Hypertension conbinsation therapy 2014
Download as PPTX, PDF10 likes3,903 views
Hypertension is a significant global health issue, affecting 26% of adults and leading to increased cardiovascular risks and healthcare costs. Effective management often requires combination therapy, with initial fixed-dose combinations improving adherence and reducing treatment discontinuation. Current guidelines suggest initiating combination therapy for patients with stage 2 hypertension and emphasize the importance of selecting drugs that minimize adverse effects while maximizing efficacy.
![1.5 Initiating and monitoring antihypertensive drug treatment, including blood pressure
targets
Initiating treatment
1.5.1 Offer antihypertensive drug treatment to people aged under 80 years with stage 1
hypertension who have one or more of the following:
target organ damage
established cardiovascular disease
renal disease
diabetes
a 10-year cardiovascular risk equivalent to 20% or greater. [new 2011]
1.5.2 Offer antihypertensive drug treatment to people of any age with stage 2 hypertension.
[new 2011]
1.5.3 For people aged under 40 years with stage 1 hypertension and no evidence of target organ
damage, cardiovascular disease, renal disease or diabetes, consider seeking specialist evaluation
of secondary causes of hypertension and a more detailed assessment of potential target organ
damage. This is because 10-year cardiovascular risk assessments can underestimate the lifetime
risk of cardiovascular events in these people. [new 2011]](https://image.slidesharecdn.com/htncombinationthrapyfinalraft-140916110250-phpapp01/85/Hypertension-conbinsation-therapy-2014-43-320.jpg)
![.6 Choosing antihypertensive drug treatment
1.6.1 Where possible, recommend treatment with drugs taken only once a day. [2004]
1.6.2 Prescribe non-proprietary drugs where these are appropriate and minimise cost. [2004]
1.6.3 Offer people with isolated systolic hypertension (systolic blood pressure 160 mmHg or more)
the same treatment as people with both raised systolic and diastolic blood pressure. [2004]
1.6.4 Offer people aged 80 years and over the same antihypertensive drug treatment as people
aged 55–80 years, taking into account any comorbidities. [new 2011]
1.6.5 Offer antihypertensive drug treatment to women of child-bearing potential in line with the
recommendations on Management of pregnancy with chronic hypertension and Breastfeeding in
'Hypertension in pregnancy' (NICE clinical guideline 107). [2010]
Step 1 treatment
1.6.6 Offer people aged under 55 years step 1 antihypertensive treatment with an angiotensin-converting
enzyme (ACE) inhibitor or a low-cost angiotensin-II receptor blocker (ARB). If an ACE
inhibitor is prescribed and is not tolerated (for example, because of cough), offer a low-cost ARB.
[new 2011]
1.6.7 Do not combine an ACE inhibitor with an ARB to treat hypertension. [new 2011]
1.6.8 Offer step 1 antihypertensive treatment with a calcium-channel blocker (CCB) to people
aged over 55 years and to black people of African or Caribbean family origin of any age. If a CCB is
not suitable, for example because of oedema or intolerance, or if there is evidence of heart failure
or a high risk of heart failure, offer a thiazide-like diuretic. [new 2011]
1.6.9 If diuretic treatment is to be initiated or changed, offer a thiazide-like diuretic, such as
chlortalidone (12.5–25.0 mg once daily) or indapamide (1.5 mg modified-release once daily or
2.5 mg once daily) in preference to a conventional thiazide diuretic such as bendroflumethiazide
or hydrochlorothiazide. [new 2011]](https://image.slidesharecdn.com/htncombinationthrapyfinalraft-140916110250-phpapp01/85/Hypertension-conbinsation-therapy-2014-44-320.jpg)
Hypertension conbinsation therapy 2014
- 1. Antihypertensive drugs combinations Dr. Muhamed Al Rohani, MD, FINS Consultant Nephrologist Head of Nephrology Dep. Dibba hospital MOH UAE
- 2. Hypertension (HTN) is a major public health concern, affecting 26% of adults worldwide1 Number of people with HTN worldwide in 20001 972 million Increase in the number of adults with HTN globally by 20251 60% Percent of all global healthcare spending attributable to high blood pressure2 10% Annual worldwide cost of hypertension2 $370 billion 1.6 Billion HTN patients estimated by 2025 1. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005 Jan 15-21;365(9455):217-23. Gaziano TA, Asaf B, S Anand, et.al. The global cost of nonoptimal blood pressure. J Hypertens 2009; 27(7): 1472-1477.
