WASHINGTON, DC — Penn Medicine experts presented research findings that could come to define new standards of cardiovascular care, including findings on the efficacy of novel interventions for treatment resistant hypertension and atherosclerosis, at the 2014 American College of Cardiology Scientific Session, ACC.14.
Late Breaking Clinical Trial Results
Saturday, March 29
Despite promising early phase research, the pivotal SYMPLICITY HTN-3 trial evaluating the use of Medtronic's renal denervation system in the U.S. in patients with treatment-resistant hypertension failed to meet its primary efficacy endpoint, researchers reported at 2014 American College of Cardiology meeting and published simultaneously in an online-first New England Journal of Medicine article.
The procedure involves inserting a catheter through an artery in the groin, which is threaded up to the renal artery, where a catheter using radio frequency energy is used to disrupt the renal nerves, thereby reducing a patient’s elevated blood pressure.
The trial randomized 535 treatment-resistant hypertension patients in 87 U.S. medical centers, including the Hospital of the University of Pennsylvania. Patients receiving the investigational treatment were compared with a sham-procedure control group (that received femoral artery puncture and renal angiogram) under conscious sedation, with all patients continuing to take their blood pressure medications. The primary efficacy endpoint was the change in office systolic blood pressure (upper blood pressure reading) at six months.
Researchers reported that while the trial did meet its safety endpoints and there were no signals that safety was a concern in the study, it did not demonstrate a significant reduction of systolic blood pressure six months after renal artery denervation versus sham control. Trials planning to enroll new patients with high blood pressure for treatment with the denervation device were suspended in January 2014 when the preliminary efficacy data was first released by the manufacturer. Patients already enrolled and treated in the trial are still in active follow-up.
The authors note that the based on positive results in previous phases of the study, that a placebo effect may have been present in the phase III trial by having an invasive procedure in the control group, which may have increased patient compliance with medication and diet. The concept has important therapeutic implications for future trial designs of antihypertensive (and other) medications, devices, and strategies.
“These trial results are, in my mind, more a sign that we need to reconsider patient selection, patient and investigator/provider expectations, as well as improve our understanding of what basically happens during renal denervation, rather than shucking the process all together,” said study co-author Raymond R. Townsend, MD , professor of Medicine and director of the Penn Hypertension Program. “Several thousand people from around the world have already been treated, seemingly effectively, with this procedure when medication therapy failed. I believe it’s too early to say where/whether renal denervation fits into resistant hypertension care, but I don’t think we are ready to give up on it at this time, and additional research is needed to acquire a more complete understanding of the procedure.”
Sunday, March 28
A novel drug in development for treatment of atherosclerosis – darapladib – did not meet its primary endpoint in the more than 15,000-patient STABILITY trial. Final results of the study were presented at the 2014 American College of Cardiology meeting and published simultaneously in an online-first New England Journal of Medicine article.
Darapladib is an inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme found in atherosclerotic plaque. Elevated levels of the enzyme have been associated with worsening atherosclerosis. The study looked at whether darapladib could safely lower the chances of having cardiovascular events in people with stable coronary heart disease.
Results of the large phase III trial showed that the drug failed to provide a significant reduction in its primary endpoint – a composite of myocardial infarction, stroke, or cardiovascular death – when compared with patients treated with placebo. However, some secondary endpoints suggested benefit, and the drug continues to be evaluated in the SOLID-TIMI 52 trial, a phase III trial involving patients with acute coronary syndrome.
Pivotal preclinical and early phase clinical research on darapladib was completed at Penn and led by STABILITY co-author Emile R. Mohler III, MD, professor of Medicine and director, Vascular Medicine.
“The ongoing SOLID clinical trial is evaluating the benefit of darapladib in patients who have just had a heart attack,” said Dr. Mohler. “The clinical information obtained from this trial will help determine if reducing inflammation favorably impacts the prognosis after suffering a heart attack.”
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