Triple-combination Therapy in the Treatment of Hypertension a Review of the Evidence
Managing Hypertension Using Combination Therapy
Am Fam Dr.. 2020 Mar 15;101(half dozen):341-349.
Related alphabetic character: Race-Based Treatment Decisions Perpetuate Structural Racism
Patient information: A handout on this topic is available at https://familydoctor.org/loftier-blood-pressure level-medicines.
This clinical content conforms to AAFP criteria for continuing medical didactics (CME). Come across the CME Quiz Questions.
Author disclosure: No relevant fiscal affiliations.
Article Sections
- Abstract
- When to Initiate Combination Therapy
- Pick of Agents
- Special Populations
- References
More than 70% of adults treated for primary hypertension will eventually require at to the lowest degree ii antihypertensive agents, either initially as combination therapy or as improver therapy if monotherapy and lifestyle modifications practice not achieve adequate blood pressure level command. Four primary classes of medications are used in combination therapy for the treatment of hypertension: thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). ACEIs and ARBs should not be used simultaneously. In blackness patients, at least one amanuensis should be a thiazide diuretic or a calcium channel blocker. Patients with middle failure with reduced ejection fraction should be treated initially with a beta blocker and an ACEI or ARB (or an angiotensin receptor–neprilysin inhibitor), followed by improver therapy with a mineralocorticoid receptor antagonist and a diuretic based on volume status. Treatment for patients with chronic kidney disease and proteinuria should include an ACEI or ARB plus a thiazide diuretic or a calcium channel blocker. Patients with diabetes mellitus should be treated similarly to those without diabetes unless proteinuria is nowadays, in which case combination therapy should include an ACEI or ARB.
Cardiovascular disease is the leading crusade of death worldwide, and hypertension is a modifiable risk factor for cardiovascular illness.1 Hazard increases with incremental increases in blood pressure, even within the normal range.ii More than 70% of adults treated for chief hypertension volition somewhen require at to the lowest degree two antihypertensive agents.three
WHAT'S NEW ON THIS TOPIC
Hypertension Therapy
A meta-analysis showed that angiotensin-converting enzyme inhibitors—just not angiotensin receptor blockers—reduced the incidence of doubling of the serum creatinine level in patients with diabetes mellitus, simply it did not affect progression to terminate-phase renal disease. Another meta-analysis showed that angiotensin-converting enzyme inhibitors were superior to angiotensin receptor blockers for reducing all-cause and cardiovascular mortality.
Compared with monotherapy, initial combination therapy achieves blood pressure control more than quickly with like tolerability. Withal, in a randomized controlled trial, patients who started on monotherapy eventually achieved blood pressure control similar to that of patients who started on combination therapy.
Although improved adherence to antihypertensive medications is expected to decrease morbidity and bloodshed, a large systematic review establish that the effects of fixed-dose combination therapy on all-crusade mortality or atherosclerotic cardiovascular disease events are uncertain.
SORT: KEY RECOMMENDATIONS FOR Exercise
| Clinical recommendation | Evidence rating | Annotate |
|---|---|---|
| For almost patients, combination antihypertensive therapy should include an ACEI or ARB, a thiazide diuretic, or a calcium channel blocker.4–6 | A | Consistent evidence showing reduced morbidity and bloodshed with each of those four drug classes in RCTs included in guidelines |
| Patients with chronic kidney disease who take proteinuria should be prescribed an ACEI or ARB as part of combination therapy.40,41 | A | Consistent evidence from RCTs showing reduced morbidity and mortality |
| The combination of an ACEI and an ARB should be avoided.43 | B | RCT showed that benefit is outweighed by increased morbidity |
Updated hypertension guidelines were published in 2017 by the American College of Cardiology and the American Heart Association (ACC/AHA), and in 2018 by the European Society of Cardiology (ESC).4,5 The American Academy of Family Physicians continues to endorse the Eighth Joint National Committee (JNC8) guidelines published in 2014.6,7 For this reason, this article emphasizes JNC8 guidelines. Because patients may receive recommendations from clinicians who follow other guidelines, some key differences between these recommendations are highlighted in Table one.4–six
Tabular array i.
