2018 Scientific Sessions: Clinical Updates on PCSK9 Inhibition
Clinical Updates in PCSK9 Inhibition
Update on ODYSSEY Outcomes
Vera A. Bittner, MD, MSPH, FNLA
Professor of Medicine
Section Head, General Cardiology,
Prevention and Imaging
University of Alabama at Birmingham
With the ODYSSEY Outcomes recently released, Vera Bittner, MD, MSPH, FNLA, gave an update on the findings in this presentation.
The study hypothesis stated Alirocumab, versus placebo, reduces cardiovascular (CV) morbidity and mortality after recent acute coronary syndrome (ACS) in patients with elevated levels of atherogenic lipoproteins despite intensive or maximum-tolerated statin therapy.
The study showed that compared with placebo in patients with recent ACS, alirocumab 75 or 150 mg subcutaneous Q2W targeting LDL-C levels 25–50 mg/dL, and allowing levels as low as 15 mg/dL reduced MACE, MI and ischemic stroke; was associated with a lower rate of all-cause death and was safe and well-tolerated over the duration of the trial.
The clinical perspective Dr. Bittner presented was In this nearly 19,000-patient placebo-controlled trial, including many patients treated for ≥3 years, there was no safety signal with alirocumab other than injection site reactions. Results showed patients with ACS and baseline LDL-C ≥100 mg/dL may benefit the most from the treatment.
Further Insights on the FOURIER Data
Robert P. Giugliano, MD, SM
Executive Committee, FOURIER Trial
Senior Investigator, TIMI Study Group
Physician, Cardiovascular Medicine
Brigham and Women's Hospital
Harvard Medical School
Results of the FOURIER trial provided valuable insight into the use of PCSK9 inhibitors and the efficacy of reducing LDL-C in at-risk patients. In this session, Robert Giugliano, MD, SM provided further insight into the study.
FOURIER summarized that LDL-C was reduced by a mean of 59%, and Evolocumab was safe and well-tolerated. It also lowered CV events in a variety of high-risk patients already on statin therap, mostly by reducing MI and ischemic stroke. Dr. Giugliano added that based on the totality of the data, an LDL-C level of 20-25 mg/dl (0.5-0.6 mmol/L) or lower would be optimal in secondary prevention for high-risk patients.
The take-home message presented was that after a quarter-century of treating LDL-C, clinical trials through the years have shown that high is bad, average is not good, lower is better, even lower is even better and lowest is best.
Clinical Relevance - An Update on Clinical Trials - How Will This Affect Practice in the Future?
Pamela B. Morris, MD, FNLA
Director, Preventive Cardiology
Co-Director, Women’s Heart Care
Medical University of South Carolina
Mt. Pleasant, SC
With all of the data surround PCSK9 inhibitor trials, what is the relevance to the clinical practice? Pamela B. Morris, MD, FNLA provided the audience with an understanding of how recent findings impact current recommendations for combination lipid-lowering therapy in at-risk patients.
Recent clinical trials have shown that non-statin therapies such as ezetimibe, alirocumab and evolocumab are safe and well-tolerated and provide additional LDL-C lowering when added to moderate, high and maximally tolerated statin therapy. They have been associated with a reduction in cardiovascular events, particularly in patient populations with clincial ASCVD with comorbidities and recent ACS.
When selecting non-statin therapies, Dr. Morris summarized is it important to consider maximizing statin intensity as tolerated, patient clinical features and FDA-approved indications, the additional percentage of LDL-C reduction desired, the cost to the patient, the route of administration and patient preferences.