PART III

Secondary prevention of atherosclerotic cardiovascular disease

Guy De Backer¹, Paul Dendale², Christiaan Vrints³

¹ Ghent University, Ghent, Belgium
² Jessa Hospital Hasselt and Hasselt University, Hasselt, Belgium
³ University of Antwerp, Antwerp, Belgium

Summary

In patients with established atherosclerotic cardiovascular disease (ASCVD) prevention of recurrent events remains a significant challenge. After a clinical event or after elective revascularization procedures, secondary prevention strategies are preferably implemented as part of a cardiac rehabilitation program that should be offered to all patients to improve quality of life and to reduce cardiovascular morbidity and mortality. In case of stable and uncomplicated ASCVD this should include adaptations of lifestyles related to smoking of tobacco, nutrition and exercise, control of arterial hypertension, dyslipidaemias and diabetes and the use of cardioprotective drugs. Randomized prospective clinical trials firmly established the effectiveness and safety of these preventive interventions, and the obtained scientific evidence resulted in strong recommendations in guidelines on cardiovascular disease prevention.

Unfortunately, results from registries and surveys show that implementing these guidelines on secondary prevention of ASCVD is far from optimal with a high prevalence of persistent smoking, sedentary lifestyle, uncontrolled hypertension and dyslipidaemias and an increasing prevalence of obesity, central obesity and diabetes. Despite the widespread use of drugs, the management of risk factors does not meet therapeutic targets in far too many patients. All this calls for a multidisciplinary approach to raise the standard of secondary prevention in patients with ASCVD.

Introduction

Advances in interventional cardiovascular medicine have contributed to the decline in ASCVD mortality. However, the correct application of secondary prevention recommendations after coronary interventions or after an initial clinical cardiovascular (CV) event remains a significant challenge [1].

In this chapter recommendations are summarized to optimize secondary prevention in patients with established ASCVD either after an acute clinical event or after an elective revascularization procedure.

The burden of the problem

Over the last decades the epidemic of ASCVD has been very dynamic. Fortunately ASCVD morbidity and mortality have declined impressively during the past decades with a reduction of more than 50% in many countries [2, 3, 4]. Changes in socio-economic development and in non-communicable disease prevention policies explain a substantial part of the ASCVD decline [5]. However, recent statistics suggest that the decline in CVD mortality among adults is plateauing in some countries especially in young adults [6, 7].

In patients with established coronary heart disease (CHD) the incidence of recurrent events has been reduced but remains high.

In a Swedish national register more than 100 000 survivors of a myocardial infarction (MI) were followed after discharge from the hospital for a composite endpoint of recurrent non-fatal MI, non-fatal stroke and CV death; percutaneous coronary intervention (PCI) was performed in 43% of the patients and coronary artery bypass grafting (CABG) in 6.2% [8]. The composite endpoint occurred in 18% of the cohort during the first year after the index event with large differences between the age groups. Among those who remained free of these recurrent events during the first year, 20% reached the composite endpoint during the following three years; that proportion varied significantly by age from < 10% in those aged < 60 years to > 40% in those aged 80+ years.

Prospective data over a median follow-up of 1.7 years are available for the EUROASPIRE IV and V surveys, including 12484 patients with established ASCVD aged < 75 years old screened between 2012 and 2017 in 27 countries [9]. In these surveys the primary endpoint, a composite of fatal CVD or new hospitalizations for non-fatal MI, stroke, heart failure, CABG or PCI occurred in 1424 patients resulting in an incidence rate of 71 / 1000 person-years.

Based on these surveys a EUROASPIRE risk calculator has been developed to estimate the risk of 1 and 2 years of recurrent events in different risk regions of Europe [9].

These and other observations in contemporary cohorts of CHD patients indicate that recurrent events are still common and mainly due to the underlying disease's progression. CHD patients are therefore to be considered at the highest risk and should receive the best preventive interventions.

Strategies of secondary prevention

There is consensus as to which factors should be addressed to halt the progression and induce regression of the disease and guidelines on this are consistent worldwide [10, 11, 12, 13, 14, 15].

a) Cardiac rehabilitation programs

The (cost-) effectiveness and safety of secondary prevention strategies in reducing recurrent ASCVD events are strong particularly when integrated into cardiac rehabilitation (CR) programs [16]. The usefulness and cost-effectiveness of CR programs have been shown in both randomized controlled trials and in observational studies [17, 18, 19, 20, 21].

