Preferred combination partner

Need of at least 2 drugs to achieve BP control

Most hypertensive patients require the combination of at least two drugs to achieve BP control1

In hypertensive patients at high CV risk, achieving target BP levels is likely to require more than one antihypertensive agent2-6. A meta-analysis of 42 trials (n=11,000) has demonstrated that combining two antihypertensive agents provided greater BP reduction compared to monotherapy with either agent (p<0.05); combining drugs from two different antihypertensive drug classes was approximately five times more effective than doubling the dose of one drug7.

Most patients require combination therapy to achieve target DBP control2-6

AASK, African-American Study of Kidney Disease
ABCD, Appropriate Blood pressure Control in Diabetes
ALLHAT, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
HOT, Hypertension Optimal Trial
IDNT, Irbesartan Diabetic Nephropathy Trial
INVEST, INternational VErapamil SR-Trandolapril Study
MDRD, Modification of Diet in Renal Disease.
RENAAL, Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan.
UKPDS, UK Prospective Diabetes Study.

Reduction of CV events with combination therapy

Combination therapy improves BP reduction and reduces major CV events compared to monotherapy

A meta-analysis of 354 clinical trials (n=56,000) of thiazides, β-blockers, ACE inhibitors, angiotensin II receptor antagonists and CCBs in fixed dose found that compared to monotherapy, combination low dose drug treatment:8

  • Increased efficacy
  • Reduced the incidence of adverse effects
  • Reduced the risk of cardiovascular events.
Law MR, et al. BMJ 2003;326:1427-31.
IHD, ischaemic heart disease.

ESH/ESC 2013 guidelines suggest initiation with a drug combination in patients at high risk or with markedly high baseline BP

The ESH/ESC 2013 guidelines recommend two-drug combinations as first-line therapy in patients with grade 2 or 3 hypertension or high/very high total cardiovascular risk1.

A switch to combination therapy is also recommended for patients with mild hypertension and lower cardiovascular risk who fail to achieve BP targets1

ESH/ESC guidelines 2013: suggested strategy to achieve target BP9

The role of CCBs in Hypertension Guidelines

ESH/ESC 2013

ESH/ESC guidelines 2013: CCBs are suitable for combination with all other antihypertensive drug classes

The advantages of initiating with combination therapy may include:1

  • Prompter response in a larger number of patients
  • A greater probability of achieving target BP in patients with higher BP values
  • A lower probability of discouraging patient adherence with many treatment changes
  • Fewer side-effects

ESH/ESC guidelines 2013: possible combinations of classes of antihypertensive drugs1

Other Guidelines

Guidelines recommend CCBs in combination therapy to improve BP control

ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure.


  1. Mancia G, et al. Eur Heart J. 2013 ;34(28):2159-219.
  2. ALLHAT Collaborative Research Group. JAMA 2002;288:2981–97.
  3. Bakris GL, et al. Am J Kidney Dis 2000;36:646–61.
  4. Brenner BM, et al. N Engl J Med 2001;345:861–9.
  5. Lewis EJ, et al. N Engl J Med 2001;345:851–60.
  6. Pepine CJ, et al. JAMA 2003;290:2805–16.
  7. Wald DS,et al. Am J Med 2009;122:290–300.
  8. Law MR, et al. BMJ 2003;326:1427-31.

Table: Guidelines recommend CCBs in combination therapy to improve BP control

  1. Mancia G, et al. Eur Heart J. 2013 Jul;34(28):2159-219.
  2. Chiang CE, et al. J Formas Med Assoc 2010;109:740-73.
  3. Flack JM, et al. Hypertension 2010;56:780-800.
  4. Canadian Hypertension Education Programm [Internet]. Available from: Accessed 15th February 2018.
  5. James PA, et al. JAMA. doi:10.1001/Jama.2013.284427.
  6. Liu LS, et al. Zhonghua Xin Xue Guan Bing Za Zhi. 2011;39:579-615.

Homepage references

  1. Mancia G, et al. Eur Heart J 2013;doi:10.1093/euroheartj/eht151.
  2. Canadian Hypertension Education Programm [Internet]. Available from: Accessed 15th February 2018.
  3. Haller H. Int J Clin Pract 2008;62:781–90.
  4. Mancia G, et al. J Hypertens 2011;29:600-9.
  5. Kuschnir E, et al. J Cardiovasc Pharmacol 2004;43:300-5.
  6. Hasebe N, et al. J Hypertens 2005;23:445-53.
  7. Ke Y-N, et al. Cardiovasc Ther 2012;30:326-32.
  8. Taddei S, et al. J Cardiovasc Pharmacol 2003;41:579-85.
  9. Toal CB, et al. Can J Cardiol 1999;15:1103-9.