Stroke* / drug therapy

RPR Commentary: Low dose aspirin probably has little benefit for stroke prevention and significant risk of intracranial bleed in older people, particularly if they are at risk for falls or other head trauma. In this study, the risk of heart attack with and without aspirin was not examined. James W. Mold, MD, MPH

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Importance Low-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischemic stroke events and increased intracranial bleeding has not been established in older individuals.

Objective To establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin.

Design, Setting, and Participants This secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, double-blind, placebo-controlled trial of daily low-dose aspirin was conducted among community-dwelling people living in Australia or the US. Participants were older adults free of symptomatic cardiovascular disease. Recruitment took place between 2010 and 2014, and participants were followed up for a median (IQR) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023.

Interventions Daily 100-mg enteric-coated aspirin or matching placebo.

Main Outcomes and Measures Stroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on prevention of initial stroke or intracranial bleeding event. Outcomes were assessed by review of medical records.

Results Among 19 114 older adults (10 782 females [56.4%]; median [IQR] age, 74 [71.6-77.7] years), 9525 individuals received aspirin and 9589 individuals received placebo. Aspirin did not produce a statistically significant reduction in the incidence of ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). However, a statistically significant increase in intracranial bleeding was observed among individuals assigned to aspirin (108 individuals [1.1%]) compared with those receiving placebo (79 individuals [0.8%]; HR, 1.38; 95% CI, 1.03-1.84). This occurred by an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin compared with placebo (59 individuals [0.6%] vs 41 individuals [0.4%]; HR, 1.45; 95% CI, 0.98-2.16). Hemorrhagic stroke was recorded in 49 individuals (0.5%) assigned to aspirin compared with 37 individuals (0.4%) in the placebo group (HR, 1.33; 95% CI, 0.87-2.04).

Conclusions and Relevance This study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke. These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma.

Author/s:

Cloud, Geoffrey, Williamson, Jeff D., Le Thi Phuong Thao

Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients

Aubrey Delammermore — Sat, 15 Jul 2023 05:00:00 +0000

Date Added:

July 15, 2023

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

July 11, 2023

Issue:

Volume:

330

Pages:

131-140

URL:

Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jama.2023.9696

Keywords

Cardiovascular Diseases

stroke

drug therapy

bempedoic acid

statin-intolerant patients

PMID (1):

37354546

MeSH

Cardiovascular Diseases* / chemically induced

Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects

Myocardial Infarction* / mortality

Stroke* / drug therapy

primary prevention

In this large RCT of patients at very high risk of CV events but no history of events, bempedoic acid 180mg daily reduced risk of MI, cardiovascular mortality, and all-cause mortality by 0.8%, 1.3%, and 1.6% (absolute risk reductions) respectively over a period of 39 months.

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Importance: The effects of bempedoic acid on cardiovascular outcomes in statin-intolerant patients without a prior cardiovascular event (primary prevention) have not been fully described.

Objective: To determine the effects of bempedoic acid on cardiovascular outcomes in primary prevention patients.

Design, setting, and participants: This masked, randomized clinical trial enrolled 13 970 statin-intolerant patients (enrollment December 2016 to August 2019 at 1250 centers in 32 countries), including 4206 primary prevention patients.

Interventions: Participants were randomized to oral bempedoic acid, 180 mg daily (n = 2100), or matching placebo (n = 2106).

Main outcome measures: The primary efficacy measure was the time from randomization to the first occurrence of any component of a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization.

Results: Mean participant age was 68 years, 59% were female, and 66% had diabetes. From a mean baseline of 142.2 mg/dL, compared with placebo, bempedoic acid reduced low-density lipoprotein cholesterol levels by 30.2 mg/dL (21.3%) and high-sensitivity C-reactive protein levels by 0.56 mg/L (21.5%), from a median baseline of 2.4 mg/L. Follow-up for a median of 39.9 months was associated with a significant risk reduction for the primary end point (111 events [5.3%] vs 161 events [7.6%]; adjusted hazard ratio [HR], 0.70 [95% CI, 0.55-0.89]; P = .002) and key secondary end points, including the composite of cardiovascular death, MI, or stroke (83 events [4.0%] vs 134 events [6.4%]; HR, 0.64 [95% CI, 0.48-0.84]; P < .001); MI (29 events [1.4%] vs 47 events [2.2%]; HR, 0.61 [95% CI, 0.39-0.98]); cardiovascular death (37 events [1.8%] vs 65 events [3.1%]; HR, 0.61 [95% CI, 0.41-0.92]); and all-cause mortality (75 events [3.6%] vs 109 events [5.2%]; HR, 0.73 [95% CI, 0.54-0.98]). There was no significant effect on stroke or coronary revascularization. Adverse effects with bempedoic acid included a higher incidence of gout (2.6% vs 2.0%), cholelithiasis (2.5% vs 1.1%), and increases in serum creatinine, uric acid, and hepatic enzyme levels.

