Only Half of Revascularized PAD Patients Receive GDMT

Despite widespread evidence that guideline-directed medical therapy (GDMT) can reduce events and symptoms in patients with peripheral artery disease, only about half of those eligible are on a GDMT regimen, even after undergoing a peripheral vascular intervention, registry data show.

Numerous prior studies have noted the dramatic undertreatment of PAD patients with recommended preventive medications like statins, as well as with lifestyle counseling. Given the lack of published national data on how underutilization of GDMT after a peripheral intervention impacts long-term outcomes, investigators led by Kim G. Smolderen, PhD (Yale University School of Medicine, New Haven, CT), examined rates of death and amputation in relation to prescribing rates at discharge in patients enrolled in the Vascular Quality Initiative (VQI) registry, which monitors procedural quality and is linked to Medicare claims data.

Those who did not receive GDMT—defined in the study as any antiplatelet, a statin, and an ACE inhibitor/ARB if the patient was hypertensive—had a nearly 40% greater risk of all-cause mortality at 2 years and an almost 20% greater risk of major amputation following peripheral vascular intervention compared with those who did receive recommended therapies.

To TCTMD, Smolderen noted that in addition to documenting the low rates of medical therapy in a contemporary cohort, the study, published in the February 13, 2023, issue of JACC: Cardiovascular Interventions, also confirms that the clinical management of PAD patients appears fragmented and oftentimes reactionary, with wide variability in prescription of GDMT across centers and across individual providers in the VQI.

“Because there are so many cooks in the kitchen, nobody takes overall responsibility for the bigger-picture management,” Smolderen said. “If you take this fragmentary approach, people are really missing out on evidence-based care.”

Mortality rates were lowest at sites with a 56.2% to 100% compliance with GDMT regimens and highest at those with compliance rates lower than 37.8%. A similar association was seen for major amputation.

Looking at individual providers in the VQI, those in the lowest two quartiles of prescribing GDMT had significantly higher patient mortality than those in the highest quartile of prescribing, with a similar pattern observed for amputation risk.

In an accompanying editorial, Connie N. Hess, MD, MHS, and Marc P. Bonaca, MD, MPH (both University of Colorado School of Medicine, Aurora), say the findings should be interpreted with caution since none of the individual components of GDMT has been proven in RCTs to reduce all-cause mortality or major adverse limb events (MALE), thus making it difficult to infer a causal relationship between those outcomes and prescription of medical therapy, particularly in light of the short median follow-up of 9.6 months.

Hess and Bonaca say the results likely reflect residual confounding.

“[F]or example, greater use of GDMT may be a proxy for overall better quality of care and other factors not captured and available for matching in the models,” they write. “Although an impressive effort, this analysis illustrates the complementary nature of randomized trials and observational investigations, with the former the gold standard for assessing actual efficacy and safety, and the latter necessary to understand use in practice and to generate additional hypotheses for further testing in trials.”

VQI Analysis and Outcomes

The study included patients (mean age 72 years; 39% female; 15% Black or African American) in the VQI who underwent peripheral vascular interventions between 2017 and 2018 at 223 centers in the United States. Patients were highly comorbid, with hypertension in 91%, CAD in 39%, prior CABG or PCI in roughly one-quarter, diabetes in 56%, and chronic kidney disease in 42%.

Most of the procedures were performed by vascular surgeons (37.6%), followed by interventional radiologists (14.2%), and interventional cardiologists (13.7%). Approximately 49% of the cohort had been prescribed a GDMT regimen of all three recommended drug classes at discharge following their intervention. After propensity matching, there were 6,120 patients who received GDMT and an equal number who did not.

All-cause mortality at 24 months in GDMT patients was lower at 24.5% compared with 31.2% in those not receiving GDMT (HR 1.37; 95% CI 1.25-1.50). The rates of major amputation were 13.2% and 16.0%, respectively (HR 1.20; 95% CI 1.08-1.35).

In GDMT patients, the highest prescription rates were for statins (83.4%) and aspirin (82.6%), while the lowest were for ACE inhibitors/ARBs (56.7%).

Inverse propensity weight-adjusted analyses confirmed the main findings: at 24 months, all-cause mortality was greater for those not on GDMT (32.4% vs 24.6%; HR 1.40; 95% CI 1.33-1.48), as was risk of major amputation (15.6% vs 13.2%; HR 1.15; 95% CI 1.08-1.24).

Furthermore, there was a dose-response relationship for mortality and amputation when stratifying the analysis by the number of medications in the GDMT, with fewer medications resulting in higher incremental risk. Individually, each of the components was associated with increased risk when not given versus given.

Data, Interdisciplinary Cooperation, Accountability Needed

Hess and Bonaca point out that unlike in ACS patients undergoing PCI, where there are data supporting medical therapy, in PAD patients undergoing interventions, the data supporting GDMT have mainly been extrapolated from subgroup analyses of atherosclerosis populations in trials conducted for MACE benefit. They also note the weak association between any medical therapy and limb benefits.

“Consistent with this paucity of evidence, there are no Class I guideline recommendations for medical therapies to reduce MALE, the primary concern after lower-extremity revascularization procedures,” Hess and Bonaca write. “Generation of better evidence for therapies targeting MALE in primary PAD populations is imperative to allow for the development of clearer treatment pathways and more clarity in future PAD guidelines.”

Smolderen and colleagues maintain that offering peripheral vascular interventions to PAD patients without optimal GDMT is “a low-value proposition” not only for patients, but for their families, health systems, and society.

Smolderen said while Hess and Bonaca’s point is well taken, she believes the problem is multifactorial and may also include ingrained prescribing behaviors and assumptions or expectations that other physicians who see the patient will take care of it.

“From a patient standpoint, there is oftentimes also lack of education about the importance of risk management,” she added. As Hess and Bonaca point out, approximately 25% of patients were active smokers despite good evidence that cessation offers multiple benefits for PAD patients. Practice guidelines from the American College of Cardiology/American Heart Association go so far as to provide strongly worded advice for PAD patients to avoid even secondhand smoke.

Importantly, Smolderen said one major implication of the VQI data is the need for improvement in interdisciplinary partnerships and communication between those who care for these patients. As has been pointed out by the National PAD Action Plan, efforts also are needed to directly address the performance of individual centers and providers who are falling below acceptable benchmarks, she said.

“Studies like ours, hopefully, can be a trigger for policy-level discussions and efforts at building in  accountability,” Smolderen added. “That is something as a community that we need to work on as a next level.”