Hypertension: ps and tricks
Dr Andrew Sharp, MBChB, MD Consultant Cardiologist
www.exeterheart.com A prologue…
• I imagine that you deal with HT every week, if not every day. • I would quite like to have had a massive round table and collected the wit and wisdom of the room • I hope you will not mind if I go through what the room will likely have a good understanding, but some individuals may not
www.exeterheart.com Why is Hypertension important?
• Responsible for up to half of all cardiovascular events • Affects 1 billion people worldwide • Expected to rise to 1.5 billion in 2025 • Half over people over the age of 60 in the UK have HT (140/90)
www.exeterheart.com BP rela onship with outcomes
• It is a rela vely linear rela onship between BP and outcomes • Above 115/70, each rise in BP of 20/10 doubles rate of stroke and MI • Age provides the denominator and hypertension the mul plier • Note that severe HT in your 50s decade is similar to normotension in your 70s Lewington et al. 2002. Lancet.
www.exeterheart.com BP rela onship with outcomes
• MI is similar rela onship • Curves are more in parallel than for stroke • I find these curves very useful for convincing pa ents that compliance is a good idea • 2mmHg rise = 10% increased risk of stroke, 7% increased risk of MI usually gets a reac on from pts • Reducing BP from 160 to 140 will halve their risk of death from IHD Lewington et al. 2002. Lancet.
www.exeterheart.com Diagnosing hypertension
• If blood pressure measured in the clinic is 140/90 mmHg or higher, take a second measurement during the consulta on • If the second measurement is substan ally different from the first, take a third measurement • Record the lower of the last two measurements as the clinic blood pressure • Beware automated BP monitors in AF – they are frequently inaccurate
www.exeterheart.com Diagnosing Hypertension • NICE guidance 2011 changed the game
• If BP >140/90, perform ABPM • Need 14+ measures during the day • If BP >135/85, treat • If severe HT, treat first, ask ques ons later
• If ABPM not tolerated, consider home BP • Two, seated measures, one minute apart • Twice daily, for a week • Discard the first day and use the average value of all the remaining measurements to confirm a diagnosis of hypertension (>135/85).
• Which is be er prognos cator? ABPM.
www.exeterheart.com White Coat Hypertension
• Office Blood Pressure >20/10 greater than day me average BP on ABPM • CV Risk appears to be in between that of normotension and hypertension • Most hypertensives have some degree of office eleva on • This is why we add 10/5 to ABPM to es mate office pressure
www.exeterheart.com White Coat Hypertension
• Pa ents can develop this more as they get older • Previous absence of WCH does not mean permanent absence • If the ‘side effects’ of drugs 3/4/5 are all similar (in par cular, dizziness, lethargy) repeat the ABPM
www.exeterheart.com Which arm?
• The same one • Check both at outset and if >20mmHg difference, measure the one with the higher reading • Typically subclavian stenosis, which in the absence of symptoms, is conserva vely managed
www.exeterheart.com Lifestyle factors • What is the magnitude of benefit of lifestyle factor modifica on? • Can be a powerful mo vator for some pa ents • Much harder to transform lifestyle than take pills • But… when offered the possibility of stopping pills once they’ve started taking them….
NICE CG127
www.exeterheart.com Lifestyle factors • Unfortunately, individual targe ng of a risk factor leads to bigger effects than summa ve targe ng • This shows how when targe ng several factors, the overall effect is less than the sum of the parts • S ll worth having – the equivalent of 1-2 drugs for the remainder of the pa ent’s life • Hence, if a pa ent genuinely has a BP of 170/100, they are very likely to need drugs to reach 140/90 NICE CG127
www.exeterheart.com Magnitude of drug treatments • We frequently see large falls in BP a er use of a drug • This is frequently an illusion of efficacy, magnified by selec on bias, white coat effects, mul plica on of secondary issue (e.g. dehydra on) and so on. • The average fall in BP from any an - hypertension drug in unblinded trials is approx 12mmHg • Against placebo, though, Felodipine reduced BP by only 4.2mmHg (FEVER trial, 2004) • Sugges on from one trial that young benefit more from lifestyle, elderly more from drugs
www.exeterheart.com Adrenergic stress
• Controversial area • Meta-analysis suggests minimal effect of lifestyle changes in this area • For some people, relaxa on therapies can achieve large gains (>10mmHg), but ?noise • My view, consider this a par cular target in: • Marked day me ABPM eleva ons • Normal night- me measures • Pa ent self-iden fies stress as problem • High level of environmental stress may be stepping stone to hypertension causing condi on (e.g. depression)
www.exeterheart.com Salt • Levels of salt in UK food are sufficiently high that ge ng to <6g/day is difficult enough • Some controversy regarding whether extreme salt reduc on has a J-shaped outcome • In the UK, achieving such low intakes is difficult anyway • More effec ve in elderly and AC subjects • Effect size about 4mmHg, so personally, I think extreme salt avoidance may not be worthwhile • Avoiding excess, through avoiding adding to cooking or the dinner table, seems reasonable
www.exeterheart.com Summary of lifestyle interven ons
www.exeterheart.com So who needs hypertension drugs?
