Predicted Risk (%)

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1 : Risk Assessment, Lifestyle, Hypertension and Cholesterol C. Noel Bairey Merz MD, FACC, FAHA Professor and Women s Guild Endowed Chair Director, Barbra Streisand Women s Heart Center Director, Linda Joy Pollin Women s Heart Health Program Cedars-Sinai Heart Institute Los Angeles, California, USA merz@cshs.org Presenter Disclosure Information Women s Heart Health (Bairey Merz) DISCLOSURE INFORMATION: The following relationships exist related to this presentation (*paid to CSMC): Grant support*: NHLBI, SWHR, Gilead Consulting*: Interquest, Dannemiller, Navvis, Voxmedia, BMS, Springer, Italian NIH Honorarium*: Gilead, Novant Health, Huntworth Health, Pri-Med, NAMS Stocks: None Validation of ASCVD Pooled Cohort Risk Equations NEJM 2014 In this cohort of US adults for whom statin initiation may be considered based on the ACC/AHA Pooled Cohort risk equations observed and predicted 5-year atherosclerotic CVD risks were similar indicating that these risk equations were well calibrated in the population for which they were designed to be used, demonstrated moderate to good discrimination. Muntner et al. JAMA March 2014 ASCVD Risk Calculator New Threshold of 7.5% 10 yr risk for women and men More adults eligible for statin treatment under the new ACC/AHA guideline: Year and Lifetime ASCVD Risks Lifetime risk for lifestyle counseling and future treatment consideration Statins: 43 million (37.5%) 56 million (48.6%) Those who were reclassified upward as contrasted to those reclassified downward: Predicted Risk No treatment at 4% risk; re assess annually ) older 2) more men 3) higher systolic blood pressure, 4) had a significantly lower level of LDL-C 5) higher rate of obesity Your 10 Year ASCVD Risk 10 Year ASCVD Risk for Someone Your Age with Optimal Risk Factor Levels (shown above in column E) Your Lifetime ASCVD Risk* Lifetime ASCVD Risk for Someone at Age 50 with Optimal Risk Factor Levels (shown above in column E) Pencina et al NEJM Guidelines_UCM_457698_SubHomePage.jsp 1

2 ASCVD Risk Calculator 55 yo AA and White Women 10-Year ASCVD Risk African American Women Your 10-Year Optimal ASCVD Risk 3.6 White Women 1.4 Your 10-Year Optimal ASCVD Risk Controversies Risk Assessment Criticism ASCVD risk overestimates risk in registry (Harvard Physician s Study, Women s Health (Nurses) Study Lifetime risk is 40% for essentially all persons! Use will increase the use of statin for primary prevention of ASCVD Response Registries of convenience do not reflect US demographic/ses/ethnic diversity; study confirms improved risk prediction 40% of Americans die of CVD! ASCVD is the leading killer of Americans without a prior diagnosis of CVD Focus on Healthy Lifestyle Two of the three guidelines presented at AHA were on lifestyle Therapeutic lifestyle change remains the cornerstone of prevention of ASCVD The cholesterol guidelines panel included three members with nutrition expertise including a co-chair of the lifestyle panel The lifetime assessment of ASCVD risk from ages is presented to help clinicians focus on lifestyle and risk factor improvement in those with elevated lifestyle but low 10 year ASCVD risk Emphasis on healthy lifestyle For those risk estimator provides lifetime risk estimate This is intended to drive discussions of greater adherence to heart-healthy lifestyle Part of risk discussion Controversies Lifestyle Criticism Healthcare providers not trained/not compensated for therapeutic lifestyle change (TLC) counseling Patients rarely adherent to TLC; support not funded No randomized trial evidence to support TLC; recent weight loss trial in DM negative! Response ACA has initiated some preventive measures Do we have the will to pass social smoking, food and physical activity legislation similar to Europe? Large, simple trials needed to advise public health guidelines. 2