- 4. Definition and classification JNC 7
- 6. Historical Lessons on the Risks of Hypertension and the Benefits of Treatment CHD Incidence Rate/ 1000 Person Years 50 40 30 20 10 0 Treatment Decreases Morbidity and Mortality Placebo Active Treatment Cumulative Fatal & Nonfatal Endpoints Hypertension Increases Morbidity and Mortality Normotension Hypertension The Framingham Study The Vet. Adm. Study II Ann Intern Med. 1961; 55:33–50. JAMA. 1970; 213:1143–1152. 140 120 100 80 60 40 20 0 Men Women
- 7. Risk Factors for Cardiovascular Disease • Smoking • Hyperlipidaemia • High salt intake • Lack of exercise • Obesity • Diabetes • Alcohol >4pints of beer/day • Genetic
- 10. CV mortality risk CV Mortality Risk Doubles With Each 20/10 mm Hg BP Increment* BP > 140/90 mmHg associated with: 69% of pts in the 1st heart attack 74% of pts with heart failure 77% of pts in the 1st stroke SBP/DBP (mm Hg) 8 7 6 5 4 3 2 1 0 115/75 135/85 155/95 175/105 *Individuals aged 40-69 years, starting at BP 115/75 mm Hg. CV, cardiovascular; DBP, diastolic blood pressure; SBP, systolic blood pressure. Lewington S et al. Lancet. 2002;360:1903-1913. Chobanian AV et al. JAMA. 2003;289:2560-2572.
- 11. HTN leads to an increased risk of death from stroke and heart disease 8x 4x Systolic BP / Diastolic BP (mmHg) 2x Cardiovascular Mortality Risk CV mortality risk doubles for every 20 mmHg increase in systolic blood pressure.1,2 Chobanian et al. Hypertension 2003;42:1206-1252; 2Lancet 2002;360:1903-1913
- 12. BP Differences of 10 mmHg Are Associated With Up to a 40% Effect on CV Risk • Meta-analysis of 61 prospective, observational studies • 1 million adults • 12.7 million person-years 30% reduction in risk of IHD mortality 10 mmHg decrease in mean SBP 40% reduction in Lewington S et al. Lancet. 2002;360:1903–1913. risk of stroke mortality
- 13. Current Antihypertensive Therapy Reduces CV Events Average Reduction in Events, % 0 –20 –40 –80 CV=cardiovascular. Neal B et al. Lancet. 2000;356:1955–1964. Major CV Events 20%–30% Stroke 30%–40% CV Death 30%–40% –60 –100 Can we do better?
- 14. Multiple Antihypertensive Agents Are Needed to Achieve Target BP Target BP (mm Hg) Number of antihypertensive agents Trial 1 2 3 4 ALLHAT SBP <140/DBP <90 UKPDS DBP <85 ABCD DBP <75 MDRD MAP <92 HOT DBP <80 AASK MAP <92 IDNT SBP <135/DBP <85 DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure. Bakris GL et al. Am J Kidney Dis. 2000;36:646-661. Lewis EJ et al. N Engl J Med. 2001;345:851-860. Cushman WC et al. J Clin Hypertens. 2002;4:393-405.
- 15. ALLHAT study: 42,418 patients with hypertension SBP >140mmHg and/or DBP >90 mmHg OR Took medication for hypertension and had at least one additional risk factor for CHD Age >55 years Diuretics vs. ACEi Stage 1 and 2 only 26% the BP controlled by single drug 30% required 3 drugs The LIFE Trial 9,200 patients with hypertension SBP 160 – 200 mmHg and/or DBP 95- 115 mmHg with LVH ARBs vs. BB Stage 2 90% had 2 drugs 50% BP achieved
- 18. Poor Compliance and Persistence with Antihypertensive Treatment
- 19. Definition of resistant hypertension: uncontrolled BP despite adherence to a regimen with at least three antihypertensive agents including a diuretic. The percentage of patients in this category is estimated at approximately 10–15% of the hypertensive population.
