Pharmacotherapy in patients with peripheral arterial disease (PAD) aims to prevent progression of atherosclerotic disease, to reduce risk of global cardiovascular events and to improve walking capacity. Since PAD is a manifestation of systemic atherosclerosis in the lower extremities, its pharmacotherapeutic goals are nearly identical to those of the cerebrovascular disease and cardiovascular disease (CVD). Smoking cessation, exercise, and an aggressive pharmacological risk factor modification, including diabetes, hypertension, lipid abnormalities, and life-long antiplatelet therapy, represent the cornerstones of treatment. The therapeutical recommendations based on solid research are included in current national and international PAD guidelines. Despite strict guideline directives, the PAD is still considered today as undertreated in many countries [
In Germany, high prescription rates for secondary preventive medication in PAD patients primarily treated by vascular specialists were recently reported [
The CONTENT (CONTinuous morbidity registration Epidemiologic NETwork) database is a national primary care research project which is created and maintained by the Department of General Practice and Health Services Research of the University Hospital Heidelberg. The structure and core elements of this datapool have been described elsewhere [
The electronic patient records of 105,026 primary care patients across a three-year period (April 1, 2007–March 31, 2010) were screened in an anonymous manner. Patients with PAD were identified using the International Classification of Disease (ICD-10) code I73.9. CVD patients were selected from the ICD-10 codes I20 and I25. This method allows extraction of all PAD/CVD patients who exhibit ensured and coded diagnoses in their electronic patients record. Thus not only patients who had become conspicuous through their symptoms and were definitively diagnostically clarified were detected, but also those who have become asymptomatic subsequent to PTA/PTCA treatment. However, we were not able to extract, for example, information about the number of therapeutic interventional or surgical procedures and their possible medical success or consequences. Asymptomatic patients, and thus the majority of PAD patients, could not be identified because ABI measurement was not available as a PAD selection criterion. Furthermore, patients presenting with atypical claudication symptoms, for example, patients with superimposing coincident neuropathy or osteoarthrosis, could not be identified. This is traced to a nonexistent ICPC code or ICD-10 code for the Doppler sonographic ABI measurement. Subjects presented coincidentally with PAD code and CVD code were excluded from the analysis. Moreover, only patients with continuous contact to their family practitioner and properly documented prescriptions were included. In order to obtain comparable cohorts, we identified determinants for PAD on the basis of binary logistic regression. Based on these variables, matching was performed with the Propensity Score (PS) method proposed by Rosenbaum and Rubin [
Sociodemographic variables (e.g., education or profession) were not available for the analysis. The “chronic conditions” were defined on the basis of ICPC codes according to the concept of O’Halloran et al. [
All prescriptions corresponding to the PAD code and the CVD code were analysed by means of the Anatomical Therapeutic Chemical Classification (ATC). The ATC system divides the drugs into different groups according to the organ or system on which they act and according to their chemical, pharmacological, and therapeutic properties. Drugs are classified in 14 main groups (first level) and spread out into therapeutic/pharmacological subgroups down to the plain chemical substances (fifth level) [
In order to assess potential differences in pharmacotherapy between PAD and CVD patients in matters of well-defined ATC subgroups, contingency comparisons were performed using Fisher's Exact Test. A significance level of 0.05 was defined for hypothesis testing. Statistical analyses were performed with “R” (Version 2.12.0).
479 PAD patients and 1,972 CVD patients met the inclusion criteria. The matched-pair procedure resulted in 958 corresponding CVD patients, that is, a PAD/CVD patient ratio of 1 : 2. Binary logistic regression defined patients’ age, gender, practice setting, and type of health insurance (statutory versus private) as significant determinants for the analysis (Table
Study patient characteristics.
PAD patients | CVD patients | ||
---|---|---|---|
Number | 479 | 958 | n.s. |
Age | |||
mean (SD) | 72.6 (12.0) | 72.9 (11.2) | n.s. |
Gender | |||
males (%) | 56.4 | 56.4 | n.s. |
females (%) | 43.6 | 43.6 | n.s. |
Number “chronic conditions” | |||
mean (SD) | 4.1 (3.7) | 4.2 (3.6) | n.s. |
Number encounters (per mille) | 38.8 (28.3) | 37.2 (29.0) | n.s. |
Practice profile | 100% |
Prevalence of PAD within different age groups of the entire study population.
Age group (years) | 3-year contact group | PAD | ||
0–10 | 7700 | 7.33 | 0 | 0.00 |
11–20 | 10443 | 9.94 | 0 | 0.00 |
21–30 | 12930 | 12.31 | 1 | 0.21 |
31–40 | 12933 | 12.31 | 3 | 0.63 |
41–50 | 17533 | 16.69 | 15 | 3.13 |
51–60 | 13893 | 13.23 | 68 | 14.20 |
61–70 | 11588 | 11.03 | 125 | 26.10 |
71–80 | 10212 | 9.72 | 155 | 32.36 |
81–90 | 6379 | 6.07 | 98 | 20.46 |
>90 | 1415 | 1.35 | 14 | 2.92 |
Total |
Table
Number of selected pharmacotherapeutical prescriptions in a 3-year study group of PAD and CVD patients by means of ATC classification.
