Update in Outpatient Medicine JNC 8, Hypertension and More March 6 th 2015 Robert Gluckman, MD, FACP CMO Providence Health Plans Disclosures Stock Holdings Abbott Labs Abbvie Bristol Myers Squibb GE Proctor and Gamble Walgreens Topics Hypertension New Guidelines Applying treatment targets to individuals Protocols to get to target Cancer screening in the elderly Colon Cancer Screening Benefit and Cost of Supplemental U/S for breast cancer screening women with dense breasts Cost Effectiveness of Lung Cancer Screening New Lipid Guidelines New Agent for CHF 2014 Evidence-Based Guideline for the Management of Hypertension: JNC 8 Evidence based review focused on 3 questions; 9 recommendations Does initiating pharmacologic therapy at specific BP thresholds improve health outcomes? Does pharmacologic treatment targeted to a specific BP goal improve health outcomes? Do various anti-hypertensive drugs/classes differ in comparative benefits/harms for specific health outcomes? JAMA 2014; 311: 507-520
2014 Evidence-Based Guideline for the Management of Hypertension: JNC 8 Recommended BP targets and treatment regimens based on age, race, presence of DM/CKD. General population age 60 treat to target SBP 150, DBP 90 (Grade A) Patients currently tolerating treatment with BP 140/90 do not require adjustment (Grade E) General population age < 60 initiate treatment to target DBP <90 (Grade A 30-59. Grade E 18-29) 2014 Evidence-Based Guideline for the Management of Hypertension: JNC 8 General population age < 60 initiate treatment to SBP < 140 (Grade E) In patients age 18 with DM or CKD initiate treatment to target BP <140/90 (Grade E) In general population non-black patients, including patients with DM, initiate treatment with thiazide or CCB or ACE or ARB (Grade B) 2014 Evidence-Based Guideline for the Management of Hypertension: JNC 8 In patients with CKD, regardless of race or DM, initiate or add ACE or ARB to treatment (Grade B) In black patients including with DM, initiate treatment with thiazide or CCB (Grade B, DM recommendation Grade C) In patients not controlled after 1 month of treatment, increase dose or add 2 nd medication. Patients uncontrolled on 3 agents consider BP med not specified in guideline or refer Impact of BP Control on Mortality Risk and ESRD Retrospective cohort study of 396,419 treated hypertensives from Kaiser Permanente Southern California Excluded ESRD and CHF Average age 64 Subgroup analyses for DM, age >70 Follow up 4-5 years JACC 2014;64:588-97
BP Lowering in Type 2 DM: A Systematic Review and Meta-analysis Forty trials deemed of low risk of bias Stratified results based on patients initial BP Noted reduced CVA and albuminuria (not other outcomes) if achieved BP lower than 130/80 Individualized targets based on age and comorbidity may result in better outcomes JAMA 2015;313:603-615 Treatment with Multiple BP Medications, Achieved BP and Mortality in NH Residents- The PARTAGE Study 1127 nursing home residents age > 80 Measured BP over 3 consecutive days 2 year follow-up Assessed medication use Excluded patients without hypertension on meds for other conditions JAMA Int Med published online 2/16/2015
Cost Effectiveness of Hypertension Therapy According to 2014 Guidelines Used a computer simulation model to predict incidence, prevalence, and mortality of CHD and CVA among persons age 35-94. Categorized patients as Stage 1 SBP 140-159, DBP 90-99 Stage 2 or higher SBP 160, DBP 100 Estimated 56,000 cardiac events and 13,000 deaths prevented in the US each year NEJM 2015:372-447-55 Summary- New BP Guidelines and Targets Implications for Performance Measurement BP targets raised for patients 60 and older BP targets raised for patients with DM, CKD ACE/ARB preference removed for hypertensive patients with DM unless CKD or albuminuria Drug choices differ by race, (use thiazide or CCB in black patients unless CKD Performance measures allow looser control Important to remember to individualize approach Younger patients with DM, CKD consider more aggressive target, Relax treatment in old, frail patients Improved BP Control with a Large Scale Hypertension Program 652,763 patients in KPNC registry compared to other California insurers participating in NCQA 5 components to program Development of a registry Sharing of performance metrics Evidence based guidelines MA BP visits Single pill combination therapy (diuretic plus ACE) JAMA 2013;310-699-705