- 26. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomized trials (2003 BMJ) Objective To determine the average reduction in BP, prevalence of adverse effects, and reduction in risk of stroke and IHD events produced by the five main categories of antihypertensive drugs, singly and in combination. Design Meta-analysis of 354 randomized double blind placebo controlled trials. 40 000 treated patients and 16 000 patients given placebo Results All five categories of drug produced similar reductions in BP. The standard dose average reduction was 9.1 mm Hg systolic and 5.5 mm Hg diastolic . The half standard dose was 7.1 mm Hg systolic and 4.4 mm Hg diastolic (20% lower) The BP lowering effects of different categories of drugs were additive. Symptoms attributable to thiazides, BB, and CCB were strongly dose related; but by ACEi (mainly cough) were not dose related. ARBs caused no excess of symptoms. The prevalence of symptoms with two drugs in combination was less than additive. Adverse metabolic effects (such as changes in cholesterol or potassium) were negligible at half standard dose. Conclusions Combination low dose drug treatment increases efficacy and reduces adverse effects. From the average blood pressure in people who have strokes (150/90 mm Hg) three drugs at half standard dose are estimated to lower blood pressure by 20 mm Hg systolic and 11 mm Hg diastolic and thereby reduce the risk of stroke by 63% and IHD events by 46% at age 60-69.
- 28. Rational of combination therapy 1. The heterogeneity of the hypertensive population. 2. Initial falls in BP from monotherapy are also opposed by reflex responses in counter-regulatory mechanisms that are activated following BP reduction.1 3. Combining selected classes of antihypertensive therapy with different modes of action. 4. RAAS blockers tolerability is the best in comparison. 5. ARBs or ACEi + duiretics reduce the incidence of hypokalemia 6. ARBs or ACEi + CCB reduce the incidence and severity of edema 1. Sever P, Messerli FH. Eur Heart J 2011;32:2499-506. 2. Law M et al. BMJ 2003;326:1427-31. 3. Alan Grdman. Current opinion nephrol hyoetens 2012,21:486-491
- 30. Drug combination (AHS) Preferred : ARBs/diuretics ARBs/CCB ACEi/diuretics ACEi/CCB Acceptable: BB/diuretics Thiazide/K+ sparing CCB/diuretics CCB/BB BB/diuretics Less effective: ACEi/BB ARB/BB CCB(nondihydropyridine)/BB Central acting agent/BB 1. Reduces risk of hypokalemia 2. Ameliorates diuretic-induced activation of RAAS 3. Ameliorates CCB edema 4. Reduction of mortality 5. Option for CKD 1. BB ameliorate thiazide-induced activation of RAAS 2. Side effect sexual dysfunction and glucose intolerance 3. BB less effect as anti-HTN 4. Carvedilol 1. BB with CCB increase the risk of bradycardia and heart block 2. the combination of ACE inhibitor/CCB was associated with a 20% reduction in major CV endpoints compared with ACE inhibitor/HCTZ. (ACCOMPLISH) 3. Abrupt discontinuation cause hypertensive crisis New combinations Valsartan/amlodipine/HCT Olmesartan/amlodipine/HCT Aliskiren/amlodipine/HCT
- 31. From: An Effective Approach to High Blood Pressure Control: A Science Advisory From the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention Figure Legend: Date of download: 9/2/2014 Copyright © The American College of Cardiology. All rights reserved. J Am Coll Cardiol. 2014;63(12):1230-1238. doi:10.1016/j.jacc.2013.11.007 Appendix
- 33. Persistence with antihypertensive therapy regimens; single-pill combination therapy vs free-drug combinations.
