Initial combination therapy is superior to sequential mono-therapy for treating hypertension. Combination therapy controls blood pressure faster by acting on multiple mechanisms, reducing complications by 40-54%. Combinations have greater efficacy, improve adherence, and have protective effects beyond blood pressure lowering like anti-inflammatory and metabolic benefits. Clinical trials show combination therapy achieves better blood pressure control rates and lowers cardiovascular events compared to mono-therapy. Therefore, guidelines recommend starting treatment for hypertension with initial combination therapy.

1. Ahmed Taha Abdelwahed, MD
Lecturer of Cardiology
Department of Cardiology, Faculty of Medicine,
Zagazig University, Egypt;
Heart Center, Department of Cardiology, Tampere University Hospital,
and School of Medicine, University of Tampere, Finland
Mono vs.
Combination therapy for
initial treatment of
Hypertension
Consultant of Cardiology

2. The Lancet, VOLUME 389, ISSUE 10064, P37-55, JANUARY 07, 2017

3. Introduction
 recent Guidelines have increasingly focused on the
stepped care approach, initiating treatment with
different mono-therapies and then sequentially adding
other drugs until BP control is achieved.
 Despite this, BP control rates have remained poor
worldwide :
 40% only of all hypertensive are treated
 35% only are controlled
Chow CK et al., JAMA: 2013;310:959–968.

4. Complications of Hypertension
51%
25%
32%
45%
13%
Oparil S et al.,Nat Rev Dis Primers. 2018 Mar 22; 4():18014.

5. Assadi F. Prehypertension: Int J Prev Med. 2014 Mar;5(Suppl 1):S4-9.

6. Failure to control
Reasons explaining failure to achieve better BP control
rates:
 Efficacy of pharmacological therapies.
 Physician or treatment inertia.
 Patient adherence to treatment.
 Insufficient use of combination treatment.
 Complexity of current treatment strategies.
Tiffe T et al., BMC Cardiovasc Disord 2017;17:276.

7. Combined vs. mono-therapy
mechanism of hypertension
 Mono-therapy act on one or at best two of these
mechanisms,
 combinations of drugs allows for action on several
different hypertensive mechanisms .
 Two to five fold greater effect on reduction.
 Increasing the dose of mono-therapy reduces coronary
events by 29% and cerebro-vascular events by 40%,
 while combining two antihypertensive agents with a
different mechanism of action reduces coronary events
by 40% and cerebro-vascular events by 54%
Art.Burnier M Curr Hypertens Rep. 2015 Jul; 17(7):51.

8. Art.Burnier M Curr Hypertens Rep. 2015 Jul; 17(7):51.

9. PB control rates
50%
Gu Q, et al. Circulation 2012;126:2105-14

10. Advantages of the combination
Reduction in adverse effects:
 RASIs prevent pretibial edema induced by calcium
channel blockers
 RASIs counteract the release of renin caused by
natriuretics
 RASIs block the release of aldosterone induced by
natriuretics and the resulting hypokalemia
 Several physiopathological mechanisms of increased
blood pressure are blocked
 Greater protection to target organs
 Faster control of blood pressure
Oparil S et al.,Nat Rev Dis Primers. 2018 Mar 22; 4():18014.

11. Combinations may have some effects that are
independent of their antihypertensive action:
 Anti-inflammatory
 Metabolic
 Anticounter regulation:
 Diuretics counteract the retention of water produced
by vasodilators
 RASIs compensate for renin release by diuretics

12. Combination Therapy
Is Superior to
Sequential Mono-
therapy for the Initial
Treatment of
Hypertension

13. Pros vs. cons
Pro
 Fixed-dose combinations (both drugs in the same
tablet) offer additional advantages, such as improved
adherence by 24%, easier indications and potentially
reduced cost.
Cons
 Their limitation is less possibility of titrating the dose
of only one of the drugs

14. Advantage of polyPill
Xinhuan Wana et al., Asian J. Pharmaceutical Sciences Volume 9, Issue 1, February 2014, 1–7

15. Recommendation

16. Core drug treatment strategy for
uncomplicated hypertension

17. Drug treatment strategy for
hypertension and CAD

18. Drug treatment strategy for
hypertension and Chronic KD

20. Major trials of conbination vs mono therapy/ Placebo

21. Jan van Gijn, PROGRESS 2002, Stroke. 2002;33:319–320

23. Incremental BP drops after direct switch to
Amlodpine/Valsartan
in patients previously uncontrolled on monotherapy
Allemann et al. J Clin Hypertens 2013;10:185–94

24. Jamerson K et al., ACCOMPLISH Trial Investigators.N Engl J Med. 2008 Dec 4; 359(23):2417-28.

25. Triple Vs. dual combination
Tóth K et al., Am J Cardiovasc Drugs. 2014 Apr;14(2):137-45.
Target BP 72% in
4 months

26. Amlodipine /Valsartan/HCT reduces BP from baseline
significantly more than dual therapy across diverse
patient sub-populations
Ferdinand KC & Nasser SA. A Am J Cardiovasc Drugs. 2013;13(5):301–313

27.  Although no RCT has compared major CV outcomes
between initial combination therapy and mono-therapy
 observational evidence suggests that the time taken to
achieve BP control is an important determinant of clinical
outcomes, especially in higher risk patients, with a
shorter time to control associated with
lower risk.

28. Take home message
 Initial combined anti-hypertensive therapy is
recommended and with earlier and better
control and better outcomes.
 it is not just the hemodynamics but in addition
there are metabolic, anti-inflammatory and
pleotropic effects.
 Gives patient more compliance and adherence to
medication
 Cost-effective
 Individualize the treatment

30. The Heart