Amlodipine and Telmisartan combination offers swift, effective BP control along with end-organ protection in hypertensive patients with diabetes: Study

Data from several studies have shown that appropriate antihypertensive treatment in diabetic patients decreases heart failure, ASCVD events and microvascular complications.(3) According to the latest guidelines from the American Diabetes Association (ADA 2021), Angiotensin receptors blockers (ARB) are one of the recommended first-line therapies for the treatment of hypertension in individuals with diabetes and coronary artery disease (CAD). Moreover, it has been acknowledged that >1 drug will be needed to achieve BP targets in this population. In patients with BP >160/100 mmHg, initiation of therapy with a single-pill combination (SPC) of two agents' has been found to decrease cardiovascular (CV) events in patients with diabetes and hypertension and can also facilitate a swift and sustained reduction in BP levels. Drugs with complementary modes of action like

Telmisartan (ARB) and Amlodipine (calcium channel blockers) have independently proven their efficacy in decreasing CV risk and their combination may thus have an additive effect in high-risk hypertensive patients such as those with diabetes, obesity or the metabolic syndrome.(6)

Both Telmisartan and

Amlodipine offer 24-hour BP control and decrease CV risk an effect independent of their BP-lowering ability. Moreover, their combination has been more effective than monotherapy with the individual agents across stages of hypertension and several patient subgroups. Specifically, the renoprotection offered by Telmisartan is maintained when it is combined with Amlodipine. Tolerability with this combination has also been better than that seen with high-dose Amlodipine therapy. The Telmisartan/Amlodipine Single-Pill Study Versus Amlodipine as first-line therapy in patients with stage 1 or 2 hypertension and T2DM (TEAMSTA diabetes) sought to determine the safety and efficacy of the Amlodipine/Telmisartan (A/T) SPC in patients with added-risk such as those with coexisting diabetes and hypertension vs. Amlodipine (A) alone.

Design of the study: The 8-week TEAMSTA diabetes study was a multinational, randomised, double-blind, parallel-group study involving hypertensive patients (n=706; baseline BP was 160.8/91.0 mmHg; 57.5% of patients obese) recruited from 64 centres in 9 countries. After a 2- to 3-week placebo run-in period, patients were initially randomised to a A/T 5/80 mg SPC (n=352) or A 5 mg (n=354) for 2 weeks and then uptitrated to A/T 10/80 mg SPC once daily or A 10 mg once daily for another 6 weeks. An ambulatory BP monitoring (ABPM) substudy was also included in the protocol with a subgroup of patients [A/T SPC (n=68) and A (n=64)].

Inclusion criteria: Men and women (>18 years old) with diagnosed type 2 diabetes (T2D) and stage 1 or 2 hypertension [office systolic BP (SBP)>150 mmHg).

• CI Patients with type 1 diabetes (T1 D) or if HbAl C>10%

• Prespecified renal or hepatic disorders, congestive heart failure, clinically relevant cardiac arrhythmias, severe obstructive CAD or any other condition that inhibited safe completion of the protocol

• Nightshift workers and pregnant or nursing women or women of childbearing age not using an approved contraceptive

• Patients with a contraindication to a placebo run-in period, those treated with any investigational therapy <1 month of providing their informed consent

• Patients with previous symptoms characteristic of angioedema when on angiotensin-converting enzyme inhibitor/ARB therapy or hypersensitivity to the study drugs

• History of drug or alcohol dependency <6 months before the study and

• Patients with a history of non-compliance to the medical protocol or any other clinical condition that makes compliance difficult or unsafe

Primary endpoint: Change in mean seated trough cuff SBP vs. baseline after 8 weeks of therapy.

Secondary endpoints: Change in mean seated trough cuff SBP vs. baseline after 1, 2, 4, 6 and 8 weeks of therapy.

Additional secondary endpoints: (a) Change in mean seated trough cuff diastolic BP (DBP) vs. baseline after 1, 2, 4, 6, and 8 weeks of treatment, (b) SBP and BP goal attainment (<140 mmHg, <140/90 mmHg and <130/80 mmHg), (c) Response rates (130 mmHg or a reduction of >10 mmHg OR 140 mmHg or a reduction of >10 mmHg), (d) Change in urine albumin: creatinine ratio (UACR) vs. baseline after 8 weeks of therapy, (e) Secondary endpoints for the ABPM substudy (after 8 weeks of therapy) included change in 24-hour ABPM mean for SBP vs. baseline, change in the hourly mean of SBP/DBP over the 24-hour dosing interval vs. baseline and the percentage of patients achieving the 24-hour mean SBP/DBP targets of <130/80 and <120/80 mmHg.

Compared to Amonotherapy, the following results were observed with A/T SPC therapy.

• 60% of the SBP reduction observed in the 1' week with A/T SPC:

Treatment with A/T SPC caused a significantly greater reduction in the mean seated trough cuff SBP vs. A alone after 8 weeks of treatment and 60% of this significant reduction was attained within the 1st week itself and was sustained till week 8 (Fig 1). Irrespective of the baseline SBP, A/T SPC resulted in a greater reduction in mean in-clinic seated trough cuff SBP vs. A monotherapy at the end of 8 weeks.

At the end of 8 weeks, A/T SPC also decreased DBP levels to a greater extent than A monotherapy (-12.5 vs. -10.5 mmHg) an impact that was again observed from the 1 week itself.

• >70% patients on A/T SPC achieved both BP and SBP goals:

At the end of 8 weeks, a greater proportion of patients on A/T SPC achieved both the BP (<140/90 mmHg) and SBP goals (<140 mmHg) vs. A alone (Fig 2). Even the more stringent BP goal (<1 30/80 mmHg) was achieved by double the number of patients in the A/T SPC group than the A group (Fig 2).

A greater SBP response (<140/90 mmHg or >10 mmHg reduction) was seen with A/T SPC vs. A alone at the end of 8 weeks (Fig 3). This enhanced response in the A/T SPC group was observed from 2 weeks onwards (Fig 3).

The geometric mean reduction in UACR at the end of 8 weeks was by 0.40 mg/g (-70% of baseline) with A/T SPC therapy whereas it remained largely unchanged with A monotherapy.

• 24hr BP control greater with A/T SPC:

Significantly greater changes in 24hr mean BP values were observed with A/T SPC vs. A alone (Fig 4) and 52.9% of patients on the A/T SPC achieved the 24hr mean BP of <130/80 mmHg compared to 39.1% in the A group The same pattern was reflected in the daytime and nighttime BP levels too.

Moreover, all the parameters studied such as mean SBP decrease, BP/SBP goal achievement and SBP response were all greater with A/T SPC vs. A alone, irrespective of the obesity status of the patient.

Lastly, both the groups showed a comparable adverse effect profile and the majority of the events were either mild or moderate with 92.2% of patients completing the study.

Patients with diabetes and coexisting hypertension are at greater risk for adverse events than those with diabetes alone. Achievement of BP targets in this patient population normally requires a two-drug combination. Moreover, rapid attainment of BP control, appropriate BP goal achievement and sustained 24hr BP control have all been found to have a beneficial impact on CV event risk. The TEAMSTA diabetes study sought to assess the efficacy and safety of the A10/T80 SPC vs. A10 alone on patients with diabetes and coexisting hypertension. The study found that SPC therapy led to a substantially greater decrease in BP levels, BP response and BP goal achievement rates vs. A10 monotherapy. Additionally, this therapy resulted in swift BP reduction, was equally effective in both obese and non-obese patients and was well-tolerated. All these aspects indicate that A/T SPC would be an effective antihypertensive option for patients at greater risk such as those with metabolic syndrome, diabetes and obesity.

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