The 2017 hypertension guidelines1 from the American College of Cardiology and American Heart Association (ACC/AHA) recommend that all adults with Stage 2 hypertension who have an average blood pressure (BP) more than 20/10 mm Hg above their BP target should be started on two first-line antihypertensive agents from different classes [Strong Recommendation (Level C-EO)]. Stage 2 hypertension is defined as 140 mm Hg or higher systolic or 90 mm Hg or higher diastolic. The guidelines recommend a blood pressure target goal of less than 130/80 mm Hg for everyone with hypertension. The exception is for people age 65 and older. The guidelines only specify a systolic BP less than 130 mm Hg. Combination drug therapy can be administered as separate agents or in a fixed-dose combination. People started on one or two antihypertensive drugs should be reassessed within one month. If the blood pressure goal is not met, intensification of therapy with either an increased dose or an additional medication from another antihypertensive class should be considered.
Evidence shows that lowering blood pressure decreases the risk of adverse cardiovascular (CV) outcomes such as heart disease, stroke, and death.2-5 It may also slow the progression of kidney damage in people with chronic kidney disease.6 Further, meta-analyses as well as national and international guidelines suggest that lowering BP decreases risk of these outcomes regardless of which agent is used. 2-5
Initial Antihypertensive Drug Treatment
Studies7-9 have shown that starting people on combination drug antihypertensive therapy results in faster blood pressure control compared to monotherapy. More rapid blood pressure control can result in greater risk reduction of CV disease.
Egan et al performed a retrospective study7 comparing records of 106,621 patients with uncontrolled hypertension who had no treatment for at least six months prior to initiating antihypertensive agents and had a minimum of at least one year of follow-up data. Patients started on single-pill combination therapy (n=9,194) had the best blood pressure control in the first year (hazard ratio [HR] 1.53, 95% confidence interval [CI] [1.47 – 1.58]) compared to those on multi-pill combination therapy (n=18,328) (HR 1.34, 95% CI [1.31 – 1.37]) or monotherapy (n=79,099) which was the reference group.
A 2013 retrospective study of matched 1,762 adults started on combination antihypertensive therapy 1:1 with patients who were started on monotherapy and later switched to combination therapy.8 Analysis found that patients started on combination therapy had a significant risk reduction for CV events, including hospitalization for heart failure, myocardial infarction, and stroke or transient ischemic attack, and all-cause death (incidence risk ratio [IRR] 0.66, 95% CI [0.52 – 0.84], p=0.0008). At 6 months of treatment, blood pressure control was reached by 40.3% of patients started on combination therapy compared to only 32.6% of those started on monotherapy. Further, the study found that reaching target blood pressure significantly reduced risk for CV events or death by 23% (HR 0.77, 95% CI [0.61 – 0.96], p=0223).
Another study of 209,650 hypertensive patients in Italy, who were newly started on antihypertensive agents found that patients who were started on combination therapy had a CV risk reduction of 11% (95% CI [ 5% - 16%]) compared to patients started on monotherapy.9
Intensification of Antihypertensive Drug Treatment
Patients started on one or two antihypertensive medications may still need to increase dosage or add additional medications from other antihypertensive classes to achieve their blood pressure goal.1 Studies have shown that delays in intensification of blood pressure treatment (raised dose or added medications) result in an increased risk of a CV event or death.10
A 2015 retrospective cohort study10 of 88,756 hypertensive adults found the risk of CV event or death increased with delay of medication intensification from the lowest delay (0 – 1.4 months) to the highest delay (4.7 months) (HR 1.12, 95% CI [1.05 – 1.20], p=0.009). This study also found that a threshold higher than 150 mm Hg systolic for intensification of therapy was associated with an increased risk of CV event or death (HR 1.03, 95% CI [0.97 – 1.10], p=0.34) compared to the baseline threshold of 140 mm Hg.
- Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2017.
- Ahluwalia M, Bangalore S. Management of hypertension in 2017: targets and therapies. Curr Opin Cardiol 2017; 32 (4): 413-421.
- James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults. JAMA 2014; 311 (5): 507-520.
- Pignone M, Viera AJ. Blood pressure treatment targets in adults aged 60 years or older. Ann Intern Med 2017; 166 (6): 445-445.
- Qaseem A, Wilt TJ, Rich R, Humphrey LL, Frost J, Forciea MA. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med 2017; 166 (6): 430-430.
- KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl (2011) 2013; 3 (1): i-150.
- Egan BM, Bandyopadhyay D, Shaftman SR, Wagner CS, Zhao Y, Yu-Isenberg KS. Initial monotherapy and combination therapy and hypertension control the first year. Hypertension 2012; 59 (6): 1124-1131.
- Gradman AH, Parise H, Lefebvre P, Falvey H, Lafeuille MH, Duh MS. Initial combination therapy reduces the risk of cardiovascular events in hypertensive patients: a matched cohort study. Hypertension 2013; 61 (2): 309-318.
- Corrao G, Nicotra F, Parodi A, et al. Cardiovascular protection by initial and subsequent combination of antihypertensive drugs in daily life practice. Hypertension 2011; 58 (4): 566-572.
- Xu W, Goldberg SI, Shubina M, Turchin A. Optimal systolic blood pressure target, time to intensification, and time to follow-up in treatment of hypertension: population based retrospective cohort study. BMJ 2015; 350: h158.