The preventive interventions within CR programs take care of the optimal use of and adherence to cardioprotective drugs, lifestyle adaptations related to smoking tobacco, nutrition, exercise, and control of arterial hypertension, dyslipidaemia and diabetes.

b) Lifestyle adaptations

Smoking cessation after a MI is very effective in secondary prevention: in a meta-analysis of stopping smoking after a MI the relative risk reduction for coronary mortality was 48% [22] and in a Cochrane meta-analysis of the effects of smoking cessation in patients with CHD a 36% reduction in all-cause mortality was observed [23]. If advice, encouragement and motivation are likely to be insufficient, drug therapies should be considered early on including nicotine replacement therapies, bupropion or varenicline. Smoking cessation pharmacotherapy is safe; it may double or triple quit rates and combining pharmacotherapy with counseling improves quit rates further [24, 25, 26, 27]. Comprehensive tobacco cessation decision pathways have been presented for patients with ASCVD who continue smoking [28, 29]. The long-term effects of e-cigarettes and waterpipe smoking in patients with established ASCVD are uncertain as results of large observational studies lack; today’s evidence suggests that these lifestyles are not healthy alternatives for tobacco smoking and should be discouraged [30, 31].

Adherence to dietary changes in patients who had survived an initial MI was assessed in the Nurses’ Health study and in the Health Professionals Follow-up study [32]. In these studies 4098 patients had completed a pre- and post-MI food frequency questionnaire and diet quality was measured using the Alternative Health Eating Index 2010(AHEI2010). A greater increase in the AHEI2010 score from pre-to post-MI was significantly associated with lower all-cause mortality (Hazard Ratio (HR) 0.71; 95% confidence interval (CI): 0.56-0.91) and CVD mortality (HR 0.60; 95%CI: 0.41-0.86) comparing the extreme quintiles.

In Greece the EPIC study examined the association between the degree of adherence to the traditional Mediterranean Diet and total and cardiac mortality in 1302 patients with CHD. Total- and cardiac mortality were respectively 27 and 31% lower by two units increment in the diet adherence score and this after adjustment for sex, age, previous treatment for hypertension or hypercholesterolaemia, diabetes, waist/hip (W/H) ratio, body mass index (BMI), education and smoking [33].

The importance of adherence to lifestyle changes was also well documented in the Fifth Organisation to Assess Strategies in Acute Ischemic Syndromes (OASIS) trial with more than 18000 patients with unstable angina or non-STEMI. Adherence to diet, physical activity and smoking cessation was assessed at 30 days follow-up. Recurrent CV events (MI, stroke and deaths) were recorded in the following six months. Patients who had reported persistent smoking and no adherence to diet or exercise had a 3.8 fold increased risk (95% CI: 2.40-5.91) of repeated events compared to never smokers who had modified their diet and activity pattern and this after adjustment for age, sex, region, history of hypertension, diabetes, prior MI, BMI and creatinine. Adherence to dietary and exercise advice was associated with a relative risk reduction in mortality of 55% [34].

The Randomized Evaluation of Secondary Prevention by Outpatient Nurse Specialists (RESPONSE-2) trial evaluated the effect of a set of comprehensive lifestyle programs (targeting weight reduction, improved physical activity and smoking cessation) on top of usual care in 824 patients after a recent acute coronary syndrome (ACS) or coronary stenting. The proportion of successful patients in the intervention group was 37% compared with 26% in the control group, a relative increase of 43% [35].

Increasing physical activity is one of the most vital lifestyle adaptations to reduce recurrent ASCVD events. However, vigorous physical activity has been linked with an increased risk for ACS and sudden cardiac death [36, 37, 38]. Therefore, the new ESC guidelines recommend for all patients with established ASCVD a personalized risk stratification and regular follow-up for exercise-induced adverse events [39]. Next to personalized risk stratification, personalized exercise prescription is essential because different recommendations for the duration, frequency and exercise intensity exist for different cardiovascular indications, comorbidities and age groups. Studies have shown that cardiologists and exercise specialists differ significantly in implementing the guidelines on exercise training on a patient-level [40]. The Exercise Prescription in Everyday practice & Rehabilitative Training (EXPERT) tool, endorsed by the ESC, may help health professionals to optimize rehabilitation prescriptions in patients with ASCVD [41].

