Antihypertensive Treatment: How to Maximize Results for Your Patients

Q: Many of my patients appear to have white-coathypertension: their pressure is elevated whenmeasured in my office-but normal when measured athome. Am I ignoring significant hypertension if I do nottreat these patients? Or am I overtreating if I do treat?

A: Most patients have lower blood pressure (BP) athome than in the physician's office. Measurementstaken with ambulatory BP instruments are lower than officereadings by about 10 mm Hg. My recommendation isto target treatment to office BP measurements. Office readingsshould be below 140/90 mm Hg in healthy adults, andbelow 135/85 to 130/80 mm Hg in adults with diabetes.Take time to measure BP correctly: for example, measurementshould be done after the patient has been sitting for 5minutes-not after he or she has just bolted up the steps.

A significant discrepancy (that is, 8 to 10 mm Hg) betweenoffice and home BPs is cause for concern. But the officemeasurement is what counts for most patients: all clinicaltrials, therapy benefits, epidemiologic reports, and risk calculationsare based on those numbers. Newer studies show thatambulatory BP may better reflect target organ damage; however,we do not have a significant number of studies in whichambulatory BP was tied to clinical outcomes such as stroke.

In rare cases, there is a dramatic difference between officeand home BPs (for example, systolic pressure of 170 mm Hg inthe office and 110 or 120 mm Hg at home). For such a patient,ambulatory BP measurement is particularly useful. Home BPinstruments are not uniformly reliable, however. If a patientneeds or wants to take BP measurements at home, have himbring the machine to the office so it can be calibrated.

Q: Should I treat a patient whose office BP is onlymildly elevated, say 144 or 148 mm Hg over 70 or80 mm Hg, if his home systolic pressure is 130 mm Hg?

A: The treatment of patients with hypertension shouldbe based on global risk rather than BP level alone.The goal of antihypertensive therapy is not simply to lowerBP but to prevent morbidity and mortality. When a patienthas what appears to be mildly elevated BP, consider ambulatoryBP monitoring or look for evidence of target organdamage. If echocardiography shows left ventricular hypertrophyor if the patient has microalbuminuria, I would recommendantihypertensive therapy. If the patient has no comorbidities,I would be less inclined to treat.

It is unlikely that we will ever have hard clinical data thatclearly show the benefits of treating patients with mildly elevatedpressures. I don't foresee a clinical trial that compares outcomesin normotensive patients with those who have mild hypertensionand no other risk factors. However, a growing bodyof evidence indicates the need to treat patients with mildly elevatedBP who have an additional risk factor, such as diabetes.

Q: For which patients with elevated BP shouldI consider a trial of diet and exercise-and forhow long?

A: The most important nonpharmacologic measures areweight loss and sodium reduction. A low-fat, low-sodiumdiet such as the DASH diet is beneficial.¹ However, ifsystolic pressure is high-for example, 160 or 170 mmHg-it is unlikely that nondrug therapy alone will make thepatient normotensive. In this setting, a recommendationthat a patient lose weight and return to your office in 6months is not advisable.

On the other hand, if a patient has stage 1 isolated systolichypertension-that is, pressures of 140 to 150 mmHg-a 3- to 6-month nondrug therapy trial may be appropriate,just as it would be for a patient with diastolic hypertension.In this situation, however, the patient needs to beclosely followed. If you don't see the patient for severalmonths, his BP may have risen significantly. Furthermore,adherence to nonpharmacologic therapy programs dependsin large measure on frequent contact between the patientand clinician.

Q: Many of my patients have a hard time complyingwith nonpharmacologic strategies. What do yousuggest?

A: Compliance success-or failure-depends on theparticular patient and on how the strategy is implemented.In general, long-term weightlossprograms are more successful ifdietary change is associated with anexercise program and with social supportand encouragement. The Trial ofNonpharmacologic Interventions inthe Elderly (TONE) investigatorsfound that after BP had been controlledfor 1 year, antihypertensivemedication could be safely withdrawnin persons aged 60 to 80 years whoseBP was 150/90 mm Hg or lower andwho had no clinical evidence of cardiovasculardisease-provided thatgood BP control could be maintainedwith nonpharmacologic therapy.² Patientswere very compliant. Moreover,patients in the combined weightloss/sodium reduction group had a 53% lower chance of remainingfree of a trial end point (sustained BP of 150/90mm Hg or higher, a clinical cardiovascular event, or a decisionto resume BP medication) for the duration of the studycompared with patients in the usual-care group.

However, this study was unusual in that patients metwith dietitians frequently. These dietitians went shoppingwith patients, taught them how to buy the right food, howto read lists of ingredients, and even how to cook.