Claret Pressure Handling Thresholds
| Eighth Articulation National Commission, 2014 | European Society of Cardiology, 2018 | American College of Cardiology/American Heart Association, 2017 | ||||
|---|---|---|---|---|---|---|
| Population | Treatment threshold (mm Hg)* | Population | Treatment threshold (mm Hg) | Handling goal (mm Hg) | Population | Treatment threshold (mm Hg) |
| Adults 18 to 59 years of historic period | ≥ 140/xc | Adults 18 to 65 years of age | ≥ 140/90 | 120 to 130/lxx to 79 | Adults† | ≥ 130/80‡ |
| Adults 60 years and older | ≥ 150/90 | Adults 65 to 79 years of historic period | ≥ 140/ninety | 130 to 139/70 to 79 | ||
| Adults eighty years and older | ≥ 160/90 | 130 to 139/70 to 79 | ||||
| Adults with diabetes mellitus | ≥ 140/90 | Adults with diabetes, 18 to 65 years of age | ≥ 140/90 | 120 to 130/lxx to 79 | Adults with diabetes | ≥ 130/lxxx |
| Adults with diabetes, 65 to 79 years of age | ≥ 140/90 | 130 to 139/lxx to 79 | ||||
| Adults with diabetes, 80 years and older | ≥ 160/xc | 130 to 139/70 to 79 | ||||
| Adults with CKD | ≥ 140/ninety | Adults with CKD, 18 to 65 years of age | ≥ 140/ninety | 130 to 139/70 to 79 | Adults with CKD | ≥ 130/80 |
| Adults with CKD, 65 to 79 years of age | ≥ 140/ninety | 130 to 139/70 to 79 | ||||
| Adults with CKD, lxxx years and older | ≥ 160/90 | 130 to 139/70 to 79 | ||||
| — | — | Adults with history of stroke, xviii to 65 years of historic period | ≥ 140/90 | 120 to 130/70 to 79 | Adults with history of stroke§ | ≥ 130/80 |
| Adults with history of stroke, 65 to 79 years of age | ≥ 140/90 | 130 to 139/70 to 79 | ||||
| Adults with history of stroke, lxxx years and older | ≥ 160/90 | 130 to 139/70 to 79 | ||||
Initial management of hypertension with lifestyle changes and single-agent medications was described in detail in a previous American Family Doc commodity.8 This article focuses on combination therapy: when to initiate it, choice of agents, and special populations whose comorbid conditions influence those choices.
When to Initiate Combination Therapy
- Abstract
- When to Initiate Combination Therapy
- Choice of Agents
- Special Populations
- References
INADEQUATE CONTROL WITH MONOTHERAPY
Inadequate command with monotherapy is the clearest indication for adding another medication, which can be washed before or later titrating the first agent to the maximal dosage. If a patient does non achieve adequate control with a lower initial dose of a single agent, it is reasonable to titrate that medication or to add a second agent (Table ii).6 Initiating a 2d agent before titration of the first may upshot in a larger reduction in blood pressure compared with increasing the dose of the outset agent.nine Response to initial monotherapy varies significantly with individual plasma renin levels, so a second mechanism of action may more accordingly address the patient's individual physiology rather than increasing the dosage of a relatively ineffective first agent.10
TABLE 2.
Strategies for Initiating and Titrating Antihypertensive Drugs
| Start 1 drug; if acceptable command is not achieved in one month, titrate to maximal dosage before adding an additional agent |
| Starting time one drug; if adequate control is not accomplished in one month, add an additional agent before titrating the initial drug to maximal dosage |
| Initiate two drugs simultaneously; if adequate control is not achieved in 1 month, titrate to maximal dosages before adding an additional agent, or add a 3rd agent |
Approximately 45% of patients with hypertension and 84% of those with uncontrolled hypertension are not adherent to their antihypertensive regimen.eleven Multiple studies report that combination pills containing 2 or three agents increase medication adherence and lower overall costs.12–14 Although improved adherence is expected to decrease morbidity and mortality, a large systematic review found that the effects of fixed-dose combination therapy on all-cause mortality or atherosclerotic cardiovascular illness events are unclear.15
INITIAL THERAPY
The use of combination antihypertensive agents equally initial therapy has increased since 2003.xvi,17 Compared with monotherapy, initial combination therapy improves the average decrease in blood pressure and achieves claret pressure command faster, with similar tolerability. 9,18,19 Nonetheless, patients who start on monotherapy eventually reach similar blood pressure control as those who started on combination therapy.10
No randomized controlled trials have shown decreased cardiac risk with initial combination therapy, although some observational data have shown decreased risk.20,21 This may be because a significant number of patients are not escalated to combination therapy after titration of monotherapy every bit directed by guidelines, a phenomenon termed therapeutic inertia.22 Furthermore, delays of even a few months in therapy escalation are associated with an increased take chances of cardiac events or decease (hazard ratio = 1.1).23
Experts disagree over the lowest blood pressure that suggests the need for initial combination therapy. Withal, there is general agreement that initial combination therapy is safe and more than effective than monotherapy in patients with systolic blood pressure higher than 160 mm Hg or greater than 20 mm Hg to a higher place goal, or with diastolic blood pressure higher than 100 mm Hg or greater than 10 mm Hg in a higher place goal.five,6,24,25 Whichever treatment strategy is called, escalation of therapy should occur inside one month, if needed, to achieve target claret pressure.
