Prevention of Recurrences of Myocardial Infarction and Stroke Study
The PREMISE programme: country projects
Effectiveness of interventions
Potential for intervention
There are 32.4 million myocardial infarctions and strokes worldwide every year. Patients with previous myocardial infarction (MI) and stroke are the highest risk group for further coronary and cerebral events. Survivors of MI are at increased risk of recurrent infarctions and have an annual death rate of 5% - six times that in people of the same age who do not have coronary heart disease. Similarly, patients who have suffered a stroke remain at an increased risk of a further stroke (about 7% per annum). There is considerable scientific evidence that specific interventions will reduce the risk of further vascular events in patients with MI and stroke. If these interventions are appropriately implemented, nearly one third of the fatal and non-fatal MI and strokes could be prevented.
The WHO MONICA Study, monitored trends in coronary heart disease across 38 populations in 21 countries over 10 years. Data from this study indicate that secondary prevention and changes in coronary care are strongly linked with declining coronary end-points.
Despite substantial benefits and generally low treatment costs, appropriate measures for secondary prevention after MI are implemented in less than half of eligible patients, even in high-income countries. Due to inequitable and inaccessible health care systems, inefficient use of limited resources and investing scarce resources in interventions that are not cost-effective, the secondary prevention coverage is far worse in low- and middle-income countries.
Furthermore, conditions such as MI or stroke with recurrent morbid events that are costly to treat provide the greatest potential for cost savings. The results of cost-effectiveness analyses of secondary prevention measures for CVD indicate that the above secondary prevention measures are highly cost-effective compared with many other routine medical interventions.
Scientific evidence of effectiveness of interventions
Evidence based interventions for secondary prevention include the use of aspirin, beta-blockers, angiotensin converting enzyme inhibitors; lipid lowering drugs and other anti- hypertensives, as well as modifying lifestyle related risk behaviours.
The benefit of aspirin in the secondary prevention of MI is well established. In 791 patients who had MI reviewed by the Antiplatelet Trialists, low to medium doses of aspirin (75-325 mg/day) led to a 12 % reduction in deaths, a 31% reduction in reinfarction and a 42% reduction in non-fatal stroke. One systematic review comparing antiplatelet treatment versus placebo suggests that at 6 months, 20 people would need to be treated with aspirin rather than a placebo to prevent one additional vascular event. With regard to cerebral vascular disease, randomised controlled trials (RCTs) have found that routine use of prolonged anti platelet treatment (aspirin 75 mg) is beneficial unless there is a clear contraindication for the prevention of vascular events in people with a prior (presumed ischaemic) stroke. Bleeding is the most important adverse effect of aspirin. However, among people at high risk of cardiac events, the large absolute reductions in serious vascular events far outweighed any absolute risk.
Firm evidence from systematic reviews of RCTs also confirm that beta blockers reduce the incidence of recurrent MI, sudden death and all cause mortality after MI. Most evidence is available for propranolol, timolol and metoprolol. In long- term trials in postmyocardial infarction patients the number needed to treat for 2 years to avoid a death is 42, which compares favourably with other treatments after MI. Serious adverse effects are uncommon with beta blockers.
Angiotensin converting enzyme inhibitors (ACEI)
Many RCTs have evaluated ACEI in-patients who have had an MI with or without left ventricular dysfunction. Systematic reviews have found that ACEI reduce rates of death, hospitalisation for congestive heart failure, and recurrent non-fatal MI in people who have had an MI with left ventricular dysfunction. Additionally, ACEI are also effective in reducing ischaemic events after MI, risk of recurrent MI, unstable angina and death from recurrent MI. There may therefore be some rationale for their use in all patients after MI because of their effect in reducing ischaemic events.
Systematic reviews and large RCTs have also found that lowering cholesterol in people at high risk of ischaemic coronary events substantially reduces the risk of CVD mortality and morbidity. One systematic review of primary and secondary prevention trials has reported that statins constitute the single most effective type of treatment for reducing fatal and non fatal myocardial infarctions and cardiovascular deaths. There is insufficient evidence about the effects of routinely reducing cholesterol in patients with a prior stroke. However evidence from large RCTs suggests benefit from reducing cholesterol with a statin in people with prior stroke who also have a definite history of coronary heart disease. In people with diabetes, available evidence indicates that glycemic control influences the rates of long-term vascular complications.
Observational studies and extrapolation of primary prevention trials of blood pressure reduction support the lowering of blood pressure in those at risk of ischaemic event. Without specific studies comparing different anti-hypertensive treatment, available evidence is strongest for $ -blockers, although not specifically in people with high blood pressure. In addition, The Perindopril Protection Against Recurrent Stroke Study has recently provided evidence of benefit of blood pressure lowering on the risk of stroke recurrence among patients with a history of cerebrovascular disease in the previous 5 years. A total of 6105 patients were randomised to perindopril alone, peridopril plus indapamide or placebo. The risk reduction in the perindopril group and combination group compared to placebo were 28% and 43% respectively.
Apart from these pharmacological measures for secondary prevention, evidence is available that lifestyle measures such as stopping smoking, encouraging a healthy diet and exercise can also significantly contribute to reduction in cardiovascular mortality in people with established CVD. Evidence from epidemiological studies indicates that people with coronary heart disease who stop smoking rapidly reduce their risk of recurrent coronary events or death. In the case of stroke survivors, observational studies have shown that the excess risk of stroke among former smokers largely disappeared 2-4 years after smoking cessation.
Although the role of exercise alone in reducing cardiovascular outcomes is not clear, systematic reviews of RCTs have found that cardiac rehabilitation which includes physical exercise improves coronary risk factors and reduces the risk of major cardiac events in people after MI.
With regard to diet, RCTs have found that advising people with MI to eat more fish, fruit and vegetables, bread, pasta, potatoes, olive oil and margarine may result in a substantial survival advantage.
Most data on efficacy and cost-effectiveness of the above pharmacological and non-pharmacological interventions come from studies done in developed countries. Their effectiveness and cost-benefits in low- and middle-income country settings remain to be evaluated.