In the United States, of the approximately 800,000 patients who develop stroke each year, approximately 1 in 4 are recurrent. The ASA 2011 edition of the secondary prevention guidelines for ischemic stroke and TIA (ASA 2011 secondary prevention guidelines) pays great attention to lipids as a risk factor to be controlled in all patients with ischemic stroke and TIA. Regarding the lipid section, I think there are 6 major highlights of the new guidelines, which are summarized as follows.
1. More emphasis on the relationship between LDL-C and ischemic stroke/TIA
In terms of research evidence analysis, the new guidelines place more emphasis on the relationship between LDL-C and ischemic stroke/TIA than the previous guidelines.
Previous epidemiological studies, especially those from East Asia, have mostly used stroke on death certificate as an event indicator, lacking the distinction between hemorrhagic and ischemic, and even less considering the type of stroke, thus making it difficult to highlight the association between LDL-C and ischemic stroke. In contrast, the Korean study in 2006 affirmed the relationship, and the MRFIT study, which was conducted in predominantly white Americans, showed the correlation even more clearly. With consideration of possible flaws in epidemiologic studies, giving full weight to the evidence from statin clinical studies can strongly support a causal relationship between high LDL-C and ischemic stroke. The results of the applied meta-analysis are certainly very convincing.
The assessment of stroke risk factors has long placed more emphasis on the magnitude of the correlation found in epidemiological studies, but this correlation does not fully and reliably reflect the magnitude of the causal relationship and must be combined with the results of studies of therapeutic interventions. For example, in the association between hypertension and stroke, epidemiological findings are highly consistent with findings from therapeutic interventions. In contrast, in the relationship between hyperhomocysteinemia and cardiovascular disease, although epidemiological findings consistently suggest that hyperhomocysteinemia is an important risk factor, several clinical trials have found no significant reduction in the risk of cardiovascular disease after correction of hyperhomocysteinemia with vitamin and folic acid supplementation. Similarly, although smoking is considered a less important risk factor for cardiovascular disease by epidemiological studies, studies have found that smoking cessation alone significantly reduces the risk of cardiovascular disease.
Therefore, the relationship between LDL-C and stroke should not only be based on epidemiological findings, but also on the effectiveness of clinical treatment, which is reflected in the fact that the new guidelines cite and rely on different evidence from previous guidelines. Furthermore, the modest correlation shown by epidemiology and the significant preventive effect of treatment suggest that statin has a neuroprotective effect beyond cholesterol lowering, and the understanding of the preventive effect of statin should not be limited to LDL-C lowering.
2. Affirm the effect of statin in preventing ischemic stroke and the findings of SPARCL study
The new guideline places statin as the first recommendation for the treatment of patients with ischemic stroke/TIA without coronary heart disease (CHD), which is different from the previous guideline that listed the use of statin as the first recommendation for people with hypercholesterolemia or CHD, reflecting the high importance the guideline makers attach to the prevention of ischemic stroke and the high recognition of the findings of the SPARCL study.
This suggests that we should pay more attention to the use of statins in secondary stroke prevention and stop focusing on the evidence and guidelines for CHD as we have done in the past. Furthermore, we must vigorously pursue clinical studies and trials on stroke to obtain as much evidence as possible to guide clinical practice, which is particularly important in China, a major stroke country in the world.
3. First mention of statin in stroke/TIA patients with LDL-C >100 mg/dl without CHD
The new guideline recommends the use of statins in stroke/TIA patients without CHD for the first time for those with LDL-C >100 mg/dl, based on the patient enrollment criteria of the SPARCL trial and the recommendations of the National Cholesterol Education Program (NCEP) III. This provides good operational guidance for clinical practice, and statins with intensive lipid-lowering effects should be used in all patients with non-cardiogenic ischemic stroke/TIA with evidence of atherosclerosis and LDL-C >100 mg/dl. Also, a subgroup analysis of the SPARCL trial suggested that the preventive effect of statins was not influenced by ischemic stroke subtype. Of course, no recommendation can be made for LDL-C <100 mg/dl and those without evidence of atherosclerosis because of lack of evidence.
4. Subgroup analysis of important clinical trials can reveal new phenomena and evidence
Analysis of the HPS trial found that CHD was well prevented with a common dose of statin (assuming all statins had a stroke recurrence prevention effect) but not reliably achieved secondary stroke prevention, although the sample size was not small (3250 cases). The results of the control SPARCL suggest that statin therapy with intensive lipid-lowering effects is the only one with reliable secondary prevention effects.
A subgroup analysis of the SPARCL trial also found that those who reduced LDL-C by more than 50% or reached less than 70 mg/dl had a better prevention effect, which was twice the effect of the overall statin-using population. This result is consistent with the results of several other previous trials on intensive lipid lowering versus regular lipid lowering controls and with the recognition that patient stratification provides a viable therapeutic target for clinical practice.
Therefore, the new guidelines re-emphasize the use of statins with intensive lipid-lowering effects, while identifying 70 mg/dl as the target target. Both the 2008 expert consensus and the 2010 version of the secondary prevention guidelines in China recommend the use of (regular) statins for stroke patients with elevated cholesterol levels, resulting in LDLC <100mg/dl (or a 30%-40% reduction); and (intensive) statins for very high-risk patients, resulting in LDL-C <80mg/dl (or a reduction of more than 40%). Comparing the guidelines of China and the United States, it can be seen that the recommendations of the new US guidelines are more aggressive, more evidence-based, and easier to follow.
5. Patients with atherosclerotic ischemic stroke/TIA without known CHD should be intensified with statin
The new guidelines recommend the use of intensive lipid-lowering statins in patients with atherosclerotic ischemic stroke/TIA without known CHD to achieve LDL-C <70 mg/dl or a reduction of 50% or more, based on a subgroup analysis of the SPARCL trial and a meta-analysis of statin trials.
It is noteworthy that the recommendation was made in people with atherosclerosis rather than those with evidence of atherosclerosis, suggesting to us that the guideline makers were more inclined to consider these patients to be in the traditionally defined very high-risk group, which is consistent with the current notion that ischemic stroke, diabetes mellitus, and carotid artery disease are all at risk for CHD, among other conditions.
A subgroup analysis of the SPARCL trial population also found comparable rates of CHD at follow-up in patients on placebo regardless of stroke type, suggesting that patients with ischemic stroke/TIA without known CHD are likely to have asymptomatic CHD and that atherosclerotic disease should be considered a systemic disease, thus making statin use more relevant than just stroke prevention. The significance of statin use goes beyond stroke prevention.
6. Increased risk of cerebral hemorrhage with statin therapy
Another important finding of the subgroup analysis was that statin use increased the risk of cerebral hemorrhage in both the HPS and SPARCL trials, with history of cerebral hemorrhage, male, advanced age and hypertension being important risk factors, and history of cerebral hemorrhage and hypertension being the most serious risk factors, while reduced LDL-C levels were not. guidance.
The recommendation for patients with combined hypercholesterolemia or CHD and for patients with low HDL-C, the new guidelines are the same as previous guidelines, reaffirming the status of NCEP.