Starting the treatment of hypertension with one medicine versus starting with a combination of two medicines


Hypertension (high blood pressure) is a long-term condition that increases the risk of having health problems such as heart attack, stroke or kidney disease. There are several types of medicines that are used to treat hypertension. Over time, frequently a person needs more than one type of medicine to control their blood pressure. When a doctor prescribes medicines to reduce the blood pressure for the first time, he or she has two options, using only one medicine (called monotherapy) or using two medicines (called combination therapy). The combination therapy can be in the same tablet or in different tablets. The potential advantage of using combination therapy is that blood pressure could fall faster, but we do not know if this is better or worse for avoiding health problems.

Study characteristics

We looked for clinical studies that compared starting the treatment of hypertension in adults with monotherapy versus starting with combination therapy. Studies had to report results in terms of deaths, events due to diseases of the heart or the vessels (heart attack, stroke or heart failure); deaths due to diseases of the heart or the vessels, or any health-related serious side effects. We only selected studies with 50 or more people per group and that lasted at least 12 months. The evidence is current to February 2016.

Key results and certainty of the evidence

We found three studies that fit our criteria with 233 people were treated with combination therapy and 335 treated with monotherapy. However, we did not find enough data to answer our question. It is necessary to perform more and larger studies that compare monotherapy with combination therapy as initial treatment of hypertension.

Authors' conclusions: 

The numbers of included participants and, hence the number of events, were too small to draw any conclusion about the relative efficacy of monotherapy versus combination therapy as initial treatment for primary hypertension. There is a need for large clinical trials that address the question and report clinically relevant endpoints.

Read the full abstract...

Starting with one drug and starting with a combination of two drugs are strategies suggested in clinical guidelines as initial treatment of hypertension. The recommendations are not based on evidence about clinically relevant outcomes. Some antihypertensive combinations have been shown to be harmful. The actual harm-to-benefit balance of each strategy is unknown.


To determine if there are differences in clinical outcomes between monotherapy and combination therapy as initial treatment for primary hypertension.

Search strategy: 

We searched the Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 2), Ovid MEDLINE, Ovid Embase, LILACS,, Current Controlled Trials, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to February 2016. We searched in clinical studies repositories of pharmaceutical companies, reviews of combination drugs in Food and Drug Administration and European Medicines Agency, and lists of references in reviews and clinical practice guidelines.

Selection criteria: 

Randomized, double-blind trials with at least 12 months' follow-up in adults with primary hypertension (systolic blood pressure/diastolic blood pressure 140/90 mmHg or higher, or 130/80 mmHg or higher if participants had diabetes), which compared combination of two first-line antihypertensive drug with monotherapy as initial treatment. Trials had to include at least 50 participants per group and report mortality, cardiovascular mortality, cardiovascular events or serious adverse events.

Data collection and analysis: 

Two authors independently selected trials for inclusion, evaluated the risk of bias and entered the data. Primary outcomes were mortality, serious adverse events, cardiovascular events and cardiovascular mortality. Secondary outcomes were withdrawals due to drug-related adverse effects, reaching blood pressure control (as defined in each trial) and blood pressure change from baseline. Analyses were based on the intention-to-treat principle. We summarized data on dichotomous outcomes as risk ratios with 95% confidence intervals.

Main results: 

We found three studies in which a subgroup of participants met our inclusion criteria. None of the studies focused solely on people initiating antihypertensive treatment so we asked investigators for data for this subgroup (monotherapy: 335 participants; combination therapy: 233 participants). They included outpatients, and mostly European and white people. Two trials included only people with type 2 diabetes, whereas the other trial excluded people treated with diabetes, hypocholesterolaemia or cardiovascular drugs. The follow-up was 12 months in two trials and 36 months in one trial. Certainty of evidence was very low due to the serious imprecision, and for using a subgroup not defined in advance. Confidence intervals were extremely wide for all important outcomes and included both appreciable harm and benefit.