ACC 2017: Positive Results for Fully Humanized PCSK9 Drug and Medtronic’s CoreValve

Hand with the stent

The search continues for chronic total occlusion (CTO) patients who would get additive benefit from percutaneous coronary intervention (PCI), and the value of embolic protection devices for patients getting surgical or transcatheter aortic valve replacement.

In addition to the reported results of  Abbott Vascular’s bioresorbable stent (which Felix Lee, M.D., will report on separately), five late-breaking trials caught my attention at the American College of Cardiology’s 2017 meeting in Washington, D.C., which will also be of interest to many HealthTrust member facilities. A summary of these studies and the implications are as follows:

FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) study – Evaluated the safety and efficacy of evolocumab, a fully humanized drug, among subjects with elevated cardiovascular risk on statin therapy. Great expectations for the incredibly expensive drug ($14,000 per year) were somewhat dampened by the results—a statistically significant 12.6 percent (drug group) vs. 14.6 percent (placebo group) incidence of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Patients randomized into the drug group received a 140 mg subcutaneous injection of evolocumab every two weeks or 240 mg monthly, and had a marked reduction in their low-density lipoprotein cholesterol (LDL-C). Serious adverse event were similar between groups. Cost-effectiveness of the drug remains the top concern.

SPIRE-1 and SPIRE-2 (Studies of PSCK9 Inhibition and the Reduction of Vascular Events) – Surprisingly, bococizumab—in the same drug class as evolocumab but 90 percent human antibody and 10 percent retained murine (from mice)—failed to show a consistent and sustained reduction in LDL-C among patients with established or high risk for cardiovascular disease on statin therapy. It is therefore not ready for clinical use. In light of the FOURIER trial results, the chief takeaway here is that PSCK9 drugs may be value if they’re fully humanized.

SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial – Assessed the safety and efficacy of TAVR with CoreValve (Medtronic) compared with surgical aortic valve replacement (SAVR) in intermediate-risk patients. The study enrolled 1,700 patients, mean age of 80 years, who were randomized to TAVR (84 percent with first-generation CoreValve device) or SAVR.  The Society of Thoracic Surgeons estimated the 30-day surgical death risk score for the study group was 3-15 percent. The primary endpoint of non-inferiority was met, based on all-cause mortality or disabling stroke at 24 months (12.6 percent for TAVR vs. 14 percent for SAVR). CoreValve is already FDA-approved for high-risk patients and Medtronic is now asking the agency to broaden its approved use to include intermediate-risk patients.

DECISION-CTO (Optimal Medical Therapy With or Without Stenting for Coronary Chronic Total Occlusion trial – Assessed the safety and efficacy of CTO-PCI compared with optimal medical therapy (OMT) among patients with at least one CTO. Approximately 800 patients were randomized to either CTO-PCI plus OMT or OMT alone. The study stopped early due to slow enrollment, with preliminary results indicating the addition of CTO-PCI has no clinical benefit for patients—incidence of major adverse cardiac event was 20.65 percent (CTO-PCI + OMT) vs. 19.6 percent (OMT) at three years and no different after five years. Although a negative trial, it provides landmark information in the field of CTO research, with further investigations to come. It may be that there is an as-yet unidentified subset of patients for whom CTO-PCI would be advantageous.

Cerebral Embolic Protection Devices During SAVR trial – The back story here is that TAVR created a market for embolic protection devices intended to decrease the associated stroke risk, but trials have failed to provide definitive proof of efficacy. So in this trial, researchers went back and looked in the surgical valve to see if the technique employed might be a contributing factor. The answer is no. Patients undergoing SAVR were randomized in equal number to CardioGard (embolic protection cannula that sits in the ascending aorta), Embol-X (intra-aortic filtration device) or a control group (routine management) and, at seven days, the primary endpoint of freedom from clinical or radiographic ischemic brain injury was similar in all arms. The trial stopped early following interim analysis for futility. The value of embolic protection devices remains in question for SAVR and TAVR.

Lynn Tarkington

Lynn Tarkington

Lynn Tarkington, RN, BS, is assistant vice president of Physician and Clinical Services at HealthTrust. She previously served as AVP of the clinical team for SourceTrust. Her background includes 30 years in the healthcare industry, with the focus of her clinical work in cardiovascular diseases. Tarkington previously worked with HCA in the corporate quality department, leading a team of professionals in improving cardiovascular quality across the organization. She is currently pursuing a master’s degree in public health and is a member of the American College of Cardiology, American Heart Association and the American College of Healthcare Executives.