Evaluation and Treatment of Hypertension

Practical Pearls for Clinical Dilemmas in Primary Care Evaluation and Treatment of Hypertension A 58 yo man is diagnosed with hypertension. His BP s are 160/96, 160/100, and 158/96 on 3 outside readings. He has been on a low sodium diet and he is not obese. PMH- hyperlipidemia, GERD and gout. What would be the most appropriate treatment? A) Low salt diet and exercise B) Hydrochlorathiazide C) Doxazosin D) ACE inhibitor When Thiazides Are Not A Good Choice History of Gout Creatinine > 1.6 Lithium use Diuretic Choice Strongly consider chlorthalidone Long acting, great data Major drawback has been hypokalemia Are Beta blockers efficacious antihypertensive therapy in the elderly? Meta analysis of 10 randomized trials (at least 1 year in duration) 16, 164 elderly ( 60 yr) patients included 2/3 of patients on diuretics controlled on monotherapy, < 1/3 patients on b-blockers well controlled Diuretics effective in CVA, CAD, cardiovascular mortality and all cause mortality. B-blockers only decreased cerebrovascular events. JAMA 1998; 279:1903-1907 1 1

A 60 yo man presents for follow-up of hypertension. He has been taking medication (Lisinopril) for the past 3 months. His most recent outside blood pressure readings are 156/94, 150/96, 158/92. PMH: Type 2 DM, GERD, depression. Meds: Lisinopril 20mg qd, Rabeprazole 20mg qd, Sertraline 50 mg qd, Glyburide 10 mg qd. What do you recommend? A) No changes in therapy B) Increase Lisinopril to 20 mg BID C) Add Hydrochlorathiazide 12.5 mg qd D) Add Amlodipine (Norvasc) 5mg qd E) Add Clonidine.1mg BID Outcomes with Different Combination Regimens for Hypertension (ACCOMPLISH) 6946 patients with diabetes and HTN randomized to benazapril and HCTZ or Benazapril and amlodipine,in addition 4,559 patients without DM were also studied. BP lowering same with both combinations, reduced CV events in patients on B +A (HR.79, CI.68-.92, p <.003) J AM Coll Cardiol 2010;56 (1): 77-85. Combination Therapy Combining a thiazide with B blocker or an ACE has a synergistic effect, controlling BP in up to 85% Combination of ACEI with amlodipine may be superior to ACEI + diuretic in patients with diabetes (less CV events) Low doses of thiazide can be very effective in combination with ACE inhibitors (12.5 mg of thiazide) Thiazide ACE combination can be further enhanced by moderate dietary salt restriction A 58 yo woman is seen for treatment of hypertension. She has not ever had good control of her hypertension since treatment was started 2 years ago. She has been taking her medications faithfully. Meds: Felodipine (Plendil), Atenolol, Clonidine, and Losartan (Cozaar). On exam her BP is 200/106 P-55.Labs- BUN 30, Cr 2.0, Na 137, K 4.0. ECG- LVH What would you recommend? A) Increase felodipine from 10mg a day to 10mg BID B) Increase losartan from 50mg BID to 100mg BID C) Add hydrochlorathiazide 12.5 mg qd D) Add hydrochlorathiazide 25 mg qd E) Add furosemide 40 mg BID Refractory Hypertension Occurs in 5% of hypertensive patients Always carefully evaluate for medication adherence. Worse with increasing obesity Think of secondary causes Sleep apnea Ingestion of substances that interfere with treatment (especially NSAIDS) Treatment of Refractory Hypertension Most have too much volume. Furosemide extremely useful, especially if renal insufficiency present Consider spironolactone Simplify regimens if possible to improve adherence 2 2