Guidelines recommend the addition of a third agent for patients whose claret pressure is not controlled with dual therapy.half-dozen Randomized controlled trials have shown significantly higher rates of claret pressure control in patients using a combination of an angiotensin receptor blocker (ARB), calcium channel blocker (CCB), and thiazide diuretic compared with those on a dual regimen of an ARB and CCB.26,27 A recent meta-analysis suggests that adding a 3rd agent to dual therapy is more than effective for lowering claret pressure than increasing dosages of dual therapy and is equally safety.28 Because of the lack of mortality data from randomized controlled trials, information technology is reasonable to either titrate individual agents to maximal dosages earlier adding an additional agent, or to add an additional agent before reaching the maximal dosage of the current agent.
Option of Agents
- Abstruse
- When to Initiate Combination Therapy
- Choice of Agents
- Special Populations
- References
Figure 1 is an algorithm that can guide combination therapy in patients with hypertension.1,6 JNC8, ESC, and ACC/AHA guidelines hold that for most patients, combination therapy should include a thiazide diuretic, a CCB, and an angiotensin-converting enzyme inhibitor (ACEI) or ARB. They farther agree that a patient should not take an ACEI and ARB simultaneously.4–6 Therapy should be escalated at one-month intervals using any of the three accepted strategies (Table 2).6
FIGURE 1
Treatment algorithm for adults with hypertension.
ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; BP = claret force per unit area; CCB = calcium channel blocker.
*—Lifestyle interventions include smoking cessation, avoiding secondhand smoke, optimizing body weight, increasing physical activity, improving diet, moderating alcohol intake, and reducing stress.1
†—The Eighth Joint National Commission states that neither strategy is demonstrably superior; the choice should reverberate shared conclusion-making with patients.half dozen
Information from references one and half-dozen.
The ACC/AHA recommends chlortha lidone as the preferred thiazide diuretic and recommends that central-acting alpha agonists exist avoided.4 JNC8 recommends that for blackness patients, at least 1 agent should be a thiazide diuretic or CCB.6 Other drug classes may be considered for patients who do not reach adequate blood force per unit area command on maximal triple therapy, or for those with comorbidities such as center failure, diabetes mellitus, or chronic kidney disease with proteinuria (Table 3).iv–6 Table four lists fixed-dose combination medications that are currently available.1,5
Table 3.
Recommended Initial Drug Classes for Specific Populations with Hypertension
| Population | Eighth Articulation National Commission, 2014 | European Order of Cardiology, 2018 | American Higher of Cardiology/American Middle Clan, 2017 |
|---|---|---|---|
| General nonblack population | ACEI/ARB or CCB or thiazide diuretic | ACEI/ARB plus CCB or thiazide diuretic | ACEI/ARB or CCB or thiazide diuretic |
| General blackness population | ACEI/ARB* or CCB or thiazide diuretic | ACEI/ARB* or CCB or thiazide diuretic | No specific recommendation |
| Adults with diabetes mellitus | ACEI/ARB or CCB or thiazide diuretic | ACEI/ARB plus CCB or thiazide diuretic | ACEI/ARB or CCB or thiazide diuretic |
| Adults with chronic kidney illness and proteinuria (regardless of race) | ACEI/ARB plus CCB or thiazide diuretic | ACEI/ARB plus CCB or diuretic (thiazide or loop)† | ACEI/ARB plus CCB or thiazide diuretic |
| Centre failure with reduced ejection fraction | No specific recommendation | ACEI/ARB/ARNI plus beta blocker‡ plus diuretic (thiazide or loop)† | ACEI/ARB or beta blocker‡ or miner-alocorticoid receptor antagonist or thiazide diuretic |
Table iv.
