines (last revised 2015) state;

“Antiplatelet treatment should be prescribed for the secondary prevention of cardiovascular events in people with:

  • Angina
  • A previous MI
  • A previous stroke or TIA
  • Peripheral Arterial disease
  • Atrial Fibrillation – although anticoagulants are normally used.”

SIGN 148 Acute coronary syndrome (April 16) section 4.4 p 13 recommend the use of aspirin on its own (e.g. self-administered or by ambulance staff) or in combination with other anticoagulants.  

SIGN 147 Management of chronic heart failure (March 2016) section 5.11 p 26 “No firm evidence to supports the use of any antithrombotic therapy in patients with HF-REF in sinus rhythm.”

SIGN 96 management of stable angina is currently being updated and is expected Spring 2018.

NICE CG68 July 2008 (last updated: March 2017) Stroke and transient ischaemic attack in over 16s: diagnosis and initial management. State: “ All people presenting with acute stroke who have had a diagnosis of primary intracerebral haemorrhage excluded by brain imaging should, as soon as possible but certainly within 24 hours, be given :

  • aspirin 300 mg orally if they are not dysphagic or
  • Aspirin 300 mg rectally or by enteral tube if they are dysphagic.”

(See full guidance for further information re aspirin intolerance and allergy updated 2017).

NICE CG68 describes initiating long term antithrombotic treatment after this but is not specific re which drugs.

JBS 3 2014 “Antiplatelet therapy with low dose aspirin (75–100 mg) is recommended indefinitely after myocardial infarction (MI).”

JBS 3 2014 “After acute ischaemic stroke, patients should initially receive 300 mg of aspirin daily for 2 weeks, then be changed to long term clopidogrel 75 mg daily. For patients who have a contraindication or intolerance to clopidogrel, modified release dipyridamole plus aspirin is an alternative. For people who have a contraindication or intolerance to both clopidogrel and aspirin, modified release dipyridamole alone is recommended.”

JBS 3 “For patients with transient ischaemic attacks (TIAs), modified release dipyridamole 200 mg twice daily plus aspirin 75–150 mg daily is an alternative treatment option to clopidogrel. For people who have a contraindication or intolerance to aspirin, modified release dipyridamole alone is an alternative treatment option.”

Atrial fibrillation (AF)

NICE Atrial Fibrillation: management (CG180) (Published 2014 Updated August 2014)  recommends that adults with AF are prescribed newer oral anticoagulants (NOACs) such as apixaban, dabigatran, etexilate, rivaroxaban or a vitamin K antagonist e.g. warfarin rather than aspirin in order to prevent stroke.

SIGN 94 Cardiac arrhythmias in coronary heart disease is currently being updated and is expected Spring 2018.



The U.S. Preventative Services Task Force (USPSTF) was created in 1984 and is an independent, volunteer panel of national experts in preventative and evidence-based medicine.  They use the following to grade their recommendations:

The USPSTF April 2016 recommends low-dose aspirin to prevent cardiovascular disease and colorectal cancer in the following groups:

Grade B Adults age 50 to 59 years with a 10 year CVD risk of greater than 10% who are not at increased risk for bleeding, have a life expectancy of at least 10 years and are willing to take low-dose aspirin for at least 10 years.

Grade C Adults age 60 to 69 years with a 10 year CVD risk of greater than 10% should consider their individual risks versus benefits of long term low dose aspirin. Those who are not at risk of bleeding, have a life expectancy of at least 10 years and are willing to take low-dose aspirin for at least 10 years are more likely to benefit.

“Persons who place a higher value on the potential benefits than the potential harms may choose to initiate low-dose aspirin.”

The USPSTF state that there is insufficient current evidence to assess the balance of benefits versus harms of initiating aspirin for primary prevention of CVD and CRC in adults younger than 50 years or 70 years or older. (Grade I).

USPSTF guidelines in development: CVD detection and prevention.

The USPSTF has recommendations on cardiovascular disease (CVD) risk and atrial fibrillation: screening with electrocardiology, cardiovascular disease: risk assessment using non-traditional risk factors and peripheral artery disease (PAD) in adults: screening with ankle brachial index at an evidence review and draft recommendation development stage. These draft guidelines focus on screening and risk assessment but this will help to identify more people who can benefit from preventative therapy. The cardiovascular screening guideline using non-traditional risk factors will include a review of treatment interventions aimed at preventing CVD events. The PAD screening review includes a section on treatment interventions in which it plans to explore antiplatelet therapy.

The American Heart Association (AHA) state (last update March 2017) that;

“Aspirin can help prevent heart attack.”

The AHA recommends;

People at high risk of heart disease should take low-dose aspirin (if told to by their healthcare provider) and that heart attack survivors regularly take low-dose aspirin.

They explain how aspirin helps prevent heart attack and stroke and provide questions for patients to ask their doctor about aspirin.

National Centre for Biotechnology Information (NCBI), National Library of Medicine (NLM), National Institute of Health (NIH) list an article in the Clinical Medicine and Research (Clin Med Res. 2014: 12(3-4):147-154) which states in its abstract:

“Aspirin therapy is well-accepted as an agent for the secondary prevention of cardiovascular events and current guidelines also define a role for aspirin in primary prevention. In this review, we describe the seminal trials of aspirin use in the context of current guidelines, discuss factors that may influence the effectiveness of aspirin therapy for cardiovascular disease prevention, and briefly examine patterns of use. The body of evidence supports a role for aspirin in both secondary and primary prevention of cardiovascular events in selected population groups, but practice patterns may be suboptimal. As a simple and inexpensive prophylactic measure for cardiovascular disease, aspirin use should be carefully considered in all at-risk adult patients, and further measures, including patient education, are necessary to ensure its proper use.”

