As far as I know, the designation ‘optimal medical treatment’ was first used by the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial1 investigators as a synonym for the state-of-the-art measures encompassing drug regime, diet and physical activity recommended by the US guidelines for stable angina and acute coronary syndrome (ACS). Looking at the most recent European Society of Cardiology (ESC) guidelines on stable angina2 and ACS with3 or without4 ST elevation, a strict recommendation for antiplatelet medication (acetylsalicylic acid [ASA] alone or in combination with clopidogrel), an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), a beta-blocker and a statin (alone or in combination with ezetimibe) can be found for both subsets (see Table 1).
In the stable angina guideline, optional recommendations for nitrate, amlodipine, nicorandil, molsidomine, ivabradine, trimetazidine and ranolazine, alone or in combination, for angina and a fibrate or nicotinic acid for high-density lipoprotein (HDL) and/or triglyceride control can be found.
The 2008 ESC heart failure guidelines5 recommend a combined approach of a device (cardiac resynchronisation therapy [CRT] and/or implantable cardioverter–defibrillator [ICD], according to clinical criteria, left ventricular ejection fraction [LVEF] and QRS length), if appropriate, and drug therapy, combining ACE inhibitors, ARBs, aldosterone antagonists and beta-blockers for improved prognosis and symptoms, together with diuretics, digoxin or warfarin for control of symptoms or atrial fibrillation.
In addition to the drug regime recommended in the guidelines, many patients follow prescriptions for additional drugs for diabetes, gout, Parkinson’s or Alzheimer’s disease, osteoporosis and osteoarthritis, and may also take other drugs for associated conditions such as tinnitus, vertigo or glaucoma. Owing to the main disease and associated conditions, many patients are supposed to follow an extensive drug regime that frequently entails taking 20 or more tablets per day.
In the real world there is a gap between the interventions recommended in clinical guidelines and clinical practice,6 since many physicians do not always prescribe the recommended drug therapy or lifestyle changes and patients frequently omit them, particularly if they are expensive or if the patient does not feel they are needed for symptom relief or improvement.
Although most clinicians are aware of this situation, the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) III survey for patients with coronary artery disease (CAD)7 is probably the most recent publication showing the current situation regarding adherence to guidelines in Europe.
In this recently published manuscript,8 comparable data from 40 centres in eight European countries included in the most recent survey (2006–2007) were evaluated versus the data from previous EUROASPIRE surveys (held in 1995–1996 and 1999–2000). As shown in Table 2, 93.2% of the patients were on an antiplatelet drug, 85.5% on a beta-blocker, 96.8% on a blood-pressure-lowering drug (ACE inhibitor, ARB, calcium channel blocker [CCB], diuretic or beta-blocker) and 88.8% on a lipid-lowering drug (in most cases a statin). Roughly speaking, the percentage of patients on each medication increased significantly from the first to the second survey and from the second to the third. The most recent data indicate that the majority of patients were following a drug regime similar to what is recommended by the ESC guidelines (see Table 3).
Although these patients were apparently following a correct drug regime and the global picture was better in the third edition than in the two earlier surveys, the clinical outcomes in terms of risk factor control were far from what was expected: only 53.8% of patients had a cholesterol level below 4.5mmol/l, 39.1% had appropriate blood pressure levels and 81.2% self-reported as non-smokers. The clinical situation was worst in the last survey in terms of reported diabetes (28.0%) and prevalence of overweight (82.7%) and obesity (38%), suggesting that patients are not being compliant to lifestyle measures such as diet and physical activity.
