David K. Buerger

The committee's previous offering, JNC-V, released in 1993, also generated a lot of excitement. Since then, however, it has become clear that the consensus hypertension assessment and treatment guidelines presented in JNC-V failed to spur major changes in clinical practice.

Even as JNC-V was released, disturbing trends were afoot. During the 1990s, previously dramatic rates of increase in hypertension awareness, treatment, and control have slowed, fueling increases in hypertension sequelae such as stroke, end-stage renal disease, and heart failure, especially among the very high-risk subpopulation of black Americans. Despite overall gains since the release of the first JNC report in 1971, many of the estimated 50 million American adults with hypertension are still not aware they have the condition, and it is thought to be poorly controlled in as many as 75%. Hypertension continues to be extremely common in Americans aged 60 and over, with an estimated prevalence of 60% in whites and 71% in blacks. The JNC-VI guidelines are intended to reverse these disturbing trends.

What's New in JNC-VI?

Notably, for the first time in a JNC report, pharmacists are specifically mentioned as important players in hypertension management. "In particular," the report says, "pharmacists should be encouraged to monitor patients' use of medication, to provide information about potential adverse effects, and to avoid drug interactions."

Will JNC-VI be an effective answer to stagnating rates of decline in hypertension incidence and costly complications? Will JNC-VI be disseminated and heeded more widely than JNC-V? And how can consultant pharmacists help make it happen?

A New Risk Assessment Scheme

Under JNC-VI, as under the previous version, detection and confirmation of hypertension begins by averaging two or more blood pressure readings taken at each of two or more separate occasions. Classification of blood pressure status is as follows (note that clinical hypertension is now classified according to a simplified three-stage system):

Optimal-Systolic blood pressure <120 mm Hg and diastolic pressure <80 mm Hg

Normal-Systolic <130 and diastolic <85

High-normal-Systolic 130-139 or diastolic 85-89

Stage I-Systolic 140-159 or diastolic 90-99

Stage II-Systolic 160-179 or diastolic 100-109

Stage III-Systolic 180 or higher or diastolic 110 or higher

Risk stratification of patients with elevated blood pressure entails a two-step process taking into account major cardiovascular (CV) risk factors such as smoking, diabetes, age over 60 years, and family history of CV disease; and the presence or absence of target organ damage or existing clinical CV disease such as heart disease, stroke, and nephropathy. Patients are then categorized into three broad groups: Risk Group A includes those with no major risk factors and no target organ damage or clinical CV disease; Risk Group B, those with one or more risk factors (not including diabetes) and no target organ damage or clinical CV disease; and Risk Group C, those with target organ damage or clinical CV disease and/or diabetes, with or without other risk factors.

Next, blood pressure status is merged with CV risk status to arrive at a structured approach to therapeutic decision making for patients at various risk levels and stages of hypertension (see page 141). In a significant departure from JNC-V, clinicians are urged to consider prompt initiation of drug therapy in patients with high-normal blood pressure who also have diabetes, heart failure, or renal insufficiency.

Compelling Indications

Of particular importance to consultant pharmacists serving geriatric populations, JNC-VI places emphasis on early use of first-line therapies in patients with significant isolated systolic hypertension (ISH). "About 80% of these patients are elderly," Beier notes. The goal of drug therapy for marked ISH is to lower blood pressure as much as is safely possible. "The idea is to go as low as you can for as long as the patient can tolerate it," Beier says. "That's one of the key take-home messages of JNC-VI. There's very strong, persuasive data that aggressive treatment of isolated systolic hypertension in the elderly can yield tremendous cost savings in reduced cardiovascular morbidity and mortality, cerebrovascular disease, myocardial infarction, angina, and sudden death."

Components of Cardiovascular Risk Assessment

Target organ damage/clinical cardiovascular disease: heart disease (left ventricular hypertrophy, angina or prior myocardial infarction, prior coronary revascularization, heart failure); stroke or transient ischemic attack; nephropathy, peripheral arterial disease; retinopathy.

Source: Adapted from JNC-VI.

Combination Therapies

JNC-VI emphasizes that combinations consisting of low doses of two agents from different classes of antihypertensives can offer enhanced efficacy in hypertension control, "thereby minimizing the likelihood of dose-dependent adverse effects." To that end, the JNC-VI guidelines support wider use of low-dose therapy with:

• Agents combining an ACE inhibitor and calcium channel blocker (e.g., benazepril/amlodipine, enalapril/diltiazem)

• Diuretic-beta blocker combinations such as chlorthalidone/atenolol and hydrochlorothiazide/bisoprolol (the latter is recommended for initial therapy)

• Agents combining a diuretic and an ACE inhibitor (e.g., hydrochlorothiazide/captopril, also recommended for initial therapy)

• Combinations of a diuretic and angiotensin II receptor blocker (e.g., hydrochlorothiazide/losartan)

• Other combinations of a diuretic (usually hydrochlorothiazide) and one of 11 other antihypertensives (e.g., triamterene, prazosin, reserpine).

