CRYSTEL was a non-interventional, multicentre, prospective, observational study conducted in healthcare facilities across the Democratic Republic of Congo between Q2 2022 and Q4 2022. The study was implemented in accordance with routine clinical practice; no investigational intervention was imposed, and treatment selection, dosing, and any subsequent dose adjustments remained entirely at the discretion of the attending physician. The total treatment/observation duration was 12 weeks. The protocol stated that approximately 482 subjects with hypertension would be enrolled across multiple sites, with site numbers able to vary according to recruitment rates or site closure. Between 15 and 18 sites participated in the study, comprising a mix of general hospitals, private hospitals, and primary health care centres in the Democratic Republic of Congo. The present analysis is based on the locked clinical database prepared at the conclusion of the field phase.

Adult patients aged ≥18 years with a diagnosis of hypertension who, in the judgment of the treating physician, were clinically suitable for either telmisartan (Teleshal^TM) monotherapy or telmisartan plus hydrochlorothiazide (Teleshal^TM-H) combination therapy were eligible for inclusion, provided they were willing to provide informed consent for the use of their personal and health-related data in the study. Patients were stratified post hoc into the two exposure cohorts of interest: telmisartan alone, or telmisartan in fixed combination with HCTZ at the doses routinely available in DRC practice (40/12.5 mg, 80/12.5 mg, or 80/25 mg).

Exclusion criteria were: 1) any contraindication to telmisartan or telmisartan/HCTZ as listed in the locally approved prescribing information; 2) any medical or non-medical factor that, in the physician’s judgment, would impede study participation; and 3) pregnancy, lactation, or being a woman of childbearing potential not willing to use an effective barrier contraceptive method throughout the observation period.

Each participant completed two protocol visits: Visit 1 (baseline) and Visit 2 (first follow-up at 3 months ± 7 days, corresponding to the protocol-specified 12-week treatment/observation duration). At Visit 1, investigators recorded demographic data, relevant medical history, baseline vital signs, and detailed information regarding the prescribed study drug, including dose strength. Visit 2 captured treatment adherence, any change in dose regimen, body weight, BP, treatment-emergent adverse events, and a physician-led four-point global assessment of combined efficacy and safety (“Poor” to “Excellent”).

Blood pressure was measured using a standard Omron digital BP monitor by the treating physician at each site, consistent with common clinical practice in the DRC, providing a reasonably standardised measurement device across sites.

Primary outcome. The primary objective was to characterize the real-world utilization pattern of telmisartan and telmisartan/HCTZ in hypertensive adults in DRC, including dose distribution by regimen.

Secondary effectiveness outcomes. Secondary outcomes were: 1) the within-group change in SBP and DBP from baseline to Visit 2; 2) the proportion of participants achieving BP control, defined as SBP ≤ 140 mmHg and DBP ≤ 90 mmHg; and 3) the dose-stratified analysis of BP change and BP control.

Secondary safety outcome. Adverse events reported between Visit 1 and Visit 2 were recorded with verbatim description, severity (mild, moderate, or severe), and the clinical action taken (none, dose reduction, discontinuation, or other). Physician global assessment of efficacy and safety (four-point scale: Poor/Fair/Good/Excellent) provided an integrated effectiveness/tolerability judgement.

Data were summarized using descriptive statistics (means, standard deviations, frequencies, and percentages) for demographic, prescribing, BP, and safety variables. For each BP outcome, within-group change from baseline to Visit 2 was tested using a paired t-test, with a two-sided P-value < 0.05 considered statistically significant. Analyses were performed on the available patient population at each study site using the locked clinical dataset; no imputation of missing values was performed. Dose-stratified BP analyses followed the same paired t-test framework.

The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and applicable local regulations governing non-interventional research. Each participant provided informed consent for the use of personal and health-related data prior to study entry. The protocol was reviewed by the relevant institutional ethics committees at participating sites.

A total of 482 patients were enrolled and 388 patients (203 in the telmisartan (Teleshal^TM) group and 185 in the telmisartan + HCTZ (Teleshal^TM-H) group) were assigned a study drug and dose. The mean age was 58.60 ± 12.00 years in the telmisartan group and 60.75 ± 11.76 years in the telmisartan + HCTZ group. In both groups, the majority of patients were in the age group 61 - 70 years (30.5% and 33.5%, respectively). Females comprised 50.7% of the telmisartan group and 60.5% of the telmisartan + HCTZ group (Table 1).

The most prevalent risk factors were alcohol consumption (50.2% in telmisartan group, 36.2% in telmisartan + HCTZ group) and physical inactivity (23.6% and 51.4%, respectively). The majority of patients were newly diagnosed or had hypertension for less than 3 years. A family history of hypertension was present in approximately 44% of patients in both groups (Table 2).

Table 1.Baseline demographic and clinical characteristics.

Table 2. Participant disposition summary.

This is an uncontrolled study conducted in a real-world clinical setting, and no protocol-mandated visit window or retention procedure was enforced. Physicians at the participating sites cited three recurring reasons for missing follow-up and non-completion: 1) inability of patients with limited financial means to continue affording medication, 2) non-adherence to the treatment regimen among some patients with alcohol use, and 3) discontinuation of follow-up visits by patients who felt their symptoms had improved.