The failure of these high-cost and intensive drug regimes to control the classic risk factors confirms that medication alone is not sufficient and that it is thus necessary to promote the adoption of a healthy lifestyle to reach therapeutic targets. In particular, physical inactivity and obesity must be addressed to counteract their malignant consequences on global and cardiovascular mortality, which increases in all age groups and in both genders when body mass index (BMI) passes 27.9
Tuhomileto and co-workers,10 among others, proved that it is possible to reduce the onset and progression of diabetes, and other authors have proved that this lifestyle intervention is the best possible approach, even compared with the use of drugs such as ACE inhibitors,11 ARBs,12–14 metformin15,16 or statins.17
In a special report Iestra and co-workers18 estimated the magnitude of the effect of the therapeutic tools recommended in the international guidelines. It became clear that the gains promoted by lifestyle and dietary changes are relevant, being similar or even higher than those attributable to each type of medication. Individually, every drug group recommended in the guidelines for secondary prevention after ACS, such as low-dose ASA, statins, beta-blockers and ACE inhibitors, will decrease mortality, with the reduction ranging from 18% for ASA to 26% for ACE inhibitors. The use of statins and beta-blockers would be responsible, respectively, for 21 and 23% of the mortality reduction. Lifestyle and dietary changes would reduce mortality by 20% for moderate alcohol intake to 35% for smoking cessation. Physical activity would decrease mortality by 25% and combined dietary changes by 45%.
Chow and co-workers,19 in a subsidiary study of Organisation to Assess Strategies in Acute Ischaemic Syndromes (OASIS 5), analysed data from a questionnaire sent to 18,809 patients following non-ST-elevation ACS who were receiving the most recent therapies. Most patients were following the guideline medication at six months after discharge (78.1% on beta-blockers, 89.8% on ACE inhibitors or ARBs and 94.7% on antiplatelet drugs), although a lot of room for improvement was found. In this questionnaire, 64.8% of the patients reported smoking cessation but only 29.9% adhered to both diet and exercise modification. At six months, even after adjustment for revascularisation (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]), a sgnificant risk reduction was found in the patients who adopted lifestyle changes, namely the combination of diet and exercise, which allowed a 48% reduction in the risk of myocardial infarction (MI), a 54% reduction in the risk of stroke, a 55% reduction in the risk of death and a 56% reduction in the risk of the combination of death/MI/stoke. Exercise alone led to a 39% reduction in the risk of death and a 31% reduction in the risk of the combination of death/MI/stroke. Quitting smoking compared with persistent smoking significantly reduced the risk of a new MI by 43%. Patients who did not quit smoking and who did not adhere to diet and exercise changes suffered a 3.8-fold increase in cardiovascular events (MI, stroke and death) compared with patients who complied to these measures.
These results clearly support the need for and interest in the implementation of behavioural advice and lifestyle changes in MI patients, with a level of priority and utilisation rate similar to other interventions, such as revascularisation procedures and drugs, that are generally recognised as mandatory to improve prognosis after MI.
It must be recognised that in everyday clinical practice, healthy behaviour changes are not actively promoted or professionally supported. There is a huge need and potential for increasing smoking cessation rates, diet change and regular physical activity.
During the hospital stay or immediately after discharge post-ACS, when most patients are especially open to the idea of adopting lifestyle changes, intense promotion of and referral for cardiac rehabilitation must be performed by the health team to lower cardiovascular morbidity in the long term.
Modern cardiac rehabilitation programmes evolved from strict exercise training programmes to a comprehensive secondary prevention approach in which patients have contact with a multidisciplinary team (cardiologist, physiotherapist, dietitian, psychologist and social worker, among others) at least three times per week. In this global approach, ‘old’ aerobic training is combined with new resistance training modalities, vocational counselling, patient and partner education, healthy lifestyle adoption, risk factor control, psychological intervention to promote changes and long-term maintenance, together with adherence to optimal medical treatment.20–22 This individualised and global approach is far better than the usual care provided in hospitals or private practice outpatient clinics, where patients are seen less frequently, meeting a very busy cardiologist in short consultations focused exclusively on disease symptoms and a drug therapy.
In five meta-analyses published between 1998 and 2005,23–27 cardiac rehabilitation proved to decrease all-cause and cardiovascular mortality from 28 to 13% and from 31 to 26%, respectively, with higher rates of reduction in programmes where exercise was the cornerstone compared with a comprehensive approach or risk factor control programmes (see Table 4). This is understandable considering the anti-atherosclerotic, anti-ischaemic, antithrombotic and antiarrhythmic proprieties of regular aerobic training.28,29
In the past there was some concern about the risk of ventricular remodelling, which vanished in 2003 after the publication of the Exercise in Left Ventricular Dysfunction and Chronic Heart Failure (ELVD-CHD) study,30 whose findings were confirmed by Haykowsky’s meta-analysis,31 in which aerobic training reduced ventricular remodelling and resistance training had a neutral effect.