PAD ( | CVD ( | ||
---|---|---|---|
Total number, mean (SD) | n.s. | ||
ATC groups level 1 | |||
A alimentary tract and metabolism | 322 (67.2%) | 618 (64.5%) | n.s. |
B blood and blood forming organs | 318 (66.4%) | 615 (64.2%) | n.s. |
C cardiovascular system | 405 (84.6%) | 849 (88.6%) | <.05 |
ATC groups level 2 | |||
A 10 antidiabetic agents | 135 (28.2%) | 194 (20.3%) | <.001 |
B 01 antithrombotic agents | 303 (63.3%) | 584 (61.0%) | n.s. |
C 01 cardiac therapy agents | 101 (21.1%) | 354 (37.0%) | <.0001 |
C 07 | 240 (50.1%) | 635 (66.2%) | <.0001 |
C 08 calcium channel blockers | 140 (29.2%) | 233 (24.3%) | <.05 |
C 09 renin-angiotensin system agents | 322 (67.2%) | 656 (68.5%) | n.s. |
C 10 antihyperlipidemics | 241 (50.3%) | 536 (55.9%) | <.05 |
ATC groups level | |||
A 10A insulins and analogues | 60 (12.5%) | 77 (8.0%) | <.05 |
A 10B oral blood glucose lowering agents | 96 (20.0%) | 156 (16.3%) | n.s. |
B 01AA Vitamin K antagonists | 56 (11.7%) | 124 (12.9%) | n.s. |
B 01AB heparin and derivates | 50 (10.4%) | 97 (10.1%) | n.s. |
B 01AC platelet aggregation inhibitors | 254 (53.0%) | 481 (50.2%) | n.s. |
C 09AA ACE inhibitors, plain | 198 (41.3%) | 439 (45.8%) | n.s. |
C 10AA HMG CoA reductase inhibitors | 222 (46.3%) | 504 (52.6%) | <.05 |
ATC groups level 5 | |||
B 01AC04 clopidogrel | 101 (21.1%) | 186 (19.4%) | n.s. |
B 01AC06 acetylsalicylic acid | 206 (43.0%) | 420 (43.8%) | n.s. |
B 01AC23 cilostazol | 0 (0.0%) | 0 (0.0%) | n.s. |
C 09AA05 ramipril | 139 (29.0%) | 310 (32.4%) | n.s. |
C 10AA01 simvastatin | 195 (40.7%) | 443 (46.2%) | <.05 |
The analysis of ATC drug levels 4 and 5 showed that the difference between prescriptions of lipid-lowering agents is mainly caused by higher HMG-CoA reductase inhibitor nominations among CVD patients, in particular simvastatin prescriptions. The ATC groups level 5 of antithrombotic agents suggested equal prescription rates for aspirin and clopidogrel between the CVD and PAD cohorts. Remarkably, no cilostazol prescriptions were registered.
In the present study, we attempt to depict the secondary medical prevention among symptomatic patients with PAD compared to CVD patients in German primary care. The analysis of the GP’s prescription dataset suggested no substantial difference in the total number of prescribed drugs between PAD and CVD patients. This concerned all medications except cardiovascular drugs, which more frequently emerged in the prescriptions for cardiac patients than in those of patients with peripheral vascular disorder. This distinction is based on significantly more dispensations of specific cardiac agents for CVD patients, for example, glycosides, antiarrhythmics, or nitrates, and particularly on more prescribed
Little is known about the secondary preventive effects of other classes of antihypertensive drugs in the presence of PAD [
As an effective secondary-preventive measure, the PAD guidelines recommend lifelong treatment of symptomatic patients with statins [
Despite PAD guideline recommendations for secondary prevention, the effect of aspirin in this population is not well established. A meta-analysis of eighteen prospective randomized trials involving 5269 participants resulted in a demand for additional randomized controlled trials of aspirin therapy to establish the real benefit and bleeding risks in PAD [
The findings of our study suggest an inadequate preventive medical therapy in patients with PAD in German family practice settings as had already been demonstrated in other studies [
We are aware of the limitations inherent to any study extracting data from electronic patient records. The main weakness of our study is the data collection by means of ICD/ICDC coded diagnoses which disregards asymptomatic patients with PAD/CVD and is more selective with regard to the advanced stages of the atherosclerotic disease. Furthermore, a potential selection bias must be admitted because a GP's participation in the CONTENT registry is voluntary and not by random selection. In view of the considerable number of participating practices and analyzed patients, it can nevertheless be assumed that our study findings give at least a realistic insight into the drug treatment of PAD patients in primary care. We should also underline that with the ATC classification we only analysed plain chemical substances and not compound medicines, and for this reason a slight underestimation of true agent use cannot be ruled out. Altogether, we believe the key information of our study findings is not substantially affected by these limitations, especially as a possible bias involves a systematic error for both the PAD and CVD cohorts.
The findings of the present study reflect an overall picture of secondary prevention drug management in patients with PAD in German primary care. In accordance with the international literature, the treatment guidelines have not been sufficiently enough translated into family practice settings. The analysed PAD patient sample was less intensively treated with