Introduction

Chronic venous disease (CVD) is a prevalent condition in Mexico, affecting 71.3% of the population¹, and imposes a major burden on the healthcare system. The pathophysiology of CVD is complex, involving genetic and environmental factors, venous hypertension, inflammation, and valvular incompetence². This creates a vicious cycle of disease progression with a 4% annual progression rate of 4% and a 50% recurrence within 5 years post-treatment. CVD tends to worsen in older populations and those with obesity³,⁴. Although non-lethal, CVD significantly impacts the quality of life (QoL), affecting patients physically and psychologically at all stages of the condition, often without a direct correlation to the severity of clinical signs⁵,⁶.

The main goals of CVD treatment are to improve venous function and alleviate clinical symptoms. However, evidence suggests that CVD is underdiagnosed and undertreated, particularly in its early stages⁷, with the specific role of venoactive drugs (VADs) remaining controversial. Gathering treatment data from individual countries to understand the disease better and improve planning for proper prevention and treatment programs at the national level is important.

We analyzed data from a population in Mexico recruited for the VEIN STEP study⁸ to evaluate the effectiveness of conservative treatments on CVD manifestations and QoL and to generate nationally representative data to improve our understanding of the disease’s different settings.

Methods

In this prospective, multicenter, cohort study, general practitioners (GPs) and vascular surgeons from 41 centers across Mexico recruited consecutive adult patients with symptomatic CVD. Patients were excluded if they were already receiving treatment with VADs or compression hosiery, had lower limb arterial disease, possessed any concomitant condition affecting lower limb pain or edema, were planning any CVD-related procedures or surgeries, or were pregnant or breastfeeding. Ethical approval was obtained, and the study complies with European Regulation EU 536/2014. Data was collected anonymously, and the study is registered on clinicaltrials.gov (NCT04574375). We adhered to the strengthening the reporting of observational studies in epidemiology guidelines when preparing this paper.

The study's primary objective was to evaluate the effectiveness of conservative treatments for CVD symptoms. Secondary objectives assessed the impact on QoL, patient and physician satisfaction, and general disease management.

Detailed demographic and medical data were recorded at the initial visit (V0). Patients were classified according to the clinical, etiological, anatomical, and pathophysiological (CEAP) classification⁹. Using a 10-cm visual analog scale (VAS)¹⁰, patients were asked to indicate the global intensity of their symptoms and the intensity of each symptom (pain, heaviness, cramps, and sensation of swelling). The intensity of paresthesia, itching, and burning sensation symptoms were assessed with a four-point scale (none, mild, moderate, or severe). The patient’s QoL was assessed using the 14-item chronic venous insufficiency QoL questionnaire (CIVIQ-14)¹¹ covering pain, physical, and psychological domains and reported as a global index score (GIS) to be standardized from 0 to 100. The questionnaire has been validated and is a reliable and sensitive instrument¹²,¹³. In addition, the venous clinical severity score (VCSS)¹⁴ was used to gauge the severity of venous symptoms based on ten clinical descriptors, with a maximum score of 30.

Following V0, patients received conservative treatments as per physicians' usual practices, which included pharmacological (oral VADs, painkillers, topical treatment, etc.,) and non-pharmacological (compression therapy, lifestyle advice, etc.,) options. Symptom improvement was first assessed at a week-2 telephone follow-up (V1) using the seven-point patient global impression of change (PGIC) questionnaire, where patients also reported symptom-specific improvements and time to improvement. At the week-4 follow-up (V2), physicians reassessed patients using the VAS, PGIC, CIVIQ-14, and VCSS and evaluated treatment satisfaction on a five-item scale. An optional week-8 follow-up (V3) through telephone further assessed PGIC and collected data on treatment adherence, lifestyle recommendations, and adverse events.

Results

Treatment effectiveness

According to the PGIC, overall symptom improvements were noted in 93.6% of patients at V1 and in 94.6% at V2. At the optional V3, of 588 patients evaluated, 99.4% reported improvements in symptoms. Benefits were observed across all CEAP stages as displayed in table 3. The individual symptoms that improved the most according to the PGIC were heaviness and pain, (77.1 and 74%, respectively) (Fig. 1). However, the relative risk at V2 was lower for itching at 0.61 (95% CI 0.56-0.67) and paresthesia at 0.63 (95% CI 0.58-0.68) (Fig. 2).

