A study published in the November issue of the Journal of the American College of Cardiology confirms that patients defined as “very high risk” for future atherosclerotic CVD (ASCVD) events by updated society guidelines do indeed carry a much higher risk of adverse outcomes down the road.
The study, penned by Lisandro D. Colantonio, MD, PhD, and colleagues sought to estimate event rates among adults with a history of ASCVD who did and didn’t meet the definition of “very high risk” according to the American Heart Association and American College of Cardiology’s 2018 cholesterol guideline. The guideline recommends that all patients at a very high risk for ASCVD events take high-intensity statin therapy—or maximally tolerated statin therapy—and non-statin lipid-lower therapies like ezetimibe and PCSK9 inhibitors.
“The ASCVD event rate among adults who meet the definition of very high risk in the 2018 AHA/ACC guideline for the management of blood cholesterol has not been reported,” Colantonio, of the University of Alabama at Birmingham, et al. wrote in JACC. “If the ASCVD event rate is high among adults who meet this definition, it would indicate that the implementation of the cholesterol guideline is directing ezetimibe and PCSK9 inhibitors toward populations likely to receive a large absolute risk reduction with these treatments.”
Colantonio and co-authors pulled data from the MarketScan database for their analysis, including 27,775 U.S. adults with health insurance and a history of ASCVD as of Jan. 1, 2016. Patients at a very high risk for ASCVD events were defined as those with a history of two or more major ASCVD events or one event plus at least two high-risk conditions.
The researchers followed their subjects through 2017 for ASCVD events including MI, ischemic stroke and major adverse limb events.
They found that 15,366 patients—55.3% of the total pool—met the definition of very high risk, with an ASCVD event rate of 53.1 per 1,000 person-years in people who met the criteria and a rate of 17 per 1,000 person-years in those who didn’t. The ASCVD event rate was 89.9 per 1,000 person-years in people with a history of two or more ASCVD events and 41.3 per 1,000 person-years in patients with at least one major event and two or more high-risk conditions.
Age- and sex-adjusted hazard ratios for ASCVD events were as follows:
- 2.98 in patients at a very high risk
- 4.89 in patients with two or more major ASCVD events
- 2.33 in patients with one event and at least two high-risk conditions
In a related editorial, Nathan D. Wong, PhD, of the University of California Irvine, pointed out that Colantonio et al.’s finding that 55% of all ASCVD patients were indeed at a very high risk is somewhat higher than in other studies. In another recent report that considered the entire VA healthcare system, researchers found that just 43% of patients met the criteria for very high risk.
But Colantonio and colleagues’ study actually likely underestimated event rates in the very-high-risk population, Wong wrote. The team included only patients with health insurance, so their results would likely be much different—and worse—if they considered people without health insurance.
Wong said the biggest takeaway from the study is that multi-society guidelines are indeed grouping heart patients effectively.
“Although one can argue about the definition used by the guidelines to define very-high-risk status, there is now evidence that, on average, patients defined as very high risk by the current definition really do carry a much higher risk than those who are not accordingly defined,” he wrote. “Also, evidence from the recent PCSK9 mAb cardiovascular outcome trials suggest such patients in particular do derive benefit that is clinically and, mostly likely, cost-effective, which should be helpful in further prioritizing patients for these and other newer and emerging therapies targeting residual risk in ASCVD patients.”