Antiplatelet therapy as a modulator of stroke aetiology: a meta‐analysis

Rajkumar, Christopher; Floyd, Christopher N.; Ferro, Albert

doi:10.1111/bcp.12630

Cited by 14 publications

(13 citation statements)

References 61 publications

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“…Oral anticoagulants have a dramatic stroke preventive effect in patients with atrial fibrillation, who have a propensity towards cardioembolic stroke (52). In contrast, large artery atherosclerotic strokes may be better prevented by use of antiplatelet therapy (53).…”

Section: Clinical Implications and Considerationsmentioning

confidence: 99%

Left atrial size and risk of stroke in patients in sinus rhythm

Overvad¹,

Nielsen²,

Larsen³

et al. 2016

Thromb Haemost

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Little is known about the risk of stroke associated with left atrial enlargement in patients in sinus rhythm, and whether such patients may have an unmet need for thromboprophylaxis. In this systematic review we summarise the existing evidence concerning left atrial size and risk of stroke in patients in sinus rhythm. Nine cohort studies were identified, analysing a total of 67,875 participants and 3,093 stroke outcomes. Rates of stroke per 100 person-years in patients with left atrial enlargement and in sinus rhythm ranged from 0.59 in a population-based cohort to 2.06 in patients referred for echocardiography. All studies reported a higher risk of stroke with larger/enlarged left atrium compared to smaller/normal sized left atrium. Two studies found indications of modification by sex, with only positive associations observed in women. Left atrial enlargement may represent an important predictor of stroke across a variety of patient populations in sinus rhythm. The underlying aetiology explaining this observed higher risk is likely to be multifactorial and not confined to a potential direct effect of left atrial enlargement on thromboembolic risk. Formal stroke risk stratification among patients with left atrial enlargement may further help identify patients who stand to gain from preventive antithrombotic therapy.

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Section: Clinical Implications and Considerationsmentioning

confidence: 99%

Left atrial size and risk of stroke in patients in sinus rhythm

Overvad¹,

Nielsen²,

Larsen³

et al. 2016

Thromb Haemost

View full text Add to dashboard Cite

show abstract

“…In secondary prevention, mean reductions in stroke (which varies with subtype 17 ) and coronary events by about 1/5 and total mortality by 1/10 were observed over 5 years. 18 Total mortality in individual studies was only significantly lower in 1 study, 19 where it was 21% lower in patients treated for 1 month after acute myocardial infarction with 160 mg daily, compared to placebo; a benefit which was sustained out to 10 years. 20 The NNTB for 5 weeks to prevent 1 vascular event was 53 and 1 death was 39.…”

Section: Aspirinmentioning

confidence: 95%

“…ADRs on aspirin therapy (Table 2) are the same whether used in patients at high or low cardiovascular risk and in lower risk settings usually outweigh the benefits. 18,21 Meta-analysis shows the net benefits of primary prevention in asymptomatic patients to be small: NNTB was 265 and NNTH 210. 22 In the recently reported ASPREE study, 23 the second largest primary prevention study to date, compared to placebo, 100 mg of aspirin daily (>3 times the estimated ED 50 ), reduced cardiovascular events by 11% (not significant, the NNTB for 1 year appeared to be around 1000) but was associated with a significant increase in total mortality (NNTH to cause a death was 699).…”

Section: Aspirinmentioning

confidence: 99%

Antithrombotic dose: Some observations from published clinical trials

Dimmitt

Floyd

Ferner

2019

Brit J Clinical Pharma

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The clinical doses of antithrombotics-antiplatelet and anticoagulant agents-need to balance efficacy and safety. It is not clear from the published literature how the doses currently used in clinical practice have been derived from preclinical and clinical data. There are few large randomised controlled trials (RCTs) that compare outcomes with different doses vs placebo. For newer antithrombotics, RCT doses appear to have been chosen to maximise the probability of demonstrating noninferiority when compared to established agents such as warfarin or clopidogrel.Data from RCTs show that aspirin is an effective antithrombotic at doses below 75 mg daily, and that direct oral anticoagulants reduce the risk of stroke in patients with coronary disease at doses 1/4 of those recommended in atrial fibrillation.Lower doses than those currently recommended are safer and still maintain substantial efficacy.

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“…Therefore, antiplatelet drugs may reduce the risk of thrombotic stroke, but conversely increase the risk of bleeding, including intracranial bleeding events. The mainstay of pharmacological management of those at high risk of stroke has been single antiplatelet therapy, which has demonstrated a clear benefit at reducing the risk of large-artery atherothrombotic stroke but not small vessel occlusion or cardiac thromboembolism [156], with either aspirin or clopidogrel. There is some evidence that clopidogrel may be modestly superior to aspirin, particularly in patients with a history of stroke or PAD [157].…”

Section: Studies Of Ticagrelor In Ischaemic Strokementioning

confidence: 99%

Ticagrelor: clinical development and future potential

Sanderson¹,

Parker²,

Storey³

2021

Rev. Cardiovasc. Med.

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Platelets participate centrally in atherothrombosis, resulting in vessel occlusion and ischaemia. Consequently, optimisation of antiplatelet regimens has the potential to further reduce the residual burden of morbidity and mortality associated with atherosclerosis. Ticagrelor is a potent oral platelet P2Y12 receptor antagonist that (1) inhibits a central amplification pathway of platelet activation directly as well as via an active metabolite, (2) has a rapid onset and offset of antiplatelet action that remains consistent in the circulation during twice-daily administration and is amenable to reversal, (3) has inverse agonist properties, and (4) demonstrates pleiotropic effects that contribute to anti-thrombotic, anti-inflammatory and vasodilatory properties. These advantageous characteristics of ticagrelor have translated to beneficial clinical outcomes in patients with acute coronary syndromes or ischaemic stroke, during prolonged maintenance therapy in specific high-risk populations, and following percutaneous coronary intervention but not definitively following coronary artery bypass graft surgery or in peripheral artery disease patients. Novel innovative strategies aim to reduce the risk of bleeding during dual antiplatelet therapy via shortening the duration of treatment and replacing the standard-of-care with ticagrelor monotherapy. In cases where aspirin is an essential component in secondary prevention, dose modification when combined with ticagrelor may hypothetically provide desirable clinical outcomes following appropriate clinical assessment as predicted by pharmacological studies. Overall, the future management of acute coronary syndromes could potentially involve the dichotomisation of antithrombotic therapies, whereby only those with high-risk of ischaemia, without a high-risk of bleeding, receive ticagrelor plus very-low-dose aspirin, while ticagrelor monotherapy is administered to the remaining majority.

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Antiplatelet therapy as a modulator of stroke aetiology: a meta‐analysis

Cited by 14 publications

References 61 publications

Left atrial size and risk of stroke in patients in sinus rhythm

Left atrial size and risk of stroke in patients in sinus rhythm

Antithrombotic dose: Some observations from published clinical trials

Ticagrelor: clinical development and future potential

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