Table 3 CVD conservative treatment outcomes results. Patient description of change from baseline to evaluation visits according to CEAP stages for Global and individual symptom severity assessed with VAS, PGI-C, VCSS, and CIVIQ-14 global index score 

Outcome evaluation	C0s-C1 (n = 240)	C2 (n = 244)	C3 (n = 154)	C4a (n = 78)	C4b (n = 43)	C5 (n = 9)	C6 (n = 26)	Overall (n = 794)
Global symptom VAS
VAS V0	5.0 (2.4)	6.0 (2.5)	5.4 (2.5)	6.4 (2.9)	7.3 (2.3)	7.8 (1.5)	6.8 (2.4)	5.8 (2.6)
VAS V2	2.6 (1.7)	3.4 (2.2)	2.6 (1.7)	4.0 (2.5)	4.5 (1.7)	4.2 (1.4)	3.8 (1.6)	3.2 (2.1)
Change from V0 to V2	2.4 (2.0)	2.6 (1.7)	2.8 (2.0)	2.4 (2.0)	2.8 (1.8)	3.6 (1.7)	3.0 (2.5)	2.6 (1.9)
Days to symptoms improvement, mean (SD)	7.1 (2.9)	7.0 (3.1)	6.2 (3.0)	6.4 (3.5)	5.2 (2.6)	6.2 (3.2)	6.9 (4.3)	6.7 (3.2)
PGI-C from V0 to V1, n (%)
Improvement	227 (94.5)	225 (92.2)	146 (94.8)	74 (94.9)	38 (88.3)	9 (100)	24 (92.3)	743 (93.6)
No change	4 (1.6)	3 (1.2)	4 (2.6)	3 (3.8)	1 (2.3)	0 (0.0)	2 (7.7)	17 (2.1)
Worsening	1 (0.4)	1 (0.4)	2 (1.3)	1 (1.3)	0 (0.0)	0 (0.0)	0 (0.0)	5 (0.6)
PGI-C from V0 to V2, n (%)
Improvement, n (%)	225 (93.7)	233 (95.4)	144 (93.5)	73 (93.5)	42 (97.7)	9 (100)	25 (96.1)	751 (94.6)
No change, n (%)	2 (0.8)	1 (0.4)	1 (0.6)	1 (1.3%)	1 (2.3)	0 (0.0)	0 (0.0)	6 (0.8)
Worsening, n (%)	3 (1.2)	3 (1.2)	5 (3.2)	2 (2.6)	0 (0.0)	0 (0.0)	0 (0.0)	13 (1.6)
VCSS, mean (SD)
V0	4.2 (2.8)	6.2 (3.4)	6.2 (3.2)	9.2 (4.3)	8.8 (2.8)	14.9 (4.1)	16.5 (3.5)	6.3 (4.1)
V2	3.0 (2.0)	4.5 (2.2)	4.7 (2.8)	6.3 (3.4)	6.4 (2.5)	9.2 (3.1)	11.0 (4.4)	4.4 (2.9)
V0-V2 score change	1.2 (2.4)	1.7 (2.5)	1.5 (2.4)	2.9 (3.5)	2.4 (2.4)	5.7 (3.1)	5.5 (4.7)	1.9 (2.8)
CIVIQ-14, mean (SD)
GIS-V0	23.6 (14.9)	33.9 (20.9)	36.7 (22.6)	45.6 (21.4)	49.0 (20.9)	58.9 (24.4)	52.8 (18.0)	34.0 (21.4)
GIS-V2	11.7 (10.6)	19.6 (15.9)	19.6 (16.1)	27.1 (17.6)	30.3 (17.3)	31.9 (13.9)	25.5 (17.9)	18.8 (15.9)
GIS from V0 to V2	11.9 (9.9)	14.3 (12.0)	17.1 (13.5)	18.5 (14.3)	18.7 (11.5)	27.0 (17.6)	27.3 (20.0)	15.2 (12.6)

CEAP: clinical-etiology-anatomy-pathophysiology; C: Clinical parameter from CEAP; VAS: visual analog scale; PGI-C: patient global impression of change; n: number of patients; V0: baseline visit; V1: week-2 visit; V2: week-4 visit; SD: standard deviation; CIVIQ-14: 14-item chronic venous insufficiency quality of life questionnaire; GIS: global index score. *p < 0.001 along all (C) stages (Inferential analysis of change from V0 to V2 calculated with Wilcoxon signed rank test p value).