The new ESC guidelines for Sport Cardiology recommend that all patients with a recent ACS participate in exercise-based CR before return to exercise [39]. However, the EUROASPIRE-V survey demonstrates disappointingly low participation and adherence rates to center-based CR [42]. Different barriers for CR participation are stated in literature such as low referral rate, lower health literacy or transport, familial,

vocational, and schedule constraints [43, 44]. Multiple trials have established that telerehabilitation is as effective as center-based with similar healthcare costs, mainly by focusing on increasing exercise participation [45]. Therefore, offering the option of remote home-based CR or telerehabilitation could potentially improve the limited uptake and adherence of the so important exercise-based CR.

c) Management of dyslipidaemias

Randomized controlled trials (RCT’s) have clearly demonstrated that reducing the low-density lipoprotein-cholesterol (LDL-C) level with diet and/or lipid-lowering drugs can reduce the risk of recurrent ASCVD events in coronary patients [46, 47]. This evidence is most significant for the use of statins. RCT’s comparing more versus less intensive lowering of LDL-C in coronary patients showed more ASCVD prevention with more intensive statin therapies [48]. Results from the SWEDEHEART register revealed that a larger early LDL-C reduction and more intensive statin therapy after MI are associated with a reduced hazard of all CV outcomes and all-cause mortality [49].

In patients with ASCVD it is recommended to initiate or continue high-intensity statin therapy aiming at a LDL-C level of < 55 mg/dL (1.4 mmol/L) and a reduction of at least 50% from baseline LDL-C [11]. If the LDL-C goal is not reached after 4-6 weeks under the maximally tolerated statin dose it is recommended to add ezetimibe, based on the results from the IMPROVE-IT trial [50]. In patients who are judged to be at extreme risk in whom the LDL-C goal is not reached under maximally tolerated statins and ezetimibe or in case of statin intolerance, adding a PCSK9 inhibitor is recommended following a clinician-patient discussion on benefits, safety and cost [51, 52]. Routine short pre-treatment or loading with high-intensity statins before PCI should be considered in patients undergoing PCI for an ACS or elective PCI [53, 54, 55].

The early reduction in cardiac event rates (within one month) observed after the initiation of a high-intensity statin therapy in patients with an ACS contrasts with the lag of approximately one to two years observed in prior studies of statins in patients with stable chronic CHD. In patients with ASCVD who experience a second vascular event within two years while taking maximally tolerated statin-based therapy an LDL-C goal of < 40 mg/dL (1.0 mmol/L) may even be considered [51, 52].

d) Control of arterial hypertension

Elevated blood pressure is one of the most powerful modifiable risk factors for ASCVD [56]. The beneficial effects of blood pressure-lowering therapies to reduce stroke, MI, heart failure and death have been shown in numerous RCT’s and in different meta-analyses [57, 58]. In a meta-analysis of RCT’s of antihypertensive therapies it was shown that for every 10 mm Hg reduction in systolic blood pressure (SBP) CHD was reduced by 17% [57].

In an analysis of 22 672 patients with stable CHD who were treated for hypertension it was found that after a median follow-up of 5.0 years, a SBP of ≥140 mmHg and a diastolic blood pressure (DBP) of ≥80 mmHg were each associated with increased risk of CV events. An SBP of < 120 mmHg was also associated with increased risk as was an DBP of < 70 mmHg [59].

Blood pressure lowering can be achieved through lifestyle changes and drug therapies.

A target SBP of 120-130 mmHg in patients aged < 70 years with CHD appears safe and has been recommended [14]; in patients aged > 70 years a target of < 140 mmHg down to 130 mmHg is recommended or even lower if tolerated [60, 61]. The DBP is targeted at < 80 mmHg in all treated patients [14].

It is also recommended to initiate therapy with a combination of two drugs, possibly in a single pill. As to the choice of drugs in hypertensive coronary patients, there is evidence of greater benefit for beta-blockers in patients with specific indications such as in patients with angina, post-MI, heart failure or the need for heart-rate control. Certain drug classes might have particular positive or negative effects in specific ASCVD patient subgroups or in the presence or absence of other comorbidities.

e) Diabetes detection and control

Another main issue in secondary prevention is the detection and control of glucose abnormalities in patients with ASCVD. Dysglycaemias are very common in these patients but remain unrecognized in a large number [62, 63, 64]; patients with ASCVD and without known diabetes should have their glycaemic state evaluated with an OGTT [15, 64, 65]. This is important because future morbidity and mortality of patients with ASCVD are considerably higher in the presence of dysglycaemia [66, 67, 68]. In the EUROASPIRE IV and V cohorts diabetes and poor glycaemic control were associated with a significantly higher rate of recurrence and death [9].

