Professor Peter Rothwell: Low-dose aspirin for secondary stroke prevention | OCC 2021

Introduction Ischemic stroke and transient ischemic attack (TIA) are the most common types of cerebrovascular diseases in my country.
Effective secondary prevention is important to reduce the recurrence, disability and mortality of patients with ischemic stroke means.

The content related to secondary stroke prevention has always been a hot topic at major conferences at home and abroad.

As one of the most commonly used antiplatelet drugs, aspirin plays a key role in the secondary prevention of stroke.

On May 27-30, 2021, the "Fifteenth Oriental Cardiology Conference (OCC 2021)" was held in Shanghai, China in the form of a combination of online and offline, with a gathering of famous experts and rich academic content, showing New ideas and new developments in the field of cardiovascular disease at home and abroad.

At the Aspirin Foundation International Symposium on May 28, Professor Peter Rothwell from the University of Oxford in the United Kingdom delivered a wonderful speech on the topic of "Low-dose Aspirin for Secondary Prevention of Stroke", summarizing the acute and long-term effects of aspirin Progress in the application of primary prevention.

Expert Professor Peter Rothwell, University of Oxford, UK.
Ischemic stroke: Early intervention, it is imperative that TIA or light stroke develops into a high risk of major stroke.

Studies have shown that the risk of stroke recurrence within 24 hours after the occurrence of TIA is as high as 5.
2%, while the 7-day risk rises to 9.
9% [1].

Therefore, rapid and effective treatment should be taken in the acute phase of stroke to reduce the risk of stroke recurrence.

Without timely intervention, the occurrence of TIA and stroke will also increase the risk and probability of dementia [2,3].

This shows that early intervention is necessary for acute ischemic stroke.

As one of the most widely used antiplatelet therapy drugs in China, aspirin has a rapid onset of action and plays an important role in the acute phase of antiplatelet therapy.

Chinese and foreign guidelines consistently recommend that antiplatelet therapy with aspirin-containing regimens should be given as soon as possible in the acute phase of ischemic stroke [4,5].

The 2018 Chinese Acute Ischemic Stroke Guidelines recommend that those without thrombolysis and no contraindications take aspirin 150-300mg/d as soon as possible (I, A); those who cannot tolerate aspirin can be treated with clopidogrel (II, C); In patients with mild stroke, start bi-antibody therapy (aspirin and clopidogrel) as soon as possible within 24 hours, and maintain it for 21 days (I, A).

 Acute phase management: Low-dose aspirin is used for the prevention of major strokes after TIA or minor stroke.
It is highly effective.
Professor Lawrence Craven from the United States first proposed in 1956 that aspirin may be effective in preventing stroke.

In 1980, the FDA approved the use of aspirin to reduce the risk of stroke after TIA.

Subsequently, more and more evidence-based evidence confirmed the important role of aspirin in the acute phase of stroke.

EXPRESS studies have shown that after the onset of TIA or mild stroke, compared with patients who did not seek medical attention in time, seeking medical help in time can significantly reduce the risk of stroke recurrence in 90 days (P=0.
0001) [6,7].

Professor Peter Rothwell published a meta-analysis in LANCET in 2016[8], which included 15,778 patients in 12 randomized controlled trials to evaluate the efficacy of low-dose aspirin compared with placebo on the risk and severity of stroke recurrence.
.

Studies have shown that compared with the control group, acute aspirin alone can significantly reduce the risk of stroke recurrence after TIA and ischemic stroke (0-6 weeks, P<0.
0001; 6-12 weeks, P<0.
0001).

In the long-term follow-up after 12 weeks, there was no significant difference in the corresponding risk between the two groups.

 At the same time, the study conducted a meta-analysis of the preventive effects of aspirin combination regimen and aspirin monotherapy on ischemic stroke and disabling ischemic stroke within 12 weeks.

The analysis confirmed that compared with the control group, both aspirin combination regimen and aspirin monotherapy can significantly reduce the risk of ischemic stroke and disabling ischemic stroke within 12 weeks (both P<0.
0001) [8 ].

 In addition, the study evaluated the severity of recurrence of ischemic stroke through the modified Rankin Scale (mRS) score.
When mRS>2, it was defined as disabling or fatal ischemic stroke.

Analysis of the risk of ischemic stroke with mRS>2 found that at 6 weeks, compared with the control group, the aspirin combination treatment group had an mRS>2 stroke risk odds ratio (OR) of 0.
40, 95% confidence interval (CI) It was 0.
23–0.
72 (P=0.
0021); at 12 weeks, compared with the control group, the aspirin combination treatment group had a significantly lower risk of stroke with mRS>2 (OR: 0.
47, 95% CI: 0.
29-0.
75, P=0.
0014) .

For aspirin monotherapy, the risk of stroke with mRS>2 was also significantly lower than that of the control group (P=0.
0094 at 6 weeks; P=0.
0093 at 12 weeks).

It can be seen that both aspirin combination regimen and monotherapy can significantly reduce the severity of ischemic stroke recurrence at 6 and 12 weeks [8].