Q:Is there an age beyond which patients no longerbenefit from antihypertensive therapy?

A: Current guidelines advise against an age-specific cutoffand recommend continuing to treat even very elderlyhypertensive patients.3 Some epidemiologic data showthat in persons 90 years or older who are not being treatedthere is no absolute proof of incremental risk of stroke, heartdisease, and mortality with increasing BP. This issue is beinginvestigated in the Hypertension in the Very Elderly Trial(HYVET)-an international study now under way that isevaluating the effect of antihypertensive therapy on incidenceof stroke and cognitive function in patients 80 yearsand older.⁴

On the other hand, in clinical trials such as the SystolicHypertension in the Elderly Program (SHEP)-where weenrolled persons 60 years and older, with no upper agelimit-there was no decrease in benefit for older people.⁵

Q: Many of my colleagues are turning to angiotensinconvertingenzyme (ACE) inhibitors as first-linetherapy for elderly patients with isolated systolic hypertension.Is there convincing evidencefor such a practice?

A: ACE inhibitors have been shownto decrease cardiovascular eventsamong patients at high risk with andwithout hypertension. However, theseagents are not recommended as firstlinetherapy for isolated systolic hypertensionin the Sixth Report of the JointNational Committee on Prevention, Detection,Evaluation, and Treatment ofHigh Blood Pressure (JNC VI). This isbecause in controlled clinical trials ofolder persons with this condition, only2 classes of drugs were more effectivethan placebo: diuretics-such aschlorthalidone-and long-acting calciumchannel blockers (CCBs)-such as nitrendipine.^5,6 TheJNC VI guidelines therefore recommend diuretics ("preferred"agents) or long-acting dihydropyridines.³

A low-dose diuretic-a thiazide or thiazidelike agent-ata dosage of 12.5 to 25 mg/d is an easy and cost-effective way toinitiate antihypertensive therapy. Elderly patients may need additionalpharmacotherapy related or unrelated to their BP-such as an ACE inhibitor for heart failure or a β-blocker orCCB for angina.The results of trials such as this argue against an agespecifictreatment cutoff.

Q: Many of my elderly patients who take athiazide diuretic for hypertension complain ofexcessive urination. Is there any remedy?

A: Patients can urinate only as much as they drink unlessthey have sodium and water retention andfailure who need a loop diuretic. Timing of the medication(and peak diuresis) may improve sleep and quality of life.

Q: What is the evidence for ACE inhibitor therapyin a normotensive diabetic patient-with orwithout microalbuminuria? Some of my colleagues areinitiating therapy with these agents even in diabeticpatients with normal renal function.

A: There is general agreement that diabetic patientswith proteinuria need either an ACE inhibitor or anangiotensin II receptor antagonist (ARB). In 3 large trials-the Irbesartan Microalbuminuria Study (IDNT), AngiotensinII Antagonist Losartan (RENAAL) study, and IrbesartanMicroalbuminuria Study (IRMA)-2-an ARB was superior to both a CCBand placebo with respect to renal outcomes.^7,8 Current trials are investigatingwhether the best agent is an ARB,an ACE inhibitor, or some combinationof agents.

I recommend an ACE inhibitoror ARB for diabetic patients with albuminuria-at least until more evidenceis in. The new guidelines of theAmerican Diabetes Association recommendan ARB for patients withtype 2 diabetes who have hypertensionand microalbuminuria, and anACE inhibitor for patients with type 1diabetes.⁹[Editor's note: For more informationon the role of ACE inhibitors,please see Dr Donald Vidt's discussionon pages 1005-1008.]

Q: What is the next step for apatient on maximum dosesof an ACE inhibitor plus a diureticwhose hypertension is stilluncontrolled?

A: The first step is to ensure that the patient is taking hismedications-and that he is doing so correctly. Itmay help to spend a few minutes to check the patient'smedication bottles, note how many tablets remain, and discusswith the patient how and when he is taking the medication.The average person takes only about 75% of medicationsprescribed.

The second step is to determine whether there arenonpharmacologic reasons for the lack of control. Factorsthat can affect drug efficacy include dietary changes, significantweight gain or loss, and drug interactions.

Third, renal artery stenosis or other insult over andabove the patient-s essential hypertension may be developing.In this setting, other pharmacologic agents may beadded. A significant number of patients need 3 or moremedications to control BP.

These steps will take care of many cases of uncontrolledhypertension. However, there are some patients inwhom BP cannot be completely controlled. For these patients,referral to a hypertension specialist is warranted.

Q: What are the most effective ways you've found toaddress the perennial problem of noncompliancewith drug therapy?

