An analysis of 12 recent randomized clinical trials (RCTs) suggests a majority of patients with ischemic heart disease (IHD) or a history of MI are eligible for new secondary prevention therapies—a finding that, if acted upon, could change a paradigm that’s been in place for decades.
Like any experts in the field, Martin Bodtker Mortensen, MD, PhD, and colleagues could tell you that the gold standard for secondary prevention of atherosclerotic CVD (ASCVD) is a well-established combo of lipid-lowering statin therapy, antihypertensive therapy and an antithrombotic agent. It’s a cocktail that’s been proven time and again to effectively reduce a person’s risk of future CVD, but patients with existing ASCVD still suffer from a high likelihood of recurrent events and mortality.
Mortensen, of Aarhus University Hospital in Aarhus, Denmark, and co-authors said that 12 major RCTs dealing with novel secondary prevention therapies have been published since 2015, including the landmark IMPROVE-IT, PEGASUS, EMPA-REG, LEADER, SUSTAIN-6, FOURIER, CANVAS, REVEAL, CANTOS, COMPASS, ODYSSEY-OUTCOMES and REDUCE-IT trials.
“The results from these RCTs are important to ASCVD prevention,” the authors wrote in JAMA Cardiology. “However, to date, little is known about the potential implications of these studies on drug eligibility and ASCVD prevention.”
Looking to apply the results of the RCTs to a more contemporary population, the researchers recruited a study population of 6,292 patients with known IHD and 2,277 with a previous MI in the Copenhagen General Population Study. Participants were enrolled between 2003 and 2015 and followed for an average of 7.7 years.
The authors reported that 80% of patients with existing IHD and 99% of those with a history of MI were eligible, based on RCT enrollment criteria, for one or more of the new medications introduced by the 12 RCTs. Dividing the therapies into four drug classes—lipid-modifying, antithrombotic, anti-inflammatory and antidiabetic medications—the team said 41% and 81% of those patients, respectively, were eligible for two or more drug classes simultaneously.
The five-year estimated percentage of major CV events that could be prevented for each new therapy ranged between 1% and 20% in patients with IHD or MI at baseline.
In an invited editorial comment, Michael G. Nanna, MD, and Eric D. Peterson, MD, MPH, both of the Duke Clinical Research Institute, called Mortensen et al.’s findings “striking.” They said that as high as the team’s estimates were, they still might underestimate practical use, “as the investigators applied trial enrollment criteria rather than assuming clinicians may prescribe drugs in a more liberal off-label fashion in routine practice.”
The editorialists also noted that actually adopting and implementing these therapies in clinical practice will take a lot of time. Cost would also likely be a point of contention—when PCSK9 inhibitor therapies were first released, they said, a yearly supply could cost upwards of $14,000. Canakinumab can put a patient out $200,000 per year, and an annual supply of an SGLT2 agent can retail for $6,000.
“Facing such prices, insurers have initiated difficult authorization policies and high patient copays that have limited access to novel prevention treatments,” Nanna and Peterson wrote. “Combined, such strategies have been effective in preventing adoption.”
Still, the pair said, it’s worth noting the “remarkable” fact that 12 novel therapies have been added so recently to the CVD prevention toolkit.
“Combined, clinicians and patients will have many therapeutic options available to profoundly lower cardiovascular disease risk,” they wrote. “While there is still a need for ongoing clinical trials to define optimal drug combinations, the focus of investigators and sponsors alike must turn toward improving the use of the effective medications already at our fingertips.”