Early Dual Therapy for Hypertension Better Than Escalating Monotherapy

From HippoEd’s Primary Care RAP:


  • For patients with poorly controlled hypertension, studies support adding a second agent from a different class rather than increasing the dose of the pre-existing antihypertensive.

  • Dual therapy is not only more efficacious at managing blood pressure, but it is also associated with fewer side effects.

  • No particular combination of blood pressure medications is superior to another — all appear to be good options.

  • Consider starting dual therapy at the time of diagnosis for those with markedly elevated blood pressure.


Case 1

A patient returns to your clinic after last being seen a month ago.  She was diagnosed with hypertension at the prior visit and was started on hydrochlorothiazide 12.5 mg daily.  Today, her blood pressure is still not controlled.  Assuming you’ve ensured compliance with therapy and done appropriate counselling regarding diet and exercise, what is your next step?  Do you increase the hydrochlorothiazide, add on a new medication, or just continue the current regimen?


  • Cardy and Selim agree that they would increase the preexisting medication rather than add a new one.  The former option is much simpler, and they have found that patients are often reluctant to start a new medicine.  Furthermore, both physicians fear the potential of a new set of side effects.

  • While is may be easier to increase the dose of the current antihypertensive agent, this may not be the best strategy.

  • Research suggests that combining hypertensive medications from different classes may be superior compared to increasing the dose of the preexisting blood pressure medication.

    • Study #1:

      • A large meta-analysis published in 2003 found that giving a half dose of a blood pressure medication had about 80% of the efficacy of a full standard does, but far less side effects.  This was true for all four classes of antihypertensives studied:  calcium channel blockers, ACE inhibitors, thiazides, and beta-blockers.  There did not seem to be one class of medications that was superior to the others.

      • The other major finding in this study was that combining hypertension medications from different classes had an additive effect on blood pressure reduction, and the adverse effects due to the combination was far less than additive.  No specific combinations of antihypertensives were superior to the others.

      • Law MR, et al. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ. 2003  Jun 28;326(7404):1427. PubMed PMID: 12829555

    • Study #2:

      • Another large meta-analysis showed that combining blood pressure medications from different classes had an additive effect on blood pressure reduction.

      • This study also showed that combining 2 different classes at lower doses was far superior to doubling the dose of a single medication.

      • In their analysis, the authors say that it’s actually 5 times more efficacious to add on a new medication from a different class than double the pre-existing medication.

      • This study found that combining medications had far less side effects than increasing the dose of the monotherapy.

      • Like the first study, this one compared calcium channel blockers, ACE inhibitors, thiazides and beta-blockers; they didn’t find any combination that was superior to another.

      • Given the dramatic reduction in blood pressure with combination therapy, the authors advocate that we initiate patients on dual medications for blood pressure control.

      • Wald DS, Let al. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med. 2009 Mar;122(3):290-300. PMID: 19272490

  • What do the guidelines say about combination antihypertensive therapy?

    • Both the American and the Canadian guidelines state that for patients on monotherapy who are not controlled, you can either increase the preexisting medication or consider adding on another agent for another class.  They do not really make any recommendation as to which option is better.

    • They also both mentioned that providers can consider initiating dual therapy at the time of diagnosis for patients who have a very high blood pressure at the beginning of therapy (greater than 160/100 mmHg).

  • The bottom line:  

    • Combining lower doses of hypertension medications from different classes seems to be more effective than increasing the dose of the preexisting medication.  It also seems to have fewer side effects.

    • There doesn’t seem to be any combination of medications that is optimal in the available studies — all appear to be good options.  Medication choices should be tailored to the patient’s comorbidities. For instance, patients with congestive heart failure and/or coronary artery disease may benefit from a beta-blocker.  Diabetics should preferentially be on an ACE inhibitor.

    • For patients with marked elevation of blood pressure at the time of diagnosis, consider initiating dual therapy

    • Single pill combination therapies are convenient options for patients who might benefit from 2 drugs but are reluctant or apprehensive about taking 2 pills.

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