3 JNC8: Key Questions In adults with HTN, does initiating antihypertensive pharmacologic therapy at specific BP thresholds improve health outcomes? In adults with HTN, does treatment with antihypertensive pharmacologic therapy to a specified BP goal lead to improvements in health outcomes? In adults with HTN, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes? Comparison of JNC Guidelines Comparison of JNC8 and IM HTN Algorithm: BP Goals JNC7 JNC8 IM HTN Algorithm JNC8 Nonsystematic literature review and expert opinion Range of study designs No grading system for recommendations Recommendations: modifications Initial therapy for HTN Compelling indications Addressed secondary HTN and resistant HTN Systematic review Randomized, controlled trials (RCT) only Graded recommendations Recommendations: No specific lifestyle recommendations Initial therapy for HTN Racial, CKD, and diabetic subgroups addressed Addressed three key questions Age 60 years Not addressed General population: < 140/90 No grade of evidence & DM: < 130/80 No grade of evidence ADA Guidelines: < 140/80 & CKD Not addressed Age 60 years: < 150/90 Grade A General population: < 140/90 Grade E (Grade A: DBP, age 30 59) & DM: < 140/90 Grade E & CKD: < 140/90 Grade E Comparison of JNC8 and IM HTN Algorithm: Preferred Agents IM HTN Algorithm General population Thiazide Diuretic : HCTZ Black population Not addressed DM ACEi or ARB CKD Excluded from algorithm JNC8 General population Thiazide, CCB, ACEi, ARB (Grade B) Black population CCB or Thiazide (Grade B) Grade C for black patients with DM DM Thiazide, CCB, ACEi, ARB (Grade B) CKD ACEi or ARB (Grade B) Strategies to Dose Antihypertensive Drugs Titrate to max dose, then add a second drug Add a second drug before achieving max dose of the initial drug Start with 2 drugs at the same time If SBP 160mmHg and/or DBP 100 mmhg If SBP 20mmHg above goal and/or DBP 10mmHg above goal ***Consider scheduling follow up with the Enhanced Care Clinic for titration of BP Meds 3

4 Controversies Recommendations not consensus group members splinted/refused to sign off No evidence does not mean Absence of Benefit how to handle subgroups including women, elderly, non caucasian ethnicity with insufficient inclusion and therefore evidence Consequences of NIH NHLBI getting out of the Guideline business politics, controversy and public health NHLBI Charge to the Expert Panel 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation, American Pharmacists Association, American Society for Preventive Cardiology, Association of Black Cardiologists, Preventive Cardiovascular Nurses Association, and WomenHeart: The National Coalition for Women with Heart Disease Evaluate higher quality randomized controlled trial (RCT) evidence for cholesterol-lowering drug therapy to reduce ASCVD risk Use Critical Questions (CQs) to create the evidence search from which the guideline is developed RCTs and systematic reviews/meta-analyses of RCTs independently assessed for quality Less expert opinion than in prior guidelines Due to transfer of process to ACC-AHA for adjudication and implementation, guidelines included RCTs with major ASCVD outcomes until July 2013 Synopsis of Recommendations 1. Encourage adherence to a healthy lifestyle 2. Statin therapy recommended for adult groups demonstrated to benefit 3. Statins have an acceptable margin of safety when used in properly selected individuals and appropriately monitored 4. Engage in a clinician-patient discussion before initiating statin therapy especially for primary prevention in patients with lower ASCVD risk Synopsis of Recommendations 5. Use the newly developed pooled cohort equations for estimation 10-year ASCVD risk 6. Initiate proper intensity of statin therapy 7. Evidence is inadequate to support treatment to specific LDL-C or non-hdl-c goals 8. Regularly monitor patients for adherence to lifestyle and statin therapy Stone NJ, et al. Ann Int Med [epub ahead of print] Stone NJ, et al. Ann Int Med [epub ahead of print] 4

