Despite JNC-7, Old Prescribing Practices Persist, While New First-Line Antihypertensive Drug Combinations Are Approved

Linda Brookes, MSc


June 17, 2009

In This Article

The National Heart, Lung, and Blood Institute (NHLBI) initially thought the results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) it supported should and would change the antihypertensive prescribing practices (and largely based their new Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [JNC-7] guidelines on those results) -- but a new review of the evidence finds otherwise. Yet another substudy of the famous Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial has teased out the protective value of increased high-density lipoprotein (HDL) cholesterol levels again, but it is the corresponding editorial commentary that draws the important treatment implications for practitioners. Finally this month, a flurry of approvals for new fixed-dose combination treatments, plus 2 new antihypertensive drug classes underscore the continuing progress in treatment approaches for hypertension and resistant hypertension.

Effect of ALLHAT and JNC 7 on Initial Antihypertensive Drug Therapy Less Than Expected

The effect of the results of the ALLHAT, published in 2002[1] and the release of the JNC 7 report[2] may not have had as great an effect as the authors hoped, according to the results of a new study. Lead author Paul Muntner, PhD (Mount Sinai School of Medicine, New York), and other US investigators report in Hypertension[3] that the initial effect of ALLHAT and JNC 7 was to reverse the previous decline in diuretic use as initial antihypertensive drug therapy.[4] Over the longer term, however, diuretic use has plateaued, and most patients are still not initiating treatment with a thiazide-type diuretic as part of their regimen.

Based largely on the results of ALLHAT, along with other outcome trials in hypertension, JNC 7 recommended thiazide-type diuretics as initial pharmacologic treatment, alone or in combination with another drug, for most patients with hypertension. At that time the NHLBI, sponsor of ALLHAT and JNC 7, launched a physician and public education program aimed at incorporating this recommendation, among others, into clinical practice. To determine whether it has affected physician practice and prescribing patterns, Dr. Muntner and his colleagues compared antihypertensive medication prescriptions filled by patients who initiated pharmacologic antihypertensive treatment in a large managed care organization during 3 periods: (1) July 1, 2001, to June 30, 2002, before release of these publications (n = 1354); (2) July 1, 2003, to June 30, 2004, to assess short-term changes (n = 1542); and (3) July 1, 2004, to June 30, 2005, to assess extended changes (n = 1865). They found that the proportion of patients initiating antihypertensive treatment with a thiazide-type diuretic increased in 2001 to 2002 and 2003 to 2004 (from 30.6% to 39.4%; P < .001), but did not increase further in 2004 to 2005 (36.5%). This result is "impressive," but "highlights a substantial disconnect between the JNC 7 clinical guidelines and clinical practice," the researchers note.

Overall, inclusion of β-blockers as part of initial antihypertensive medication did not change (20.1% in 2001-2002 vs 19.0% in 2004-2005). Use of calcium-channel blockers (CCBs) as initial therapy decreased in the short term (16.7% to 13.8%), but returned to pre-publication levels later (16.9% in 2004-2005). ALLHAT and JNC 7 appeared to have resulted in a reduction in the use of angiotensin-converting enzyme inhibitors as initial therapy, from 32.8% to 28.9% in 2001 to 2001 and 2004 to 2005. However, prescriptions of angiotensin receptor blockers (ARBs), a drug class that was not included as a treatment arm in ALLHAT, increased over the same period, from 8.6% to 15.9%. By 2004 to 2005, renin-angiotensin blocking agents were the class of antihypertensive drugs most often prescribed as initial treatment, alone or with other drugs.


In an editorial accompanying this analysis,[4] Canadian authors Ross D. Feldman, MD (University of Western Ontario, London), and Finlay A. McAlister, MD (University of Alberta, Edmonton), attribute the study's findings to "the fact that the ALLHAT message was not universally accepted by many key opinion leaders in the United States," which "undoubtedly negatively impacted its ability to influence practice." In addition, "divergent goals of the pharmaceutical companies representing non-ALLHAT recommended drugs" could have significantly lessened the impact of the study, they suggest. They point out that "a single study, no matter how large and how well done, may not be seen as the 'last word' in any field." Incorporating clinical trials' findings into clinical practice requires "a concerted effort," making use of strategies such as "pathways, real-time clinical reminders, disease management strategies, local opinion leaders, academic detailing, and audit and feedback," they say. Guideline developers should "foster active implementation processes that incorporate such proven strategies to ensure that the outstanding contribution of trialists such as the ALLHAT team move beyond the printed page and into clinical practice."

Elsewhere, the ALLHAT findings have been revisited, to address some of the controversies and questions that arose from its initial publication, and the results reported in the Archives of Internal Medicine.[5] Jackson T. Wright Jr, MD, PhD (Case Western Reserve University Cleveland, Ohio), and other members of the ALLHAT Collaborative Research Group conclude, perhaps not surprisingly, that further analyses of ALLHAT data and the results of other trials and meta-analyses continue to support ALLHAT's original findings. Dr Wright and co-authors reiterate the original conclusions from ALLHAT that "neither the α-blocker, angiotensin-converting enzyme inhibitor, nor the CCB surpasses the thiazide-type diuretics as initial therapy for control of blood pressure or reduction of cardiovascular or renal clinical outcomes (when compared at appropriate dosage)." They look forward to additional insights from continuing "passive follow-up of ALLHAT participants for morbidity and mortality using administrative databases."