Figure 1 CVD conservative treatment individual symptoms outcomes results. The graphic represents the percentage of patients, according to the PGIC, who reported an improvement in each evaluated CVD symptom at V2 (although symptoms may persist). PGIC: patient global impression of change; V2: week-4 visit. 

Figure 2 CVD conservative treatment individual symptoms outcomes results. The graphic represents individual CVD symptoms reported by patients at V0 that persisted at V2. CVD: chronic venous disease, V0: baseline visit; V2: week-4 visit; RR: relative risk; CI: confidence interval. 

According to the VAS, global symptom intensity improved from a mean of 5.8 ± 2.6 at V0 to 3.2 ± 2.1 at V2 (p < 0.001). Improvement was achieved within a mean time of 6.7 ± 3.2 days and was observed regardless of whether VADs were prescribed as monotherapy or in combination with other treatments. Improvements were greatest in CEAP classes C4b and above, which also had the highest VAS scores at baseline. The population exhibited an overall decrease in the VCSS at V2, from a mean of 6.3 ± 4.1 to 4.4 ± 2.9 (p < 0.001) and this was more evident in patients with higher CEAP classes. The CIVIQ-14 GIS improved from V0 to V2 by a mean of 15.2 ± 12.6 points (p < 0.001). This was observed across all three CIVIQ-14 dimensions. The VAS, VCSS, and CIVIQ-14 GIS overall mean differences from V0 to V2 are summarized in figure 3.

Figure 3 Chronic venous disease conservative treatment outcomes. Overall mean and median VCSS, VAS, and CIVIQ-14 GIS calculated values at V0 and V2. VAS: visual analog scale; CIVIQ-14 GIS: 14-item chronic venous insufficiency quality of life questionnaire global index score; VCSS: venous clinical severity score; V0: baseline visit; V2: week-4 visit. Median values were used to calculate the Mann-Whitney U test value of p. 

89.3% of the patients and 88.7% of physicians were satisfied with the prescribed treatment.

Discussion

This study provides insight into the management of CVD in daily clinical practice in a population in which 95.3% of patients were of Latino/Hispanic origin. This is particularly important since CVD data from Mexican populations are scarce, especially from multicenter studies.

Compared to the VEIN STEP-Global study, Mexican data revealed higher rates of a BMI > 30 (34.3 vs. 30.4%), sedentary lifestyle (48.7 vs. 40%), and diabetes mellitus (17.1 vs. 13.3%). In addition, Mexican patients had a higher incidence of advanced CVD (C4-C6 classification) at 19.5 versus 12.8% in the global cohort. These differences highlight the importance of collecting region-specific data, as CVD characteristics and risk factors may vary by geographic location¹⁵.

In this study, the reported symptoms are in line with previous epidemiological data on CVD in Mexico¹ where symptoms affected QoL even at early stages of the disease. Despite this, only 25.3% of our patients had received previous treatment for venous leg disorders.

Clinical guidelines recommend conservative therapy as the initial treatment to improve symptoms and QoL in patients with CVD as an adjunct or alternative to interventional treatment¹⁶, with lifestyle advice, compression stockings, and VADs forming the mainstay of management². CVD patients are generally less physically active than those without CVD, potentially leading to weight gain and disease progression¹⁷. Caggiati et al.¹⁸ concluded that lifestyle protocols should be tailored to the specific needs of each patient and should depend not only on the severity of CVD but also on age, motor deficits, comorbidities, and psychosocial conditions. Although physicians recommended lifestyle changes to most patients at V0, these recommendations varied, and their impact was difficult to assess, as outcomes from lifestyle changes, such as weight loss, diet, and exercise typically require extended periods to manifest.

