Patients in Germany with PAD—especially those with critical limb ischemia (CLI)—continue to experience high rates of amputation and mortality many years after research studies demonstrated the benefit of intervention, according an analysis of health insurance data from 2009 to 2011 published online February 2, 2015, ahead of print in the European Heart Journal. The data suggest that such poor prognosis may partially stem from the failure to live up to guideline recommendations backing revascularization.

Given the underuse of revascularization, “vascular diagnostics and revascularization… should be more strictly recommended in all patients with CLI or a risk for amputation,” the authors say.

Drawing on data from BARMER GEK, the largest public German health insurer, investigators led by Holger Reinecke, MD, PhD, of the University Hospital of Muenster (Muenster, Germany), looked at 41,882 patients (mean age 71.4 years; 44% women) who were hospitalized with lower-limb PAD from 2009 to 2011.

Classic risk factors such as hypertension, dyslipidemia, and smoking declined in prevalence with higher Rutherford categories, while diabetes, chronic kidney disease, and chronic heart failure increased (each P < .001). In addition, angiography and endovascular revascularization were less common in advanced PAD, with the latter declining from 54.7% for patients in Rutherford categories 1-3 to 29.5% for those in Rutherford category 6.

Higher Rutherford Categories Equal Poorer Outcomes

Major complications including acute renal failure, MI, infection, sepsis, and death occurred more frequently in higher Rutherford categories (each P < .001). Ischemic stroke occurred at similar rates in all subgroups except for a peak in those with Rutherford 6 (P < .001).

Of a total of 4,401 patients amputated during the index hospitalization, 4,298 had CLI (Rutherford 4-6). Yet 44% of amputees with CLI had not received diagnostic angiography in the hospital before amputation. Even taking into account all inpatient and outpatient vascular procedures during the previous 24 months, 37% had not undergone angiography or revascularization.

Over 4-year follow-up, Kaplan-Meier estimated risk of outcomes generally increased with Rutherford category for major adverse events, including death and amputation (table 1). More than one-third (34.2%) of Rutherford 6 patients died within 12 months after index hospitalization.

In Cox regression models incorporating multiple baseline parameters and comorbidities, the Rutherford categories were associated with stepwise increases in the long-term risks of death and amputation. Furthermore, patients with CLI had increased risk for both MI and stroke compared with claudicants (Rutherford 1-3), but there were no additional increases between categories 4, 5, and 6. 

Mean length of hospital stay and treatment costs also increased with higher Rutherford categories (each P < .001). The total cost of index hospitalizations was 219 million Euros (about $304 million at 2011 exchange rates) and of follow-up hospital treatments was 598 million Euros (about $831 million). Interestingly, roughly 65% of payments for hospitalization and 56% for follow-up were allocated to CLI patients, even though they accounted for only 49% of the overall PAD cohort.

Why Are Outcomes Still Poor?

According to the study authors, the observed 1-year mortality risk of 16% to 35% among CLI patients remains virtually unchanged from the 25% incidence reported by the Inter-Society Consensus for the Management of Peripheral Arterial Disease (known as TASC II) more than 10 years earlier. The 1-year rate of amputations is also in line with TASC II findings.

“The question is why these results are still so unfavorable and unchanged over more than a decade,” Dr. Reinecke and colleagues say, and offer a multifaceted explanation:

• Advanced systemic alterations in CLI patients at the time they become symptomatic
• Increases in relevant comorbidities such as diabetes and heart failure in PAD patients over time
• Underutilization of vascular procedures

In fact, the investigators note, the German findings are in accord with a recent report from the US-based Nationwide Inpatient Sample showing that amputations have increased despite markedly higher rates of revascularization.

Revascularization Should Be a Priority in CLI Patients

In an accompanying editorial, Iris Baumgartner, MD, of University Hospital Bern (Bern, Switzerland), observes that the prevalence of PAD is steadily increasing as the German population ages, becomes more obese, and develops diabetes. As trials have highlighted, asymptomatic PAD patients “have a prognosis almost as poor as that of patients with symptomatic disease,” she adds.

While PAD is the primary cause of amputation, it is often not promptly recognized or addressed, the editorial observes. “Revascularization is the recommended primary treatment option, since [CLI] is associated with potential limb loss and raised mortality if left untreated,” Dr. Baumgartner writes. “Revascularization should be attempted without delay in all patients presenting with [CLI], whenever technically possible and if clinical status is not hopelessly nonambulatory.”

Underuse of revascularization is all the more surprising since the cost of PAD is very high, and it remains unclear whether more effective prevention, such as use of risk-reduction medications, supervised exercise programs, and smoking cessation strategies, would reduce disease progression and costs associated with downstream resources, she says.

“There is no doubt that major efforts need to be made in order to heighten awareness of the problem among the medical community and the general population,” Dr. Baumgartner concludes.

Sources:
1. Reinecke H, Unrath M, Freisinger E, et al. Peripheral arterial disease and critical limb ischaemia: still poor outcomes and lack of guideline adherence. Eur Heart J. 2015;Epub ahead of print.
2. Baumgartner I. Peripheral artery occlusive disease a major contributor to cardiovascular public health burden [editorial]. Eur Heart J. 2015;Epub ahead of print.

Related Stories:

• Endovascular Therapy Promising for Critical Limb Ischemia
• New PAD Recommendations Build Support for Endovascular Treatment
• Rise in Endovascular Therapy for PAD Parallels Improved Outcomes