Combination Medications for the Treatment of Hypertension
| Combination | Medication | Dose | Cost* | ||||
|---|---|---|---|---|---|---|---|
| ACEI plus CCB | Amlodipine/benazepril (Lotrel) | 2.5 mg/ten mg | $14 ($215) | ||||
| 5 mg/ten mg | $sixteen ($290) | ||||||
| v mg/20 mg | $16 ($305) | ||||||
| 5 mg/twoscore mg | $xvi (NA) | ||||||
| 10 mg/20 mg | $16 ($355) | ||||||
| 10 mg/xl mg | $16 ($390) | ||||||
| Perindopril/amlodipine (Prestalia) | 3.5 mg/ii.5 mg | NA ($180) | |||||
| vii mg/v mg | NA ($180) | ||||||
| fourteen mg/ten mg | NA ($180) | ||||||
| Trandolapril/verapamil extended release (Tarka) | 1 mg/240 mg | $65 ($185) | |||||
| 2 mg/180 mg | $47 ($185) | ||||||
| 2 mg/240 mg | $47 ($185) | ||||||
| four mg/420 mg | $47 ($185) | ||||||
| ACEI plus diuretic | Benazepril/HCTZ (Lotensin HCT) | 5 mg/6.25 mg | $21 (NA) | ||||
| 10 mg/12.five mg | $24 (NA) | ||||||
| 20 mg/12.five mg | $22 ($65) | ||||||
| twenty mg/25 mg | $22 (NA) | ||||||
| Enalapril/HCTZ (Vaseretic) | five mg/12.5 mg | $10 (NA) | |||||
| 10 mg/25 mg | $10 ($395) | ||||||
| Lisinopril/HCTZ (Zestoretic) | 10 mg/12.v mg | $six ($400) | |||||
| xx mg/12.five mg | $4 ($400) | ||||||
| 20 mg/25 mg | $4 ($400) | ||||||
| Quinapril/HCTZ (Accuretic) | 10 mg/12.5 mg | $17 ($150) | |||||
| 20 mg/12.5 mg | $17 ($150) | ||||||
| twenty mg/25 mg | $17 ($150) | ||||||
| ARB plus diuretic | Azilsartan/chlorthalidone (Edarbyclor) | 40 mg/12.five mg | NA ($200) | ||||
| 40 mg/25 mg | NA ($200) | ||||||
| Candesartan/HCTZ (Atacand HCT) | 16 mg/12.5 mg | $48 ($150) | |||||
| 32 mg/12.five mg | $fifty ($155) | ||||||
| 32 mg/25 mg | $l ($165) | ||||||
| Irbesartan/HCTZ (Avalide) | 150 mg/12.v mg | $15 ($235) | |||||
| 300 mg/12.5 mg | $twenty ($255) | ||||||
| Losartan/HCTZ (Hyzaar) | l mg/12.5 mg | $four ($130) | |||||
| 100 mg/12.v mg | $9 ($175) | ||||||
| 100 mg/25 mg | $9 ($175) | ||||||
| Olmesartan/HCTZ (Benicar HCT) | 20 mg/12.5 mg | $fourteen ($225) | |||||
| 40 mg/12.v mg | $16 ($310) | ||||||
| forty mg/25 mg | $16 ($310) | ||||||
| Telmisartan/HCTZ (Micardis HCT) | 40 mg/12.5 mg | $47 ($220) | |||||
| eighty mg/12.5 mg | $47 ($220) | ||||||
| eighty mg/25 mg | $47 ($220) | ||||||
| Valsartan/HCTZ (Diovan HCT) | lxxx mg/12.5 mg | $xiv ($270) | |||||
| 160 mg/12.v mg | $9 ($295) | ||||||
| 160 mg/25 mg | $nine ($330) | ||||||
| 320 mg/12.5 mg | $17 ($370) | ||||||
| 320 mg/25 mg | $18 ($420) | ||||||
| Beta blocker plus ARB | Nebivolol/valsarten (Byvalson) | five mg/80 mg | NA ($130) | ||||
| Beta blocker plus diuretic | Atenolol/chlorthalidone (Tenoretic) | l mg/25 mg | $15 ($360) | ||||
| 100 mg/25 mg | $19 ($155) | ||||||
| Bisoprolol/HCTZ (Ziac) | 2.5 mg/half-dozen.25 mg | $9 ($200) | |||||
| 5 mg/6.25 mg | $thirteen ($200) | ||||||
| ten mg/six.25 mg | $12 ($200) | ||||||
| Metoprolol/HCTZ (Lopressor HCT) | 50 mg/25 mg | $xx ($70) | |||||
| 100 mg/25 mg | $25 (NA) | ||||||
| 100 mg/l mg | $29 (NA) | ||||||
| Nadolol/bendroflumethiazide (Corzide) | 40 mg/5 mg | $64 ($245) | |||||
| 80 mg/v mg | $78 ($320) | ||||||
| CCB plus ARB | Amlodipine/olmesartan (Azor) | 5 mg/xx mg | $23 ($280) | ||||
| 5 mg/xl mg | $28 ($350) | ||||||
| x mg/20 mg | $28 ($280) | ||||||
| 10 mg/40 mg | $28 ($350) | ||||||
| Amlodipine/valsartan (Exforge) | v mg/160 mg | $twenty ($270) | |||||
| 5 mg/320 mg | $25 ($340) | ||||||
| 10 mg/160 mg | $20 ($305) | ||||||
| x mg/320 mg | $25 ($385) | ||||||
| Telmisartan/amlodipine (Twynsta) | twoscore mg/5 mg | $50 (NA) | |||||
| forty mg/10 mg | $50 (NA) | ||||||
| 80 mg/five mg | $50 ($240) | ||||||
| 80 mg/10 mg | $55 ($240) | ||||||
| CCB plus diuretic plus ARB | Amlodipine/valsartan/HCTZ (Exforge HCT) | 5 mg/160 mg/12.5 mg | $43 ($270) | ||||
| 5 mg/160 mg/25 mg | $46 ($270) | ||||||
| 10 mg/160 mg/12.5 mg | $53 ($305) | ||||||
| 10 mg/160 mg/25 mg | $55 ($305) | ||||||
| 10 mg/320 mg/25 mg | $55 ($390) | ||||||
| Olmesartan/amlodipine/HCTZ (Tribenzor) | 20 mg/v mg/12.5 mg | $58 ($280) | |||||
| 40 mg/5 mg/12.5 mg | $55 ($350) | ||||||
| xl mg/five mg/25 mg | $57 ($350) | ||||||
| 40 mg/10 mg/12.5 mg | $65 ($350) | ||||||
| 40 mg/10 mg/25 mg | $60 ($350) | ||||||
