BPLTTC: Using Antihypertensive agents as risk modifiers for prevention of CV events irrespective of baseline criteria: Scope of Amlodipine
Hypertension, a prominent cause of premature mortality, affects ~1.13 billion people worldwide, though blood pressure (BP) control rates remain dismal at <20%. (1) Though several trials have shown that BP-lowering with antihypertensive agents is an effective strategy for reducing cardiovascular (CV) risk, the treatment and control rates of patients with hypertension (BP>140/90 mm Hg) across the world remain disappointing.
This discrepancy can be partly attributed to the fact that ambiguities continue to exist about the efficacy and safety of BP-lowering. Some of the issues include the lack of expert consensus on the suitable BP threshold for initiation of therapy and whether this should vary based on the patient's age or baseline disease status. Similarly, data is frugal on the effects of antihypertensive therapy on safety and non- vascular outcomes. (2)
The Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) sought to analyse individual patient-level data (IPD) from 3,48,854 participants from 48 clinical trials across the world 2 to determine the efficacy of BP-lowering for prevention of CV events across different levels of BP. (3)
The participants in the analysis were primarily split into two groups - with and without prior diagnosis of CV disease. Each group was additionally subdivided into 7 groups based on the individual's baseline systolic BP (i.e. at study entry). The BP thresholds (in mmHg) for this subdivision were 1) <120, 2)120- 129, 3) 130-139, 4) 140-149, 5) 150-159, 6) 160-169 and 7) ≥170 with an average follow-up of 4 years.
The results, presented at European Society of Cardiology Congress 2020, showed that every 5 mmHg reduction in systolic BP decreased the relative risk (RR) of major CV events by nearly 10%. Similarly, reductions in the risk for other events were also observed, irrespective of the baseline BP values and CV risk status (Fig 1). 4 This landmark analysis reaffirmed the benefit of BP-lowering medication in preventing CV events across hypertensive populations, establishing these agents as risk modifying treatments for all patients at elevated risk.( 3),(4)
Amongst the available antihypertensive agents, Amlodipine continues to be regarded as the "GOLD STANDARD" in terms of BP reduction. (5) This aspect is well-substantiated with the presence of outcome data via several long-term landmark trials which show that Amlodipine-based regimens successfully reduce CV morbidity and mortality. (6),(7)
The reduction in CV events was further confirmed by a meta-analysis of 7 large-scale, actively controlled, long-term outcome trials which showed that compared to non-calcium channel blocker (CCB) antihypertensive therapy, Amlodipine-based regimens decreased myocardial infarction by 9%, stroke by 16%, total CV events by 10% and total mortality by 7%. (8)
Amlodipine's effectiveness in lowering BP along with its excellent tolerability and minimal side effects has made it a preferred agent across the globe as a part of both single and combination drug regimens targeted towards decreasing CV disease burden. 7,9 Amlodipine, which has been in use for >2 decades, should thus be considered a first-line antihypertensive agent for the management of hypertension, not only for its BP-lowering effect but also for safely improving CV outcomes in patients. (9)
References
1. Hypertension. WHO [Internet] 2019 [cited 2020 Sep 30] Available from https://www.who.int/news- room/fact-sheets/detail/hypertension
2. Rahimi K, Canoy D, Nazarzadeh M, Salimi-Khorshidi G, Woodward M, Teo K, Davis BR, Chalmers J, Pepine CJ; Blood Pressure Lowering Treatment Trialists' Collaboration. Investigating the stratified efficacy and safety of pharmacological blood pressure-lowering: an overall protocol for individual patient-level data meta-analyses of over 300 000 randomised participants in the new phase of the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC). BMJ Open. 2019 May 22;9(5):e028698.
3. BPLTTC Science News from ESC 2020. American Heart Association [Internet] 2020 [cited 2020 Sep 30] Available from https://professional.heart.org/-/media/phd-files/meetings/esc/2020/bplttc.pdf?la=en
4. Blood pressure-lowering is even more beneficial than previously thought BPLTTC trial presented in a Hot Line Session today at ESC Congress 2020. ESC Press Office [Internet] 2020 [cited 2020 Sep 30] Available from https://www.escardio.org/The-ESC/Press-Office/Press-releases/Blood-pressure-lowering-is-even- more-beneficial-than-previously-thought
5. Neutel J, Smith DH. Evaluation of angiotensin II receptor blockers for 24-hour blood pressure control: meta-analysis of a clinical database. J Clin Hypertens (Greenwich). 2003 Jan-Feb;5(1):58-63.
6. de la Sierra A. Amlodipine in the Prevention and Treatment of Cardiovascular Disease. European Cardiology Reviews 2007;3(2):66-68.
7. Owen AJ, Reid CM. Cardio classics revisited: focus on the role of amlodipine. Integr Blood Press Control. 2012;5:1-7.
8. Lee SA, Choi HM, Park HJ, Ko SK, Lee HY. Amlodipine and cardiovascular outcomes in hypertensive patients: meta-analysis comparing amlodipine-based versus other antihypertensive therapy. Korean J Intern Med. 2014 May;29(3):315-24.
9. Fares H, DiNicolantonio JJ, O'Keefe JH, Lavie CJ. Amlodipine in hypertension: a first-line agent with efficacy for improving blood pressure and patient outcomes. Open Heart. 2016 Sep 28;3(2):e000473.
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