- 35. Initial Fixed-Dose Combination Therapy ADVANTAGES • 2 drugs needed for control of Stage 2 BP • Low (therapeutic) dose of 2 drugs – more effective than higher dose of single drug – usually well tolerated – adverse effects can be reduced • Simplified treatment regimen: adherence improved by 26% compare to free combination • and potential for improved outcomes • Economic benefits – Fewer copayments – health care costs reduced – fewer office visits
- 38. Reduced discontinuation of antihypertensive treatment by two-drug combination as first step. Evidence from daily life practice OBJECTIVES: To measure persistence with antihypertensive drug therapy in patients initiating treatment with mono or combination therapy. METHODS: Data were limited to patients aged 40-80 years who received their first antihypertensive drug prescription (n = 433,680 and 41,199, respectively) CONCLUSION: Initiating treatment with a combination of two drugs is associated with a reduced risk of treatment discontinuation. Corrao G1, et al, J Hypertens. 2010 Jul;28(7):1584-90. MILANO ITALY
- 39. Strategies for Combination Therapy in Hypertension Conclusion Combination therapy is necessary in approximately 75% of patients with hypertension. Rational combination therapy begins with the selection of two-drug combinations that exhibit additive BP reduction, excellent tolerability and a demonstrated ability to reduce CV endpoints in long-term clinical trials. The latter include ACE inhibitors, ARBs, CCBs and low-dose diuretics. More than 25% of patients need at least three drugs. Strategies for clinical use of combination therapy continue to evolve. Current guidelines recommend routine initiation of a combination in patients with Stage 2 hypertension. More recent studies suggests a potential for hastening goal attainment and improving long-term outcomes through the use of initial combination therapy in a broader spectrum of patients with hypertension. • In a meta-analysis of nine studies comparing administration of SPCs or their separate components, the adherence rate was improved by 26% in patients receiving SPCs • initial combination treatment consistently reduces the time taken to reach target BP compared with initial monotherapy. After 8 weeks, 48% of patients achieved their target compared with 75% begun on a combination. • Initial combination therapy was associated with a 33% reduction in major CV events compared with patients initiated on monotherapy and later switched to a combination treatment by their treating physician. • Initial combination treatment should be used sparingly in frail or very elderly patients (the presence of orthostatic hypotension) Alan H. Gradman, Curr Opin Nephrol Hypertens. 2012;21(5):486-491
- 40. Initial Fixed-Dose Combination Therapy DISADVANTAGES • BP may be controlled with 1 drug in some patients – However, majority of patients require 2 drugs • Combination ‘too potent’ causing hypotension – Benefit risk profile for each combination should be assessed in appropriate patient population – Individualize therapy • Additive risk for dose independent adverse effects – However, mono components likely to be taken as part of a multi drug regimen – Balance against risk of dose dependent side effects with high dose monotherapy and risk of inadequate BP control (stroke, heart failure and MI) • If adverse effects – must discontinue both drugs: – more office visits – more lab tests
- 41. Cost-effectiveness analysis of cardiovascular disease prevention with a multidrug regimen Sanz G and Fuster V (2008) Fixed-dose combination therapy and secondary cardiovascular prevention: rationale, selection of drugs and target population Nat Clin Pract Cardiovasc Med doi:10.1038/ncpcardio1419
- 42. Thank you for Patience and Sacrifice
- 43. 1.5 Initiating and monitoring antihypertensive drug treatment, including blood pressure targets Initiating treatment 1.5.1 Offer antihypertensive drug treatment to people aged under 80 years with stage 1 hypertension who have one or more of the following: target organ damage established cardiovascular disease renal disease diabetes a 10-year cardiovascular risk equivalent to 20% or greater. [new 2011] 1.5.2 Offer antihypertensive drug treatment to people of any age with stage 2 hypertension. [new 2011] 1.5.3 For people aged under 40 years with stage 1 hypertension and no evidence of target organ damage, cardiovascular disease, renal disease or diabetes, consider seeking specialist evaluation of secondary causes of hypertension and a more detailed assessment of potential target organ damage. This is because 10-year cardiovascular risk assessments can underestimate the lifetime risk of cardiovascular events in these people. [new 2011]
- 44. .6 Choosing antihypertensive drug treatment 1.6.1 Where possible, recommend treatment with drugs taken only once a day. [2004] 1.6.2 Prescribe non-proprietary drugs where these are appropriate and minimise cost. [2004] 1.6.3 Offer people with isolated systolic hypertension (systolic blood pressure 160 mmHg or more) the same treatment as people with both raised systolic and diastolic blood pressure. [2004] 1.6.4 Offer people aged 80 years and over the same antihypertensive drug treatment as people aged 55–80 years, taking into account any comorbidities. [new 2011] 1.6.5 Offer antihypertensive drug treatment to women of child-bearing potential in line with the recommendations on Management of pregnancy with chronic hypertension and Breastfeeding in 'Hypertension in pregnancy' (NICE clinical guideline 107). [2010] Step 1 treatment 1.6.6 Offer people aged under 55 years step 1 