From Clinical Trials to Clinical Practice
2006; Lippincott Williams & Wilkins; Volume: 48; Issue: 2 Linguagem: Inglês
10.1161/01.hyp.0000229712.18111.b3
ISSN1524-4563
Autores Tópico(s)Pharmaceutical industry and healthcare
ResumoHomeHypertensionVol. 48, No. 2From Clinical Trials to Clinical Practice Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBFrom Clinical Trials to Clinical PracticeWhy the Gap? Theodore A. Kotchen Theodore A. KotchenTheodore A. Kotchen From the Department of Medicine, General Clinical Research Center, Medical College of Wisconsin, Milwaukee. Originally published19 Jun 2006https://doi.org/10.1161/01.HYP.0000229712.18111.b3Hypertension. 2006;48:196–197Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: June 19, 2006: Previous Version 1 Based on an analysis of National Health and Nutrition Examination Survey data, the prevalence of hypertension in the United States increased from 25.0% in 1988 to 1991 to 28.7% in 1999 to 2000.1 Despite compelling evidence for the cardiovascular and renal benefits of hypertension control, during that same decade, hypertension control rates increased from 24.6% to only 31.0%. At a time when he was director of the National Heart, Lung, and Blood Institute, Claude Lenfant expressed the concern that the potential benefits of clinical research are lost in the translation into clinical practice.2 Others have also pointed out the slow pace of diffusion of new scientific knowledge into health care and have recommended strategies for decreasing the gap between knowledge and clinical practice.3In this issue of Hypertension, Stafford et al4 describe prescription patterns for antihypertensive agents and suggest that prescriptions for specific classes of agents do not reflect incorporation of lessons learned from clinical trial outcomes. Based on data extracted from the National Disease and Therapeutic Index, which is a continuing survey of a national sample of US office-based physicians, between 1990 and 2004, overall, the most frequently prescribed agents were angiotensin-converting enzyme inhibitors (ACEIs) and calcium channel blockers (CCBs); diuretics were the third most frequently prescribed agents. After publication of the results of the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) in 2002, diuretic prescriptions increased by early 2003 and surpassed CCBs. However, by 2004, although the use of diuretics exceeded pre-ALLHAT levels, their use had declined from their peak use in early 2003. The authors concluded that thiazide diuretics are underprescribed despite clear evidence that they are the most cost-effective antihypertensive agent.ALLHAT was a randomized, double-blind clinical trial, involving >40 000 high-risk hypertensive patients, that compared cardiovascular outcomes in patients treated with diuretics as first-step therapy with outcomes in patients treated with an ACEI (lisinopril), a CCB (amlodipine), or an α-antagonist (doxazosin). The intended follow-up was 4 to 8 years, although the doxazosin arm was terminated early, because the incidence of combined cardiovascular events, particularly congestive heart failure, was significantly higher for the doxazosin-treated than the chlorthalidone-treated patients.5 The primary end point of the study, the combination of fatal coronary heart disease and nonfatal myocardial infarction, was identical in the chlorthalidone, amlodipine, and lisinopril groups.6 Other large clinical trials have also failed to detect an overall cardiovascular advantage for different classes of antihypertensive agents.7 The ALLHAT investigators concluded that, "Thiazide type diuretics are superior in preventing one or more major forms of cardiovascular disease and are less expensive. They should be preferred for first-step antihypertensive therapy." Similarly, for &3 decades, Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) recommendations for initial drug treatment have included a diuretic (Table). With the increasing availability of generic drugs, although the cost differential between diuretics and other agents has lessened, it has not been obliterated. JNC Recommendations for an Initial Antihypertensive AgentCommitteeYearRecommendationBB indicates β blocker, ARB, angiotensin receptor blocker.JNC 11977Thiazide-type diureticJNC 21980DiureticJNC 31984Thiazide-type diuretic or BBJNC 41988Diuretic or BB or CCB or ACEIJNC 51993Diuretic or BBJNC 61997Diuretic or BBJNC 72003Thiazide-type diuretic, either alone or in combination with ACEI, ARB, BB, or CCBSimilar to the observations of Stafford et al,4 previous studies of the trends of antihypertensive drug use in the United States also point out that JNC recommendations and ALLHAT have had relatively little long-term impact on prescribing patterns.8–10 A number of factors may contribute to the gap between these recommendations and the prescribing patterns of practicing physicians who are responsible for the care of individual patients. These include the following: (1) the newer and more expensive antihypertensive agents have been aggressively marketed to physicians and consumers by the pharmaceutical industry11,12; (2) different comorbidities may influence the selection of an antihypertensive agent; (3) different agents may have cardiovascular and renal protective effects beyond their capacity to lower blood pressure in select groups of high-risk patients13; (4) the ALLHAT conclusion that diuretics are superior to other agents in preventing cardiovascular disease has been overstated, because it is based on an analysis of secondary end points and because the potential long-term consequences of the metabolic side effects of diuretics remain unknown14; and (5) in apparent contrast to the ALLHAT results, in an Australian randomized trial of >6000 older subjects, ACEI-based antihypertensive therapy resulted in fewer cardiovascular events or death from any cause than diuretic based therapy.15A recent