First-line combination therapy versus first-line monotherapy for primary hypertension

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• Clinical guidelines suggest initiating hypertension treatment with either monotherapy or combination therapy.
• Evidence supporting these recommendations regarding clinically relevant outcomes is lacking.
• Potential harm from certain antihypertensive combinations is known, but the overall harm-benefit balance remains unclear.

Purpose of the Study:

• To compare clinical outcomes between initial monotherapy and combination therapy for primary hypertension.

Main Methods:

• Systematic search of multiple databases (Hypertension Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, ClinicalTrials.gov, WHO ICTRP) up to February 2016.
• Included randomized, double-blind trials with ≥12 months follow-up, ≥50 participants/group, comparing first-line antihypertensive drug combinations with monotherapy.
• Primary outcomes: mortality, cardiovascular mortality, cardiovascular events, serious adverse events.

Main Results:

• Analysis included data from three studies, focusing on subgroups of participants initiating treatment (monotherapy: 335; combination: 233).
• Participants were outpatients, predominantly European and white; trial populations varied regarding diabetes and other comorbidities.
• Very low certainty of evidence due to serious imprecision and extremely wide confidence intervals, encompassing both potential harm and benefit.

Conclusions:

• The number of participants and events were insufficient to draw conclusions on the comparative efficacy of initial monotherapy versus combination therapy for hypertension.
• Large-scale clinical trials are necessary to address this question using clinically relevant endpoints.