Don t let the pressure get to you:

Transcription

1 Balanced information for better care Don t let the pressure get to you: Current evidence-based goals for treating hypertension

2 A cornerstone of primary care: Lowering high blood pressure prevents cardiovascular events FIGURE 1. Treating hypertension prevents stroke, coronary heart disease, heart failure, and cardiovascular (CV) death across all risk groups. Benefit is greatest in those at highest risk. 1 8 CV events avoided per 1 treated patients year risk of cardiovascular disease (CVD) >21% 15-21% 11-15% <11% Reduction in systolic blood pressure (mm Hg) Nearly 1 in 3 American adults have hypertension. FIGURE 2. About 17% of Americans with hypertension are unaware they have it.* Of those with hypertension, not all are being treated and just over half are controlled. 2 Patients with hypertension (%) % 83% Patients aware they have hypertension 23% 77% Patients being treated 46% 54% Patients with controlled hypertension (BP <14/9) no yes * Based on NHANES data from 29 to Current evidence-based goals for treating hypertension

3 With new data, what is the best blood pressure (BP) target? Select a blood pressure goal based on patient factors FIGURE 3. Blood pressure goals in mm Hg, based on an overview of the current evidence 3-8 PATIENT CHARACTERISTICS Diabetes or prior stroke YES TARGET SBP <14 mm Hg NO Increased CV risk* or age 75 YES BP <12/9 mm Hg NO All others BP <15/9 mm Hg * CVD (other than stroke), chronic kidney disease (CKD), or Framingham risk > 15%, without diabetes (SPRINT study inclusion/exclusion criteria) Key considerations for hypertension treatment: Counsel patients on a low salt diet. Ensure patient adherence to medication. Intensify therapy for patients not at goal. Achieving the BP target is more important than the specific drug class used to get there. 9 Alosa Health Balanced information for better care 3

4 Diabetes and prior stroke: Target an SPB <14 mm Hg SBP target of 12 mm Hg didn t prevent major CV events. FIGURE 4. The ACCORD trial found that intensive therapy (target SBP <12 mm Hg) was not better than standard therapy (target SBP <14 mm Hg) in preventing CV outcomes in patients with hypertension and diabetes. 3 Major CV events.4.2 p= Study years Standard (target SBP <14) Intensive (target SBP <12) Lower SBP targets required more medication and led to more adverse events. FIGURE 5. In ACCORD, both serious adverse events and transient laboratory abnormalities were more common in patients with diabetes who were treated to SBP <12 mm Hg. 3 Intensive (target SBP <12) Standard (target SBP <14) % Serious adverse events (%) % 1.3% Overall events.7%.% Hypotension.5%.1% Bradycardia 2.1% 1.1% Hypokalemia 8.4% Acute kidney injury in men 1.9% 7.1% Acute kidney injury in women SERIOUS ADVERSE EVENTS LABORATORY ABNORMALITIES Patients with a history of stroke should achieve an SBP <14 mm Hg, but select patients may benefit from an SBP target <13 mm Hg based on SPS Current evidence-based goals for treating hypertension

5 Increased cardiovascular risk or age 75 and over: SBP goal <12 mm Hg prevents CV events FIGURE 6. SPRINT was a randomized controlled trial of over 9,3 patients with increased CV risk. 5 Proportion of patients with MI,stroke, HF, ACS, or CV death p<.1 Standard (target SBP <14) Intensive (target SBP <12) 25 % Relative risk reduction for SBP goal <12 mm Hg vs. <14 mm Hg Years SPRINT patient eligibility Eligible patients had: Age 5, and SBP mm Hg, and Increased risk of a CV event: CVD other than stroke, or CKD, or Framingham risk 15%, or Age 75 years. Excluded patients had: diabetes, or prior stroke, or heart failure, or dementia, or residence in a nursing home, or life expectancy <3 years. Alosa Health Balanced information for better care 5

6 Patients age 75 and over: Older patients benefit more than younger from intensive BP control FIGURE 7. In SPRINT, the 2636 patients 75 and over had a greater relative risk reduction in CV outcomes than did patients younger than 75. 5,1 Relative risk reduction (%) The number needed to treat (NNT) to prevent 1 event over 3 years: Age 75 and older 34% NNT = 27 Age under 75 2% NNT = 93 OVERALL STUDY 25% NNT = 6 Older patients will require even more intensive follow-up and monitoring. Side effects occurred in nearly 5% of trial participants over age 75, regardless of treatment group. FIGURE 8. Serious adverse events in SPRINT by age group. 5,1 All ages Age 75 or older There was no difference in the number of injurious falls between 5.5% the treatment groups. Absolute risk (%) % 1.4% 3.1% 2.3% 4.1% 2.5% 2.4% 1.4% 4.% 2.7% 4.% 1. Hypotension Electrolyte abnormalities Acute kidney injury/ renal failure Hypotension Intensive (target SBP <12) Standard (target SBP <14) Electrolyte abnormalities Acute kidney injury/ renal failure 6 Current evidence-based goals for treating hypertension