meta-analysis suggests essentially equivalent blood pressure–lowering effects of thiazide diuretics, β-blockers, ACEIs, angiotensin receptor blockers, and CCBs when used as monotherapy.16 Earlier JNC reports advocated a stepped care approach, whereby before adding a second agent, the recommendation was to gradually increase the dose of the initial agent until goal blood pressure was attained, side effects became intolerable, or the maximum dose was reached. However, for most agents, blood pressure reductions at half-standard doses are only &20% less than at standard doses.16 The most recent JNC report recommends initiating therapy with either a diuretic alone or a diuretic in combination with another agent.17 This is based on the recognition that most hypertensive patients will require ≥2 antihypertensive medications to achieve blood pressure goals. Appropriate combinations of agents at lower doses have additive or almost additive effects on blood pressure with a lower prevalence of side effects. With increasing emphasis on the use of combinations of antihypertensive agents, generally including a diuretic, it will be of interest to determine whether there continues to be a gap between these newer recommendations and future prescription patterns. Consistent with these recommendations, between 1988–1994 and 1999–2002, multiple antihypertensive drug use increased, whereas monotherapy with a diuretic or β blocker decreased.18The high rate of uncontrolled hypertension, despite the availability of effective antihypertensive agents, represents a more disturbing gap than the selection of an initial agent in the translation of scientific knowledge into clinical practice. Strategies to improve blood pressure control should be our number one priority for the treatment of hypertension.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.DisclosuresNone.FootnotesCorrespondence to Theodore A. Kotchen, General Clinical Research Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail [email protected] References 1 Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988–2000. JAMA. 2003; 290: 199–206.CrossrefMedlineGoogle Scholar2 Lenfant C. Clinical research to clinical practice—lost in translation? N Engl J Med. 2003; 349: 868–874.CrossrefMedlineGoogle Scholar3 Berwick DM. Disseminating innovations in health care. JAMA. 1003; 289: 1969–1975.CrossrefMedlineGoogle Scholar4 Stafford RS, Monti V, Furberg CD, Ma J. Long-term and short-term changes in antihypertensive prescribing by office-based physicians in the United States Hypertension. 2006; 48: 213–218.LinkGoogle Scholar5 The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs. chlorthalidone: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attach Trial (ALLHAT). JAMA. 2000; 283: 1967–1975.CrossrefMedlineGoogle Scholar6 The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288: 2981–2997.CrossrefMedlineGoogle Scholar7 Mancia G. Role of outcome trials in providing information on antihypertensive treatment; importance and limitations. Amer J Hyperten. 2006; 19: 1–7.CrossrefMedlineGoogle Scholar8 Siegel D, Lopez J. Trends in antihypertensive drug use in the United States: do the JNC V recommendations affect prescribing? JAMA. 1997; 278: 1745–1748.CrossrefMedlineGoogle Scholar9 Nelson CR, Knapp DA. Trends in antihypertensive drug therapy of ambulatory patients by US office-based physicians. Hypertension. 2000; 36: 600–603.CrossrefMedlineGoogle Scholar10 Guo JD, Liu GG, Christensen DB. How well have practices followed guidelines in prescribing antihypertensive drugs: the role of health insurance. Value in Health. 2003; 6: 18–28.CrossrefMedlineGoogle Scholar11 Rosenthal MB, Berndt ER, Donohue JM, Frank RG, Epstein AM. Promotion of prescription drugs to consumers. N Engl J Med. 2002; 346: 498–505.CrossrefMedlineGoogle Scholar12 Saul S. Doctors object as drug makers learn who's prescribing what. New York Times. May 4, 2006: A1.Google Scholar13 Verdecchia P, Reboldi G, Angeli F, Gattobigio R, Bentivoglio M, Thijs L, Staessen JA, Porcellati C. Angiotensin-converting enzyme inhibitors and calcium channel blockers for coronary heart disease and stroke prevention. Hypertension. 2005; 46: 386–392.LinkGoogle Scholar14 Messerli FH. ALLHAT, or the soft science of the secondary end point. Ann Intern Med. 2003; 139: 777–780.CrossrefMedlineGoogle Scholar15 Wing LMH, Reid CM, Ryan P, Beilin LJ, Brown KA, Jennings GLR, Johnston CI, McNeil JJ, Macdonald GJ, Marley JE, Morgan TO, West MJ for the Second Australian National Blood Pressure Study Group. Comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretic for hypertension in the elderly. N Engl J Med. 2003; 348: 583–592.CrossrefMedlineGoogle Scholar16 Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ. 2003; 326: 1427–1434.CrossrefMedlineGoogle Scholar17 Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Roccella EJ, and the National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003; 42: 1206–1252.LinkGoogle Scholar18 Gu Q, Paulose-Rain R, Dillon C, Bart V. Antihyperetensive drug use among US adults with hypertension. Circulation. 2006; 113: 213–221.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Myanganbayar M, Baatarsuren U, Chen G, Bosurgi R, So G, Campbell N, Erdenebileg N, Ganbaatar K, Magsarjav P, Batsukh M, Munkherdene T, Unurjargal T, Dashtseren M, Tserengombo N, Batsukh B, Bungert A, Dashdorj N and Dashdorj N (2018) Hypertension, knowledge, attitudes, and practices of primary care physicians in Ulaanbaatar, Mongolia, The Journal of Clinical Hypertension, 10.1111/jch.13320, 20:8, (1187-1192), Online publication date: 1-Aug-2018. Basile J and Neutel J (2009) Overcoming clinical inertia to achieve blood pressure goals: the role of fixed-dose combination therapy, Therapeutic Advances in Cardiovascular Disease, 10.1177/1753944709356012, 4:2, (119-127), Online publication date: 1-Apr-2010. 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