Starting Antihypertensive Drug Treatment With Combination Therapy

HomeHypertensionVol. 77, No. 3Starting Antihypertensive Drug Treatment With Combination Therapy Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree ArticlePDF/EPUBStarting TherapyControversies in Hypertension - Pro Side of the Argument Alexandre Persu , Marilucy Lopez-Sublet, Engi Abd El-Hady Algharably, Reinhold Kreutz Correspondence to: Persu, Division Cardiology, Cliniques Universitaires St-Luc, Unversité catholique de Louvain, 10 Ave Hippocrate, 1200, Brussels, Belgium. Email E-mail Address: [email protected] https://orcid.org/0000-0002-4007-9695 Saint-Luc and Pole Cardiovascular Research, Institut Recherche Expérimentale et Clinique, Université Belgium (A.P.). Search for more papers by this author Lopez-SubletMarilucy Lopez-Sublet AP-HP Hôpital Avicenne, Excellence Center, Department Internal Medicine, Bobigny, France (M.L.-S.). AlgharablyEngi Algharably Charité Universitätsmedizin Berlin, corporate member Freie Universität Humboldt-Universität zu Berlin Institute Health, für Klinische Pharmakologie und Toxikologie, Germany. DZHK (German Centre Research), partner site Germany (E.A.E.-H.A., R.K.). https://orcid.org/0000-0002-4818-211X Originally published10 Feb 2021https://doi.org/10.1161/HYPERTENSIONAHA.120.12857Hypertension. 2021;77:800–805is corrected byCorrection Starting Therapy: Controversies ArgumentOne highlights current recommendations European Society Cardiology (ESC) (ESH) management arterial hypertension published 20181 is strong position favor a single-pill combination (SPC) comprising 2 antihypertensive drugs as first-line treatment most hypertensive patients. The scope article summarize background evidence supporting recommendation. First, we review recommendation detail show that it did not come out blue but rather reinforces strategies already proposed 2013 guidelines2 consistent with other major guidelines.3–5 Second, dual therapy per se compared therapeutic achieve blood pressure (BP) goals, well specific use SPC instead prescribing free combination. Third, discuss advantages strategy pragmatic approach improve BP control and, therefore, decrease cardiovascular risk.What Do 2018 ESC/ESH Guidelines Say?The guidelines recommend initiate an 2-drug combination, preferably exceptions are (1) frail older patients/patients ?80 years whom, due baroreflex impairment, risk hypotension may be higher, (2) patients grade 1 at low or moderate (particularly if systolic <150 mm Hg) possibly, (3) high normal because only small reduction required target.1First-Line SPC—a Revolution Guidelines?As acknowledged writing committee, revolution normalizes concept initial expressed guidelines,2 which showed preference two-drug marked elevation high/very risk. However, contrast guidelines,1 object than advice applies wider spectrum patients, thus becoming standard approach.Is Initiation Dual Supported Other Guidelines?The American College Cardiology/American Heart Association guidelines3 initiation adults stage (corresponding ESH classification)1 (Table) average >20/10 Hg above target. Although SPCs left decision physician, its potential usefulness drug adherence free-drug equivalents acknowledged.3 Similarly, without specification level, Japanese Guidelines4 outright when ?20/10 targeted. Finally, optimal advocated International Global Guidelines5 includes first choice all possible exception hypertension, very old (?80 years) while leaving door open equivalent combinations case unavailable unaffordable. There wide worldwide consensus on treatment, form SPC, patients.Table. Classification Based Office Blood Pressure Current GuidelinesCategoriesSystolic, HgDiastolic, HgESC/ESH 2018*ISH 2020†ACC/AHA 2017‡NormalNormalElevated120–129and/or80–84High normalHigh normalStage hypertension130–139and/or85–89Grade hypertensionGrade hypertensionStage hypertension140–159and/or90–99Grade hypertension160–179and/or100–109Grade 3 hypertension?180and/or?110ACC indicates Cardiology; AHA, Association; ESC, ESH, ISH, Hypertension.* Williams al.1† Unger al.5‡ Whelton al.3What Is Evidence Supporting Therapy?The committee guidelines1 needs interpreted context lower goals document, is, diastolic <80 <130 below age 65 within range 130 139 older. Randomized controlled studies needed reach even less strict majority patients.6 Furthermore, French randomized trial STRATHE (Strategies Hypertension: Evaluation)7 has shown higher rate success achieving target after 3, 6, 9 months previously untreated prescribed low-dose (62%) sequential monotherapy (49%, P=0.02) stepped-care (47%, P=0.005). These results were confirmed further expanded large observational studies.8,9 Along same lines, meta-analysis including 11 000 participants from 42 trials adding another class dose efficient reduce doubling drug, irrespective class.10 retrospective analysis 1700 median time was significantly shorter (9.7 versus 11.9 months, p=0.004) initially treated those who shifted monotherapy.11 findings relevant view importance early achievement target, especially at-risk clearly Valsartan Long-term Use Evaluation (VALUE).12 A subanalysis based technique serial matching13 indeed hazard ratios fatal nonfatal events (cardiac: ?25%; stroke: ?45%) all-cause death (?21%) substantially decreased reached 6 uncontrolled arm trial. crucial role diagnosis supported study (n=88 756) delays intensification 1.4 4.7 associated progressive increase ratio combined end point any cause 1.12 