7 All other patients: Aim for an SPB <15 mm Hg in patients under 75 TABLE 1. In JATOS 6 and VALISH, 7 an SBP target <14 mm Hg didn t prevent CV events in older adults when compared to target SPB <15-16 mm Hg. JATOS VALISH Study outcomes Strict control (n = 2,212) Mild control (n = 2,26) Strict control (n = 1,545) Moderate control (n = 1,524) Achieved SBP (in mm Hg) Primary outcome 3.9% 3.9% 2.4% 2.3% Study discontinuation due to adverse effects 1.6% 1.6% 1.9% 1.2% Although more aggressive blood pressure targets have not consistently demonstrated benefits, clinical data still overwhelmingly supports treating patients with SBP>15 mm Hg, including the elderly. What about diastolic blood pressure? Based on data from the 197s and 8s, active treatment for younger adults to reduce diastolic blood pressure to <9 mm Hg prevented stroke and CV events more effectively than placebo. 8 After achieving the SBP goal, keep DBP <9 mm Hg. Alosa Health Balanced information for better care 7

8 Once a goal is established, implement a comprehensive plan to bring down BP A low sodium DASH diet, aerobic exercise as tolerated, and weight loss are key parts of a hypertension treatment plan. FIGURE 9. Reducing dietary sodium to under 18 mg/day can reduce the risk of CV events by 25%, based on long-term follow-up after an educational intervention. 11 Cumulative incidence of CVD events Control Years 25 % Sodium intervention Relative risk reduction Achieving the correct BP goal is more important than choosing the right first-line drug class. FIGURE 1. A 29 meta-analysis of 147 trials involving 464, patients found that no one class was better than another in preventing cardiac events in patients with hypertension. 9 Blood pressure difference (mm Hg) Coronary heart disease events Systolic Diastolic No of trials No of events Relative risk (95% CI) Relative risk (95% CI) Thiazides v any other (.91 to 1.8) Angiotensin converting.9 enzyme inhibitors v any other (.9 to 1.3) Angiotensin receptor blockers v any other (.94 to 1.16) Calcium channel blockers v any other (.91 to 1.1).7 Specified drug better Specified drug worse ACCOMPLISH, a large randomized trial, found that an ACEI + CCB was better than an ACEI + thiazide for preventing CV events in patients requiring two antihypertensives. 12 Beta blockers are worse at preventing stroke than ACEI/ARBs, thiazides, or CCBs. 9 8 Current evidence-based goals for treating hypertension

9 Putting it all together FIGURE 11. Algorithm for treating hypertension 5,13,14 Identify SBP goal based on current evidence (see figure 3). Counsel patients about a low sodium diet. Advise to exercise and lose weight, if needed. Is the SBP >2 mm Hg above goal? N Y Initiate a single agent,* either a: thiazide, long acting ACEI / ARB, or CCB. Prescribe two agents (e.g., ACEI + CCB). Monitor response to treatment, assess adherence, and screen for side effects. If not at SBP goal or if DBP >9 mm Hg, up-titrate a single medication or add another agent. * For African Americans, initiate a thiazide or CCB. Combining an ACEI and an ARB confers no additional benefit and may increase adverse events. For patients age 75 and over, start one medication and intensify therapy at the first follow-up visit. Other medications such as beta blockers and alpha blockers are no longer recommended for the initial treatment of blood pressure, but may have BP benefits when used for other indications. A recent study found that over 26% of Medicare beneficiaries did not take their antihypertensive medications as prescribed. 15 Adherence was better in patients: taking one antihypertensive who used fixed-dose combinations who saw one doctor for blood pressure related care Alosa Health Balanced information for better care 9

10 Costs FIGURE 12. Price of a 3-day supply of drug classes commonly used to treat hypertension ACE-Inhibitors trandolopril 2 mg ramipril 2.5 mg quinapril 15 mg perindopril 4 mg moexipril 15 mg lisinopril 1 mg fosinopril 15 mg enalapril 1 mg benazapril 7.5 mg $14 $49 $45 $35 $4 $35 $23 $4 $68 ARBs valsartan (Diovan) 8 mg valsartan 8 mg telmisartan (Micardis) 4 mg telmisartan 4 mg olmesartan (Benicar) 2 mg losartan (Cozaar) 5 mg losartan 5 mg irbesartan (Avapro) 15 mg irbesartan 15 mg eprosartan (Taventen) 6 mg eprosartan 6 mg candesartan (Atacand) 8 mg candesartan 8 mg azilsartan (Edarbi) 4 mg $45 $61 $84 $9 $114 $17 $132 $151 $146 $19 $181 $19 $226 $247 Calcium channel blockers nifedipine ER (Procardia XL) 3 mg nifedipine ER 3 mg felodipine 5 mg amlodipine (Norvasc) 5 mg amlodipine 5 mg $36 $4 $39 $148 $193 Diuretics indapamide 2.5 mg hydrochlorothiazide 25 mg clorthalidone 25 mg $4 $4 $28 Other aliskiren (Tekturna) 15 mg $21 ACEIs and CCBs amlodipine / benazepril 5 mg/1 mg $76 ACEIs and diuretics quinapril / HCTZ 2 mg/25 mg moexipril / HCTZ 15 mg/25 mg lisinopril / HCTZ 1 mg/12.5 mg fosinopril / HCTZ 1 mg/12.5 mg enalapril / HCTZ 1 mg/25 mg benazepril / HCTZ 1 mg/12.5 mg $4 $43 $43 $45 $3 $55 ARBs and diuretics valsartan / HCTZ 8 mg/12.5 mg telmisartan / HCTZ 4 mg/12.5 mg olmesartan / HCTZ (Benicar HCT) 2 mg/12.5 mg losartan / HCTZ 5 mg/12.5 mg irbesartan / HCTZ 15 mg/12.5 mg candesartan / HCTZ 16 mg/12.5 mg $65 $13 $119 $129 $166 $229 $ $5 $1 $15 $2 $25 Prices from goodrx.com, September 216. Listed doses are based on Defined Daily Doses by the World Health Organization, and should not be used for dosing in all patients. All prices shown are for generic products unless otherwise noted. 1 Current evidence-based goals for treating hypertension