AHA Recommendations For Treatment of Hypertension Indication BP goal Initial therapy B Blocker Low risk <140/90 ACE/CCB/Thi No High risk <130/80 ACE/CCB/Thi No With CAD <130/80 BB and ACE Yes CHF < 120/80 BB/ACE/Aldo Yes Diuretics Hypertension Pearls Losartan can lower uric acid A low potassium level in a patient with untreated hypertension suggests a hyperaldosterone state ( hyperaldosteronism due to adrenal hyperplasia > renal artery stenosis) Treat renal artery stenosis medically, not surgically or with stents How Can You Tell What Kind Of Headache It Is? A 29 yo woman is evaluated for headaches. She reports having headaches about twice a month. She feels pain behind her right eye and frequently pain on her forehead. Her headaches often get better with 550 mg of Naprosyn. She has never had visual problems or nausea with her headaches. The headaches are worse with exercise. About once a month the headache is bad enough to force her to leave work early. What is the Most Likely Type of Headache? A)Migraine B)Cluster C)Muscle tension D)Nitrate headache Clinical Features of Tension Type Headache Mild Headache Often described as tightness, vice like Neck to forehead can be involved Often helped by NSAIDS Worse during times of stress Not disabling 3 3

Clinical Features of Migraine Headaches Family history common Pulsating quality Worse with activity Mild to Severe in intensity Can be disabling History of motion sickness common Nausea, photophobia, phonophobia may occur Diagnosing Migraine POUNDing Pneumonic Pulsating Duration 4-72 hours Unilateral Nausea Disabling If 4 criteria met LR is 24 for migraine If 3 met LR 3.5 If 2 or fewer LR.41 JAMA 2006: 296: 1274-1283 Frequency of Headache Types Tension Type Most common Migraine - Common Cluster - Rare Role of Metoclopramide Good efficacy when combined with NSAID. Equivalent to sumatriptan oral if patient has nausea. My boost effect of oral triptan or other oral migraine treatments Metoclopramide vs Hydromorphone Retrospective cohort study to evaluate metoclopramide vs hydromorphone for initial ED treatment of migraine 200 patients, 51 received IV or IM hydromorphone, 95 received IV metoclopramide and 54 received a different medication. Using a 1-10 pain scale, mean pain scale reductions were 2.3 for hydromorphone, 3.7 for metoclopramide and 2,8 for all other meds (p<.001). Less rescue meds and faster ED discharge with metoclopramide J Pain 2008;9 (1): 88-94. Oral treatment protocol for moderate to severe HA NSAID + motility drug (Metoclopramide) no relief Oral triptan no relief Oral narcotic no relief ER/office visit for IV therapy 4 4

Vascular Headache Prophylaxis Effective B Blocker (propranolol, metoprolol) Tricyclic antidepressant (amitriptyline) Riboflavin Valproate/Topiramate> Gabapentin Migraine Prophylaxis Options for the patients who fail standard prophylaxis Leukotriene inhibitors ACE inhibitors (Lisinopril 10-20 mg) Calcium channel blockers (Candesartan 16 mg) Less Effective Calcium channel blocker Memantine for Prevention of Refractory Migraine Patients with refractory migraine studied (8-14 headache days per month or failure of 2 previous preventive treatments in patients with transformed migraine) received 10-20 mg of memantine daily for 3 months 28 patients in this open labeled study. HA frequency reduced from 21.8 days to 16.1 days (p<.01), Days with severe pain reduced from 7.8 to 3.2 (p<.01). Side effects in 37.5 %, with 5.5% drop out due to side effects. Headache 2008;48 (9): 1337-42 Prophylaxis of migraine headaches Riboflavin B-blocker No response x 3 months No response x 3 months Add TCA No response x 3 months Valproate/topir>gaba Topiramate And Acidosis Topiramate acts as a carbonic anhydrase inhibitor Metabolic non anion gap hyperchloremic acidosis can occur Average drop in bicarbonate is 4, but can be severe, especially in the setting of surgery Lipid Treatment 5 5

