Primary prevention of coronary heart disease refers to the prevention of the first cardiovascular event by controlling or reducing the existing cardiovascular risk factors before a clinical coronary event occurs or when coronary atherosclerosis is in a subclinical stage. 2004 Interheart study confirmed that coronary heart disease can be prevented and controlled by controlling 8 cardiovascular risk factors: high cholesterol, smoking, hypertension, diabetes, obesity, lack of exercise, lack of vegetables and fruits in the diet, and mental stress. Lack of exercise, lack of vegetables and fruits in the diet, and mental stress can reduce the risk of future acute myocardial infarction by 90%. The goal of primary prevention intervention remains to reduce the risk of coronary events, especially acute coronary syndromes. The above risk is closely related to platelet activation and inflammation, in addition to traditional cardiovascular risk factors, so that antiplatelet and anti-inflammatory therapy given to high-risk patients in the subclinical phase of coronary atherosclerosis is theoretically necessary.
Currently, aspirin is widely used clinically, and the drug is effective in the secondary prevention of cardiovascular disease, reducing the risk of serious cardiovascular events by 25% and reducing the risk of nonfatal myocardial infarction (infarction), nonfatal stroke, and all vascular events by 1/3, 1/4, and 1/6, respectively. aspirin treatment reduces acute infarction by 40 cases and acute stroke by 10 cases per month per 1,000 patients with acute cardiovascular disease. The efficacy of aspirin in secondary prevention is not controversial, as the cost is only 0.2 additional hemorrhagic strokes per 1,000 patients taking the drug for 1 year.
However, the need for low-dose aspirin for primary prevention in people without co-morbid cardiovascular disease has been controversial. On the one hand, the 2006 report of the National Committee on Prevention Priorities (NCPP) rated aspirin use (for men ≥40 years of age and women ≥50 years of age) as one of the top 3 primary disease prevention measures in terms of efficacy and cost-effectiveness (along with childhood immunizations and smoking cessation). The report also shows that tens of millions of Americans are taking aspirin, at a rate of 50 percent. On the other hand, a recent meta-analysis published in the Lancet in May 2009 by the International Antithrombotic Clinical Trials (ATT) Collaboration questioned the effectiveness of primary prevention with aspirin, raising widespread concern. The results of the Aspirin for Asymptomatic Atherosclerosis trial (AAA), presented at the 2009 ESC meeting, have reinforced the doubts about the need for primary prevention with aspirin.
The focus of primary prevention with aspirin is whether or not low-dose aspirin should be used for primary prevention in the middle-aged and elderly population without co-morbid cardiovascular disease (including healthy people and people with risk factors). Who can benefit from primary prevention with aspirin? Who will not benefit?
I. The benefits of primary prevention with aspirin outweigh the risks
AAA was a double-blind randomized clinical study (RCT) with 8.2 years of follow-up. 3350 UK patients with ABI ≤0.95 and no symptoms of atherosclerosis were randomized to the aspirin 100 mg/d group and the placebo group, with similar basic characteristics in both groups, mean ABI 0.86, SBP 147 mmHg, total cholesterol 6.2 mmol/l, and smoking rate 33%. RESULTS: There was no reduction in cardiovascular events in the primary and secondary endpoints (HR 1.02; 95% CI, 0.76 to 1.36) and an increase in bleeding events, but no statistical difference (HR 1.26; 95% CI, 0.62 to 2.65).ATT’s meta-analysis published in the Lancet in May 2009 included a total of six primary prevention studies: the BMD (British Male Physician Study), PHS (Physician Health Study), TPT (Thrombosis Prevention Study), HOT (Hypertension Optimal Treatment Study), PPP (Primary Prevention Study), and WHS (Women’s Health Study), with the following results: aspirin primary prevention reduced serious cardiovascular events by 12% (HR 0.88; 95% CI, 0.82 to 0.94), with nonfatal myocardial infarction by 1/5 and an increase in bleeding events (HR 1.54; 95% CI, 1.30 to 1.82).The AAA study was little changed from the ATT meta-analysis combined, with an 11% reduction in the primary endpoint event (HR 0.89; 95% CI, 0.83 to 0.95) and an essentially unchanged increase in bleeding events (HR 1.51; 95% CI 1.29 to 1.78). The results showed that the primary prevention aspirin group had 0.6 fewer serious cardiovascular events and 0.3 more bleeding events per 1000 cases treated than the placebo group. The secondary prevention medication group reduced serious cardiovascular events by 15 cases per 1000 cases compared to the placebo group, while increasing bleeding by 0.9 cases. It should be noted that the average 10-year risk of cardiovascular events in the overall population of the ATT study was only 5.1%, and the 10-year risk of cardiovascular events in the WHS population, which accounted for more than half of the cases in the six studies, was only 2.5%, and the efficacy in the higher risk population would certainly be higher than this level.