With regard to angiotensin II receptor blockers, the latest addition to the antihypertension armamentarium, JNC-VI cautions that sufficient clinical data demonstrating efficacy comparable to that of ACE inhibitors is still lacking; thus these agents should be used mainly in patients unable to tolerate ACE inhibitors.

A Nod to Reality

Recommended strategies for achieving optimal cost-effectiveness in hypertension therapy include use of generics, when available; use of combination agents; encouraging patients to shop around for the best prices; and scoring and cutting of tablets when appropriate. On that last point, JNC-VI cautions that dividing certain sustained-release formulations can negate their sustained-release action.

The JNC-VI guidelines emphasize that further gains in the war on hypertension will require "a major commitment from clinicians and managed care organizations," further emphasizing that "the cost of managing hypertension is lower overall than the sum of direct and indirect costs that may be avoided by reducing hypertension-associated heart disease, stroke, and renal failure, especially because these adverse events often lead to expensive hospitalizations, surgical procedures, and [use of] high-cost technologies." In particular, the report notes, managed care programs present an opportunity for "a coordinated approach to care, using various health care professionals" to marshal supportive counseling, formulary management, and monitoring of clinical and economic outcomes.

Increased use of specialist referrals may be warranted, JNC-VI says. "Hypertension specialists may play an important role in providing more cost-effective management of high blood pressure by adapting national guidelines for local implementation, providing guidance for new drugs and diagnostic methods, and managing patient with identifiable causes of hypertension, resistance to therapy, or complex concomitant conditions." Clearly, all of these direct care and managed care initiatives are eminently conducive to direct or supportive involvement by consultant pharmacists.

Lessons Learned

Why weren't the JNC-V guidelines picked up and adhered to more widely? The authors of the SAGE-based study cited several possible reasons, including patchy dissemination in various practice settings and clinicians' disappointment with published clinical trials demonstrating less-than- expected benefits from blood pressure reduction on coronary artery disease outcomes.

F. Randy Vogenberg, FASCP, says another flaw of JNC-V was that the guidelines were "squishy," with no strong call for physician action that might have helped foster wide use. "There was no groundswell of support. JNC-V had a very specific, black-and-white treatment algorithm, but clinicians had problems applying it to real patient populations and individual patients." Pharmaceutical companies' efforts to take advantage of the JNC-V guidelines and aggressively promote their own drugs in managed care formularies further muddied the waters, says Vogenberg, president of the Institute for Integrated Healthcare in Wellesley, Massachusetts.

He also cites another important implementation barrier: reluctance on the part of physicians to tamper with antihypertension drug regimens, even if those regimens are not optimally effective. "Physicians generally don't like to mess with cardiovascular medications," he notes. "With the current increased interest in algorithmic approaches to congestive heart failure, physicians and others are becoming more familiar with pharmaceutical treatment algorithms, but we're still only at the beginning of the curve."

Local Implementation Is Key

This time around, the Joint National Committee acknowledged the need for creative local implementation approaches right up front in the introduction to JNC-VI: "[The] responsible clinician's judgment of the individual patient's needs remains paramount. Therefore, these national guidelines should serve as a tool to be adapted and implemented in local and individual situations." Therein lies the real key to achieving wide adherence to JNC-VI, Vogenberg says. Broad consensus standards are certainly valuable, as far as they go, "but they need to be translated into something local that people can relate to and implement in a way that's meaningful to their particular patient population."

This is nothing new to pharmacy providers, especially for the big pharmacy companies with dozens of practice sites across the country, he points out. "They pull their hair out trying to get a buy-in [on practice guidelines] from medical directors and physicians at all their sites." For the JNC-VI guidelines to be fully effective, Vogenberg says, "implementation needs to take place on a facility-by-facility basis."

Special Considerations for the Elderly

Pharmacotherapy-If weight loss, restricted salt intake, and other lifestyle modifications prove ineffective, drug therapy is indicated. Thiazide diuretics, alone or in combination with beta blockers, are preferred for first-line therapy. For elderly patients with isolated systolic hypertension, diuretics are preferred. "Drugs that exaggerate postural changes in blood pressure (peripheral adrenergic blockers, alpha blockers, and high-dose diuretics) or drugs that can cause cognitive dysfunction (central alpha2 agonists) should be used with caution." With any antihypertensive, the starting dose should be about half of that used for younger patients.

Treatment Goals-As with younger patients, the overall goal is reduction of blood pressure to less than 140/90 mm Hg. In marked systolic hypertension, an interim goal of systolic blood pressure below 160 mm Hg may be necessary.

Source: Adapted from JNC-VI.