Recent outcome trials, including patients with ASCVD, indicate that the prognosis can be improved by using GLP agonists or SGLT2 inhibitors [69, 70, 71, 72, 73, 74, 75, 76, 77].

In patients with ASCVD and diabetes combined, the prognosis can also be improved utilizing comprehensive drug therapies including renin-angiotensin-aldosterone system inhibitors, beta-blockers, antiplatelets and statins.

f) Use of cardioprotective drugs

The aims of using cardioprotective drugs, beyond those needed to control elevated blood pressure, dyslipidaemias and dysglycaemias, in patients with ASCVD are to prevent recurrent events. The use of these drugs has to be adapted to each patient's characteristics and preferences and a timely review of the patient’s response to drug therapies is recommended [78]

1) Antiplatelet agents

Antiplatelet agents are essential to prevent recurrent events in patients after a clinical event or after interventional procedures. For many years a lifelong therapy with aspirin has been recommended. Nowadays different antiplatelet drugs have become available such as clopidogrel, ticlopidine, prasugrel or ticagrelor. Guidelines on the use of antithrombotic therapy have been developed by the ESC [79] and more specifically for patients after myocardial revascularization [80]. There is a dedicated and updated chapter on antithrombotic therapy in this Textbook (chapter 3.28). For information on this important topic see that chapter.

2) Angiotensin-converting-enzyme inhibitors (ACEI) and Angiotensin II-receptor-blockers (ARB)

The use of ACEIs (or ARBs, in case of ACEIs intolerance) should be considered in patients with ASCVD at very high risk of recurrent events and in particular in patients with diabetes, heart failure or hypertension [78]. The dosage of ACEIs /ARBs should be adapted to patient tolerance in terms of blood pressure and biology, aiming to attain the doses, which have been proven efficacious in these populations.

3) Beta-blockers

Beta-blockers are recommended after a STEMI or a non-STEMI in the presence of heart failure, and/or a LVEF <=40% unless contraindicated [81, 82]. They should be considered during and after hospitalization in all patients with STEMI unless contraindicated [81]. After myocardial revascularization it is indicated to continue beta-blockers in all patients after MI, ACS or LV dysfunction unless contraindicated

However, in an era where PCI has become more used, the evidence supporting benefits of long-term therapy with beta-blockers in stable ASCVD patients without prior MI, ACS or LV dysfunction remains controversial.

g) Combining lifestyle adaptations and cardioprotective drugs

In a systematic review of cohort studies and RCT’s of the effects of smoking cessation, increased physical activity and dietary changes in coronary patients, total mortality was reduced by respectively -35, -24 and -44% [82]. In the OASIS 5 trial the combination of dietary and exercise modifications was associated with a total mortality reduction of 55% [34]. These figures compare favorably with the effect size estimations for cardioprotective drugs as presented in Table 1 based on the literature [35, 83, 84, 85, 86, 87, 88]. All this clearly suggests that the combination of adherence to lifestyle changes and compliance with cardioprotective drugs results in optimal secondary prevention outcomes.

The medical evidence on the efficacy and safety of numerous secondary prevention strategies is extensive.

The objectives of secondary prevention for most of the patients with ASCVD are presented in Focus Box 1.

FOCUS BOX 1Objectives of secondary prevention of CVD

No exposure to tobacco (not even second hand smoke)
Diet: avoid dietary trans fats, reduce saturated fatty acids; increase wholegrain, vegetables, fruits, fish
Physical activity: participation in a cardiac rehabilitation program followed by a medically prescribed aerobic exercise training program
Body mass index: < 30 kg/m2; ideally between 20 and 25 kg/m2
Waist Circumference: < 102 cm (men), < 88 cm (women); ideally < 94 cm (men), < 80 cm (women)
Blood pressure: < 130/80 mmHg in patients aged < 70 yrs; < 140/80 mmHg in patients aged > 70 yrs or even lower if tolerated.
LDL-C: < 1.4 mmol/L (55 mg/dL) and a reduction of at least 50% from the baseline level
Diabetes: HbA1c < 7% (53 mmol/mol)
Use of cardioprotective drugs as appropriate

How well is secondary prevention of ASCVD implemented in daily practice?

a) Participation in cardiac rehabilitation programs

In the 2016 ESC guidelines on CVD [10] it is recommended to implement strategies for prevention in CVD patients, including lifestyle changes, risk factor management and pharmacological optimization, after an acute event before hospital discharge to lower risk of mortality and morbidity. Furthermore, participation in a cardiac rehabilitation program for patients hospitalized for an acute coronary event or revascularization, is recommended.

