Many patients with hypertension require more than one medication to achieve adequate blood pressure control.1-5
Studies of antihypertensive treatments have shown that, for many patients, combination therapy is more effective than monotherapy in lowering blood pressure (BP).2,3,5,6 In the Systolic Blood Pressure Intervention Trial (SPRINT), achieving even the standard blood pressure goal of 140/90 mm Hg required more than one medication on average.3 In the large Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), after five years of follow up, approximately 41% of participants were taking two or three medications.5 According to a meta-analysis of 42 randomized trails combination therapy using two antihypertensive drugs of different classes is five times more effective in lowering blood pressure than doubling the dose of one drug.6
Multiple practice guidelines, including the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) Task Force and the 2013 European Society of Hypertension/European Society of Cardiology, state that most patients will require more than one drug to control their blood pressure.7,8 In fact, the ACC/AHA Task Force recommends beginning antihypertensive therapy with a two-drugs in patients with stage 2 hypertension (systolic BP >129 mm Hg or diastolic BP >89 mm Hg) with an average BP that is 20/10 mm Hg above their target BP.7
Lack of adequate blood pressure control is likely multifactorial. Some prescription and over the counter medications such as NSAIDs can interfere with the effects of antihypertensives.9-11 The American Heart Association (AHA) Professional Education Committee of the Council for High Blood Pressure Research therefore suggests discontinuing other medications that may interfere with the action of the antihypertensives in order to improve blood pressure control.12
Goal blood pressure for hypertensive patients is an area of ongoing research and controversy. In a 2017 report, the ACC/AHA Task Force recommended a target blood pressure of less than 130/80 mm Hg.8 This recommendation is strongest for hypertensive adults with known cardiovascular disease (CVD) or with a 10-year atherosclerotic cardiovascular disease (ASCVD) risk of 10% or higher.8 However, for hypertensive adults without CVD, not at risk for ASCVD, the strength of the BP goal recommendation is considered weak.8 8 The 2013 European Society of Hypertension/European Society of Cardiology practice guidelines recommend a target systolic blood pressure (SBP) of 140 or less for patients at low to moderate cardiovascular risk, patients who have had stroke or transient ischemic attack (TIA), and patients with diabetes, cardiovascular heart disease, or chronic kidney disease.7 The same guidelines recommend a diastolic blood pressure (DBP) target of 90 mm Hg or less for all patients except those with diabetes, for whom a target of 85 mm Hg or less is recommended.7
However, SPRINT provided evidence of benefits with a target systolic blood pressure of <120 mm Hg.3 This trial had a median follow-up of 3.26 years and enrolled 9,361 participants older than 50 years of age with a systolic blood pressure between 130 and 180 mm Hg and an increased risk of cardiovascular events.3 Subjects were randomized to intensive-treatment (blood pressure target ≤120/90 mm Hg), or standard-treatment (≤140/90 mm Hg). After one year, the composite outcome (myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes) was significantly less common in the intensive treatment arm (1.65% versus 2.19%; HR 0.75; 95% CI [0.64, 0.89]; p<0.001).3 The relative risk of death from cardiovascular causes was 43% lower in the intensive-treatment group than in the standard-treatment group (p=0.005).3 However, 38.3% of patients in the intensive-treatment group experienced serious adverse events such as hypotension, syncope, electrolyte abnormalities, and acute kidney injury or acute renal failure compared with 37.1% of patients in the standard-treatment group (HR with intensive-treatment, 1.04; p=0.25).3 Rates of orthostatic hypotension were significantly higher in the intensive-treatment group (4.7%) compared with the standard-treatment group (2.5%) (HR 1.88, p<0.001).3
A 2017 systematic review by Bavishi et al. of four trials of intensive blood pressure treatment, investigated the efficacy and safety of intensive blood pressure lowering strategies for patients 60 years of age and older. The definition of intensive and standard treatment varied somewhat with three trials defining intensive as SBP <140 mm Hg and one defining it as <120 mm Hg. The trials were each rated high quality and had no evidence of high risk of bias. The primary outcome measure was major adverse cardiovascular events (MACE) [cardiovascular mortality, stroke, and myocardial infarction (MI)]. Serious adverse events and renal failure were assessed. The review included 10,587 participants across the four trials of which 5,437 were randomized to intensive blood pressure lowering and 5,420 were randomized to standard blood pressure lowering. In all trials, participants randomized to the intensive BP control strategy achieved a systolic BP <140 mm Hg. Compared to standard BP control, intensive BP control resulted in a 29% reduction in MACE (p=0.0001), 33% reduction in cardiovascular mortality (p=0.04), and a 37% reduction in heart failure (p=0.04).14 Rate of MI, stroke, and serious adverse events between the two BP control strategies did not differ. Intensive treatment was associated with a 1.1% risk of renal failure while the standard BP control group was associated with 0.6% risk of renal failure (p=0.12).14 These findings provide evidence that there may be a benefit to treating patients ≥60 years to a SBP goal of <140 mm Hg.14
- Brown MJ, McInnes GT, Papst CC, Zhang J, MacDonald TM. Aliskiren and the calcium channel blocker amlodipine combination as an initial treatment strategy for hypertension control (ACCELERATE): a randomised, parallel-group trial. Lancet (London, England). Jan 22 2011;377(9762):312-320.
- Mourad JJ, Waeber B, Zannad F, Laville M, Duru G, Andrejak M. Comparison of different therapeutic strategies in hypertension: a low-dose combination of perindopril/indapamide versus a sequential monotherapy or a stepped-care approach. Journal of hypertension. Dec 2004;22(12):2379-2386.
- Group SR, Wright JT, Jr., Williamson JD, et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. Nov 26 2015;373(22):2103-2116.
- Mori H, Ukai H, Yamamoto H, et al. Current status of antihypertensive prescription and associated blood pressure control in Japan. Hypertension research : official journal of the Japanese Society of Hypertension. Mar 2006;29(3):143-151.
- Officers A, Coordinators for the ACRGTA, Lipid-Lowering Treatment to Prevent Heart Attack T. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. Dec 18 2002;288(23):2981-2997.
- Wald DS, Law M, Morris JK, Bestwick JP, Wald NJ. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. The American journal of medicine. 2009;122(3):290-300.
- Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Journal of hypertension. Jul 2013;31(7):1281-1357.
- 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. A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. 2017.
- Minuz P, Pancera P, Ribul M, et al. Amlodipine and haemodynamic effects of cyclo-oxygenase inhibition. Br J Clin Pharmacol. Jan 1995;39(1):45-50.
- Bhala N, Emberson J, Merhi A, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet (London, England). Aug 31 2013;382(9894):769-779.
- Solomon SD, Wittes J, Finn PV, et al. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation. Apr 22 2008;117(16):2104-2113.
- Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. Jun 2008;51(6):1403-1419.
- James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. Feb 5 2014;311(5):507-520.
- Bavishi C. Outcomes of Intensive Blood Pressure Lowering in Older Hypertensive Patients. Journal of the American Medical College of Cardiology. 2017;69(5):486-493.