5 4 Statin Benefit Groups Statin Effects on Major Vascular Events 1. Secondary Prevention 2. Diabetes 40 to 75 yrs LDL-C mg/dl Statin Rx not automatic, requires clinician-patient discussion 3. LDL-C 190 mg/dl Rx: Optimal benefit with high intensity statins lower LDL-C 50% Use moderate intensity if age >75 or can t tolerate high intensity 4. Primary Prevention 40 to 75 yrs LDL-C mg/dl ASCVD Risk 7.5 % Rx: Moderate intensity or high intensity statin Endpoint CTT. Lancet : Events Treatment Control Rate Ratio (CI) Non-fatal MI 2001 (4 4) 2769 (6 2) 0 74 ( ) CHD death 1548 (3 4) 1960 (4 4) 0 81 ( ) Any major coronary event 3337 (7 4) 4420 (9 8) 0 77 ( ) CABG 713 (3 3) 1006 (4 7) 0 75 ( ) PTCA 510 (2 4) 658 (3 1) 0 79 ( ) Unspecified 1397 (3 1) ( ) Any coronary revascularisation 2620 (5 8) (3 9) 3434 (7 6) 0 76 ( ) Haemorrhagic stroke 105 (0 2) 99 (0 2) 1 05 ( ) Presumed ischaemic stroke 1235 (2 8) 1518 (3 4) 0 81 ( ) Any stroke 1340 (3 0) 1617 (3 7) 0 83 ( ) Any major vascular event 6354 (14 1) 7994 (17 8) 0 79 ( ) Favors statin Intensity of Statin Therapy High- Moderate- and Low-Intensity Statin Therapy (Used in the RCTs reviewed by the Expert Panel)* High-Intensity Statin Therapy Daily dose lowers LDL-C on average, by approximately 50% Atorvastatin (40 )-80 mg Rosuvasatin 20 (40) mg Moderate-Intensity Statin Therapy Daily dose lowers LDL-C on average, by approximately 30% to <50% Atorvastatin 10 (20) mg Rosuvastatin (5) 10 mg Simvastatin mg Pravstatin 40 (80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2-4 mg Low-Intensity Statin Therapy Daily dose lowers LDL-C on average, by <30% Simvastatin 10 mg Pravastatin mg Lovastatin 20 mg Fluvastatin mg Pitavastatin 1 mg *Individual responses to statin therapy varied in the RCTs and should be expected to vary in clinical practice. There might be a biologic basis for a less-than-average response. Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in IDEAL (Pedersen et al). Although simvastatin 80 mg was evaluated in RCTs, initiation of simvastatin 80 mg or titration to 80 mg is not recommended by the FDA due to the increased risk of myopathy, including rhabdomyolysis. Moderate & High Intensity Statins CVD Risk Reduction vs New Diabetes Mellitus Risk Moderate intensity statin assumptions High intensity statin assumptions 35% RRR & NNH=100 45%RRR & NNH= % NNH = % 70 NNT to prevent 1 70 NNT to prevent 1 CVD event over years 5.0% CVD event over years % NNH=33 7.5% 10.0% % % 20.0% % % 15.0% % 25.0% 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 10 year CVD risk 10 year CVD risk Statin Benefits Compared to Adverse Effects 2013 Cochrane Review *(18 RCTs, 19 trial armsn=56,394) 14 trials recruited patients with specific conditions (raised lipids, DM, HTN, microalb) 14% mortality 27% CHD (fatal and non fatal) events 22% in stroke (fatal and non fatal) 33% in nonfatal MI 38% in revascularization 18% in diabetes (2.8% on statin vs. 2.4% controls) No significant increase in short-term risk of - Muscle adverse events - Liver adverse events - Cancer, memory loss - Hemorrhagic stroke Taylor F, Huffman M et al Cochrane Criticism Controversies Cholesterol Why not continue to treat to target? What about HDL, non- HDL and TG? What about uncertain risk (older asymptomatic, younger with family history) Response Unknown benefit for titration compared to known benefit:risk with fixed dose statin Single and multi-drug trials do not support these targets or agents LDL C 160 mg/dl, lifetime risk, FH, hscrp>2, CAC>300, ABI can be used 5

6 validated and ready for use good ideas but not evidence based may harm women and elderly strong evidence and ready for use 6