Although there is compelling medical evidence in favor of cardiac rehabilitation following ASCVD events and procedures, its application in daily practice is still incomplete. In the hospital arm of the EUROASPIRE V survey 8261 patients, aged < 80 years, from 27 countries were interviewed in 2016-17, at least 6 months but no more than 2 years after being hospitalized because of a coronary event [42]. The outcome measures of that survey were the proportions of coronary patients achieving the lifestyle, risk factor and therapeutic targets for the secondary prevention of ASCVD. A cardiac rehabilitation program had been offered to 46% of all patients; 69% of those advised attended at least half of all sessions.

In the PATIENT CARE registry modifiable CV risk factors especially LDL-C were substantially improved in 1408 patients who attended a cardiac rehabilitation program after a MI in Germany [89].

b) Lifestyle adaptations

In addition to the objectives of secondary prevention, the 2016 ESC guidelines on CVD prevention [10] stipulate:

in the presence of an exercise capacity >5 METS without symptoms, return to routine physical activity is recommended; otherwise the patient should resume physical activity at 50% of maximal exercise capacity and gradually increase. Physical activity should include activities like walking, climbing stairs, cycling and supervised medically prescribed aerobic exercise training.
in low-risk patients at least 2 hours/week aerobic exercise at 55-70% of the maximum workload (METs) or heart rate at the onset of symptoms are recommended. In moderate to high- risk patients, an individualized program is recommended that starts with <50% maximum workload (METs), resistance exercise at least 1 hour/week with 10-15 repetitions per set to moderate fatigue.
a healthy diet is recommended as a cornerstone of ASCVD prevention in all individuals.
it is recommended to consistently encourage weight control through an appropriate balance of physical activity, caloric intake, and formal behavioral programs when indicated to achieve and maintain a healthy BMI.

Unfortunately, the implementation of lifestyle changes in patients with ASCVD is generally limited.

In the Prospective Urban and Rural Epidemiology Study (PURE) among more than 150 000 adults from all over the world 7517 were selected with self-reported CHD or stroke [90]. Smoking status was assessed as well as the level of exercise and the quality of the diet using standardized methods; 19% continued to smoke; only 35% were engaging in high level of physical activity and 39 % of them had a healthy diet; 14% of them did not undertake any of the 3 healthy lifestyle behaviors; only 4% had all 3. In that worldwide study the prevalences of healthy lifestyle behaviors were poor and even lower in less affluent countries.

In the EUROASPIRE V survey [42] the prevalence rate of smoking at the time of the interview was 19 % ranging from 10 to 29% between countries. In patients less than 50 yrs old the prevalence rate of smoking was still 20% in women and 36% in men.

The prevalence of smoking among those patients who were smokers in the month before the index event was 55% which means that 45% of the smokers had stopped their habit since the event. Although 85% of the persistent smokers had been offered professional advice to quit, only 23% tried to stop smoking after their index event and only a small proportion (5%) attended a smoking cessation clinic. Pharmacological support in the form of nicotine replacement therapy, bupropion and varenicline were prescribed to a small minority: 7%, 1% and 2% of these patients respectively. Two-thirds of the patients in EUROASPIRE V (66%) were not achieving their physical activity target of regular activities of at least 30 minutes duration on average five times a week.

These results from EUROASPIRE V strongly suggest that clinicians should pay more attention to lifestyle adaptations in coronary patients and a more professional support should be given.

The results of EUROASPIRE V are in line with observations in other surveys of secondary prevention practice in different parts of the world [91, 92, 93]. Major geographical variation exists.