Another matter of concern was the risk of re-infarction and sudden death secondary to the exercise programme. In the French registry,32 published in 2006, there were no fatal events during exercise sessions or exercise stress tests in more than 25,000 patients from 65 centres. These figures are similar to those found in previous studies.33
The Global Secondary Prevention Strategies to Limit Event Recurrence after Myocardial Infarction (GOSPEL) study,34 with a population of 3,241 patients randomised to cardiac rehabilitation or usual care, is the most recent study aiming to compare these two modalities. Giannuzzi et al. demonstrated that cardiac rehabilitation (a multifactorial intervention) over three years reduced the risk of several cardiovascular outcomes, particularly non-fatal MI. Although the primary composite end-point (cardiovascular mortality, non-fatal MI, non-fatal stroke, hospitalisation for angina or heart failure and urgent revascularisation) was not reached, two secondary composite end-points were: the first was a combination of cardiovascular mortality, non-fatal MI and non-fatal stroke and the second was a combination of cardiac death and non-fatal MI. Non-fatal MI was the major isolated positive finding of the study, with a hazard ratio of 0.52 (95% confidence interval [CI] 0.31–0.86 ; p=0.01).
Regarding secondary prevention factors, a greater proportion of the cardiac rehabilitation group had a healthy diet and were undertaking physical activity and using stress management techniques during the three years of follow-up. In terms of risk factor control, the intervention group showed a better blood lipid profile (higher levels of HDL and lower levels of total cholesterol, low-density lipoprotein [LDL] cholesterol and triglycerides), higher rates of smoking discontinuation, lower systolic blood pressure and lower BMI. Concerning drug therapy, the intervention group showed greater adherence to guideline medication, with higher rates of regular ACE inhibitor, beta-blocker and statin intake and no difference regarding aspirin. Cardiovascular rehabilition also brings advantages in the field of psychology, and has demonstrated major improvements in depression, anxiety, hostility, somatisation and quality of life. These improvements may be more evident in younger patients, who usually have more adverse psychological and classic risk profiles.35,36
Although difficult to achieve in clinical practice, smoking cessation is a priority after ACS as it has the most relevant isolated survival benefit compared with each group of drugs and each secondary prevention measure.18 The Prospective Registry Evaluating Myocardial Infarction: Events and Recovery (PREMIER),37 with a population of 2,498 patients from 19 US centres, verified that only 46% of patients who were previous smokers had quit smoking six months after ACS and found that individual smoking cessation counselling was not effective enough to reach the goal. By multivariate analysis, referral to cardiac rehabilitation and a smoking cessation programme in hospital were identified as the only factors related to smoking cessation.
Cardiac rehabilitation, a comprehensive approach to the management of post-ACS patients, may be considered the best known secondary prevention programme since it has repeatedly demonstrated important reductions in all-cause and cardiovascular mortality in modern populations submitted to the most recent revascularisation techniques and drug regimes. These benefits can be explained by the positive effects of regular aerobic training and behaviour changes that are voluntarily adopted in the acute phase and maintained in the long term.
Educating patients and partners about cardiovascular topics makes them understand that CAD is controllable by implementing long-term lifestyle changes and lifetime drug therapy. To achieve healthy lifestyle changes and aderence to the drug regime, it is vital that the treating cardiologist (the best option) and other team members address the patient and family members in the very first moments after an ACS or revascularisation, advising them to join a cardiac rehabilitation programme to obtain a better quality of life and longer survival.
This lifetime intervention is not easily sustainable because, due to modern therapies, many patients are sedentary and fully revascularised and do not experience any limitation after the ACS. Only through an information and education programme will it be possible to make them understand the need to keep taking the medication and maintain a healthy lifestyle in the long term.
The individual and group approach promoted in cardiac rehabilitation programmes has already proved to be the best intervention to change the mind of reluctant patients and make them understand that it is important to respect the evidence-based drug regimes. This finding, by itself, is a collateral and additional gain inherent to cardiac rehabilitation.