| Diuretic plus diuretic | Spironolactone/HCTZ (Aldactazide) | 25 mg/25 mg | $17 ($85) | ||||
| 50 mg/50 mg | NA ($150) | ||||||
| Triamterene/HCTZ (Maxzide) | 37.5 mg/25 mg | $4 ($55) | |||||
| 75 mg/50 mg | $4 ($115) | ||||||
| Renin inhibitor plus diuretic | Aliskiren/HCTZ (Tekturna HCT) | 150 mg/12.5 mg | NA ($215) | ||||
| 150 mg/25 mg | NA ($215) | ||||||
| 300 mg/12.5 mg | NA ($270) | ||||||
| 300 mg/25 mg | NA ($270) | ||||||
Special Populations
- Abstract
- When to Initiate Combination Therapy
- Choice of Agents
- Special Populations
- References
These general antihypertensive therapy recommendations complement treatment recommendations for each illness state. In some cases, antihypertensive medications may be used to treat the underlying disease regardless of blood pressure level. For this reason, these recommendations should be used in conjunction with disease-specific guidelines.
HEART FAILURE
ACEIs are associated with decreased cardiovascular mortality in patients with eye failure with reduced ejection fraction (HFrEF).29 A Cochrane review showed that ARBs are no ameliorate than ACEIs or placebo in reducing morbidity or bloodshed in patients with HFrEF,xxx but they are a reasonable culling for patients who cannot tolerate ACEIs. The Prospective Comparison of ARNI with ACEI to Make up one's mind Impact on Global Mortality and Morbidity in Heart Failure (Prototype-HF) trial showed that angiotensin receptor–neprilysin inhibitors reduce morbidity and mortality in patients with HFrEF compared with ACEIs and may be a 2d-line alternative to ACEIs or ARBs.31 The JNC8 found insufficient show to recommend preferential use of ACEIs or ARBs in patients with centre failure and hypertension6; however, the JNC8 recommendations were published before the PARADIGM-HF results.
The beta blockers carvedilol (Coreg), extended-release metoprolol (Toprol Twoscore), and bisoprolol (Zebeta) take shown improvements in morbidity and bloodshed. One of these agents should be initiated in patients with HFrEF unless they have contraindications.32–34 Beta blockers are usually added in one case the patient no longer has symptoms of volume overload.
The addition of eplerenone (Inspra) or spironolactone to ACEI therapy decreases morbidity and bloodshed in patients with HFrEF, especially after acute myocardial infarction.35,36
CHRONIC KIDNEY DISEASE
Long-term follow-upward of the Modification of Diet in Renal Disease (MDRD) trial and the African American Study of Kidney Disease and Hypertension (AASK) trial showed that improved blood pressure control decreases mortality.37,38 A 2017 meta-analysis of patients with stage 3 to five chronic kidney disease found a decreased risk of all-cause mortality in patients who received more intensive blood pressure command compared with less intensive control (systolic claret force per unit area decrease of 16 vs. 8 mm Hg, respectively).39
ACEIs and ARBs reduce proteinuria and decrease progression to end-stage renal illness in patients with proteinuria.40,41 The MDRD and AASK studies did not discover benefit in patients without proteinuria, and a systematic review suggests that improved renal outcomes associated with renin-angiotensin-aldosterone blockade may be entirely due to their blood pressure–lowering effect.42 The combination of an ACEI and ARB is not recommended because of the increased hazard of cease-phase renal disease and lack of mortality benefit.41,43 The JNC8 recommends that patients with chronic kidney disease be treated with an ACEI or an ARB, in addition to a thiazide diuretic or a CCB.6 A loop diuretic may be considered if the estimated glomerular filtration rate is less than 30 mL per minute per 1.73 m2, based on low-quality bear witness that thiazide diuretics have decreased effectiveness in people with reduced renal function.5,44
Direct renin inhibitors (eastward.g., aliskiren [Tekturna]) were non considered past the JNC8 because there were no studies showing their benefits on kidney or cardiovascular outcomes. The ESC notes that aliskiren combined with an ACEI or ARB led to adverse events in patients with diabetes.5 Although newer directly renin inhibitors are being adult, they are not yet widely used.
