World Stroke Organization The Paper of The Month – July
24 Jul 2024Should we always use lipid-lowering therapies for long-term secondary stroke prevention?
Should we always use lipid-lowering therapies for long-term secondary stroke prevention?
By Prof. Dr. Anita Arsovska – WSA Associate Commissioning Editor
This article is a commentary on the following: Guo BQ, Li HB, Xu PW, Zhao B. Lipid-lowering Therapies and Long-term Stroke Prevention in East Asians: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Int J Stroke. 2024 Jun 18:17474930241264686. doi: 10.1177/17474930241264686. Epub ahead of print. PMID: 38888036.
Summary of the findings
The authors conducted a systematic review and meta-analysis of large-scale randomized controlled trials (RCTs) with at least 3 years of follow-up to evaluate the long-term impact of lipid-lowering therapies on stroke incidence in East Asians (1). They incorporated data from 9 large-scale RCTs involving 54,354 participants. Their findings of overall analyses revealed that lipid-lowering therapies did not significantly affect the long-term incidence of all strokes (9 RCTs; 54,354 participants; RR, 0.98 [95% CI, 0.87-1.10]; P = 0.75), ischemic stroke (7 RCTs; 52,059 participants; RR, 0.91 [95% CI, 0.79-1.04]; P = 0.16), or hemorrhage stroke (7 RCTs; 52,059 participants; RR, 1.24 [95% CI, 0.97-1.59]; P = 0.09) in East Asians. In conclusion, lipid-lowering therapies did not demonstrate any beneficial effects on long-term stroke prevention among East Asians.
Commentary
Lipid-lowering therapies play a major role in secondary stroke prevention. AHA/ASA guidelines recommend use of atorvastatin 80 mg daily to reduce the risk of stroke recurrence in patients with ischemic stroke with no known coronary heart disease, no major cardiac sources of embolism, and LDL cholesterol (LDL-C) >100 mg/dL. In patients with ischemic stroke or TIA and atherosclerotic disease (intracranial, carotid, aortic, or coronary), lipid-lowering therapy with a statin and also ezetimibe, if needed, to a goal LDL-C of <70 mg/dL is recommended to reduce the risk of major cardiovascular events. In patients with ischemic stroke who are very high risk (defined as stroke plus another major ASCVD or stroke plus multiple high-risk conditions), are taking maximally tolerated statin and ezetimibe therapy and still have an LDL-C >70 mg/dL, it is reasonable to treat with PCSK9 inhibitor therapy to prevent ASCVD events (2).
European Stroke Organisation (ESO) guidelines have recommended the use of HMG-CoA reductase inhibitors (statins) for prevention of recurrent major adverse cardiovascular events and conclude, that statins should be prescribed in all individuals with ischemic stroke or TIA (Quality of evidence: high, strength of recommendation: strong for intervention), and that a low-density lipoprotein (LDL) level of <1.8 mmol/L (<70 mg/dL) should be targeted (Quality of evidence: moderate, strength of recommendation: strong for intervention) (3).
However, some authors have challenged this “one size fits it all” principle and felt that this recommendation may be oversimplifying a complex matter, emphasizing the benefit of individualized secondary prevention treatments (4).
A recent meta-analyses investigated the statin overuse in acute cerebral ischemia (ACI) without indications (5). Statin therapy was associated with an increased risk of the occurrence of 6 conditions: diabetes, myalgia or muscle weakness, myopathy, liver disease, renal insufficiency, and eye disease. It was concluded that more than one-fifth of patients with ACI do not have an indication for statins, and statin overuse in these patients could annually lead to over 5600 adverse events each year in the United States.
The utilization of statins for stroke prevention remains a subject of ongoing research and debate within the medical community. Divergent findings from various studies contribute to the uncertainty surrounding the efficacy of statins in reducing the risk of stroke, although there is strong evidence suggesting that statins are associated with a reduction in the absolute risk of ischemic strokes and cardiovascular events (6, 7).
The main limitation of this meta-analysis is that it combined all RCTs of primary and secondary prevention of stroke (1). Only one trial (J-STARS) included 100% of patients with previous stroke (secondary prevention). The proportion of patients with previous stroke in the other eight trials was extremely low (0-8%) or not reported (data from Table 1). J-STARS was a Japanese trial that examined the stroke preventive effect of statin on 1,578 patients who were assigned to either the pravastatin group (10 mg/day) or the control group. After 4.9 years of follow-up, although the occurrence of total stroke and TIA was not different with the use of pravastatin, the occurrence of atherothrombotic infarction was suppressed in the pravastatin group. This raised the hypothesis that statins may reduce the occurrence of stroke due to larger artery atherosclerosis.
Conclusion
Taking into consideration that the overall consensus and guidelines regarding the use of statins for stroke prevention may vary, a personalized approach is needed to ensure the optimized treatment for secondary stroke prevention. Also, the results of this meta-analysis are mainly directed to primary stroke prevention and may not be easily extrapolated to secondary prevention in stroke patients.
References
- Guo BQ, Li HB, Xu PW, Zhao B. Lipid-lowering Therapies and Long-term Stroke Prevention in East Asians: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Int J Stroke. 2024 Jun 18:17474930241264686. doi: 10.1177/17474930241264686.
- Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, Kamel H, Kernan WN, Kittner SJ, Leira EC, Lennon O. 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke. 2021.
- Dawson J, Béjot Y, Christensen LM, et al. European Stroke Organisation (ESO) guideline on pharmacological interventions for long-term secondary prevention after ischaemic stroke or transient ischaemic attack. European Stroke Journal. 2022;7(3):I-XLI. doi:10.1177/23969873221100032
- Nolte CH, Scheitz JF, Erdur H, Audebert HJ. Regarding the new ESO guideline on pharmacological interventions for long-term secondary prevention after ischemic stroke or transient ischemic attack: Current evidence does not allow simplified recommendations. European Stroke Journal. 2022 Sep;7(3):339-40.
- Sung EM, Saver JL. Statin Overuse in Cerebral Ischemia Without Indications: Systematic Review and Annual US Burden of Adverse Events. Stroke. 2024 Jun 14.
- Deolikar V, Raut SS, Toshniwal S, Kumar S, Acharya S. Navigating the Statin Landscape: A Comprehensive Review of Stroke Prevention Strategies. Cureus. 2024 Feb 4;16(2):e53555. doi: 10.7759/cureus.53555.
- Tramacere I, Boncoraglio GB, Banzi R, Del Giovane C, Kwag KH, Squizzato A, Moja L. BMC Med. 2019;17:67. Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis.
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