High blood pressure is very common and the leading cause of cardiovascular morbidity and mortality worldwide. In Germany, about 30% of females and 33% of males aged 18–79 years are estimated to have arterial hypertension [1]. In the age range of 70–79 years, prevalence increases up to 75% in both genders [1]. With respect to the potential health implications and the epidemiological significance of uncontrolled blood pressure, the current European Society of Hypertension/European Society of Cardiology (ESH/ESC) hypertension guidelines recommend early intervention to normalize elevated blood pressure to < 140/90 mmHg [2]. Despite the improvements in awareness and therapeutic options attained in recent decades, only 72% of the patients treated with antihypertensive drugs reach blood pressure values < 140/90 mmHg, indicating a high medical need for further improvement in treatment strategy [3, 4].

The majority of hypertensive patients require a combination of at least two antihypertensive drugs to achieve timely blood pressure control and avoid the occurrence of early events. Unfortunately, adherence to treatment is low [4]. To improve adherence, ESH/ESC guidelines recommend single pill combination (SPC) therapy, since reducing the number of pills to be taken daily may simplify treatment and enhance adherence to prescribed therapeutic regimes [2, 4–6]. Better adherence to cardioprotective treatments, in turn, has been shown to translate into reduced morbidity and mortality [7, 8]. In addition, combining two drugs with complementary mechanisms of action can increase the rate of blood pressure control [4, 5] and exert a blood pressure-lowering effect approximately five times greater than doubling the dose of an antihypertensive monotherapy [9]. Furthermore, there is evidence that initiating antihypertensive therapy with two drugs results in a more rapid achievement of target blood pressure and a reduced risk of cardiovascular events or death in comparison to a delayed onset of combination treatment [10].

As one of the best antihypertensive treatment strategies available, the guidelines suggest the combination of a calcium channel blocker (CCB) and an angiotensin-converting enzyme (ACE) inhibitor [2]. Addition of an ACE inhibitor to a dihydropyridine CCB may also reduce the risk of CCB-associated peripheral edema in comparison to a high-dose CCB monotherapy, thereby improving tolerability of the antihypertensive treatment [11].

In RCT studies, the majority of patients require a combination of drugs to achieve target blood pressure. Moreover, when choosing a strategy to control blood pressure with 1 drug gradually increasing the dose will increase the risk of side effects and prolong the time blood pressure above the target threshold. This is evidenced by the MANCIA study, a multinational, double-blind, parallel, randomized controlled study conducted to determine the efficacy and safety of the perindopril/amlodipine fixed-dose combination strategy for hypertension versus a stepwise treatment strategy (starting with valsartan monotherapy, increase the dose to valsartan/amlodipine after 2 months) in the treatment of moderate hypertension. Lying positional blood pressure was noted at each visit (baseline, 1, 2, 3, and 6 months) [12].

In the group of patients treated with perindopril/amlodipine fixed-dose combination tablets starting with a dose of 3.5/2.5 mg, then increasing to 7/5 and 14/10 mg, the rate of control of BP was statistically significantly higher than the valsartan stepwise strategy. The difference occurred as early as the first 4 weeks of treatment and was statistically significant over the entire study period. In this study, the early combination group used fixed-dose combination tablets, which is also one of the treatment trends recommended in recent guidelines to increase the likelihood of reaching blood pressure goals. According to an observational study of more than 100,000 hypertensive patients, initiation with fixed-dose combination tablets (9% of the study population) resulted in faster lowering of blood pressure, as well as better control of blood pressure after 1 year of treatment [12].

References
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2. Mancia G, Fagard R. ESH/ESC guidelines for themanagement of arterial hypertension. J Hypertens. 2013;31:1281–1357. 
3. Sarganas G, et al. Trends in antihypertensive medicatrion use and blood pressure control among adults with hypertension in Germany. Am J Hypertens. 2016;29(1):104–113. 
4. Claxton A, Cramer J, Pierce C. A systematic review of the association between dose regimens and medication compliance. Clin Ther. 2001;23:1296–1310. 
5. Gupta A, Arshad S, Poulter NR. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents. Hypertension. 2010;55:399–407. 
6. Bangalore S, et al. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med. 2007;120(8):713–719. 
7. Corrao G, et al. Cardiovascular protection by initial and subsequent combination of antihypertensive drugs in daily life practice. Hypertension. 2011;58(4):566–572. 
8. Simpson SH, Simpson SH, Eurich DT, Majumdar SR, et al. A meta-analysis of the association between adherence to drug therapy and mortality. BMJ. 2006;333(7557):15. 
9. Wald DS, et al. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med. 2009;122(3):290–300. 
10. Gradman AH, et al. Initial combination therapy reduces the risk of cardiovascular events in hypertensive patients. Hypertension. 2013;61:309–318. 
11. Makani H, et al. Effect of renin-angiotensin system blockade on calcium channel blocker-associated peripheral edema. Am J Med. 2011;124(2):128–135. 

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