In the STABILITY study with 15828 patients with CHD from 39 countries on five continents, recruited in 2010, 36% of the participants were obese and 54% had an increased waist circumference (≥102 cm in men and ≥88 cm in women) [94]. In the CLARIFY registry among 32 954 patients with CHD from seven geographical areas obesity ranged from 20 to 42% [95].

c) Management of dyslipidaemias

In the 2016 ESC guidelines on CVD prevention in clinical practice [10] the target for LDL-C in patients with established ASCVD was set at < 70 mg/dL (< 1.8 mmol/L). In the EUROASPIRE V survey conducted in 2016-17 71% of patients had a LDL-C ≥70 mg/dL (1.8 mmol/L) [42]. This high proportion was observed despite the fact that 84 % reported using lipid lowering drugs. Most of these drugs were statins. Among those on statins only 32% had a LDL-C < 70 mg/dL (1.8 mmol/L). One could speculate that these poor results are due to a lack of compliance of the patients. In EUROASPIRE V the patients were asked regarding their compliance with the prescribed drugs: a large majority (76 %) reported full compliance in taking their drugs.

More worrying are observations regarding drug and dosage titration to control elevated LDL-C. High-intensity LDL-C lowering drug therapies (LLT) were defined as daily dosages that are on average associated with an LDL-C reduction of at least 50%. A significant shift in statin therapy prescription was observed between hospital discharge and interview as shown in Table 2 [96].The changes that occurred went in the wrong direction: up-titration was found in only 12.4% of all patients and down titration in 20.8% while 5% was not on LLT on both occasions.

There was a clear association between the lipid-lowering drug regimens and goal achievement: 37 % of those on a high-intensity LLT were at goal compared to only 26 and 14 % of those on respectively a low/moderate - intensity LLT or no LLT.

In other surveys it was also shown that despite the clear evidence of the benefits of LLT with statins in secondary prevention, many coronary patients with dyslipidaemia are still inadequately treated and a significant number of patients on LLT is still not reaching the LDL-C treatment goal. In the Veterans Affairs health care system a graded association was found between the intensity of statin therapy and mortality in patients with ASCVD, suggesting that there is a substantial opportunity for improvement in the secondary prevention of ASCVD through optimization of the intensity of statin therapy [49]. The reasons why physicians often prescribe low-intensity statin treatment instead of high-intensity therapy when needed are different and complex but quite often it is the fear of adverse effects of statins. Patients are also frequently confused with the information from the media suggesting that statins have many serious adverse effects, so they stop taking the statins after some time or do not adhere to the prescribed dose.

In Table 3 recommendations are summarized for LLT from the 2019 EAS/ESC guidelines on the management of dyslipidaemias for very-high-risk patients with an acute coronary syndrome (ACS) and for patients undergoing PCI [11].

d) Control of arterial hypertension

In the EUROASPIRE V survey 95% of the coronary patients were on antihypertensive drugs; despite this the proportion with a blood pressure ≥140/90 mmHg (≥140/85 mmHg in the presence of diabetes) was 42% [42]. This is very similar to the 46% with comparable blood pressure elevation in the STABILITY study [94] despite the fact that 96% were on antihypertensives. If the target is set at <130/80 mmHg the results become even more dramatic with in EUROASPIRE V only 29% of the patients achieving that level [42].

e) Detection and control of diabetes

The detection of type II diabetes is not only a problem in the population at large and in patients with established ASCVD.

In EUROASPIRE V special attention went into the detection of diabetes [42]. In patients who were not known with diabetes a 2-hour oral glucose tolerance test was offered. The detection of diabetes was based on a self-reported history of diabetes and/or prescribed glucose lowering drugs; overall 29% of the patients were previously known with diabetes. Among the 4422 patients with a negative personal history of diabetes and in whom full information on the glycaemic state was available 16% were detected with type 2 diabetes, 25% with impaired glucose tolerance and 13% with impaired fasting glucose. These results show that the prevalence of self-reported diabetes underestimates the true prevalence of dysglycaemia in coronary patients. A systematic approach to screen for diabetes in coronary patients is required. Regarding the control of diabetes in those with previously known diabetes, the HbA1c was < 7.0% (53 mmol/mol) in 54%.

In the STABILITY study more than half of the patients with diabetes had a HbA1c > 7.0% [94].

f) Use of cardioprotective drugs

Besides the widespread use of antihypertensive and LDL-C lowering drug therapies in EUROASPIRE V, antiplatelet medication use was reported by 93% of patients, 81% were on beta-blockers and 75% on ACEI or ARB [42].

