Atherosclerosis: Finally, The Big Picture of Morbidity and Mortality in Peripheral Arterial Disease?

Atherosclerosis 293 (2020) 92–93
Contents lists available at ScienceDirect
Atherosclerosis
journal homepage: www.elsevier.com/locate/atherosclerosis
Editorial
Finally, the big picture of morbidity and mortality in peripheral arterial disease? T
ARTICLE INFO
Keywords:
Peripheral arterial disease
Morbidity
Mortality
In the last decades, due to aging communities and worse risk factor did not provide data on changes of secondary prevention medication
profiles, incidences of peripheral artery disease (PAD) increased both in with the 2008 threshold, while generally there was need of improve-
western and developing countries and are predicted to drastically in- ment, especially with only 55% of statin intake in the CLI subgroup (see
crease globally in the next years [1,2]. Yet, PAD remains still highly Table 1). Apart from the vast number of patients, the observation
undetected [3]. Moreover, definitions and diagnostic assessment of PAD period of approximately 1.3 years per patient remains short for out-
widely differ in the current literature. Clinicians will agree that com- come analyses. In a subgroup analysis, the all-cause mortality event-
parability between intermittent claudication (IC) and a low ankle-bra- rate for studies with a long observation period (> 1.3 years) was lower
chial index (ABI < 0.9), which might be asymptomatic, is not met. In than in those with a short observation period (< 1.3 years) (Appendix
addition, the diagnosis of critical limb ischemia (CLI) in diabetic pa- 4b). Since 85% of these studies were of observational character, lost to
tients with feet ulcers without vascular assessment is weak. In this follow-up might have provoked this disparity. Furthermore, a wide
minefield of problems, most of our evidence is derived from observa- range of 25–468 events per 1000 person-years was found in the CLI
tional trials. Only a few randomized controlled trials like COMPASS-MI group and CLI patients had less outcome events in the RCT than in the
[4] and FOURIER [5] with distinct PAD subgroups contributed stronger observational trial branch. Apart from the expectable better-than-real-
evidence to our secondary prevention and therapy goals in PAD. life situation in RCTs, these disparities indicate a proportion of mis-
Nevertheless, guidelines challenged us to improve treatment of PAD diagnosed diabetic foot patients, which have worse outcome than CLI
patients with stricter risk factor optimisation goals during the last patients, in the CLI branch. Interestingly, stroke rates were not higher in
decade [6,7]. However, the big picture for the effect of changes in CLI compared to PAD patients. However, one should be cautious with
treatment of PAD was not drawn. this result, since only a small proportion of less than 15% of the ana-
In this issue of Atherosclerosis, Agnelli et al. [8], accepted the chal- lysed studies reported stroke events and the authors did not provide the
lenge. The authors report results in terms of morbidity and mortality in actual sample size of this sub-analysis.
PAD patients of a meta-analysis with approximately 570,000 patients So, what can we learn from the biggest up to date picture for PAD?
with about 855,000 person-years out of 124 eligible studies from 2003 In fact, apart from the problems derived from the vast heterogeneity
to 2017. They built the bridge between the vast amount of hetero- of the studies analysed and the short observation period of approxi-
geneity between RCTs (only 15%, n = 19) and observational studies. mately 1.3 years, the presented data teaches us the future direction for
Unfortunately, but expected, PAD and outcome definitions highly dif- the clinical pathway. All obstacles from differing diagnostic assessment
fered between the groups (ABI < 0.9 vs IC; differing CLI criteria). and definitions to unmet treatment goals of PAD/CLI result in higher
Nevertheless, the authors made remarkable findings with event rates mortality event-rates than in comparable atherosclerotic diseases of
comparable to other atherosclerotic diseases with especially high event- different vascular beds.
rates in the CLI branch. All-cause and cv mortality rates in patients with Thus, we as a community should tackle this problem and once again
an ABI < 0.9 were 113 and 39 per 1000 person-years, respectively, and raise awareness of PAD in the clinical setting. Furthermore, the de-
for CLI 183 and 81 per 1000 person-years, respectively. In fact, the monstrated rates of secondary prevention therapy have a scope of im-
overall event-rate of 113 per 1000 person-years surpasses comparable provement, especially in CLI patients. Thus, with the implementation of
coronary heart disease data [9,10]. Interestingly, trials starting from recently proposed stricter treatment goals [7,13] future trials might
2008, after the publication of the TASC II guidelines [11] and the 2005 report smaller event-rates both in RCTs as well as observational trials.
ACC/AHA PAD guidelines [12], had lower cv event-rates (36 vs 46 per In summary, the results of Agnelli et al. can be seen as a challenge
1000 person-years) than trials before 2008. Unfortunately, the authors for optimisation both of diagnostic criteria and therapy of PAD in future
DOI of original article: https://doi.org/10.1016/j.atherosclerosis.2019.09.012
https://doi.org/10.1016/j.atherosclerosis.2019.11.006
Received 17 October 2019; Received in revised form 7 November 2019; Accepted 12 November 2019
Available online 23 November 2019
0021-9150/ © 2019 Elsevier B.V. All rights reserved.
Editorial Atherosclerosis 293 (2020) 92–93
trials. disease: a systematic review, Atherosclerosis 293 (2020) 94–100.

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Declaration of competing interest [10] L. Whiteley, S. Padmanabhan, D. Hole, et al., Should diabetes be considered a
coronary heart disease risk equivalent?: results from 25 years of follow-up in the
The authors declared they do not have anything to disclose re- Renfrew and Paisley survey, Diabetes Care 28 (2005) 1588–1593.
[11] L. Norgren, W.R. Hiatt, J.A. Dormandy, et al., Inter-society consensus for the
garding conflict of interest with respect to this manuscript. management of peripheral arterial disease (TASC II), J. Vasc. Surg. 45 (Suppl S)
(2007) S5–S67.
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Gerit-Holger Schernthaner∗
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E-mail address: [email protected].
[8] Agnelli, Morbidity and mortality associated with atherosclerotic peripheral artery
∗
Corresponding author.
93

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Atherosclerosis 293 (2020) 92–93

Contents lists available at ScienceDirect

DOI of original article: https://doi.org/10.1016/j.atherosclerosis.2019.09.012

trials. disease: a systematic review, Atherosclerosis 293 (2020) 94–100.

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