Graduated compression therapy, which alleviates CVD symptoms and controls edema¹⁹,²⁰, was prescribed to 70.9% of patients in this study, achieving an 88% compliance rate. However, adherence remains a significant challenge, particularly over time²¹,²². This issue is exacerbated among older adults with limited mobility, individuals with morbid obesity, and those residing in hot, tropical climates²,¹⁹.

In Mexico, VADs are often prescribed alongside lifestyle advice and elastic compression for symptom relief in CVD¹. However, the effectiveness of VADs in CVD management remains debated. A Cochrane review of 56 randomized trials with 7,690 participants indicated that VADs might reduce leg edema and some CVD symptoms but showed moderate-certainty evidence of higher adverse event risks and no significant impact on QoL²³. In contrast, a meta-analysis by Kakkos et al.²⁴,²⁵ specifically on MPFF found improvements in CVD symptoms, edema, and QoL. In this study, physicians prescribed oral VADs to 95.8% of patients, either as monotherapy for early-stage CVD (C0s-C3) or in combination for advanced stages (C4-C6), with MPFF prescribed to 76.8% of patients and diosmin to 12%. Adherence to VAD treatment was high. Supporting this, Kim et al. found that while VADs may have more adverse events, these events were generally mild, with patients prioritizing symptom improvement over potential risks. European guidelines recommend VADs due to their benefits in alleviating clinical CVD manifestations, and adverse events are typically mild and non-disruptive to adherence²,²⁴.

Consistent with VEIN STEP- Global results, in Mexico, overall symptom intensity was reduced from a mean of 5.8 ± 2.6 at baseline to 3.2 ± 2.1 at V2, with significant improvements for all CEAP classes. VCSS scores were also improved at 4 weeks. These results complement other large international observational studies on CVD, such as VEIN CONSULT²⁵,²⁶ and VEIN ACT²⁷, by focusing on the effectiveness of current CVD management from the perspectives of the patient and the physician.

Reductions in symptom severity also improved QoL overall and across the three CIVIQ-14 dimensions. Bogachev et al. reported similar findings in a smaller-scale real-world study, in which MPFF was added to conservative therapy for 6 months²⁸. In the present study, CIVIQ-14 scores showed progressive deterioration in QoL from CEAP C0s to C6, which is similar to the observation made by Radak et al.²⁹ on the relationship between CIVIQ-14 and CEAP that primarily involved pain and physical limitations in older patients and women. The RELIEF trial also demonstrated that age had a highly significant effect on global scores but not on psychological scores³⁰. The results of this study are in line with previous data showing that QoL can be affected by even mild or moderate CVD symptoms³¹. This highlights the importance of an early CVD diagnosis and treatment initiation to reduce symptoms and prevent progression to more severe forms of the disease.

This study’s strengths include its observational design, providing real-world data, a large, multi-region and consecutive patient recruitment for better representativeness, and a high completion rate for V2 evaluations. However, limitations include potential selection bias due to physician choice, variability in patient management, and non-randomized treatment allocation. The study only included patients with CVD-related complaints and did not assess the reliability or responsiveness of the CIVIQ-14 QoL questionnaire. Diagnoses were mainly made by GPs without specialist confirmation, and the CEAP classification used was limited to its clinical component.

Conclusion

The VEIN STEP study in Mexico provides valuable data on the management of patients with CVD. We observed that patients with CVD present with a broad range of symptoms and clinical stages, and the impact on QoL is usually greater in patients with more severe CVD. This study supports the effectiveness of conservative therapies, including VADs, as monotherapy or in combination with other treatments, in managing CVD symptoms and improving QoL. These results from a Mexican population could serve as a basis for future research and help inform potential future updates to CVD prevention and treatment programs in Mexico.

Disclaimer

This study was presented at the American Venous Forum Annual Meeting, Tampa, Florida, USA, March 03-06, 2024.

Data availability

Data can be provided through the corresponding author upon reasonable request.