DIABETES
Using a fixed-dose combination of an ACEI and a thiazide diuretic in adults with diabetes, the Fugitive Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that a blood pressure level decrease of 5.6/ii.2 mm Hg led to lower rates of microvascular and macrovascular events and of cardiovascular and all-cause mortality.45
ACEIs or ARBs should be used in patients with proteinuria, including those with diabetes. In patients with diabetes who do not take proteinuria, at that place is no benefit in using an ACEI or ARB compared with a CCB or thiazide diuretic.v,6 A meta-analysis showed that ACEIs—but not ARBs— reduce the incidence of doubling of the serum creatinine level in patients with diabetes, but they do not affect progression to end-stage renal affliction.46 Another meta-analysis showed that ACEIs are superior to ARBs in reducing all-cause and cardiovascular mortality.47 The Achieve trial showed that patients with diabetes who are treated with a combined ACEI/CCB have a lower risk of fatal and nonfatal cardiovascular events compared with those treated with a combined ACEI/thiazide diuretic.48
This commodity updates previous articles on this topic past Frank,49 and past Skolnik, et al.50
Data Sources: A PubMed search was completed using the central terms hypertension, hypertension treatment, and hypertension combination therapy. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. We also searched the Cochrane database, Essential Evidence Plus, and the National Guideline Clearinghouse. In addition, references in these resources were searched. Search dates: March to September 2019.
The contents of this article are solely the views of the authors and do not necessarily represent the official views of the Uniformed Services University of the Health Sciences, the U.S. Navy, the U.S. armed forces at large, the U.S. Department of Defense, or the U.S. authorities.
Editor's Note: As we keep to navigate the complexities of managing chronic affliction in our patients, we must remember that many atmospheric condition, including hypertension, are affected by environmental, behavioral, and sociocultural factors as opposed to genetics alone. While guidelines from the U.s.a. and other countries go on to apply race every bit a surrogate in determining pharmacotherapy, information technology is critical for usa to determine the truthful underlying cause for differences in morbidity/mortality and differences in response to therapies rather than bold information technology is based on ane'south peel tone or identifying every bit Black.A1 For instance, the variability in response to ACEI monotherapy is greater inside races than it is between races.A2,A3 And ACEIs remain an important therapy for chronic kidney disease, diabetes, and hypertension requiring multiple drugs irrespective of race.A3
As nosotros interpret guidelines and make decisions on therapy, we must continue to discuss the current limitations of the evidence with our patients. In addition, nosotros demand to claiming ourselves and our organizations to encourage researchers and guideline developers to reach across our traditional use of race as a "chance cistron". An private'due south race is an unmitigable social construct. Using race as a proxy limits our ability to identify and address the actual, likely multifactorial, and peradventure mitigable qualities of concern. These areas are where we need to focus our research efforts.—Sumi Sexton, MD, Editor-in-Chief, and Renee Crichlow, Doctor, Medical Editor for Variety, Equity, and Inclusion
A1. Williams SK, Ravenell J, Seyedali Due south, et al. Hypertension treatment in Blacks: word of the U.S. Clinical Practice Guidelines. Prog Cardiovasc Dis. 2016;59(iii):282-288.
A2. Sehgal AR. Overlap between whites and blacks in response to antihypertensive drugs. Hypertension. 2004 Mar;43(3):566-572.
A3. Peck RN, Smart LR, Beier R, et al. Difference in blood pressure response to ACE-Inhibitor monotherapy between black and white adults with arterial hypertension: a meta-analysis of 13 clinical trials. BMC Nephrol. 2013;26(14):201.
To see the full article, log in or purchase access.
References
evidence all references
1. Lennon RP, Claussen KA, Kuersteiner KA. Land of the heart: an overview of the disease burden of cardiovascular disease from an epidemiologic perspective. Prim Intendance. 2018;45(1):i–15. ...
2. Kannel WB. Hypertension: reflections on risks and prognostication. Med Clin Northward Am. 2009;93(3):541–558.
iii. Cushman WC, Ford CE, Cutler JA, et al.; ALLHAT Collaborative Enquiry Group. Success and predictors of claret pressure level control in various Northward American settings: the Antihypertensive and Lipid-Lowering Treatment to Prevent Center Attack Trial (ALLHAT). J Clin Hypertens (Greenwich). 2002;4(6):393–404.
4. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high claret pressure in adults: a study of the American College of Cardiology/American Center Association Task Force on clinical practice guidelines [published correction appears in JAm Coll Cardiol. 2018;71(19):2275–2279]. J Am Coll Cardiol. 2018;71(19):e127–e248.
5. Williams B, Mancia Thou, Spiering Westward, et al.; ESC Scientific Certificate Group. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Centre J. 2018;39(33):3021–3104.
6. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high claret pressure in adults: report from the panel members appointed to the 8th Joint National Committee (JNC 8). JAMA. 2014;311(5):507–520.
