Hypertension Rx: Start Strong to Stay Strong

November 30, 2018

Under what circumstance/s is it appropriate to initiate treatment for hypertension with a single drug (followed by titration, additional agents)?

I have recently been struggling with an essential primary care issue – the early management of hypertension. Most patients who are initially treated with monotherapy (>95%)1 return uncontrolled despite dose escalation and/or additional medications. I recently saw a patient on 80 mg lisinopril as monotherapy, the same drug and dose he had been on for a year. Not surprisingly, this patient’s blood pressure was above target. He also is a real-world representative for thousands of research participants for whom initial treatment for hypertension with one drug has failed to bring blood pressure under control in a timely manner.1-4 The literature is telling us something. So, how can this unsuccessful and dangerous, approach be remedied?

Learn more by considering these 2 quick questions.  

1. Which of the following statements regarding initial combination vs monotherapy followed by increasing doses of medication or add-on agents is/are TRUE:

A. In people with initial blood pressures >150/95 mm Hg, early vs delayed control in the VALUE trial, attained with >1 antihypertensive medication prescribed at the onset of therapy provided better control over the first 3 months with fewer cardiovascular events vs monotherapy.

B. In the VALUE and ASCOT trials, blood pressure control in the less effective monotherapy-treated patients never caught up with the levels achieved in the combination antihypertensive group despite ongoing follow-up and “stepped care.”

Please click here for answer, discussion, and next question.


Answer: Both statements are true.1

Patients with hypertension who achieve blood pressure control more quickly, do better over time. Starting them on low doses of 2 or 3 agents initially gets them to their goal in less time vs initial monotherapy.2-4 Patients who lag behind are at increased cardiovascular risk and it seems that blood pressure control in patients initiated on one-drug regimens never really catches up to levels attained in the combination group.


2. Which one of the following statements is true?

A. Major randomized, blinded antihypertension trials (eg, PATHWAY, STITCH, and STRATHE) all proved the superiority of >1 antihypertensive agent at initiation of therapy vs monotherapy with adjustments and additions over time.

B. The difference in one randomized clinical trial between groups initiated on monotherapy and combination (triple) antihypertensive drug therapy at 6 months was 30% vs 55%. 

C. There were more adverse reactions in the combination treatment groups in all studies.

Please click here for answer and discussion.


Answer: A. is True

In the randomized clinical trial in option B, the percentage of patients controlled on combination therapy vs monotherapy was 70% vs 55%, respectively.3 Across numerous studies of combination antihypertensive agents, adverse events were not increased;2-4option C is not true.

The paradigm for treating hypertension has really shifted.1-4 In patients with stage 2 (140/90 mm Hg) hypertension, control will not be attained with single-agent titration, ie, monotherapy. Patients treated with monotherapy are at higher cardiovascular risk after only 3 months.

It is also possible that the advantages of a combination approach from the start will never be realized in a monotherapy-driven regimen.

What combination will make sense for your next pateint requiring hypertension management for the first time? 


1. Weir S, Juhasz A, Puelles J, Tierney TS. Relationship between initial therapy and blood pressure control for high-risk hypertension patients in the UK: a retrospective cohort study from the THIN general practice database. BMJ Open 2017; 7:e015527.

2. MacDonald TM, Williams B, Webb DJ, et al. Combination therapy is superior to sequential monotherapy for the initial treatment of hypertension: a double-blind randomized controlled trial. JAHA 2017; 6:e006986.

3. Webster R, Salam A, de Silva A, et al. Fixed low-dose triple combination antihypertensive medication vs. usual care for blood pressure control in patients with mild-to-moderate hypertension in Sri Lanka: a randomized clinical trial. JAMA. 2018; 32:566-579.

4. Mazza A, Lenti S, Schiavon L, et al. Fixed-dose triple combination antihypertensive drugs improves blood pressure control: from clinical trials to clinical practice. Adv Ther. 2017; 34:975-985.