 From the stroke risk-time curve, it can be seen that aspirin combination therapy significantly reduces the risk of disabling ischemic stroke and myocardial infarction (MI).
The clinical benefit is most obvious at 0-2 weeks and lasts until 12 weeks.
[8].

 In addition, two large studies of IST and CAST showed that administration of aspirin in the acute phase of ischemic stroke can effectively reduce the incidence and mortality of ischemic stroke, which established the position of aspirin in the acute phase of ischemic stroke [9,10].

The data from these two landmark studies were pooled and analyzed, and the initial stroke severity was classified as mild, moderate or severe, and the risk of 14-day ischemic stroke between aspirin and the control group was assessed.

The results show that regardless of the severity of the initial stroke, aspirin can significantly reduce the risk of ischemic stroke at 14 days [8].

A pooled analysis of patients with mild and moderate initial strokes in the two studies showed that aspirin did not show significant clinical benefit within the first 24 hours.
Starting from day 2-3, the risk of recurrence of ischemic stroke decreased significantly (HR: 0.
44, 95% CI: 0.
25–0.
76, p=0.
0034), and at 4-6 days and 7-14 days, the risk continued to decrease significantly (4-6 days HR: 0.
45, 95% CI: 0.
31–0.
67, p <0.
0001; 7-14 days HR: 0.
64, 95%: 0.
45–0.
91, p=0.
0121).

After 14 days, the risk stabilized (p=0.
45) [8].

Long-term secondary prevention: Low-dose aspirin can effectively reduce the occurrence of major vascular events (MVE).
A study published in 2003 by Professor Peter Rothwell's team [11] included 290 TIA patients and followed up for more than 10 years , To assess the long-term risk of stroke and other vascular events.

Studies have shown that "low-risk" patients who have not relapsed for a long time after TIA have a high overall risk of major cardiovascular events (stroke, MI, vascular death, etc.
) within 10 years.

Within 10 years, the incidence of first stroke, MI, or vascular death was as high as 42.
8% (95% CI: 36.
4-48.
5).

It can be seen that even if patients survive for many years after TIA, they still need to be alert to the occurrence of MVE, and stroke requires long-term management.

Aspirin is a basic drug for long-term secondary prevention of stroke recommended by domestic and foreign guidelines [12,13].

For the long-term secondary prevention of patients with non-cardiac ischemic stroke/TIA, the AHA/ASA guidelines recommend aspirin monotherapy (I, A) as the first choice.
This shows the important role of aspirin in the long-term secondary prevention of stroke.

The UK-TIA trial is the longest follow-up secondary stroke prevention clinical trial conducted by Professor Peter Rothwell's team to evaluate whether aspirin used for long-term secondary prevention of stroke will reduce the incidence of long-term MVE in patients (the results of this study have not yet been officially published).

Research data shows that in the 7-year follow-up period, compared with the control group, aspirin can significantly reduce the incidence of long-term MVE in patients.

In addition, a pooled analysis of three studies including UK-TIA, ESPS-2, and SALT showed that aspirin during treatment can significantly reduce the risk of major vascular adverse events after TIA or mild stroke, and the clinical benefit is significantly better than the control group.

When the treatment was stopped, there was no significant difference between the two groups.

From the overall data, aspirin still has significant clinical benefits for major vascular adverse events after TIA or mild stroke.

This shows that aspirin plays an important role in the long-term secondary prevention of stroke.

Summary Professor Peter Rothwell concluded that aspirin plays an important role in acute stroke management and long-term secondary prevention of stroke.

For acute ischemic stroke, aspirin can reduce the 90-day ischemic stroke recurrence rate by 50%, and the 90-day disabling ischemic stroke recurrence rate can be reduced by 70%.

At the same time, aspirin DAPT double antibody treatment may have better clinical benefits.

For long-term secondary prevention of stroke, aspirin can reduce the incidence of major ischemic vascular events by 20%.

But at the same time, we should pay attention to the patient's long-term treatment compliance, and be alert to the occurrence of gastrointestinal bleeding, and use PPI when necessary.

 References: 1.
Neurology.
2009 Jun 2;72(22):1941-1947.
2.
Lancet Neurol.
2019;18: 248-258.
3.
Lancet Neurol.
2002;8:1006-1018.
4.
Chinese Journal of Neurology.
2019; 51 (9): 666-682.
5.
Stroke.
2019 Dec; 50(12): e344-e418.
6.
Lancet.
2007;370: 1432-1442.
7.
Lancet Neurol.
2009, 8: 235-243.
8.
Lancet.
2016 Jul 23 ;388(10042): 365-375.
9.
Lancet.
1997;349;1569-81.
10.
Lancet.
1997;349:1641-49.
11.
J Neurol Neurosurg Psychiatry.
2003;74:577-580.
12.
Stroke.
2014 Jul;45( 7):2160-236.
13.
Chinese Journal of Neurology.
2015;48(4):258-273.