Effectiveness of a prevention program in the incidence of cardiovascular outcomes in a low-income population from Colombia: a real-world propensity score-matched cohort study

This was a propensity score-matched retrospective cohort study that used prospectively collected patient-level data of the population of patients enrolled in the DTC program of Mutual Ser. Mutual Ser is one of the largest health insurance companies in Colombia and has almost 1.4 million affiliates distributed in five departments of the Caribbean region of the country (Atlántico, Bolívar, Córdoba, Magdalena, and Sucre). The majority of affiliated patients have granted access to the benefits package of the Colombian Health Care System through governmental subsidies (i.e., subsidized regime). The effectiveness of the DTC program on the incidence of the first fatal or non-fatal CVO was evaluated by comparing incident cases between adherent and non-adherent patients to the program activities through a time-to-event analysis. As the DTC program is targeted at individuals based on their cardiovascular risk at enrollment, we stratified the study sample in four different groups according to their estimated baseline Framingham Risk Score (low risk, medium risk, high risk without DM, and high risk with DM). Time-to-event analyses were further conducted for adherent and non-adherent patients within each risk group over the time of exposure to the program interventions. Propensity-score matched samples from these groups were retrieved and analyzed to account for potential confounding variables that could produce biased effectiveness estimations. The STROBE guidelines for reporting cohort studies were followed [14].

Adult patients (> = 18 years) with a diagnosis of hypertension (HTA), DM, CKD, or dyslipidemia affiliated to the DTC program between 2013 and 2018 were considered as the study population. Individuals with 30 to 75 years, enrolled between July 01–2015 and July 01–2018, and without a history of CVOs at enrollment were considered eligible. Among these, patients with less than 6 months of follow-up time in the program were excluded. Patients were also excluded if they experienced any of the following events in the first 3 months after the date of enrollment: a CVO, a prolonged hospitalization (≥ 30 days), died due to a non-CVD-related cause or reached an age of 76 years, whichever occurred first (Fig. 1).

The primary data source was an administrative database of the open cohort of patients enrolled in the DTC Program between January 2013 and December 2018. Patient-level data on demographic (i.e. age, sex), clinical and anthropometric (i.e., body weight, height, serum glucose, total cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, low-density lipoprotein cholesterol [LDL-C], blood pressure (BP), glycated hemoglobin (hba1c), glomerular filtration rate, ICD-10 diagnoses), and epidemiological (i.e., self-reported frequency of physical activity, smoking status, place of residence, and family history of HTA and DM) variables recorded in the outpatient setting by health care professionals at each medical visit was available for the study.

The frequency of CVOs between the time of exposure (July 01–2015 and December 31–2018) was retrieved from the all-cause consolidated hospitalization database of Mutual Ser. Incident cases of stroke, MI and CHF, were identified if an associated ICD-10 code was registered at discharge (stroke = I69, I67, I66, I65, I64, I63, G46, G45, I68; MI = I25, I24, I23, I22, I21, I20; CHF = I50, I13, I11). Information regarding the date and place of occurrence of the hospitalization event, length of stay, and vital status at discharge was also available for the study. Only records of deaths and CVOs in the inpatient setting were available for the study.

The primary outcome of interest was the reduction in the risk of the first incident CVO between adherent and non-adherent patients to the program activities within each cardiovascular risk category over the time of exposure. Secondary outcomes were the crude incidence rates of CVOs for each risk group (using only the first observed event as the numerator and the total person-time years as the denominator) and the time from enrollment to CVO onset.

The adherence to the program was evaluated based on the observed frequency of medical appointments with health care professionals for clinical follow-up (general or specialized physicians and nurses, nutritionists, and psychologists), and the control of cardiovascular risk factors. The criteria defined for considering a patient as an adherent to the program activities were evaluated according to the cardiovascular risk stratification as follows: > = 2 visits to the general physician or nurses for the low-risk group, and > =4 and > =6 visits to general or specialized physicians and nurses for the medium and high-risk with and without DM groups, respectively. A general criterion of at least one visit to nutritionists and psychologists was defined.

Regarding the control of cardiovascular risk factors, the following criteria were evaluated equally for all patients in the study sample as follows: mean systolic BP/diastolic BP < 140/90 mmHg for patients with HTA, mean hba1c < 7% for patients with DM or HTA + DM, mean LDL-C < =100 mg/dL, a reported frequent or occasional history of physical activity or being non-smoker in all medical visits. A patient was considered adherent to the program if at least four of the main criteria were met (80%). Patients with insufficient information for the evaluation of adherence were excluded.

The DTC program is a structured evidence-based intervention focused on the primary prevention of CVOs. Patients are enrolled based on pre-defined screening criteria and are treated by different health care professionals according to the estimated cardiovascular risk at baseline (Framingham Risk Score). A minimum recommended frequency of health care services per year is offered through different private health care companies located in each department where the program is offered (Supplementary material 1). Interventions include pharmacological treatment, appointments with general physicians and nurses trained in cardiovascular health, specialized physicians, nutritionists, psychologists, and educational sessions focused on the adoption of healthy lifestyle habits. Mutual Ser uses a performance-based contract scheme in which health care companies receive financial incentives for achieving specific goals of cardiovascular risk factors control and frequency of CVOs in the enrolled population.

