Efficacy of Amlodipine as an anti Hypertensive in India: Results from a real-world study

Hypertension is now well established as a major risk factor for cardiovascular disease(1). There has been an exponential rise in hypertensive cases, both globally as well as in India. (2)

Although there is a huge body of evidence supporting the beneficial effects of antihypertensive therapy on reducing the mortality rates in known hypertensives (3), adequate blood pressure management remains a challenge for physicians.

Calcium channel blockers (CCBs), one of the oldest groups of drugs prescribed in hypertension (HTN), have gained wide recognition for their efficacy. Studies have repeatedly shown that among the CCBs, amlodipine is preferred by 75.7% of Indian physicians. (4)

The effectiveness of amlodipine is based on its mechanism of action revolving around its high vascular selectivity that reduces peripheral resistance while preserving myocardial contractility [5]. Furthermore, amlodipine has a long elimination half-life and binds to the target receptors in a slow and sustained manner, resulting in a smooth onset of action and 24-h BP control. Amlodipine has also been reported to reduce the risk of cardiovascular events and all-cause mortality.

Amlodipine which is regarded as a first-line drug in hypertensives (5), is generally provided as a monotherapy as well as a combination therapy; customizing the treatment depending on the clinical condition of the patients. (6)

Even though many clinical trials (7,8) have investigated the efficacy of amlodipine monotherapy versus its combination with other agents, including diuretics, ACE inhibitors (ACEIs), andangiotensin receptor blockers (ARBs), but there remains a dearth of evidence on the same in a real-world setting i.e. in clinical practice in India.

Addressing this lack of knowledge, in 2020, Mohammed Yunus Khan et al, researchers from Dr Reddy's Laboratories, Hyderabad, designed a first-of-its-kind study to evaluate the effectiveness of amlodipine prescribed to Indian patients with hypertension during routine clinical practice in India. (9)

In a retrospective observational study, the electronic medical records (EMR)data of 462 Indian patients diagnosed with essential hypertension were assessed.

From January 2018 to September 2019, adult patients (≥ 18 years old) who were diagnosed with essential hypertension by their physicians as per ESC/ESH 2018 guidelines (≥140/90 mmHg) at baseline, were prescribed amlodipine either as monotherapy or as add-on therapy, and data available for at least two visits with a minimum gap of 1 month after initiation of amlodipine, were included in the study.

Patients were classified based on the number of AHD classes prescribed on the initiation of amlodipine. Change in systolic (SBP) and diastolic (DBP) blood pressure from baseline was the primary endpoint. Evaluation of the proportion of patients who achieved treatment goals as per the 2018 European Society of Cardiology/European Society of Hypertension guidelines was the secondary endpoint.

On statistical analysis, the following key facts emerged.

• A majority (90.7%) were prescribed amlodipine monotherapy or amlodipine+1AHD among the study population.

• Mean change in the amlodipine monotherapy group was: SBP (− 12.1 [− 14.9, − 9.3] mmHg) and DBP (− 7.5 [− 8.9, − 6.1] mmHg) and mean change in the amlodipine+1AHD group was: SBP (− 17.8 [− 21.0, − 14.6] mmHg) and DBP (− 9.5 [−11.0, − 8.0] mmHg). These drops were significant

• SBP and DBP goals were achieved by 31.4% and 42.9% of patients on amlodipine monotherapy and by 38.9% and 51.8% of patients on amlodipine+1AHD, respectively.

• Among the patients aged≤45 years, mean change in the amlodipine monotherapy group was: SBP(− 11.7 [− 16.0, − 7.4] mmHg; P<0.001) and DBP (− 7.2 [− 9.7, − 4.7] mmHg;P<0.001) and mean change in the amlodipine+1AHD group was: SBP (− 14.6 [− 21.9, −7.3] mmHg; P<0.05) and DBP (− 10.6 [− 14.8, − 6.4]mmHg; P<0.01).

• In this segment, SBP and DBP goals were achieved by 35.4% and 33.8% of patients on amlodipine monotherapy and by 48.0% and 56.0% of patients on amlodipine+1AHD,respectively.

• Among the patients aged≥65 years, mean change in the amlodipine monotherapy group was: SBP (− 13.9 [− 20.2, − 7.6] mmHg; P<0.01) and DBP (− 8.5 [− 11.4, − 5.7]mmHg;P<0.001) and mean change in the amlodipine+1AHD group was: SBP (− 22.4 [− − 28.8,− 16.0] mmHg; P<0.001) and DBP (− 10.8 [− 14.0, − 7.6] mmHg; P<0.001).

• In this segment, SBP and DBP goals were achieved by 25.5% and 13.7% of patients on amlodipine monotherapy and by 29.8% and 14.0% of patients on amlodipine+1AHD.

• The average duration between visits 1 and 2 was 91.2 days, 100.9 days,78.8 days, and 51.2 days for patients on amlodipine monotherapy, amlodipine + 1AHD, amlodipine +2AHDs, and amlodipine+3AHDs, respectively.

The interesting findings made the team put forth some important observations.

1. Prescription of amlodipine either as monotherapy or add-on therapy reduced overall mean SBP and DBP by 13.6 mmHg and 8.0 mmHg, respectively.

2. Overall, 34.4% of the patients achieved the SBP goal and 46.5% achieved the DBP goal as specified in the ESC/ESH 2018 and 2019 IGH-IV guidelines (<140/90 mmHg).

Acknowledging some limitations in the study like the retrospective design, small sample size, and patient dependence for adhering to study designs, the team highlighted that future studies with a larger sample size and a uniformly monitored drug adherence protocol for patients are recommended with amlodipine.

Based on the results, the authors concluded that "Amlodipine prescribed as monotherapy or add-on therapy during routine clinical practice significantly reduced BP in≤45- and≥65-year-old Indian patients with mild to moderate hypertension, emphasizing that amlodipine may be a good candidate for BP control in Indian patients with essential hypertension in these age groups.

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9. Khan MY, Pandit S, Ray S, Mohan JC, Srinivas BC, Ramakrishnan S, Mane A, Mehta S, Shah S. Effectiveness of Amlodipine on Blood Pressure Control in Hypertensive Patients in India: A Real-World, Retrospective Study from Electronic Medical Records. Drugs Real World Outcomes. 2020 Dec;7(4):281-293. doi: 10.1007/s40801-020-00211-w. PMID: 32901435; PMCID: PMC7581658.