They conclude that aspirin despite evidence-based guidelines for both primary prevention in CVD is not optimally used – there is both underuse and overuse. They advocate research to help optimise aspirin use in the groups most likely to benefit.

Launched in 2012, Million HeartsR  ( is a national initiative in the USA set up to prevent 1 million heart attacks and strokes by 2017. It is co-lead by The Centers for Disease Control and Prevention and the Centers for Medicare and Medicaid Services Services on behalf of the U.S. Department of Health and Human Services.

Over the next 5 years until 2022 Million HeartsR  plans to build on its experience, expertise and partnerships and seeks commitment to preventing a million CVD events in five years by:

  • Optimizing care for the ABCS of heart health:
  • Aspirin when appropriate
  • Blood pressure control
  • Cholesterol management
  • Smoking cessation

And increase the use of cardiac rehabilitation and healthy living behaviours

The FDA on a consumer advice sheet (last update 30/12/2016) does not currently recommend the use of aspirin for the primary prevention of CVD;

“The FDA has reviewed the available data and does not believe the evidence supports the general use of aspirin for the primary prevention of a heart attack or stroke. In fact, there are serious risks associated with the use of aspirin, including increased risk of bleeding in the stomach and brain, in situations where the benefit of aspirin for primary prevention has not been established.”


American Stroke Association recommends that to prevent another stroke occurring patients create a stroke prevention plan with their  doctor that may include discussing an aspirin regimen or other medications in addition to; managing high blood pressure, reducing blood sugar, eating better, stopping smoking, controlling cholesterol, being active and losing weight. They point out that aspirin is not appropriate for everyone.

European Guidelines


Key Message: “Antiplatelet therapy is not recommended in individuals free from CVD, due to the increased risk of major bleeding.” ESC 2016

The 2016 European guidelines on CVD prevention review the evidence for antiplatelet therapy in individuals without CVD and conclude that current evidence does not support the use of aspirin in those without CVD due to the risk of a major bleed.

The guidelines state that the results of four major primary prevention trials;

•          Two in patients with diabetes mellitus (ASCEND, ACCEPT-D)

•          One in individuals of advanced age (ASPREE)

•          One in individuals with moderate CV risk (ARRIVE)

are anticipated over the next 5 years. This may alter the current recommendations.


The 2016 European Guidelines for CVD prevention make the following recommendations for antiplatelet therapy (see table below). This is a based on a careful appraisal of risks versus benefits of aspirin or other antiplatelet therapy.  The guidelines state that there is a gap in the evidence concerning new antiplatelet drugs in patients with stable coronary artery disease as well as a gap in the understanding about the use of new antiplatelet drugs used in combination with anticoagulation treatment.

Source 2016 European guidelines for cardiovascular disease prevention

Third sector agencies such as the European Heart Network (EHN) play an important role in providing education around clinical data and its interpretation. The EHN’s mission statement is;

“The European Heart Network plays a leading role in the prevention and reduction of cardiovascular diseases, in particular heart disease and stroke, through advocacy, networking, capacity- building and patient support, so that they are no longer a major cause of premature death and disability throughout Europe.”

The EHN’s vision is that;

“Every European has a right to a life free from avoidable cardiovascular diseases.”

One of their objectives in order to achieve this vision is;

  • Gathering and disseminating information relevant to heart health promotion and cardiovascular disease prevention.

The European Stroke Organisation (ESO) aims to

“improve stroke care by providing medical education to healthcare professionals and the lay public. By offering best practice approaches, the ESO’s goal is to harmonise stroke management in Europe. ESO works as the voice of stroke in Europe to bring about political change. The ESO focuses on European level projects while working towards global solutions.”

And is therefore a useful source of information around stroke prevention and management.



Cardiovascular disease (CVD) is a growing health burden in China and the primary prevention strategies are important because over 70% of those experiencing a first Coronary Heart Disease (CHD) event in China died outside of the hospital setting1.

Primary prevention of CVD in China is a top priority especially lifestyle factors such as  smoking, diet, weight and increasing activity levels in order to reduce risk factors such as high blood pressure, high cholesterol and control diabetes2.

CVD risk assessment is an important way to identify those at high-risk in the Chinese population without current CVD. Specific risk assessment tools for the Chinese population have been developed based the Chinese Multi –provincial cohort study.

The 2012 China National Plan for Non-Communicable diseases [NCD] prevention and treatment3 has clear targets for CVD prevention.  The 2016 China guidelines of dyslipidemia management and the 2017 Chinese guidelines for CVD prevention have new recommendations for risk assessment in China.

The 2016 China expert consensus advocates that for individuals with a ten year arteriosclerotic cardiovascular disease (ASCVD)4 risk of greater than or equal to 10%, aspirin should be used for the primary prevention of CVD.


The Chinese clinical guidelines for the secondary prevention of ischemic stroke and TIA recommend an optimal dosage of aspirin between 75 and 150 mg/day. A combination of aspirin and clopidogrel for 21 days is recommended for patients with minor stroke or high-risk TIA within 24 h of onset5. These recommendations are based on the CHANCE trial6.


1.Chin J Cardiol, March 2012; Vol 40 No 3.

2. Walker J, Hutchison P, Ge J et al 2018 Aspirin:120 years of innovation. A report from the 2017 Scientific Conference of the International Aspirin Foundation. ecancer 12 813 

3.China National Plan for NCD Prevention and Treatment (2012-2015). http://www.chinaede.en.en  [accessed June 14, 2014].


5. Wang Y, Liu M and Pu C 2014 Chinese guidelines for secondary prevention of ischemic stroke and transient ischemic attack. Int J Stroke 2017; 12(3):302-320.

6.Wang Y, Pan Y, Zhao X et al Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) Trial: One-Year outcomes [j]. Circulation 2015; 132(1):40-46.