‘Cardiovascular disease at crossroads’: practitioners call for a definitive randomized trial comparing precision medicine and polypill

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Michael J. Joyner

The prospect of death rates from cardiovascular disease once again ticking upward after more than a half century of decline has led to a call for a randomized trial comparing the two new—and distinct—approaches to prevention: precision medicine and the polypill method.

The argument was made in an opinion paper by Michael J. Joyner, MD, and Nigel Paneth, MD, published in JAMA: The Journal of the American Medical Association.

“These two conceptually different approaches should be compared using equivalent standards of measure in a randomized prevention trial so that physicians and health systems can implement the most effective strategy as soon as possible,” the authors wrote.

Joyner, of the department of anesthesiology and perioperative medicine, the Mayo Clinic, Rochester, Minnesota, and Paneth, of the departments of epidemiology and biostatistics at Michigan State University, College of Human Medicine, East Lansing, Michigan, penned the viewpoint entitled “Cardiovascular disease prevention at a crossroads: Precision medicine or polypill?,” in light of evidence that disease death rates, having leveled off since 2016, “may even be rising slightly.”

This, Joyner and Paneth argue, necessitates consideration of the next phase of how to address cardiovascular disease. “Currently, prevention options are to advocate broadly for primary prevention and to test for conventional risk factors and assign an estimated risk as the basis for treatment (secondary prevention),” they write. “Although clinicians can continue to do what they have always done to encourage patients to adhere to traditional [cardiovascular disease] prevention strategies, a major crossroads in prevention has arrived with two very different options for moving forward.”

While several formulations have been suggested for polypill, they write it commonly involves low doses of “off-patent statins and more than one class of antihypertensive agents, sometimes combined with low-dose aspirin, with the goal of reducing elevated levels of low-density lipoprotein cholesterol and blood pressure.”

Precision medicine, meanwhile, “is a form of secondary prevention, adding genomic information to the array of tools available to health professionals to decide who, when and how to treat with the goal of preventing [cardiovascular disease],” Joyner and Paneth point out. The precision medicine approach is individualized and driven by measurement of risk factors like cholesterol, blood pressure and blood glucose levels, they add.

Both bear limitations, the authors went on.

For the polypill approach, these include include overtreatment, exposing individuals at low risk to drugs with known adverse effects and the difficulties of going to market in the current pharma ecosystem. Yet, Joyner and Paneth write that initial reports suggest these factors are not insurmountable.

“Potential limitations to the precision approach include marginal patient adherence with complex costly drug regimens, the costs of individual screening and patient case management, the fact that many events will occur in individuals deemed at lower risk, and the administrative burden (perhaps exacerbated by electronic medical records) associated with managing such efforts,” Joyner and Paneth observe.

The authors acknowledge the existence of a pair of trials—one a multinational study of polypill strategy primarily taking place in lesser-resourced countries, another more modest-sized trial that took place in Tennessee—which they consider underpowered. Therefore, they argue a more definitive study armed with three intervention groups, which is both large enough and long enough to power key outcomes, is required.

“A trial comparing precision medicine vs. the polypill will help determine whether an approach involving complexity vs. simplicity will be more effective in meeting the ongoing challenge of preventing [cardiovascular disease],” the authors wrote in conclusion.

Source: doi.org/10.1001/jama.2019.19026

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