PCSK9 inhibitors safer than statins in people with elevated risk of hemorrhagic stroke: Study
USA: A recent study comparing the lipid-lowering therapies statin and PCSK9 inhibitors found statin to be associated with an increased risk of hemorrhagic stroke (HS) but not PCSK9Is.
The study, published in the journal Stroke, suggests PCSK9Is be a preferred lipid-lowering medication class in patients with increased risk of hemorrhagic stroke, including patients with prior HS.
Dyslipidemia is an established risk factor for stroke and cardiovascular diseases (CVDs) and it is crucial to appropriately manage the elevated low-density lipoprotein cholesterol (LDL-C) levels, a known atherogenic risk factor, for reducing the risk of atherosclerotic vascular events and death.
In patients with a first cerebrovascular event in 2006 (SPARCL), statins were shown to increase hemorrhagic stroke likely due to off-target antithrombotic effects. Despite this, it is continued to be used sometimes in patients with elevated HIS risk due to the absence of alternative medications. Recently, the PCSK9Is (proprotein convertase subtilisin kexin 9 inhibitors) have become available as a potent lipid-lowering class with potentially less hemorrhagic propensity.
Against the above background, Borja E. Sanz-Cuesta and Jeffrey L. Saver from UCLA, Los Angeles, CA, performed a systematic comparative meta-analysis to evaluate hemorrhagic stroke rates across all completed statin and PCSK9I randomized clinical trials with treatment > 3 months, following PRISMA guidelines.
In addition to HS rates across all trials, causal relation was probed by evaluating for dose-response relationships by medication (low versus high medication dose/potency) and by presence and type of preceding brain vascular events at inception (none versus ischemic stroke/transient ischemic attack versus HS).
A total od 36 statin randomized clinical trials (204 918 patients) and 5 PCSK9I randomized clinical trials (76 140 patients) were identified.
Key findings of the study include:
- Across all patient types and all medication doses/potencies, statins were associated with increased HS: relative risk 1.15; PCSK9Is were not.
- In the medication dose/potency analysis, higher dose/potency statins (7 trials, 62 204 patients) were associated with magnified HS risk: relative risk, 1.53; higher dose/potency PCSK9Is (1 trial, 27 564 patients) were not.
- In the type of index brain vascular injury analysis for statins (5 trials, 9772 patients), prior ischemic stroke/transient ischemic attack was associated with a magnified risk of HS: relative risk, 1.43; and index intracerebral hemorrhage was associated with an extremely high effect estimate of risk of recurrent HS: hazard ratio, 4.06. For PCSK9Is, prior ischemic stroke/transient ischemic attack (1 trial, 5337 patients) was not associated with increased HS risk.
"Our findings show that statins increase the risk of HS in a medication dose- and type of index brain vascular injury-dependent manner; PCSK9Is do not increase HS risk," concluded the authors. "PCSK9Is may be a preferred lipid-lowering medication class in patients with elevated HS risk, including patients with prior HS."
Reference:
The study titled, "Lipid-Lowering Therapy and Hemorrhagic Stroke Risk: Comparative Meta-Analysis of Statins and PCSK9 Inhibitors," is published in the AHA journal Stroke.
DOI: https://www.ahajournals.org/doi/abs/10.1161/STROKEAHA.121.034576