• All pa ents with ABPM BP BP >135/85 on ABPM (Office >150/95 (Office 160/100) 140/90) and one of • Target organ damage • CV disease • Renal disease • Diabetes • 10-year cardiovascular risk equivalent to 20% or greater
www.exeterheart.com Special cases – young hypertensives
• Under 40 – refer for secondary cause inves ga on and assessment of end- organ damage • LVH/Diastolic dysfunc on on echo may alter decision to treat • That age cut-off is a cost effec veness/capacity based approach • Diagnos c yield for secondary causes remains important in resistant older pa ents (12-15%) • RAS/renal parenchymal diseases rise with age
www.exeterheart.com Special cases – 80yrs +
• UK recommends relaxing targets for new diagnoses to 150 systolic on office • That means maintaining 140/90 in known hypertensives as they reach that age • With ageing, stroke reduc on curve for SBP is fla er (though less so with MI) • With ageing, risk of lability, falls, syncope is higher
www.exeterheart.com Secondary causes
• Most organisa ons say refer for inves ga on when a fourth drug is required • There is a list of things to look for with poten ally important confounders for many of the inves ga ons
www.exeterheart.com Secondary causes
Common Less common • Hyperaldosteronism (Conn’s) • Hypercor solism (Cushing’s) • Renal intrinsic disease • Phaeochromocytoma • OSA • Thyroid/Parathyroid disease • Renal Artery disease • Acromegaly • Drugs (esp NSAIDs) • Coarcta on
www.exeterheart.com www.exeterheart.com Drug treatment
• In the elderly, a diure c may be more effec ve at an earlier stage • Fourth line agent is controversial • I use spironolactone in most pa ents
www.exeterheart.com Spironolactone – a game changer in severe, resistant HT?
• Approx 12% of resistant hypertensives have hyperaldosteronism • Even those with normal aldosterone/ renin ra os frequently have good response • Two effects –combina on diure c and aldosterone blockade • Used as fourth line agent in ASCOT with marked success • No randomised data, but will come soon Chapman et al, Hypertension, 2007
www.exeterheart.com Spironolactone – how to use • Principal concerns are • K+ • Renal func on deteriora on • Hyperkalaemia more likely in pa ents with • Diabetes • Reduced GFR • Don’t start if K is >4.5 in these groups • Cau on in others, but this problem is manageable McDonagh et al, BMJ. 2010.
www.exeterheart.com Managing potassium
• Firstly, make sure your pa ents aren’t taking Lo Salt! • Review diet and ensure low K • Second, consider increasing the thiazide to offset the potassium • BFZ doses first studied were 10mg • Third, start with 12.5mg daily and then double • Check K+ at 5 and 14 days if you have concerns • Increased vulnerability to secondary insult, but uncontrolled HT on 4+ drugs is higher risk a er 14 days
www.exeterheart.com When a B-Blocker? • ASCOT ended Atenolol as a first line drug • Demonstrated that good drop of pressure in the arm, but up to 4mmHg less in the aorta • Higher stroke rates, probably as a result and higher diabetes rates • S ll have crucial role in pts who also have IHD and HF Williams, et al. Circula on, 2006. • Important in pa ents with high renin resistant HT • Otherwise, now fi h on my algorithm • Atenolol, though, is not nebivolol or carvedilol. • Carvedilol did not increase the rate of diabetes in the GEMINI study (metoprolol Dahlof et al, did) Lancet, 2005 www.exeterheart.com Improving Compliance
• Non-compliance is endemic in the HT popula on • Up to half of all pa ents do not take all their tablets regularly • What can we do to improve ma ers?