7. Crawford C. AAFP decides to non endorse AHA/ACC hypertension guideline: Academy continues to endorse JNC8 guideline. Accessed April 18, 2019. https://world wide web.aafp.org/news/health-of-the-public/20171212notendorseaha-accgdlne.html
8. Langan R, Jones Grand. Mutual questions nigh the initial management of hypertension. Am Fam Physician. 2015;91(3):172–177. Accessed July 29, 2019. https://www.aafp.org/afp/2015/0201/p172.html
ix. Wald DS, Constabulary G, Morris JK, et al. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on xi,000 participants from 42 trials. Am J Med. 2009;122(3):290–300.
ten. MacDonald TM, Williams B, Webb DJ, et al. British Hypertension Society Programme of Prevention and Handling of Hypertension with Algorithm-based Therapy (PATHWAY): combination therapy is superior to sequential monotherapy for the initial treatment of hypertension: a double-blind randomized controlled trial. J Am Centre Assoc. 2017;half dozen(11):e006986.
xi. Abegaz TM, Shehab A, Gebreyohannes EA, et al. Nonadherence to anti-hypertensive drugs: a systematic review and meta-analysis. Medicine (Baltimore). 2017;96(4):e5641.
12. Kawalec P, Holko P, Gawin 1000, et al. Effectiveness of fixed-dose combination therapy in hypertension: systematic review and meta-analysis. Arch Med Sci. 2018;14(v):1125–1136.
xiii. Ferrario CM, Panjabi S, Buzinec P, et al. Clinical and economical outcomes associated with amlodipine/renin-angiotensin system blocker combinations. Ther Adv Cardiovasc Dis. 2013;7(one):27–39.
xiv. Baser O, Andrews LM, Wang L, et al. Comparison of real-globe adherence, healthcare resource utilization and costs for newly initiated valsartan/amlodipine unmarried-pill combination versus angiotensin receptor blocker/calcium channel blocker gratis-combination therapy. J Med Econ. 2011;xiv(v):576–583.
fifteen. Bahiru E, de Cates AN, Farr MR, et al. Stock-still-dose combination therapy for the prevention of atherosclerotic cardiovascular diseases. Cochrane Database Syst Rev. 2017;(3):CD009868.
16. Byrd JB, Zeng C, Tavel HM, et al. Combination therapy as initial treatment for newly diagnosed hypertension. Am Centre J. 2011;162(2):340–346.
17. Tedesco MA, Natale F, Calabrò R. Effects of monotherapy and combination therapy on claret pressure level control and target organ damage: a randomized prospective intervention study in a big population of hypertensive patients. J Clin Hypertens (Greenwich). 2006;viii(9):634–641.
18. Egan BM, Bandyopadhyay D, Shaftman SR, et al. Initial monotherapy and combination therapy and hypertension control the first yr. Hypertension. 2012;59(6):1124–1131.
xix. Salam A, Kanukula R, Atkins E, et al. Efficacy and safety of dual combination therapy of blood pressure level-lowering drugs equally initial treatment for hypertension: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2019;37(9):1768–1774.
twenty. Garjón J, Saiz LC, Azparren A, et al. First-line combination therapy versus first-line monotherapy for primary hypertension. Cochrane Database Syst Rev. 2017;(1):CD010316.
21. Gradman AH, Parisé H, Lefebvre P, et al. Initial combination therapy reduces the hazard of cardiovascular events in hypertensive patients: a matched cohort written report. Hypertension. 2013;61(ii):309–318.
22. Rea F, Corrao Thou, Merlino L, et al. Initial antihypertensive handling strategies and therapeutic inertia. Hypertension. 2018;72(4):846–853.
23. Xu Due west, Goldberg SI, Shubina M, et al. Optimal systolic blood pressure target, time to intensification, and fourth dimension to follow-upwards in treatment of hypertension: population based retrospective accomplice study. BMJ. 2015;350:h158.
24. Weber MA, Schiffrin EL, White WB, et al. Clinical practise guidelines for the management of hypertension in the customs: a statement by the American Society of Hypertension and the International Society of Hypertension. JHypertens. 2014;32(1):3–15.
25. Cifu As, Davis AM. Prevention, detection, evaluation, and direction of high blood pressure in adults. JAMA. 2017;318(21):2132–2134.
26. Weir MR, Hsueh WA, Nesbitt SD, et al. A titrate-to-goal study of switching patients uncontrolled on antihypertensive monotherapy to fixed-dose combinations of amlodipine and olmesartan medoxomil ± hydrochlorothiazide. J Clin Hypertens (Greenwich). 2011;13(half-dozen):404–412.
27. Volpe Thou, Christian Rump L, Ammentorp B, et al. Efficacy and safety of triple antihypertensive therapy with the olmesartan/amlodipine/hydrochlorothiazide combination. Clin Drug Investig. 2012;32(10):649–664.
28. Salam A, Atkins ER, Hsu B, et al. Efficacy and safety of triple versus dual combination blood pressure-lowering drug therapy: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2019;37(viii):1567–1573.
