Introduction

Accurate blood pressure (BP) measurement is crucial in clinical practice for diagnosis and management of hypertension (HTN). Single BP measurement is generally not adequate to assess BP fluctuations. Moreover, night-time BP also robustly predicts coronary heart disease and stroke than clinic BP. A non-dipping BP pattern has also been associated with increased risk of cardiovascular (CV) events. Currently there is a dearth of studies that compare the impact of single drug and combination therapy on BP reduction, including circadian BP in patients with HTN but not resistant HTN.

Aim

To compare the circadian efficacy of a telmisartan 40 mg/S-amlodipine 2.5 mg fixed-dose combination (Telmisartan40/S-Amlodipine2.5) vs. telmisartan 80 mg (Telmisartan80) in patients with essential hypertension

Patient Profile

• Patients with essential hypertension [age ≥19 years, clinic mean sitting systolic blood pressure (MSSBP) ≥140 mmHg, or ≥ 130 mmHg in those with diabetes mellitus or chronic kidney disease]
• The patients had not responded to 2–4 weeks’ treatment with telmisartan 40 mg.

  Methods

  Study Design

• A multicenter, randomized, parallel-group comparative phase IV clinical trial followed by an 8- week open-label extension period.

  Treatment Strategy

• Patients were randomized 1:1 to Telmisartan40/S-Amlodipine2.5 or Telmisartan80 for 8 weeks.
• All patients underwent ambulatory BP monitoring (ABPM) at baseline and 8 weeks later.

Outcomes

Primary Outcomes

• Changes in mean 24-h SBP and diastolic blood pressure (DBP) on 24-h ABPM from baseline after 8 weeks.

  Secondary Outcomes

• Changes in daytime, nighttime, and morning SBP and DBP, and clinic MSSBP and mean sitting DBP (MSDBP).

  Results

• The study population comprised of 316 Korean patients, of these, 217 patients were randomized to treatment and 192 of them completed the study.
• Patients treated with Telmisartan40/S-Amlodipine2.5 had significantly better reductions in 24-h mean SBP and DBP after 8 weeks, vs. those treated with Telmisartan80 SBP (Fig. 1).

  Fig. 1: Reductions in 24-h mean BP during the study

  

• At 8 weeks, the Telmisartan40/S-Amlodipine2.5 group had significantly greater reductions in mean nighttime SBP and DBP and in mean daytime SBP and DBP, vs. Telmisartan80 group (Table 1).
• The Telmisartan40/S-Amlodipine2.5 group had significantly lower reductions in mean morning SBP and DBP and in clinic MSSBP and MSDBP, vs. the Telmisartan80 group (Table 1).

Table 1: Reduction in the secondary outcomes during the study

• A higher proportion of patients treated with Telmisartan40/S-Amlodipine2.5 vs. Telmisartan80 (70.8% vs. 45.5%) achieved 24-h-mean SBP/DBP <130/80 mmHg in 8 weeks.
• Similarly, a higher proportion of patients treated with Telmisartan40/S-Amlodipine2.5 vs. Telmisartan80 achieved daytime mean SBP/DBP <135/85 mmHg (77.1% vs. 59.1%) and nighttime mean SBP/DBP <130/80 mmHg in 8 weeks (50.0% vs. 34.1%).
• A significantly higher proportion of patients treated with Telmisartan40/S-Amlodipine2.5 vs. Telmisartan80 achieved a better control of office BP (<140/90 mmHg; 19.8% vs. 9.1%).
• A significantly higher proportion of patients treated with Telmisartan40/S-Amlodipine2.5 vs. Telmisartan80 achieved 24-h-mean SBP/DBP reduction ≥10/10 mmHg after 8 weeks (20.8% vs. 9.1%; P=0.027).
• A significantly higher proportion of patients treated with Telmisartan40/S-Amlodipine2.5 vs. Telmisartan80 achieved clinic MSSBP/MSDBP reduction ≥10/10 mmHg after 8 weeks (30.2% vs. 15.9%; P=0.022).
• The incidence of adverse events did not differ significantly in the study groups.

Conclusions

• Telmisartan40/S-Amlodipine2.5 was more effective than Telmisartan80 in lowering Circadian BP in patients with essential hypertension not responding adequately to Telmisartan40.
• These findings support the concept of using a combination of S-amlodipine and telmisartan rather than increasing the dose of telmisartan monotherapy.

Clin Hypertens, 2022;28:7:doi:10.1186/s40885-021-00184-0.