antihypertensive treatment with an angiotensin-converting enzyme (ACE) inhibitor or a low-cost angiotensin-II receptor blocker (ARB). If an ACE inhibitor is prescribed and is not tolerated (for example, because of cough), offer a low-cost ARB. [new 2011] 1.6.7 Do not combine an ACE inhibitor with an ARB to treat hypertension. [new 2011] 1.6.8 Offer step 1 antihypertensive treatment with a calcium-channel blocker (CCB) to people aged over 55 years and to black people of African or Caribbean family origin of any age. If a CCB is not suitable, for example because of oedema or intolerance, or if there is evidence of heart failure or a high risk of heart failure, offer a thiazide-like diuretic. [new 2011] 1.6.9 If diuretic treatment is to be initiated or changed, offer a thiazide-like diuretic, such as chlortalidone (12.5–25.0 mg once daily) or indapamide (1.5 mg modified-release once daily or 2.5 mg once daily) in preference to a conventional thiazide diuretic such as bendroflumethiazide or hydrochlorothiazide. [new 2011]
- 45. Display Settings: •Abstract A2absb0trasctt (rteaxtc) t J Hypertens. 2010 Jul;28(7):1584-90. doi: 10.1097/HJH.0b013e328339f9fa. Reduced discontinuation of antihypertensive treatment by two-drug combination as first step. Evidence from daily life practice. Corrao G1, Parodi A, Zambon A, Heiman F, Filippi A, Cricelli C, Merlino L, Mancia G. Author information •1Department of Statistics, Unit of Biostatistics and Epidemiology, University of Milano-Bicocca, Milan, Italy. [email protected] Abstract OBJECTIVES: To measure persistence with antihypertensive drug therapy in patients initiating treatment with mono or combination therapy. METHODS: Data analysis was based on two cohorts of patients, that is, a cohort derived from the registration of drug prescriptions in all residents of the Lombardy region receiving Public Health Service and a cohort of patients followed by general practitioners throughout the Italian territory. Data were limited to patients aged 40-80 years who received their first antihypertensive drug prescription (n = 433,680 and 41,199, respectively) in whom persistency of treatment was examined over 9 months. A proportional hazards model was fitted to estimate the association between the pattern of initial antihypertensive drug therapy and risk of treatment discontinuation. Data were adjusted for available potential confounders. RESULTS: Taking patients starting with diuretic monotherapy as reference, the adjusted risk of treatment discontinuation was progressively lower in patients starting with monotherapy other than a diuretic, a two-drug combination, including a diuretic and a two-drug combination without a diuretic. No significant difference in the risk of discontinuation was seen between extemporaneous and fixed dose combinations, including a diuretic, that is, the only combination reimbursable by Public Health Service and, thus, available in the database. Data were similar for the two cohorts. CONCLUSION: Initiating treatment with a combination of two drugs is associated with a reduced risk of treatment discontinuation.
- 54. There is great concern over the impact of patients not achieving BP goals. Poor BP control is associated with a marked increase in the risk of CV fatal and non-fatal events.1 A meta-analysis of 1 million patients in 61 prospective studies demonstrated that the relationship between BP and cardiovascular disease events is continuous, consistent and age-dependent – each 20 mmHg increase in SBP or 10 mmHg increase in DBP is associated with at least a twofold increase in the risk of death from stroke, ischaemic heart disease or other vascular cause.2 The US study using NHANES III data (Third National Health and Nutrition Examination Survey) highlighted in this slide shows that uncontrolled and untreated hypertension is associated with an increased risk of total and CV mortality in the general hypertensive population.3 Relative to treated controlled hypertensive patients, treated uncontrolled patients had a 57% and 74% increased risk of all-cause and CVD mortality, with untreated hypertensives having a 34% and 37% increased risk, respectively. This association was persistent and remained significant after excluding subjects with hypertension co-morbidities at baseline.3 1. Grassi G et al. Eur Heart J 2011;32:218-25. 2. Lewington S et al. Lancet 2002;360:1903-13. 3. Gu Q et al. Am J Hypertens 2010;23:38-45.
- 55. 69% 1st heart attack 74% Heart failure 77% 1st stroke Too low BP may leads to cardiac events The J-CurvThe J-curve effect describes an inverse relation between low blood pressure (BP) and cardiovascular complications. This effect is more pronounced in patients with preexisting coronary artery disease (CAD), hypertension or left ventricular hypertrophy (LVH). e phenomenon The recent large clinical outcomes trials have observed a J-curve effect between a diastolic BP of 70-80 mmHg as well as a systolic BP <130 mmHg. The J-curve phenomenon does not appear in stroke or renal disease. This is because the coronary arteries are perfused during diastole, but the cerebral and renal perfusion mainly occurs in systole. Therefore, caution should be taken to maintain the diastolic blood pressure (DBP) at minimum of 70 mmHg and possibly to maintain the DBP between 80-85 mmHg in patients with severe LVH, CAD or vascular diseases. BP control in high-risk elderly patients should be carefully done as undergoing aggressive therapy to lower the systolic blood pressure below 140 mmHg can cause cardiovascular complications due to the severely reduced DBP and increased pulse pressure.