All effectiveness and safety estimates in this report are available-case analyses—that is, they are calculated using all patients with data at the relevant timepoint (s), rather than a fixed intention-to-treat cohort carried forward. Because attrition was not random (it was associated with cost, adherence, and perceived improvement), available-case estimates of BP reduction may be biased toward patients who remained engaged in care and could, in principle, over- or under-estimate the true population-level effect.

Dose Distribution

In the telmisartan group, the majority of patients (45.8%) were prescribed the 40 mg dose, followed by 80 mg (33.0%) and 20 mg (20.7%). In the telmisartan + HCTZ group, the most commonly prescribed dose was 40/12.5 mg (48.6%), followed by 80/12.5 mg (30.3%) and 80/25 mg (21.1%). This distribution indicates that most patients were initiated on moderate doses, with dose escalation based on response and tolerance (Figure 1 and Figure 2).

Figure 1.Distribution of drug potency of telmisartan.

Figure 2.Distribution of drug potency of Telmisartan + HCTZ.

3.3.1. Systolic Blood Pressure

Significant reductions in systolic blood pressure were observed in both groups from baseline to week 12 (Table 3).

Table 3. Changes in systolic blood pressure from baseline to week 12.

In the telmisartan group (n = 166 with paired baseline and Week 12 measurements), mean SBP decreased from 161.54 ± 20.69 mmHg at baseline to 144.29 ± 17.70 mmHg at week 12 (−10.68%; P < 0.001). In the telmisartan + HCTZ group (n = 163), mean SBP decreased from 174.54 ± 24.24 mmHg to 144.01 ± 15.61 mmHg (−17.49%; P < 0.001). Both reductions were statistically significant within their respective groups; no between-group statistical comparison was performed.

3.3.2. Dose-Response Relationship for SBP

A dose-related pattern was observed in both groups, with SBP reduction increasing at higher doses: 1) Telmisartan Group: 20 mg, 3.27% reduction (P = 0.2020); 40 mg, 8.80% reduction (P < 0.001); 80 mg, 15.91% reduction (P < 0.001). 2) Telmisartan + HCTZ Group: 40/12.5 mg, 12.90% reduction (P < 0.001); 80/12.5 mg, 19.87% reduction (P < 0.001); 80/25 mg, 23.93% reduction (P < 0.001).

3.3.3. Diastolic Blood Pressure

Significant reductions in diastolic blood pressure were also observed in both groups (Table 4).

Table 4.Changes in diastolic blood pressure from baseline to week 12.

In the telmisartan group (n = 165), mean DBP decreased from 95.54 ± 16.06 mmHg at baseline to 84.91 ± 14.05 mmHg at week 12 (−11.13%; P < 0.001). In the telmisartan + HCTZ group (n = 160), mean DBP decreased from 100.85 ± 18.15 mmHg to 83.89 ± 12.82 mmHg (−16.82%; P < 0.001).

3.3.4. Dose-Response Relationship for DBP

1) Telmisartan Group: 20 mg, 5.69% reduction (P = 0.032); 40 mg, 10.12% reduction (P < 0.001); 80 mg, 14.64% reduction (P < 0.001). 2) Telmisartan + HCTZ Group: 40/12.5 mg, 12.21% reduction (P < 0.001); 80/12.5 mg, 17.88% reduction (P < 0.001); 80/25 mg, 24.89% reduction (P < 0.001).

3.3.5. Blood Pressure Control Achievement

Overall, 38.14% of patients achieved blood pressure control (SBP ≤ 140 mmHg and DBP ≤ 90 mmHg) by week 12. In the telmisartan group, 36.94% achieved control, while in the telmisartan + HCTZ group, 39.45% achieved control. The highest control rates were observed with telmisartan 20 mg (45.23%) and telmisartan + HCTZ 80/25 mg (46.15%) (Table 5).

Table 5. Duration of hypertension.

At week 12, adherence to treatment was assessed. In the telmisartan group, 57.1% of patients were rated as having good adherence, while in the telmisartan + HCTZ group, 60.9% were rated as having good adherence. The moderate to high adherence rates observed are encouraging and suggest that patients were generally compliant with their medication regimen.

Adverse events were reported in only 4.79% of patients in the telmisartan group (8 out of 167 patients) and 4.91% of patients in the telmisartan + HCTZ group (8 out of 163 patients). The reported adverse events included dizziness, headache, physical asthenia, and insomnia. All adverse events were of mild to moderate severity. In most cases, no action was taken, and the issues resolved spontaneously. In a small number of cases, the dose of study medication was reduced. No serious adverse events were reported.

Physicians rated the global efficacy and safety of telmisartan and telmisartan + HCTZ as: (Figure 3)

Figure 3.Global assessment of efficacy and safety.

Overall, 81.6% of physicians rated the efficacy and safety of telmisartan as excellent or good, while 89.9% rated telmisartan + HCTZ as excellent or good, indicating a high level of clinical satisfaction with both therapies, with a preference for the combination therapy.