A: The first step is to persuade thepatient that the therapy is necessary-even though he may have nosymptoms from the hypertension andmay experience side effects from themedication. Some newer studies showthat patients feel better once their BPis controlled. Although hypertension isconsidered a "silent" disease, some patientsdo experience headaches; thesetend to abate with medication. For example,in controlled trials with ARBs,headache was more common amongplacebo recipients than in those giventhe active drug.

The second step is to persuadethe patient to take the medications asprescribed-and educate him aboutthe importance of doing so. It's not realisticto think that we'll be 100% successfulin this endeavor; it's wise toadjust the dosage accordingly.

The third step-and an extremelyimportant one-is consistent followup.In many cases, a patient's initialoffice visit was prompted by something specific: either thepatient or a relative had a cardiovascular event, or the patient'sfamily insisted that he seek care. At this point, thepatient is quite concerned about his health and is likely totake the medication you prescribe. If you wait 3 or 4 monthsbefore initiating therapy, the patient may no longer perceivethe precipitating event as a motivating factor, and compliancemay not be as good.

Frequent patient contact results in improved adherence.The patient need not actually see the physician: thecontact can be made by one of the office staff by phone, fax,or e-mail. The staff member can check the patient's homeBP, verify that he has sufficient medication, and answer anyquestions. The importance of hypertension treatment isthus continuously on the patient's mind. [Editor's note: Suggestionsfor improving adherence are listed in the Table.]

Q: We all know that only 27% of Americans withhypertension are being treated to target goal.How can we improve our performance?

A: Vigilance is key. The point is to make sure that hypertensivepatients are being treated. Controlling systolicBP is not easy, and it is imperative to follow currenttreatment guidelines. The future may bring us more potentpharmacologic agents with fewer side effects.

Patients need to understand the clinical implications ofuntreated, uncontrolled hypertension. If we tell a patientwith a blood pressure of 152/86 mm Hg that he has "mild"hypertension, he may underestimate the potential gravity ofhis condition. For example, he may leave the office thinking,"If it's mild, it can't be so bad. I'll eat less salt and losea little weight." Five years later, he may not have eaten lesssalt and lost the weight, and the BP may be even higher; hemay be at risk for a catastrophic cardiac event.

Most patients have stage 1 hypertension. It is in thesepatients that clinicians can have a real impact. Although thecardiovascular risk for individual patients with stage 1 hypertensionis low, there are so many people in this categorythat the aggregate risk is huge. Statistically, we willsee far fewer strokes if we treat all the patients whose systolicpressure is between 140 and 159 mm Hg than if wejust treat those whose pressure is much higher (eg,190/120 mm Hg).It will always be a challenge to find and treat all thosewho have hypertension, but thankfully, we now have a varietyof effective medications.

References:

REFERENCES:1. Sacks FM, Svetkey LP, Vollmer WM, et al, for the DASH-Sodium CollaborativeResearch Group. Effects on blood pressure of reduced dietary sodium andthe Dietary Approaches to Stop Hypertension (DASH) diet. N Engl J Med. 2001;344:3-10.
2. Kostis JB, Espeland MA, Appel L, et al, for the Trial of Nonpharmacologic Interventionsin the Elderly (TONE) Cooperative Research Group. Does withdrawalof antihypertensive medication increase the risk of cardiovascular events? Am JCardiol. 1998;82:1501-1508.
3. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation,and Treatment of High Blood Pressure. Rockville, Md: National Institutes ofHealth; 1997. NIH publication 98-4080.
4. Bulpitt C, Fletcher A, Beckett N, et al. Hypertension in the Very Elderly Trial(HYVET): protocol for the main trial. Drugs Aging. 2001;18:151-164.
5. Kostis JB, Berge KG, Davis BR, et al. Effect of atenolol and reserpine on selectedevents in the systolic hypertension in the elderly program (SHEP). Am J Hypertens.1995;8(pt 1):1147-1153.
6. Fagard RH, Staessen JA, for the Systolic Hypertension in Europe (Syst-Eur)Trial Investigators. Treatment of isolated hypertension in the elderly: the Syst-Eur trial. Clin Exp Hypertens. 1999;21:491-497.
7. Sica DA, Bakris GL. Type 2 diabetes: RENAAL and IDNT-the emergence ofnew treatment options. J Clin Hypertens (Greenwich). 2002;4:52-57.
8. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal andcardiovascular outcomes in patients with type 2 diabetes and nephropathy. N EnglJ Med. 2001;345:861-869.
9. American Diabetes Association: clinical practice recommendations 2002.Diabetes Care. 2002;25(suppl 1):S1-S147.