www.exeterheart.com Improving compliance
Educa on • Con nually re-iterate that each 2 point drop equals 10% drop in stroke risk • Event curves seem to be quite effec ve • Con nually re-itera ng at each BP check that regular use = op mal effect
www.exeterheart.com Improving compliance
Eliminate side effects at the first hint of presence • I directly ask about each of the three most common side effects at first follow-up a er star ng drug • If the pa ent hints at a problem, their compliance rates will be much lower than they will admit to • I switch them out if there is even a hint and they are willing to change
www.exeterheart.com Improving compliance - CCBs
• Amlodipine causes more ankle swelling (and other SE) than lercanidipine • Ankle swelling is caused by decrease in arteriolar resistance that is not mimicked in veins • Less likely if ACE started before a CCB • Amlodipine 10mg has much higher rates of AE, with modest addi onal efficacy that can be achieved in other ways
www.exeterheart.com Improving compliance - Diure cs
• Ironically, telling pa ents they don’t have to take diure cs every day and at the same me seems to improve compliance! • Avoiding ge ng ‘caught short’ important factor in keeping the pa ents on treatment • Can take their diure cs at differing mes to suit social life
www.exeterheart.com Improving compliance – ACE-I
• At first BP contact a er ins ga on of treatment, a direct ques on on ‘ ckly cough’ • Switch out to ARB if a hint of cough • Accept up to 30% rise in crea nine in pts without advanced CKD
www.exeterheart.com Improving compliance - Spironolactone
• Gynaecomas a will usually lead to non-compliance in men • Best to ask directly and switch out to (less effec ve) eplerenone if they have had a BP response • If poor response to taken therapy, switch to another drug class
www.exeterheart.com Improving compliance – B- Blockers
• Where do we start? • A direct ques on on impotence in men • Vasodila ng B-Blockers have fewer of most side effects (Carvedilol, Nebivolol) • In some pa ents, it’s a summer drug…
www.exeterheart.com Improving compliance – General measures
• Pill boxes • Combina on therapies • Ge ng rid of ineffec ve drugs • Smartphone reminders • Trying to associate drug-taking with fixed points - toothbrush! • …and more
www.exeterheart.com What else can we do for treatment resistant HT?
• There are new, invasive treatments for HT • Renal denerva on remains one poten al op on • Effec ve programme at the RD&E with good results • Recent nega ve trial, but remains an op on for the genuinely untreatable (about 12% of severe ‘resistant’ hypertensives in our clinic)
www.exeterheart.com Early results of renal denerva on in Exeter
• Average starting Office pressure:195/93 on >5 drugs • Average SBP fall 32mmHg
• Average starting ABPM pressure: 183/95 • Average ABPM SBP drop of 30mmHg
www.exeterheart.com Renal Denerva on registries
• GLOBAL simplicity registry showed impressive BP falls in resistant pa ents • Open-label • Interpret with cau on
www.exeterheart.com HTN-3 randomised trial
• Nega ve headline result White Europeans African Americans • Significant response in White European popula on • No response in salt-sensi ve African-Americans • Pre specified analysis • Some aspects of procedural technique and pa ent handling may have muddied the waters here • We con nue to treat pa ents within ethically approved research P=0.01 for trials RDN effect
www.exeterheart.com Conclusion • Science vs art • HT management is a good example of the need for nego a on and pragma sm • Protocols help (we are about to start a trial of a new one, integra ng primary and secondary care) • Pro-ac ve approach to side effect management • Uncontrolled hypertension is no longer necessary in more than 85% of hypertensives • Pa ent choice (compliance) is a crucial factor, but we can help there • ‘Whatever works’ is, mostly, the right way. • It is cheaper to treat HT, than not treat HT
www.exeterheart.com 1. Start ACE inhibitor (e.g. Perindopril 4mg od) 2. Start Ca2+ Antagonist (e.g. Amlodipine 5mg) 3. Start Thiazide-like Diure c (e.g. Indapamide 2.5mg) 4. Start Spironolactone (25mg od) 5. Start B-Blocker (e.g. Bisoprolol 2.5mg od)
What if BP not at target and/or pa ent descibes? -Cough (switch to Candesartan 16mg) -Ankle swelling (switch to Lercanidipine 10mg) -Low Potassium (add potassium sparing agent) -High Potassium (increase thiazide-like diure c dose, low K diet) -Crea nine slips (accept <30% change from baseline and re-check) -Raynaud’s phenomenon with B-Blocker (try carvedilol/nebivolol) -High renin off drugs (bring B-Blocker up list) -Asthma (try verapamil instead of amlodipine) -Suspected poor compliance (reduce diuresis potency, once daily treatments, night- me treatments, use ARB over ACE, combina on therapies, avoid B-Blockers, observed therapy as part of educa on package) -Labile HT (priori se adrenergic blockade)
www.exeterheart.com