Patient characteristics at baseline were summarized descriptively. Quantitative variables were summarized with means and standard deviations and categorical variables with absolute and relative frequencies. Baseline values were retrieved by selecting the first observation of these variables after the date of enrollment. Differences in patient characteristics between adherent and non-adherent patients before and after matching were assessed using absolute standardized mean differences (SMD).

We used the nearest neighbor propensity score matching method with a 3:1 optimal ratio to reduce selection bias and correct for possible imbalances between adherent and non-adherent patients within each risk group [15‐17]. Multiple logistic regression models were used to obtain a set of propensity scores for each risk category using the adherence status variable as the outcome. The stepwise backward selection method was used to select relevant predictors of adherence. Sex, age, BMI, Systolic BP, Diastolic BP, LDL-C, HDL-C, total cholesterol, triglycerides, stage of renal function based on the glomerular filtration rate, and the department of residence were considered as potential predictors.

The non-parametric Kaplan-Meier survival method was used to evaluate differences in the probability of remaining CVO-free through the exposure time between the matched samples of adherent and non-adherent patients within each risk group. Patients were censored if after the first 3 months of exposure to the program they experienced a prolonged hospitalization (≥ 30 days), died due to a non-CVD-related cause, reached the age of 76 years, or the study period ended, whichever occurred first.

The identification and selection process of the study sample is shown in Fig. 1. A final sample of 52,507 patients was obtained. Baseline characteristics of the matched and unmatched samples by adherence status are shown in Table 1. After propensity score matching, a sample of 35,574 patients was analyzed and the baseline characteristics of the adherent and non-adherent patients within each cardiovascular risk category were balanced (Fig. 2) (See Supplementary material 2 for further details). Mean (SD) exposure time of the analyzed sample was 1.97 (0.92) years, with a minimum and maximum time of 6.24 and 3.49 years, respectively.

A total of 20,613 patients (39.2%) were considered adherents to the program. The highest proportion of adherent patients was found in the low-risk group (53.9%) followed by the medium (43.8%) and high-risk groups (diabetic = 27.7% and non-diabetic = 18.9%, respectively). Non-smoking status, controlled blood pressure, and visits to nurses and general or specialized physicians were the most frequently meet adherence criteria. Only 41.2% of patients in the unmatched sample had a mean hba1c < 7% in the study period. The relative frequency of patients in the matched and unmatched samples meeting each adherence criterion according to clinical diagnosis and cardiovascular risk category is shown in the Supplementary material 3.

A total of 879 (1.6%) patients in the unmatched sample experienced any CVO during the time of exposure (July 01–2015 and Dec 31–2018). Of these, 44.1% (374), 33.6% (285), and 22.2% (188) had a MI, stroke, and CHF diagnosis at discharge, respectively. A total of 32 patients had more than one CVO diagnosis (0.1%). After propensity-score matching, 560 CVOs were observed in the sample obtained. A similar distribution of events between the unmatched and matched samples was found with AMI (47.8%) as the most frequent CVO, followed by stroke (33.2%) and CHF (22.6%). The overall rates of any CVO per 1000 person-years were 8.45 (95% CI 7.90–9.03) and 8.11 (95% CI 7.45–8.81) in the unmatched and matched samples.

According to cardiovascular risk, the rates of CVOs per 1000 person-years were 4.08 (95% CI 3.13–5.22), 8.59 (95% CI 7.82–9.41), 8.66 (95% CI 7.64–9.78), and 18.93 (95% CI 15.37–23.07) in the low-risk, medium-risk, high-risk with DM and high-risk without DM groups, respectively. A similar trend in rates were observed in the matched sample with an overall rate of 8.11 (7.45–8.81) CVOs per 1000 person year and 3.99 (95% CI 2.97–5.25), 9.07 (95% CI 8.15–10.0), 7.58 (95% CI 6.28–9.07) and 21.86 (95% CI 15.39–30.13) in the low-risk, medium-risk, high-risk with DM and high-risk without DM groups, respectively.

The frequency of CVOs according to risk group and adherence status for the matched and unmatched samples are shown in Table 2. The overall rates of the first CVO per 1000 person-years were 4.70 (95% CI 4.04–5.42) and 10.74 (95% CI 9.96–11.7) for adherent and non-adherent patients in the unmatched sample. After propensity score matching, the overall rates were 4.71 (95% CI 4.04–5.45) and 15.88 (95% CI 14.46–17.40) for adherent and non-adherent patients.

Weighted Kaplan-Meier survival curves describing the proportion of patients without CVOs over the study period for adherent and non-adherent patients in each cardiovascular risk group are shown in Fig. 3. The Cox Proportional Hazard model showed a 68.9% reduction in the risk of the first CVO in adherent patients compared to non-adherent patients in the overall sample (HR 0.31; 95% CI 0.24–0.38; p < 0.001). According to risk group, being adherent to the program was associated to a 85.4, 71.9, 32.4 and 78.9% risk reduction of in the low (HR 0.14; 95% CI 0.05–0.37; p < 0.001), medium (HR 0.28; 95% CI 0.21–0.36; p < 0.001), high-risk with DM (HR 0.67; 95% CI 0.43–1.04; p = 0.075) and hig-risk without DM (HR 0.21; 95% CI 0.09–0.48; p < 0.001) categories, respectively.