Second, the higher the risk of cardiovascular events, the greater the benefit for the population
A 2002 British Medical Journal meta-analysis showed that as patients’ risk of coronary heart disease increased, the benefit of aspirin increased while the risk remained the same, and the benefit of aspirin was twice the risk for those at 6% 10-year risk of cardiovascular events. Table 1 lists the eight primary cardiovascular prevention RCTs of aspirin to date and their primary outcomes, showing significantly better than average efficacy in people over 65 years of age, those with diabetes, and those with hypertension.
Table 1 Primary cardiovascular prevention trials of aspirin and their primary outcomes
Year of publication
Trial
Study subjects
Mean age (years)
Primary outcome (HR, 95% CI) or (P value)
2009
AAA
ABI 40 years, smoking, dyslipidemia, hypertension (130/80 mmHg), family history of cardiovascular disease, micro or significant proteinuria, and aspirin therapy should be considered in patients aged 30-40 years with diabetes mellitus especially those with other cardiovascular risk factors.
US ACCP 8 guidelines
For primary prevention in patients with moderate risk of cardiac events, 75-100 mg/d aspirin therapy is recommended over no antithrombotic therapy or vitamin K antagonist (VKA) therapy (recommendation level 1A).
US JNC7 guidelines
Consider aspirin in hypertensive patients with controlled blood pressure.
2008 US ASH Guidelines
Antiplatelet therapy with aspirin (dose 75-162 mg/d) is generally indicated in patients with hypertension and diabetes.
2009 U.S. ADA Guidelines
Aspirin (75-162 mg/d) should be used for primary prevention of cardiovascular disease risk in patients with type 1 or type 2 diabetes with any 1 of the following risk factors: age >40 years, family history of cardiovascular disease, hypertension, smoking, dyslipidemia, and proteinuria.
2009 Chinese Expert Consensus
1.Men aged 45-79 years with 10-year risk of coronary heart disease ≥ 4%-12% and no high-risk factors for gastrointestinal bleeding.
2.Females aged 55-79 years with 10-year risk of stroke ≥ 3%-11% and no high-risk factors for gastrointestinal bleeding.
3.Patients with diabetes >40 years old, or over 30 years old with 1 other cardiovascular risk factors, such as family history of early onset cardiovascular disease, hypertension, smoking, dyslipidemia or albuminuria.
4, suffering from hypertension, but blood pressure is basically controlled (40 years old with two or more risk factors, > 50 years old with one or more risk factors; women > 50 years old with two or more risk factors, > 60 years old with one risk factor, their 10-year cardiovascular disease risk is more than 6% to 10%, risk factors include: hypertension, diabetes, hyperlipidemia, obesity, smoking and family history of coronary heart disease (First-degree relatives male 50-year-old female middle-aged and elderly population commonly take low-dose aspirin for cardiovascular disease prevention because of the lack of evidence of benefit. We should perform primary prevention with aspirin in populations where the clinical benefit outweighs the risk, and those with a 10-year cardiovascular disease risk >6% to 10% according to national guidelines (including those with hypertension, diabetes and several other risk factors) should be considered for low-dose aspirin for cardiovascular disease prevention. When screening high-risk populations, our cardiovascular disease risk assessment methods may be more appropriate for the national population. Ongoing clinical studies will further elucidate the role of aspirin in primary prevention of cardiovascular disease in different populations.