Dr Rutecki is with the Cleveland Clinic National Consultation Service.
Find out what you know about how to avoid therapeutic inertia in treatment of hypertension.
Contemporary treatment of hypertension is plagued by therapeutic inertia. Inadequate response to blood pressures that remain above recommended target levels can lead to serious negative health consequences for patients. The time-to-target blood pressure interval (the quicker the better) is critical to optimize outcomes.1 When the hypertension “clock is ticking” decisions on appropriate steps to lower blood pressure need to be timely, but not hasty.
Let’s look at 3 interventions that lower blood pressure effectively by way of 3 case scenarios.
From a therapeutic perspective, what is the best initial approach?
A. Initiate treatment with 25 mg of hydrochlorothiazide.
B. Consider initiating treatment with a 2-agent combination pill.
C. Delay pharmacologic intervention and treat with salt restriction.
ANSWER: B. Consider initiating treatment with a 2-agent combination pill.
The patient qualifies for a diagnosis of stage 2 hypertension (blood pressure >160/>100 mm Hg). A single agent will not suffice to lower the patient’s blood pressure to target level. Many studies have also demonstrated that combination therapy reduces the risk of cardiac events,1 is more efficacious,2 and improves adherence, blood pressure control, and time-to-target blood pressure.3 Combination therapy with appropriately chosen agents (such as amlodipine and an angiotensin receptor blocker [ARB]) augments effects of either agent taken alone. The days of “maxing out” monotherapy before initiating combinations are over!
Your next step should be:
A. Add an agent from another class, such as hydralazine or clonidine.
B. Characterize the patient as having resistant hypertension and initiate therapy with 25 mg of spironolactone (potassium levels permitting).
C. Add an ARB.
D. Switch from amlodipine to verapamil.
ANSWER: B. Characterize the patient as having resistant hypertension and initiate therapy with 25 mg of spironolactone (potassium levels permitting).
Resistant hypertension is defined as blood pressure not controlled on a complimentary 3-drug regimen with a diuretic as one of the agents. Spironolactone has become a “go-to” agent for treating resistant hypertension.4 If it works, it may allow the patient to discontinue other antihypertensive agents. It is a pharmaceutical backbone for resistant hypertension treatment.5
You should (choose all that apply):
A. Switch the diuretic to chlorthalidone.
B. Consider other medications in lieu of hydralazine and atenolol.
C. Add clonidine
D. Increase hydrochlorothiazide to 25 mg.
ANSWERS: A. and B. Switch the diuretic to chlorthalidone and consider other medications in lieu of hydralazine and atenolol.
The years since the author’s graduation from medical school (1974) have seen widespread use of many new and more effective antihypertensive agents: (angiotensin converting enzyme inhibitors [ACEIs], ARBs, and dihydropyridine calcium channel blockers [DHP Ca++] such as amlodipine. Medications utilized in earlier generations-such as clonidine and hydralazine-have been largely marginalized. Did you know that a Cochrane Data Base review found insufficient evidence to make any conclusion about the effects of hydralazine versus placebo on mortality, morbidity, adverse effects, or systolic/diastolic blood pressures?6 At the 2013 American Society of Hypertension Meeting, a speaker was asked if he still prescribed clonidine for hypertension. He answered, “Yes, for people I don’t like.” In the presence of renal disease, hydrochlorothiazide is not as effective a diuretic agent as chlorthalidone. Landmark blood pressure control studies (ASCOT, ACCOMPLISH) demonstrated greater cardiovascular protection with other classes of antihypertensive agents (ACEIs/DHP Ca++) versus beta blockers (atenolol).
To initiate therapy to lower this patient’s blood pressure, hydrochlorothiazide should be changed to chlorthalidone, and next, a substitute should be found for hydralazine (either amlodipine or combination ACEI/ARB, preferably in a combination tablet).
Three maneuvers can lead to better blood pressure control over shorter periods of time. First, use combination antihypertensive agents earlier and more often, especially in hypertension stage 2 or higher; second, identify resistant hypertension earlier and utilize spironolactone when possible. Third, avoid less efficacious medications (hydralazine and clonidine) from days gone by!
1. Gradman AH, Parise H, Lefebvre P, et al. Initial combination therapy reduces the risk of cardiovascular events in hypertensive patients: a matched cohort study. Hypertension 2013; 61:309-318. http://hyper.ahajournals.org/content/61/2/309.long
2. Neldam S, Schumacher H, Kjeldsen SE, Neutel JM. Telmisartan in combination with hydrochlorothiazide 12.5 mg for the management of patients with hypertension. Curr. Med. Res. Opin. 2014;9:1715-1724. http://www.tandfonline.com/doi/abs/10.1185/03007995.2014.924912?journalCode=icmo20
3. Kjeldsen SE, Messerli FH, Chiang CE, et al. Are fixed-dose combination antihypertensives suitable as first line therapy? Curr. Med. Res. Opin. 2012;28:1685-1697. http://www.ncbi.nlm.nih.gov/pubmed/?term=Curr.+Med.+Res.+Opin.+2012%3B28%3A1685-1697.
4. Williams B, Macdonald TM, Morant S, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomized, double-blind, crossover trial. Lancet. 2015; 386:2059-2068. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655321/
5. Adams M, Bellone J, Wright BM, Rutecki GW. Evaluation & pharmacologic approach to patients with resistant hypertension. Postgrad. Med. 2012;124:74-82. http://www.ncbi.nlm.nih.gov/pubmed/22314117
6. Kandler MR, Mah GT, Stabler SN, Salzwedel DM. Hydralazine for essential hypertension. Cochrane Database Syst. Rev. 2011;11:CD004934. http://www.ncbi.nlm.nih.gov/pubmed/?term=Cochrane+Database+Syst.+Rev.+2011%3B+11%3ACD004934.
7.) Taddei S. Combination therapy in hypertension: What are the best options according to Clinical Pharmacology principles and controlled trial evidence? Am. J. Cardiovasc. Drugs 2015; 15:185-194. http://www.ncbi.nlm.nih.gov/pubmed/?term=Am.+J.+Cardiovasc.+Drugs+2015%3B+15%3A185-194.