Improved BP Control with a Large Scale Hypertension Program 4 step drug therapy Thiazide or Thiazide plus ACEI Thiazide plus ACEI CCB (i.e. amlodipine) Spironolactone or beta blocker PHP2013 70.1% MA visit 2-4 weeks after med change No co-pay Allowed more rapid treatment intensification JAMA 2013;310:699-705 Epidural Steroids for Spinal Stenosis 400 patients age 50 with lumbar central spinal stenosis and moderate to severe leg pain and disability Epidural Steroids for Spinal Stenosis Randomized to receive epidural injections of glucocorticoid plus lidocaine vs. lidocaine alone Received one or two injections before outcome evaluation 6 weeks after first injection Primary Outcome Roland-Morris Disability Questionnaire Rating intensity of leg pain (0-10)
Epidural Steroids for Spinal Stenosis Treatment of lumbar spinal stenosis with glucocorticoid plus lidocaine injections offered minimal to no benefit at 6 weeks Although sham injections were not performed, there is no evidence to support injections for the treatment of spinal stenosis. Consider behavioral/pt programs for non-surgical candidates Cancer Screening in Patients with Limited Life Expectancies Retrospective cohort analysis of 27,911 patients aged 65 and older Data derived from the National Health Interview Survey, self reported cancer screening rates Mortality index developed and patients grouped into low (<25%), intermediate (25-49%), high (50-74%, or very high (>75%) mortality in 5 and 9 years. JAMA IM 2014;174(10):1558-65 Estimating Prognosis for Elders www.eprognosis.ucsf.edu Charlson Co-Morbidity Index Calculator http://farmacologiaclinica.info/scales/charlson_comorbidity/
Should CRC Screening be Considered in Previously Unscreened Elderly Persons Microsimulation modeling study using observational and experimental studies One time screening with colonoscopy, sigmoidoscopy, or FIT in previously unscreened persons aged 76-90 with no, moderate, severe comorbid conditions Cost effectiveness threshold $100,000 per QALY Ann Intern Med 2014;160:750-759 Multi-target Stool DNA Testing for CRC Screening 12,776 patients age 50-84 at average risk for CRC enrolled at 90 sites Excluded patients with previous colonoscopy within 9 years, + fecal blood in past 6 months. Multi-target Stool DNA Testing for CRC Screening 9989 participants could be fully evaluated 1168 did not undergo colonoscopy 723 had insufficient stool or other sample issues 304 had incomplete colonoscopy Specificity for stool DNA lower in patients over 65 Lower cutoffs for positive FIT (20µg/g produces similar sensitivity/specificity to stool DNA
Multi-target Stool DNA Testing for CRC Screening Multitargeted Stool DNA testing is significantly more sensitive than FIT for colorectal cancer detection FIT is more specific for colorectal cancer detection than multitargeted stool DNA testing Lowering threshold of a positive FIT may result in equivalent performance Baseline risk is an important consideration in determining the best test for patients Multitargeted DNA may be appropriate in previously unscreened patients who refuse colonoscopy or have comorbidities FIT may be more appropriate for older patients with previous negative colonoscopy where colonoscopy may pose higher risks and lower benefit Long Term CRC Mortality After Adenoma Removal Cohort study Cancer Registry and Cause of Death Registry of Norway 40,826 patients followed median 7.7 years after adenoma removal Norwegian standard of care 10 year surveillance for high risk adenoma 5 year surveillance for 3 or more adenomas No surveillance for low risk adenomas or for patients > 74 years old CRC mortality primary endpoint Reviewed 442 pathology reports and reclassified 8.2% of cases from high to low risk and 30.2% from low risk to high risk Thus the risk may have been overstated in both cohorts if patients were correctly classified.