The results of EUROASPIRE V are in accordance with earlier multinational surveys of secondary prevention practices conducted in Europe, United States and other parts of the world. The results of the Reduction of Atherothrombosis for Continued Health (REACH) Registry [91], the World Health Organization study on Prevention of Recurrences of Myocardial Infarction and Stroke (WHO-PREMISE)[92], Stabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial[94] and the Prospective Urban Rural Epidemiology (PURE) Study [97] demonstrated high prevalences of under-treatment and poor control of cardiovascular risk factors in coronary patients in many regions of the world. These regional differences were more marked for obesity and LDL-C attainment. Findings from the PURE study among 7519 patients with self-reported ASCVD from 17 high-, middle- or low-income countries worldwide showed lower use of cardioprotective medications compared with EUROASPIRE V, with only 25% being on antiplatelet drugs, 17% on beta-blockers, 20% on ACEIs or ARBs and 15% on statins.

Strategies of secondary prevention of ASCVD can only be effective to the extent that they are accepted, put into practice and maintained over a lifetime. The latter is a problem in many patients. Usually, a reduction in compliance is seen over time. In a systematic review and meta-analysis general adherence was estimated to be 66% in patients in secondary prevention after a median period of 24 months [98]. Interrupting treatments for CVD prevention translates in an increase of morbidity and mortality [99]. From a recent review of medication nonadherence among patients with ASCVD it was concluded that socio-economic, health care systems and therapy-related factors had the most influence on adherence rates [100]. Among the latter polypharmacy is a key issue; the 2016 ESC guidelines on CVD prevention state that reducing dosage demands is the most effective single approach to increase treatment adherence and that the use of the polypill to increase adherence to drug therapy may be considered [10].

Conclusions

To summarize some of the observations presented above, results from the hospital arm of EUROASPIRE V [42] are given in Table 4 and compared to what is recommended in ESC guidelines on prevention of CVD [10], management of dyslipidaemias[11] and of hypertension [14]. In the most optimal situation all the figures in the column should be 100% or close to. Most of the results are rather disappointing in this respect.

From all this the conclusion is therefore that much more is possible and needed; the risk of recurrence after PCI remains high, and the potential for a better secondary prevention is great both at the level of a better adherence to lifestyle changes by the patients and a more rigorous control of major risk factors such as hypertension, dyslipidaemias and diabetes. All this is well addressed in guidelines but guidelines must be implemented and this is a challenge for the community as a whole but in particular for all cardiologists regardless of their subspeciality.

Personal perspective - Guy De Backer

The main objective of secondary prevention in patients with ASCVD is to reduce recurrent events and to prevent premature mortality and disability-adjusted life years. Despite significant advances in revascularisation and myocardial protection the burden caused by recurrent CV events remains high in contemporary cohorts of patients with ASCVD. Most of these events are the result of the progression of the underlying CHD.

Cardiac rehabilitation programs and strategies of secondary prevention have been tested in RCT’s demonstrating their efficacy, safety and cost-effectiveness in preventing recurrent CV morbidity and mortality. Secondary prevention programs include lifestyle adaptations (smoking cessation, increased physical activity, a healthy balanced diet), good control of risk factors such as elevated blood pressure, dyslipidaemia and dysglycaemia and the optimal use of cardioprotective drugs.

Unfortunately, results from numerous registry studies in different parts of the world show suboptimal implementation of guidelines regarding secondary prevention in daily practice. Barriers exist at the level of the patients, of the health care providers and of the health care systems. On the patient’s side one should realize that changing habits that have been settled for many years is not easy and the immediate rewards to the patient are less well perceived; some of these changes may be expensive for some patients. On the physician’s side the interest goes more into acute care; working as a team in rehabilitation programs is not considered as a priority and in financial terms secondary prevention programs may be less rewarding. On the health care system’s side rehabilitation centers are insufficiently decentralized; greater and affordable access to cardiac rehabilitation is a prerequisite. Cardiac rehabilitation and secondary prevention programs should be incorporated into universal health coverage.

A comprehensive approach to secondary prevention is required integrating cardiac rehabilitation and secondary prevention into modern preventive cardiology programs involving a multidisciplinary workforce of health care providers with a focus on the lifestyle of the patients and their families, on good control of CV risk factors and on an optimal compliance with long term cardioprotective drug therapies. This can result in a further substantial reduction of premature cardiac deaths and disability-adjusted life years.