Conclusions: In a subgroup of high-risk primary prevention patients, bempedoic acid treatment was associated with reduced major cardiovascular events.

Author/s:

Nissen, S. E., Menon, V., Nicholls, S. J., Brennan, D., Laffin, L., Ridker, P., Ray, K. K., Mason, D., Kastelein, J. J. P., Cho, L., Libby, P., Li, N., Foody, J., Louie, M. J., Lincoff, A. M.

Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis The CASSISS Randomized Clinical Trial

Aubrey Delammermore — Thu, 11 Aug 2022 05:00:00 +0000

Date Added:

August 11, 2022

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

August 8, 2022

Issue:

Volume:

328

Pages:

URL:

Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis The CASSISS Randomized Clinical Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jama.2022.12000

Keywords

randomized controlled trial

Multicenter Study

Treatment Outcome

Pathologic Constriction

stroke

Stent

PMID (1):

35943472

MeSH

Constriction

Pathologic / complications

Stroke* / drug therapy

Intracranial Arteriosclerosis* / therapy

Ischemic Attack

Transient* / complications

Stents / adverse effects

Platelet Aggregation Inhibitors / therapeutic use

Carotid artery angioplasty and stenting of intracranial arteries in patients with cerebrovascular symptoms adds nothing to medical management. James W. Mold, MD, MPH

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Importance: Prior randomized trials have generally shown harm or no benefit of stenting added to medical therapy for patients with symptomatic severe intracranial atherosclerotic stenosis, but it remains uncertain as to whether refined patient selection and more experienced surgeons might result in improved outcomes.

Objective: To compare stenting plus medical therapy vs medical therapy alone in patients with symptomatic severe intracranial atherosclerotic stenosis.

Design, setting, and participants: Multicenter, open-label, randomized, outcome assessor-blinded trial conducted at 8 centers in China. A total of 380 patients with transient ischemic attack or nondisabling, nonperforator (defined as nonbrainstem or non-basal ganglia end artery) territory ischemic stroke attributed to severe intracranial stenosis (70%-99%) and beyond a duration of 3 weeks from the latest ischemic symptom onset were recruited between March 5, 2014, and November 10, 2016, and followed up for 3 years (final follow-up: November 10, 2019).

Interventions: Medical therapy plus stenting (n = 176) or medical therapy alone (n = 182). Medical therapy included dual-antiplatelet therapy for 90 days (single antiplatelet therapy thereafter) and stroke risk factor control.

Main outcomes and measures: The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. There were 5 secondary outcomes, including stroke in the qualifying artery territory at 2 years and 3 years as well as mortality at 3 years.

Results: Among 380 patients who were randomized, 358 were confirmed eligible (mean age, 56.3 years; 263 male [73.5%]) and 343 (95.8%) completed the trial. For the stenting plus medical therapy group vs medical therapy alone, no significant difference was found for the primary outcome of risk of stroke or death (8.0% [14/176] vs 7.2% [13/181]; difference, 0.4% [95% CI, -5.0% to 5.9%]; hazard ratio, 1.10 [95% CI, 0.52-2.35]; P = .82). Of the 5 prespecified secondary end points, none showed a significant difference including stroke in the qualifying artery territory at 2 years (9.9% [17/171] vs 9.0% [16/178]; difference, 0.7% [95% CI, -5.4% to 6.7%]; hazard ratio, 1.10 [95% CI, 0.56-2.16]; P = .80) and 3 years (11.3% [19/168] vs 11.2% [19/170]; difference, -0.2% [95% CI, -7.0% to 6.5%]; hazard ratio, 1.00 [95% CI, 0.53-1.90]; P > .99). Mortality at 3 years was 4.4% (7/160) in the stenting plus medical therapy group vs 1.3% (2/159) in the medical therapy alone group (difference, 3.2% [95% CI, -0.5% to 6.9%]; hazard ratio, 3.75 [95% CI, 0.77-18.13]; P = .08).

Conclusions and relevance: Among patients with transient ischemic attack or ischemic stroke due to symptomatic severe intracranial atherosclerotic stenosis, the addition of percutaneous transluminal angioplasty and stenting to medical therapy, compared with medical therapy alone, resulted in no significant difference in the risk of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The findings do not support the addition of percutaneous transluminal angioplasty and stenting to medical therapy for the treatment of patients with symptomatic severe intracranial atherosclerotic stenosis.

Trial registration: ClinicalTrials.gov Identifier: NCT01763320.

Author/s:

Gao, P., Wang, T., Wang, D., Liebeskind, D. S.", H., Li, T., Zhao, Z., Cai, Y., Wu, W., He, W., Yu, J., Zheng, B., Wang, H., Wu, Y., Dmytriw, A. A., Krings, T., Derdeyn, C. P., Jiao, L., CASSISS Trial Investigators