Long Term CRC Mortality After Adenoma Removal Patients with 1-2 low risk adenomas have a lower risk of CRC death than average population Current guidelines recommend surveillance 5-10 years after resection of low risk adenomas Difficult to justify surveillance sooner than 10 years in low risk adenoma patients Surveillance Colonoscopy in Elderly Patients Retrospective cohort study 27,763 patients age 50 undergoing surveillance colonoscopy from 20001 through 2010 at Southern California Kaiser 4834 patients age 75 Primary outcome- incidence of CRC Secondary outcome- 30 day post procedure hospitalization Procedure related (i.e. GI bleed, perforation, arrhythmia) Other GI disorder Other JAMA IM 2014;174(10):1675-82 Low incidence of CRC in elderly possibly explained by previous removal of potentially malignant lesions or death from other comorbid conditions
PHP Colonoscopy Indications in the Elderly Surveillance colonoscopy in the elderly Surveillance colonoscopy in older patients appears to be low yield Healthy patients with previous high risk findings likely benefit most Risks of colonoscopy increase with age and co-morbidity Assessing co-morbidities may help guide decisions for individual patients Surveillance strategies in the elderly should consider opportunity for cancer prevention vs mortality reduction Stool based surveillance may be a reasonable alternative for selected patients, especially over age 75. (My opinion: Current guidelines for surveillance in the elderly are based on opinion) Benefits, Harms, and Cost Effectiveness of Supplemental U/S for Women with Dense Breasts 19 states, including Oregon, require providers to notify patients about their breast density Evidence is limited but suggests increased cancer detection at the expense of increased biopsies Used 3 established models to develop estimates of benefits, harms and cost effectiveness of supplemental U/S in women with dense breasts Annals of IM published online Dec 9, 2014
Supplemental Screening Strategy Biennial Screening Age 50-74 QALY s Gained Cost per QALY Supplemental ultrasound for BI-RADS 4 Supplemental ultrasound for BI-RADS 3-4 Annual Screening age 40-74 1.1 per 1000 women 1.7 per 1000 women $246,000 $325,000 Supplemental ultrasound for BI-RADS 4 3.1 per 1000 women $553,000 Supplemental ultrasound for BI-RADS 3-4 3.0 per 1000 women $728,000 Cost Effectiveness of CT Screening in the NLST NLST enrolled patients age 55-74 with 30 pack-yr smoking history Current smokers or quit within 15 years USPTF Grade B recommendation age 55-80 Medicare coverage limited to patients age 55-74 Screening consisted of 3 annual low dose CT scans Benefits are much greater in high risk patients NNS 161 vs. 5276 in highest vs. lowest risk patients NEJM 2014;371:1793-1802; NEJM 2013;369:245-54
Lung Cancer Risk Calculator http://www.brocku.ca/lung-cancer-risk-calculator Medicare requires shared decision making for coverage of lung cancer screening. Further Insight into the Cardiovascular Risk Calculator: Data from the Women s Health Study 27,542 women free from CV disease with complete ascertainment of lipids and other risks Followed median 10 years with annual questionnaires Analyses adjusted for statin use and revascularization Statin use increased to 37.5% of higher risk women at 10 years 1.4% underwent revascularization;5.2% in highest risk patients JAMA IM 2014;174 (12) 1964-71 Statin Usage In PHP Patients With ASCVD and DM
New Lipid Guidelines Controversy over lipid calculator for primary prevention Emphasis on statin prescribing at appropriate dose for patients with known CVD or DM Patient adherence is much lower than can be explained by side effects Strategies to assess and promote adherence essential Statin use in risk populations new proposed performance measure Angotensin-Neprilysin Inhibition vs. Enalapril in Heart Failure 8442 patients with CHF, EF < 40%, NYHA Class II- IV, elevated BNP randomized to LCZ696 vs enalapril 70% NYHA Class II, 30% Class III Protocol changed to EF 35% mid trial Excluded patients with BP <100, CrCl < ml/min Primary Outcome- Death from CV causes or 1 st hospitalization for worsening CHF Trial terminated at 27 months due to overwhelming benefit NEJM 2014;371:993-1004 Angotensin-Neprilysin Inhibition vs. Enalapril in Heart Failure LCZ696 Enalapril NNT Total Mortality 17% 19.8% 36 CV mortality or 21.8% 26.5% 21 1 st CHF Hosp 1 st CHF Hosp 12.8% 15.6% 36 Angotensin-Neprilysin Inhibition vs. Enalapril in Heart Failure Combined angiotensin/neprilysin inhibition was superior to angiotensin inhibition in reducing death, CHF hospitalization and symptoms without significant differences in adverse events. LCZ696 patients had improved symptoms on KCCQ
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