1.2.14 option selection adequate individual extended availability multiple comparing different (Anglo-Scandinavian Cardiac Outcomes Trial [ASCOT];ONgoing Telmisartan Alone Ramipril Endpoint [ONTARGET])15,16 fixed-dose (Avoiding Events Patients Living Systolic (ACCOMPLISH)).17What Favor Versus Free-Drug Therapy?Although superior terms timing achievement, why shall therapy? main argument improves adherence, key factor subsequent prevention BP-related complications. In widely quoted systematic various clinical conditions, Claxton al18 have inverse relation between number daily doses adherence. directly tool summarized Gupta al.19 This demonstrated 17 999 enrolled 5 improved assessed indirect methods (drug pill count medication possession ratio) corresponding (odds ratio, 1.21, p=0.02). several indicated shifting being one effective ways adherence.20 More recently, Salam al21 conducted 33 therapy. Compared standard-dose monotherapy, initiating low-to-standard-dose proved efficacious control, increasing withdrawals adverse events.Notably, favorable impact reducing burden underestimated real life known positive participation behavior (Hawthorne effect), persistence.22 All investigators involved recruitment renal denervation experienced difficult treat suddenly during run-in period, either spontaneously shift standardized triple therapy.23–25Which Availability Worldwide?We checked databases listing information about medications authorized countries around world (drugs.com [the Drugs.com Name Database], drugbank.com, ema.europa.eu [Public data Article 57 database] fda.gov [Orange Book: approved products equivalence evaluations]) ACE (angiotensin-converting enzyme) inhibitors angiotensin receptor blockers SPCs, thiazide/thiazide-like diuretic calcium channel blocker. Research available these classes Anatomical Therapeutic Chemical (ATC) codes provided World Health Organization–ATC defined (DDD) index (https://www.whocc.no/atc_ddd_index/). least inhibitors/calcium blockers, 12 inhibitors/diuretics, 8 blockers/calcium blockers/diuretic many marketed dosing levels, potentially globally. there significant regional differences. Indeed, although some Europe, North America (Canada United States), Asia (China, Japan, India, South Korea), fewer Middle East Australia, particularly renin system-blocker blocker, Africa retrieve.Accordingly, mentioned, recent distinguish essential measures. perspective, considered therapy, unaffordable (see higher). Such 2-level advantage propose applicable measures, low-resource countries, setting ambitious standards likely encourage local initiatives such standards.Beyond Evidence-Based Which Are Tentative Advantages Improve Overall Control?We aware mentioned limitations often somewhat weak contradictory. benefit monotherapy-based lacking. conduct they nevertheless capture full benefits real-life medical practice. fact companies actively promoting allow them capitalizing existent beyond patent expiration raises suspicion strategy, sometimes elicits visceral reactions. Nevertheless, Organization added (or combination) Essential Medicines List26 thereby acknowledges emerging best practice safe, effective, rapid, convenient worldwide.27We agreement recognition reasons common sense experience support strategy. still specialists until validated does require expertise should ?80% [ACCOMPLISH])17 events.19 Timely few no important risk13 also avoid discouragement reluctant escape follow-up unsuccessful attempts. contrast, quick using well-tolerated strengthen physician-patient relationship, reinforce discontinuation.28,29 It once improvement BP, both physicians will tempted delay therapy.30 Standard therefore prevent poor inertia.1 decreasing critical decades ago, 75% factor.31 Thus, candidates lipid-lowering32 antidiabetic drugs, providing rationale polypill targeting factors.33 Still, discussion pros cons polypill, way entire populations partly differs article.Importance Accurate Measurement Outside Physician’s OfficeSafe implementation recommendation1 requires accurate evaluation level patient according repeated office measurements, ideally complemented out-of-office strongly guidelines.1 particular, mild ambulatory measurement necessarily frail, old, orthostatic hypotension, risk.1 been listed pointed beginning article.ConclusionsIn conclusion, appears means worldwide. simple algorithm Figure. medicine remains art, tailored patient.Download figureDownload PowerPointFigure. Decision start pressure; CV, cardiovascular; OR, odds ratio.Sources FundingNone.Disclosures A. reports honoraria consultancy travel grants Ablative Solutions Quantum Genomics. M. consultancy, lectures, trials, research AddMedica, Astra Zeneca, Elsevier, Servier. R. lectures Bayer Pharma, Berlin-Chemie Menarini, Daiichi Sankyo, Ferrer, Sanofi, conflicts.FootnotesThe opinions editors Association.For Sources Funding Disclosures, see page 804.Correspondence alexandre.[email protected]beReferences1. B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier Clement DL, Coca A, Simone Dominiczak al.; ESC Scientific Document Group. hypertension.Eur J. 2018; 39:3021–3104. doi: 10.1093/eurheartj/ehy339CrossrefMedlineGoogle Scholar2. Fagard R, Narkiewicz K, Redón J, Zanchetti Böhm Christiaens T, Cifkova De Backer Task Force Members. ESH/ESC hypertension: (ESC).J Hypertens. 2013; 31:1281–1357. 10.1097/01.hjh.0000431740.32696.ccCrossrefMedlineGoogle Scholar3. 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