Strategies to Dose Antihypertensive Drugs Strategy Description Details A Start one drug, titrate to maximum dose, and then add a second drug If goal BP is not achieved with the initial drug, titrate the dose of the initial drug up to the maximum recommended dose to achieve goal BP If goal BP is not achieved with the use of one drug despite titration to the maximum recommended dose, add a second drug from the list (thiazide-type diuretic, CCB, ACEI, or ARB) and titrate up to the maximum recommended dose of the second drug to achieve goal BP If goal BP is not achieved with 2 drugs, select a third drug from the list (thiazide-type diuretic, CCB, ACEI, or ARB), avoiding the combined use of ACEI and ARB. Titrate the third drug up to the maximum recommended dose to achieve goal BP B Start one drug and then add a second drug before achieving maximum dose of the initial drug Start with one drug then add a second drug before achieving the maximum recommended dose of the initial drug, then titrate both drugs up to the maximum recommended doses of both to achieve goal BP If goal BP is not achieved with 2 drugs, select a third drug from the list (thiazide-type diuretic, CCB, ACEI, or ARB), avoiding the combined use of ACEI and ARB. Titrate the third drug up to the maximum recommended dose to achieve goal BP C Begin with 2 drugs at the same time, either as 2 separate pills or as a single pill combination Initiate therapy with 2 drugs simultaneously, either as 2 separate drugs or as a single pill combination. Some committee members recommend starting therapy with 2 drugs when SBP is >160 mm Hg and/or DBP is >100 mm Hg, or if SBP is >20 mm Hg above goal and/or DBP is >10 mm Hg above goal. If goal BP is not achieved with 2 drugs, select a third drug from the list (thiazide-type diuretic, CCB, ACEI, or ARB), avoiding the combined use of ACEI and ARB. Titrate the third drug up to the maximum recommended dose. Abbreviations: ACEI, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; CCB, calcium channel blocker; DBP, diastolic blood pressure; SBP, systolic blood pressure. 2014 Guideline for Management of High Blood Pressure Special Communication Clinical Review & Education jama.com JAMA Published online December 18, 2013 E11 ing entities and encourage continued attention to rigorous meth- ods in guideline development, thus raising the standard for future guidelines. Discussion The recommendations based on RCT evidence in this guideline dif- fer from recommendations in other currently used guidelines sup- guidelines recommended treatment to lower BP goals in patients with diabetes and CKD based on observational studies.12 Recently, several guideline documents such as those from the American Dia- betesAssociationhaveraisedthesystolicBPgoalstovaluesthatare Other guidelines such as those of the European Society of Hyper- tension also recommend a systolic BP goal of lower than 150 mm Hg, albeit in patients older than 80 years (not 60 years as recom- Thischanginglandscapeisunderstand- ablegiventhelackofclearRCTevidenceinmanyclinicalsituations. History of JNC 8 The panel was originally constituted as the Eighth Joint National Committee on the Prevention, Detection, Evaluation, and Treat- ment of High Blood Pressure (JNC 8). In March 2008 NHLBI sent letters inviting the co-chairs and committee members to serve on JNC 8. The charge to the committee was as follows: The JNC 8 will review and synthesize the latest available scientific evidence, up- dateexistingclinicalrecommendations,andprovideguidancetobusy primary care clinicians on the best approaches to manage and con- trol hypertension in order to minimize patients risk for cardiovas- cular and other complications. The committee was also asked to identify and prioritize the most important questions for the evi- dence review. In June 2013, NHLBI announced its decision to dis- continue developing clinical guidelines including those in process, instead partnering with selected organizations that would develop Importantly, participation in this process re- quired that these organizations be involved in producing the final content of the report. The panel elected to pursue publication in- dependentlytobringtherecommendationstothepublicinatimely manner while maintaining the integrity of the predefined process. This report is therefore not an NHLBI sanctioned report and does not reflect the views of NHLBI. Conclusions Itisimportanttonotethatthisevidence-basedguidelinehasnotre- nition from JNC 7 remains reasonable. The relationship between naturallyoccurringBPandriskislineardowntoverylowBP,butthe benefitoftreatingtotheselowerlevelswithantihypertensivedrugs is not established. For all persons with hypertension, the potential benefits of a healthy diet, weight control, and regular exercise can- notbeoveremphasized.Theselifestyletreatmentshavethepoten- tial to improve BP control and even reduce medication needs. Al- Table 6. Guideline Comparisons of Goal BP and Initial Drug Therapy for Adults With Hypertension Guideline Population Goal BP, mm Hg Initial Drug Treatment Options guideline General 60 y <150/90 Nonblack: thiazide-type diuretic, ACEI, ARB, or CCB General <60 y <140/90 Black: thiazide-type diuretic or CCB Diabetes <140/90 Thiazide-type diuretic, ACEI, ARB, or CCB CKD <140/90 ACEI or ARB General nonelderly <140/90 -Blocker, diuretic, CCB, ACEI, or ARB General elderly <80 y <150/90 Diabetes <140/85 ACEI or ARB CKD no proteinuria <140/90 ACEI or ARB CKD + proteinuria <130/90 General <80 y <140/90 Thiazide, -blocker (age <60y), ACEI (nonblack), or ARB Diabetes <130/80 ACEI or ARB with additional CVD risk ACEI, ARB, thiazide, or DHPCCB without addi- tional CVD risk CKD <140/90 ACEI or ARB Diabetes <140/80 ACEI or ARB CKD no proteinuria 140/90 ACEI or ARB CKD + proteinuria 130/80 General <80 y <140/90 <55 y: ACEI or ARB General 80 y <150/90 55 y or black: CCB Black, lower risk <135/85 Diuretic or CCB Target organ damage or CVD risk Abbreviations: ADA, American Diabetes Association; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; CHEP, Canadian Hypertension Education Program; CKD, chronic kidney disease; CVD, cardiovascular disease; DHPCCB, dihydropyridine calcium channel blocker; ESC, European Society of Cardiology; ESH, European Society of Hypertension; ISHIB, International Society for Hypertension in Blacks; JNC, Joint National Committee; KDIGO, Kidney Disease: Improving Global Outcome; NICE, National Institute for Health and Clinical Excellence. Clinical Review & Education Special Communication 2014 Guideline for Management of High Blood Pressure E12 JAMA Published online December 18, 2013 jama.com though the authors of this hypertension guideline did not conduct anevidencereviewoflifestyletreatmentsinpatientstakingandnot takingantihypertensivemedication,wesupporttherecommenda- tions of the 2013 Lifestyle Work Group.45 Therecommendationsfromthisevidence-basedguidelinefrom panel members appointed to the Eighth Joint National Committee (JNC 8) offer clinicians an analysis of what is known and not known about BP treatment thresholds, goals, and drug treatment strate- gies to achieve those goals based on evidence from RCTs. How- ever, these recommendations are not a substitute for clinical judg- ment, and decisions about care must carefully consider and incorporatetheclinicalcharacteristicsandcircumstancesofeachin- dividual patient. We hope that the algorithm will facilitate imple- mentationandbeusefultobusyclinicians.Thestrongevidencebase of this report should inform quality measures for the treatment of patients with hypertension. ARTICLE INFORMATION Published Online: December 18, 2013. doi:10.1001/jama.2013.284427. Author Affiliations: University of Iowa, Iowa City (James, Carter); University of Alabama at Birmingham School of Medicine (Oparil); Memphis Veterans Affairs Medical Center and the University of Tennessee, Memphis (Cushman); Johns Hopkins University School of Nursing, Baltimore, Maryland (Dennison-Himmelfarb); Kaiser Permanente, Anaheim, California (Handler); Medical University of South Carolina, Charleston (Lackland); University of Missouri, Columbia (LeFevre); Denver Health and Hospital Authority and the University of Colorado School of Medicine, Denver (MacKenzie); New York University School of Medicine, New York, New York (Ogedegbe); University of North Carolina at Chapel Hill (Smith); Duke University, Durham, North Carolina (Svetkey); Mayo Clinic College of Medicine, Rochester, Minnesota (Taler); University of Pennsylvania, Philadelphia (Townsend); Case Western Reserve University, Cleveland, Ohio (Wright); National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland (Narva); at the time of the project, National Heart, Lung, and Blood Institute, Bethesda, Maryland (Ortiz); currently with ProVation Medical, Wolters Kluwer Health, Minneapolis, Minnesota (Ortiz). Author Contributions: Drs James and Oparil had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, administrative, technical, and material support, and study supervision: All authors. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Oparil reports individual and institutional payment related to board membership from Bayer, Daiichi Sankyo, Novartis, Medtronic, and Takeda; individual consulting fees from Backbeat, Bayer, Boehringer-Ingelheim, Bristol Myers-Squibb, Daiichi Sankyo, Eli Lilly, Medtronic, Merck, Pfizer, and Takeda; receipt of institutional grant funding from AstraZeneca, Daiichi Sankyo, Eisai Inc, Gilead, Medtronic, Merck, Novartis, Takeda Global Research and Development Inc; individual payment for lectures from Daiichi Sankyo, Merck, Novartis, and Pfizer; individual and institutional payment for development of educational presentations from ASH/AHSR (Daiichi Sankyo); and individual and institutional payment from Amarin Pharma Inc, Daiichi Sankyo, and LipoScience Inc for educational grant(s) for the Annual UAB Vascular Biology & Hypertension Symposium. Dr Cushman reports receipt of institutional grant support from Merck, Lilly, and Novartis; and consulting fees from Novartis, Sciele Pharmaceuticals, Takeda, sanofi-aventis, Gilead, Calpis, Pharmacopeia, Theravance, Daiichi-Sankyo, Noven, AstraZeneca Spain, Merck, Omron, and Janssen. Dr Townsend reports board membership with Medtronic, consultancy for Janssen, GlaxoSmithKline, and Merck, and royalties/educational-related payments from Merck, UpToDate, and Medscape. Dr Wright reports receipt of consulting fees from Medtronic, CVRx, Takeda, Daiichi-Sankyo, Pfizer, Novartis, and Take Care Health. The other authors report no disclosures. Funding/Support: The evidence review for this project was funded by the National Heart, Lung, and Blood Institute (NHLBI). 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