Combination Hypertension Rx: Why Wait?

The facts are compelling: monotherapy as an approach to treating hypertension is seldom effective.¹ In fact, in as many as 20% of hypertensive patients, blood pressures below target cannot be achieved with 2 agents.² Clinical trials also have demonstrated that as many as 25% of patients enrolled in hypertension studies may need a 3-drug antihypertensive regimen to be controlled.²

Intensifying therapy by combining drugs from different, but complementary, classes is superior to raising the dose of an initial agent.³ It has been estimated that raising the dose of an initial antihypertensive agent has only 20% of the blood-pressure lowering effect of adding a drug from another class.³

We also know that patient adherence to an antihypertensive drug regimen is inversely related to the number of medications prescribed.² For example, adherence to a 3-drug and a 4-drug antihypertensive regimen was found to be only 63% and 56%, respectively.²

Some good news here is that as of 2011, there were at least 30 combinations of therapeutic antihypertensives in 2- and 3-drug combination pills.²

Do combos work?

Evidence-based medicine supports the safety and efficacy of combination pills for the treatment of hypertension. In the STITCH (Simplified Therapeutic Intervention To Control Hypertension) trial,³ the chance of reaching a blood pressure target increased 20% among participants initiated to antihypertensive therapy with low-dose, fixed dose combination pills versus those who were treated by adding single agents one at a time. Another study reported an 11% reduction in cardiovascular risk in individuals with hypertension who started therapy on combination agents versus those patients taking monotherapy as initial treatment.¹ So the answer to the question “Do combos work?” is “Yes, plus.” (I suspect, too, that when used to initiate antihypertensive therapy, fixed-combination agents result in below-target levels in less time, as well.) 

So, how should we respond to the facts at hand? The combination antihypertensive armamentarium has diuretics combined with ACEIs (eg, benazepril or enalapril with HCT); ARBs combined with diuretics; diuretic combinations (eg, HCTZ/spironolactone or triamterene); and calcium channel blockers with ACEIs, ARBs, and direct renin inhibitors (aliskiren).² There are also 3-agent combination pills available: amlodipine/HCTZ and either olmesartan, valsartan, or alikiren.²

The revised 2017 ACC/AHA hypertension management guidelines in fact recommend the use of fixed-dose combination agents. When a patient is newly diagnosed as having stage 2 hypertension (either a systolic BP ≥ 20 mmHg above target or a diastolic BP ≥ 10 mmHg above target), treatment is to be initiated with 2 medications, not initial monotherapy.⁵

The time has definitely come for a combination drug approach to hypertension treatment with fewer pills and “more bang for the buck.” We have the data to support this approach, which documents better medication adherence, less time to BP control, and reduction in cardiovascular complications down the road.

Let’s not pass up a great opportunity.

References:

1. Feldman R. Single pill combinations as initial therapy in the management of hypertension: What is taking you so long? Am J Hypertens. 2017; doi:10.1093/ajh/hpx194.

2. Chrysant SG. Single-pill triple-combination therapy: an alternative to multiple-drug treatment of hypertension. Postgrad Med. 2011;123:21-31.

3.  Wald DS, Law M, Morris JK, et al. Combination therapy vs monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am. J. Med. 2009; 122:290-300.

4. Feldman RD, Zou GY, Vandervoort MK, Wong CJ, Nelson SA, Feagan BG. A simplified approach to the treatment of uncomplicated hypertension: a cluster randomized, controlled trial. Hypertension. 2009;53:646-53. doi: 10.1161/HYPERTENSIONAHA.108.123455.

5. Whelton PK, Carey RM, Aronow WS, et al. ACC/AHA 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. Hypertension. [published online 11-13-2017]. Hypertension.doi:10.116/HYP.