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Cholesterol Lowering and Stroke: No Longer Room for Pleiotropic Effects of Statins - Confirmation from PCSK9

Tanya Salvatore1, Riccardo Morganti2, Roberto Marchioli3

  • 1Institute of Cardiology, "G. d'Annunzio" University, Chieti, Italy.

The American Journal of Medicine
|July 14, 2019
PubMed

Insights

Lowering cholesterol levels significantly reduces stroke risk, regardless of the medication used. This meta-regression confirms that the extent of cholesterol reduction directly correlates with stroke risk reduction, refuting "pleiotropic" drug effects.

Area of Science:

  • Cardiovascular Medicine
  • Clinical Trials
  • Epidemiology

Background:

  • The link between cholesterol levels and stroke risk is less understood than for coronary heart disease.
  • Previous studies were limited by low statistical power and less effective cholesterol-lowering interventions.
  • Statin medications have shown stroke reduction, leading to theories of non-cholesterol-related "pleiotropic" effects.

Purpose of the Study:

  • To analyze the relationship between changes in total cholesterol and stroke risk across various lipid-lowering interventions.
  • To confirm or refute the hypothesis that cholesterol reduction itself, rather than other drug effects, impacts stroke risk.

Main Methods:

  • An updated meta-regression analysis was performed on randomized trials of cholesterol-lowering treatments.
  • The analysis correlated changes in total cholesterol with corresponding changes in stroke risk compared to control groups.
  • Included data from recent trials like FOURIER, SPIRE-1/2, and ODYSSEY OUTCOMES.

Main Results:

  • Observed relative risks for stroke in recent trials (e.g., FOURIER, SPIRE-1/2, ODYSSEY OUTCOMES) closely matched predictions from the meta-regression.
  • The data demonstrated a consistent relationship between the degree of total and low-density lipoprotein cholesterol reduction and stroke risk reduction.
  • No evidence supported the need for

Conclusions:

  • Cholesterol reduction is the primary driver for stroke risk reduction across all lipid-lowering interventions.
  • The observed stroke risk reduction is directly proportional to the extent of cholesterol lowering achieved.
  • This confirms that specific lipid-lowering effects, not
Abstract

Keywords:
AtherosclerosisCholesterolEzetimibeLipid-loweringPCSK9 inhibitorsStatinsStroke

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