A 36 yo man comes to clinic for an annual evaluation. He does not smoke and has no history of diabetes. He exercises for 45 minutes each day. His father had an MI at age 75 last year. His exam is normal (BP 120/70). Lipid testing shows TC 170, Tri 150, HDL 45, LDL 120 HSCRP 2.1. What would you recommend for him? A) Niacin B) Fenofibrate C) Rosuvastatin D) No treatment Rosuvastatin To Prevent Vascular Events With High CRP 17,802 men and women (men >50, women > 60) with LDL less than 130 and HSCRP >2 randomized to Rosuvastatin 20 mg or placebo Primary end point (MI/Stroke/Unstable angina/revasc/death from CV).77/100 person years treatment vs 1.36 / 100 in placebo, p<.00001 NNT= 82 NEJM 2008;359 (21): 2195-2207. Should We Use Niacin? Lowers LDL by 8% Lowers Lp(a ) by 20% Raise HDL-C cholesterol by 29% Side effects of niacin FLUSHING (about 1/3 have severe flushing, and 25% D/C because of it) (1) increased uric acid Slight effect on glucose 1) Clin Ther 2009; 31 (1):130-140. Statins Alone or With Niacin or Ezetimibe Open label, 12-week study of 292 patients who qualified for lipid lowering therapy Patients randomized to 4 arms, atorvastatin/niacin ER, Rosuvastatin/niacin ER, simvastatin/ezetimibe or rosuvastatin alone. All groups lowered LDL cholesterol by 50% or more, statin ER niacin combinations raised HDL cholesterol by 20%, where non niacin combinations raised HDL by 8%, p<.001 90% in simvastatin ezetimibe and rosuvastatin arms completed the study, only 75% in the niacin arms Atherosclerosis 2007;192:432-437. A 70 yo man presents for primary care. He has a history of CAD with an MI 2 years ago. His current medications include Atorvastatin, Aspirin, Isosrbide mononitrate, Omeprazole, Metoprolol, Folate, Vitamin E, Calcium, Multiple vitamin, Fish Oil. What do you most strongly recommend stopping in this patient? A) Aspirin B) Folate C) Vitamin E D) Calcium E) Multiple Vitamin Vitamin E and Statins Don t Mix Methods: Double blind trial of 160 patients with CAD, low HDL, normal LDL randomly assigned to simvastatin + niacin, antioxidents, simvastatin+ niacin +antioxidants, or placebo. Endpoints were arteriographic evidence of a change in coronary stenosis and occurance of 1 st cardiovascular event 6 6

Vitamin E and Statins Don t Mix The protective increase in HDL 2 with simvastatin plus niacin was attenuated by antioxidant use. Average stenosis increased by 3.9% with placebo, 1.8% with antioxidants,.7% with simvastatin/niacin/antioxidants and regressed by.4% with simvastatin-niacin. Cardiovascular events: 24% placebo, 21% antioxidants, 14% simvastatin/niacin antioxidants and 3% simvastatin/niacin NEJM 2001; 345:1583-1592 How to Use Niacin Rarely useful by itself (limited by flushing at higher doses) If you are going to use it by itself, best for patients with low HDL, normal LDL Very underused in combination with statins (can use lower doses of niacin and get good effect) Tricks to Using Niacin Use ER product Dose it at night! Give it with ASA Side Effects of Statins Rhabdomyolysis (rare) 3.4/100,000 py Hepatotoxicity (rare) Liver failure.1-.5/ 100,000 py Myalgias 10-15% Drugs That Increase Risk of Statin Toxicity Fibrates (Gemfibrozil >> Fenofibrate) Azole antifungals Amiodarone Erythromycin/Clarithromycin Protease inhibitors Verapamil/Diltiazem Niacin (do not use high doses) Approach To Statin-Related Muscle Symptoms Use lowest possible statin dose Use lower doses in Asians Discontinue medicine and report sudden onset of symptoms No need to monitor CK levels in asymptomatic patients(except in patients with drug interaction) If myalgias are severe, stop drug,let symptoms resolve, then start different statin In muscle cell toxicity studies pravastatin and rosuvastatin least toxic, simvastatin the most. 7 7