11 Key messages Patient characteristics are the best guide for setting blood pressure goals. For patients with diabetes or prior stroke, aim for an SBP <14 mm Hg. For patients at high risk for CV disease, aim for a BP <12/9 mm Hg. For all other patients, aim for a BP <15/9 mm Hg. The blood pressure goal is more important than the choice of drug. Educate patients about reduced salt diet, exercise, weight loss, and medication adherence throughout treatment. There is solid data that treatment with a thiazide diuretic, ACEI / ARB, or CCB prevents cardiovascular events. Regularly assess response to treatment: ask about adherence, screen for side effects, and intensify treatment to achieve a patient s SBP goal. Visit AlosaHealth.org/modules/hypertension for more information and resources about hypertension References: (1) Sundstrom J, Arima H, Woodward M, et al. Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet. 214;384(9943): (2) Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics 215 update: a report from the American Heart Association. Circulation. 215;131(4):e (3) Accord Study Group, Cushman WC, Evans GW, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 21;362(17): (4) SPS Study Group, Benavente OR, Coffey CS, et al. Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial. Lancet. 213;382(9891): (5) SPRINT Research Group, Wright JT, Jr., Williamson JD, et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 215;373(22): (6) Principal results of the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS). Hypertens Res. 28;31(12): (7) Ogihara T, Saruta T, Rakugi H, et al. Target blood pressure for treatment of isolated systolic hypertension in the elderly: valsartan in elderly isolated systolic hypertension study. Hypertension. 21;56(2): (8) MRC trial of treatment of mild hypertension: principal results. Medical Research Council Working Party. Br Med J (Clin Res Ed). 1985;291(6488): (9) Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 29;338:b1665. (1) Williamson JD, Supiano MA, Applegate WB, et al. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged 75 Years: A Randomized Clinical Trial. JAMA. 216;315(24): (11) Cook NR, Cutler JA, Obarzanek E, et al. Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP). BMJ. 27;334(7599): (12) Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 28;359(23): (13) Bangalore S, Ogedegbe G, Gyamfi J, et al. Outcomes with Angiotensin-converting Enzyme Inhibitors vs Other Antihypertensive Agents in Hypertensive Blacks. Am J Med. 215;128(11): (14) ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 28;358(15): (15) Ritchey M CA, Powers C, et al. Vital Signs: Disparities in Antihypertensive Medication Nonadherence Among Medicare Part D Beneficiaries United States, 214. Morbidity and Mortality Weekly Report. epub:13 September 216. DOI: Alosa Health Balanced information for better care 11

12 About this publication These are general recommendations only; specific clinical decisions should be made by the treating physician based on an individual patient s clinical condition. More detailed information on this topic is provided in a longer evidence document at AlosaHealth.org. The Independent Drug Information Service (IDIS) is supported by the PACE Program of the Department of Aging of the Commonwealth of Pennsylvania. This material is provided by Alosa Health, a nonprofit organization which is not affiliated with any pharmaceutical company. IDIS is a program of Alosa Health. This material was produced by Jing Luo, M.D., M.P.H., Instructor in Medicine; Michael A. Fischer, M.D., M.S., Associate Professor of Medicine (principal editor); Niteesh K. Choudhry, M.D., Ph.D., Professor of Medicine; Jerry Avorn, M.D., Professor of Medicine; Dae Kim, M.D., M.P.H., Sc.D., Assistant Professor of Medicine; all at Harvard Medical School, and Ellen Dancel, PharmD, MPH, Director of Clinical Material Development, Alosa Health. Drs. Avorn, Choudhry, Fischer, and Luo are physicians at the Brigham and Women s Hospital, and Dr. Kim practices at the Beth Israel Deaconess Medical Center, both in Boston. None of the authors accepts any personal compensation from any drug company. Medical writer: Stephen Braun. Copyright 216 by Alosa Health. All rights reserved.