29. Yusuf Due south, Pitt B, Davis CE, et al.; SOLVD Investigators. Issue of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive middle failure. NEngl JMed. 1991;325(5):293–302.
xxx. Heran BS, Musini VM, Bassett K, et al. Angiotensin receptor blockers for heart failure. Cochrane Database Syst Rev. 2012;(4):CD003040.
31. McMurray JJ, Packer M, Desai AS, et al.; Prototype-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993–1004.
32. Packer K, Colucci WS, Sackner-Bernstein JD, et al. Double-blind, placebo-controlled study of the furnishings of carvedilol in patients with moderate to astringent center failure. The PRECISE Trial. Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise. Apportionment. 1996;94(11):2793–2799.
33. Groenning BA, Nilsson JC, Sondergaard L, et al. Antiremodeling effects on the left ventricle during beta-blockade with metoprolol in the treatment of chronic eye failure. J Am Coll Cardiol. 2000;36(7):2072–2080.
34. CIBIS Investigators and Committees. The Cardiac Insufficiency Bisoprolol Report (CIBIS). A randomized trial of beta-blockade in middle failure. Circulation. 1994;90(iv):1765–1773.
35. Pitt B, Remme West, Zannad F, et al.; Eplerenone Post-Acute Myocardial Infarction Centre Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction [published correction appears in Northward Engl J Med. 2003;348(22):2271]. N Engl J Med. 2003;348(fourteen):1309–1321.
36. Pitt B, Zannad F, Remme WJ, et al.; Randomized Aldactone Evaluation Study Investigators. The effect of spironolactone on morbidity and bloodshed in patients with severe heart failure. N Engl J Med. 1999;341(10):709–717.
37. Ku E, Gassman J, Appel LJ, et al. BP control and long-term adventure of ESRD and mortality. J Am Soc Nephrol. 2017;28(2):671–677.
38. Ku Due east, Glidden DV, Johansen KL, et al. Association between strict claret pressure control during chronic kidney disease and lower mortality after onset of stop-phase renal disease. Kidney Int. 2015;87(5):1055–1060.
39. Malhotra R, Nguyen HA, Benavente O, et al. Association between more intensive vs less intensive blood pressure level lowering and risk of mortality in chronic kidney disease stages 3 to 5: a systematic review and meta-analysis. JAMA Intern Med. 2017;177(10):1498–1505.
xl. Kent DM, Jafar TH, Hayward RA, et al. Progression adventure, urinary poly peptide excretion, and handling effects of angiotensin-converting enzyme inhibitors in nondiabetic kidney disease. J Am Soc Nephrol. 2007;18(6):1959–1965.
41. Kunz R, Friedrich C, Wolbers M, et al. Meta-assay: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal affliction. Ann Intern Med. 2008;148(i):xxx–48.
42. Casas JP, Chua W, Loukogeorgakis Southward, et al. Consequence of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet. 2005;366(9502):2026–2033.
43. Tobe SW, Clase CM, Gao P, et al. Cardiovascular and renal outcomes with telmisartan, ramipril, or both in people at high renal run a risk: results from the ONTARGET and TRANSCEND studies. Circulation. 2011;123(10):1098–1107.
44. Sinha Ad, Agarwal R. Thiazide diuretics in chronic kidney affliction. Curr Hypertens Rep. 2015;17(3):13–19.
45. Patel A, MacMahon Southward, Chalmers J, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370(9590):829–840.
46. Wu HY, Huang JW, Lin HJ, et al. Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and Bayesian network meta-assay. BMJ. 2013;347:f6008.
47. Cheng J, Zhang W, Zhang X, et al. Outcome of angiotensin-converting enzyme inhibitors and angiotensin Two receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-assay. JAMA Intern Med. 2014;174(5):773–785.
48. Weber MA, Bakris GL, Jamerson K, et al.; ACCOMPLISH Investigators. Cardiovascular events during differing hypertension therapies in patients with diabetes. J Am Coll Cardiol. 2010;56(1):77–85.
49. Frank J. Managing hypertension using combination therapy. Am Fam Dr.. 2008;77(nine):1279–1286. Accessed July 30, 2019. https://world wide web.aafp.org/afp/2008/0501/p1279.html
fifty. Skolnik NS, Beck JD, Clark M. Combination antihypertensive drugs: recommendations for employ. Am Fam Physician. 2000;61(x):3049–3056. Accessed July thirty, 2019. https://www.aafp.org/afp/2000/0515/p3049.html
Copyright © 2020 past the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may brand i printout of the material and may apply that printout only for his or her personal, non-commercial reference. This fabric may non otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later on invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.
Almost Contempo Issue
April 2022
Access the latest result of American Family Dr.
Read the Outcome
Email Alerts
Don't miss a single issue. Sign upwardly for the gratis AFP email tabular array of contents.
Sign Upward Now
Source: https://www.aafp.org/afp/2020/0315/p341.html
0 Response to "Triple-combination Therapy in the Treatment of Hypertension a Review of the Evidence"
Post a Comment