Some Important Drug Interactions A 49 yo woman with a recent history of breast cancer comes to clinic with worsening hot flashes. She is waking up several times at night with symptoms. Her breast cancer was diagnosed 18 months ago. She had 2 positive axillary lymph nodes. The cancer was ER+. She was placed on tamoxifen. What do you recommend for her hot flashes? A) Estrogen + Progesterone B) Estrogen C) Sertraline D) Paroxetine E) Citalopram SSRI s and Tamoxifen All women started on Tamoxifen over a 30 month period and continued for 2 years were studied (National Medco intergrated database) 1,298 women were identified. Divided into 2 groups, those who took a CYP2D6 inhibitor (353, 27%) and those who didn t (945,73%) Of those who took an SSRI (60%), those who took a potent inhibitor,213 (fluoxetine, sertraline,paroxetine) had a recurrence rate of 16% compared to those who took a less potent inhibitor, 137 (citalopram, escitalopram or fluvoxamine) 8.8% Aubert RE et al Increased risk of breast cancer recurrence in women taking tamoxifen and CYP2D6 inhibitors, ASCO annual meeting,may 2009 Hot Flashes in Women on Tamoxifen Avoid fluoxetine, sertraline and paroxetine (if you must use one of these, could switch tamoxifen to an aromatase inhibitor If you choose an SSRI, use citalopram, escitalopram or fluvoxamine Venlafaxine Gabapentin Clonidine Pharmacist calls to tell you that you are prescribing a triptan for a patient who is on an SSRI (citalopram 20 mg a day). She is on no other meds. What should you do? A) Switch to another migraine treatment B) Have patient not take citalopram for 24 hours after taking the triptan C) Cut the dose of triptan by 50 % D) Don t worry Triptans and SSRI s Concern for serotonergic syndrome Extremely unlikely if only a triptan + SSRI (especially at lower doses of SSRI) Beware of patients on multiple drugs that can trigger serotonergic syndrome ( tramadol, linezolid,meperidine, dextromethorphan, TCA, MAOI, buspirone, trazadone) 8 8

Pharmacist calls you to tell you that she did not fill the Tadalafil (10mg) prescription you wrote for your patient because he is on tamsulosin. What do you do? A) Switch Tamsulosin to Finaseride B) Switch Tamsulosin to Alfuzosin C) Switch Tadalafil to Sidenafil D) Ask that the prescription be filled Alpha blockers and Tadalafil.4 mg of tamsulosin was given for 7 days in healthy volunteers, then tadalafil 10mg,20 mg or placebo were given two hours after tamsulosin dose No significant difference in standing SBP with either dose of tadalafil and placebo, no one had a SBP < 85, no dizziness. J Urol 2004; 172: 1935-1940. Managing Drug Interactions with PDE5 Inhibitors Nitrates Ok to give NTG > 4 hours after sildenafil use, 24 hours after vardenafil use and 48 hours after tadalafil use Alpha Blockers Ok to use in patients who are on stable alpha blocker therapy. For patients on doxazosin or terazosin, should not take within 4 hours of a dose to avoid potential drop in BP A 72 y.o. male S/P AVR replacement two years ago for aortic stenosis presents with wide spread bruising on his back/legs and some bruising on the back of both hands. His last INR was three weeks ago and was 3.0. He states he saw an M.D. six days ago for a cough and was put on a medication described as a white tablet. His chronic medications include: Coumadin 5 mg qd, Albuterol inhaler 2 puffs 4 times a day and Nortryptiline 25 mg qhs. What medication was he placed on? a) Amoxicillin b) Codeine c) Cefixime d) Azithromycin e) TMP/Sulfa Warfarin Interactions Decrease metabolism (increase PT) Most Severe Possible* TMP/Sulfa Quinolones Erythromycin Omeprazole Amiodarone Clarithromycin Propafenone Azithromycin Ketoconazole/fluconazole Itraconazole Metronidazole * Especially in elderly and polypharmacy 9 9

Antibiotics and Warfarin Retrospective cohort study 104 patients on stable warfarin therapy. Effect on INR of Terazocin (control), Azithromycin (32 patients), Levofloxacin (27) and TMP/Sulfa (16) Mean change in INR: Terazocin -.15, Azithromycin +.51, Levofloxacin +.85, TMP/Sulfa +1.76 Percent patients having a INR > 4: Terazocin 5%, Azithromycin 31%, Levofloxacin 33%, TMP/Sulfa 69% JGIM 2005;20 (7);653-6. 10 10