'Facilitators and Integrators'

The guidelines stress that selection of initial therapy for individual patients must take into account a range of special considerations: racial differences in response to some antihypertensives, quality-of-life concerns, the potential for both unfavorable and favorable drug interactions, physiologic and biochemical measurements that can refine product selection, the potential impact of some drugs in worsening-or in some cases improving-concomitant conditions, and cost constraints. "Selection of an antihypertensive agent that also treats a co-existing disease will simplify therapeutic regimens and reduce costs," the guidelines note. Judicious product selection is an area in which consultant pharmacists can make enormous contributions, Vogenberg says.

Striking the right balance of clinical efficacy and cost-effectiveness will be increasingly important in the tough arena of the Medicare nursing facility prospective payment system (PPS). "It's quite possible that PPS may help drive better adherence to JNC-VI," but consultant pharmacists will need to be closely involved in making it happen, Vogenberg says. "The good news is that PPS is forcing everyone to look at total costs of care and overall treatment outcomes. The bad news is that PPS payment methodology is largely based on old ways of doing things." Federal payments during the first few years under PPS will be largely determined by individual facilities 1995 cost reports. "Many of the drugs mentioned in JNC-VI simply weren't around four or five years ago," Vogenberg notes, so promoting their wide use within the rigid PPS payment structure will be an ongoing challenge.

One way consultant pharmacists can help tackle that challenge is by making facility administrators and medical directors understand the high downstream costs of failure to optimize hypertension pharmacotherapy, Vogenberg says. He outlined a hypothetical but typical scenario: A nursing facility resident who develops chest pain or other symptoms due to poorly managed hypertension therapy and is sent to the hospital for evaluation. "He gets an extensive cardiovascular work-up, but he's in the hospital for less than 10 hours, so he's not officially admitted. The nursing facility would have to eat the costs associated with that hospital work-up, which can be enormous," Vogenberg explains.

In a broader sense, he says, "Consultant pharmacists' input will be crucial in choosing low-cost combinations with maximal clinical effect." With many of the newly recommended antihypertension drugs, the alpha blockers in particular, "there's lots of wiggle room to try to optimize therapy." Consultant pharmacists will need to work closely with physicians to "tweak" drug regimens to arrive at the lowest cost combination without putting patients at risk. "For example, if a patient is on once-daily therapy, it's essential to avoid loss of blood pressure control at the nadir of the drug blood level in the early morning, which could lead to postural hypotension or myocardial infarction." Helping physicians and other health care team members understand such pharmacokinetic subtleties will be important to maintaining good hypertension control and avoiding costly hospitalizations. "We need to help physicians navigate the many gray areas in the JNC-VI algorithm. There's lots of room for individual professional judgment."

In Vogenberg's view, tactful diplomacy by pharmacists will be just as important as clinical acumen in bringing the JNC-VI guidelines down from the ivory tower and into the real world. "It won't serve us to approach this role in a gate-keeping or police-action mode. It needs to be a soft sell. Rather than taking a heavy-handed approach-'Here are the JNC-VI guidelines, and here's what you need to do'-we need to say, 'Let's go through the guidelines together and figure out what we like and don't like relative to our particular patient population.' It's a matter of cultivating relationships that are consultative, not adversarial, and working to change the physician's thought process. By doing so, you'll be creating a role for yourself, and you'll be viewed in a more positive light."

Real-World Results

In one of the first published studies of a therapeutic interchange program based on JNC-VI recommendations, 60 patients with mild-to-moderate hypertension already well-controlled with calcium channel blocker monotherapy were switched to fixed-dose therapy with bisoprolol/ hydrochlorothiazide-one of the combinations newly recommended in the guidelines for first-line therapy. Three months after the switch, blood pressure was deemed to be adequately controlled in 55 of the patients (92%), with a significantly reduced overall incidence of side effects (10%, compared with 42% of patients receiving calcium channel blocker therapy). In these 60 patients alone, the interchange program yielded a total of $16,868 in annual acquisition cost savings. Some of those savings were offset by an increased need for clinical visits, lab tests, and side-effect management costs, but net savings during the first year of the conversion were still $5,144. The investigators projected even more substantial future savings (Pharmacy and Therapeutics 1998;23:563-9).

Despite its limited size and short duration, "this study suggests that with appropriate follow-up and monitoring, [bisoprolol/hydrochlorothiazide] can be substituted as a cost-effective alternative to selected [calcium channel blockers] in the vast majority of patients with uncomplicated mild-to-moderate hypertension," the investigators concluded.

A Jumping Off Point

He believes tapping the full potential of JNC-VI will probably entail implementation of not just one all-encompassing algorithm, but "several algorithms targeting patients with various subgroups of cardiovascular disease-myocardial infarction, congestive heart failure, simple hypertension, complex hypertension, and so on. "In the long run, that's what's going to make good clinical sense and good economic sense," Vogenberg says. "That's what's going to save money-and lives."

Copyright © 1999, American Society of Consultant Pharmacists, Inc. All rights reserved.