how to treat hypertension in patients with coronary heart disease disease

the JOurNAL Of CLiNiCAL hYperteNsiON VOL. 10 NO. 5 MAY 2008390

Dr MOser: Do we have any evidence that low-ering blood pressure beyond the usual goal of 140/90 mm hg in patients with coronary disease is important? is it necessary? Are outcome results any better than just treating these patients to achieve the goal pressures established for other patients? several committees have looked at the data and have reached conclusions about the treatment of these patients. i’d like to ask the panel to critique some of the conclusions.

Joel, the framingham investigators have come up with a coronary risk score approach that i personally believe is fairly cumbersome and may not be necessary to make informed treatment decisions. some of the recommendations for the treatment of people with coronary artery disease or with multiple coronary heart disease risk fac-tors note that if risk is >10% in 10 years, then blood pressure should be lowered not just to 140/90 mm hg but to 130/80 mm hg. if clinical coronary artery disease or left ventricular dysfunc-tion is present, the target blood pressure should be 120/80 mm hg. Can we use the framingham risk score concept empirically without calculating exact scores and conclude that if some of the above factors are present, more vigorous and aggressive treatment is indicated?

Dr hANDLer: i believe that practitioners have had some experience with the framingham risk calculator looking at patients with dyslipi-demia and prescribing antilipemic therapy on the basis of the calculated risk.

there is minimal experience with it at the primary care level in treating patients with hyper-tension. i believe that it would be difficult to get practitioners to prescribe blood pressure therapy on the basis of a framingham score.

Dr MOser: if you had a patient with a blood pressure of 160/95 mm hg or so who also had dys-lipidemia, was diabetic, and had a history of angina, in other words a very high–framingham risk score individual, would you just conclude that goal blood pressure should be <140/90 mm hg or lower in some instances if this can be accomplished without going through a calculation? in other words, make a clinical judgement?

Dr hANDLer: Yes, i believe so. With such high-risk patients, practitioners should find it rea-sonable to reduce blood pressure to <130/80 mm hg. We have a lot of well-tolerated medications in our armamentarium.

Dr MOser: Jackson, what do you think? the American heart Association (AhA) has recom-mended that if a patient has a high framingham risk score, in other words 2, 3, or 4 major

E x p e r t P a n e l D i s c u s s i o n

How to Treat Hypertension in Patients With Coronary Heart Disease

Marvin Moser, MD; Jackson T. Wright, Jr, MD, PhD; Ronald G. Victor, MD; Joel Handler, MD

Following a hypertension symposium in Los Angeles in October 2007, a panel was convened to discuss how to treat hypertension in patients with coronary artery disease or with evidence of multiple major risk factors for coronary heart disease . Marvin Moser, MD, Clinical Professor of Medicine at the Yale University School of Medicine, New Haven, CT, moderated the discussion . Jackson T . Wright Jr, MD, PhD, Professor of Medicine, Program Director of William T . Dahms Clinical Research, and Director of the Clinical Hypertension Program at Case Western Reserve University, Cleveland, OH; Ronald G . Victor, MD, Professor and Division Chief, Hypertension, University of Texas Southwestern Medical Center, Dallas, TX; and Joel Handler, MD, Hypertension Lead, Care Management Institute, Kaiser Permanente, Anaheim, CA, participated in the discussion . (J Clin hypertens (Greenwich) . 2008;10:390–397) ©2008 Le Jacq

www.lejacq.com ID: 8014

The Journal of Clinical Hypertension® (ISSN 1524-6175) is published monthly by Le Jacq, located at Three Enterprise Drive, Suite 401, Shelton, CT 06484. Le Jacq is an imprint of Blackwell Publishing, which was acquired by John Wiley & Sons in February 2007. Blackwell’s programme has been merged with Wiley’s global Scientific, Technical, and Medical business to form Wiley-Blackwell. Copyright ©2008 by Le Jacq. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Ben Harkinson at [email protected] or 781-388-8511.

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VOL. 10 NO. 5 MAY 2008 the JOurNAL Of CLiNiCAL hYperteNsiON 391

important coronary heart disease risk factors, there is enough justification for advocating a decrease in blood pressure to 130/80 mm hg. Do we have any data to validate this conclusion, or is this just a reasonable assumption? is there any trial evidence to justify this recommendation?

Dr WriGht: it’s more than speculation. there are observational data available from a number of studies. in addition, in most studies, those in whom the lowest blood pressure is achieved generally do better. the question, though, is whether those patients do better because they have a lower blood pressure or because they were less sick. Generally, when you look at the characteristics of the patients in whom lower blood pressure was reached, they are somewhat different than of those in whom it is not. the most effective way to differentiate these effects is with a study design in which these partici-pants are randomized to different blood pressure goals rather than simply comparing outcomes in patients in whom different blood pressure levels are reached.

Dr MOser: We do have data from the hypertension Optimal treatment (hOt) study that reported a better outcome in high-risk diabet-ics in whom an average of 81 mm hg diastolic compared with 85 mm hg diastolic was achieved. so there is one bit of evidence to favor lower goal blood pressure in high-risk people. Did the systolic hypertension in the elderly program (shep) report more benefit with lower pressures?

Dr WriGht: people in the shep trial did not generally have their systolic blood pressure reduced to levels the 130s [mm hg] (mean systolic blood pressure was 146 mm hg). And even in hOt, the mean systolic blood pressure was only about 138 mm hg. Generally, it is easier to reduce diastolic blood pressure to <80 mm hg than to achieve a systolic pressure <130 or 135 mm hg, especially in patients older than 55 years and par-ticularly in people with wide pulse pressures, who are the highest-risk patients referred to in the AhA recommendations.

Dr MOser: so, perhaps the goals are desir-able but difficult to achieve, and there is not too much evidence from good trials to confirm the recommendation. ron, the AhA recommenda-tions include aortic aneurysm, peripheral arterial disease, angina, left ventricular dysfunction, and other criteria to define the category of coronary heart disease. the question is, if the trial evidence is not too solid about lowering systolic blood pres-sure to <140 mm hg, can we justify the recom-mendation of <130 mm hg?

intuitively, we believe that this would be better and observational data certainly suggest it, especially in the coronary disease patient. What about decreasing the blood pressure too much, especially in the elderly?

Dr ViCtOr: that’s the old knotty problem of the J curve. it is still debated as to whether over-zealous treatment of blood pressure can impair coronary perfusion and precipitate ischemic events in patients with clinical or subclinical coronary dis-ease. roughly 2 out of every 3 papers on this topic come out against the J curve hypothesis for every 1 that supports it. there have been several studies in which patients with isolated systolic hyperten-sion have had diastolic pressure decreases at least into levels down to the 70-mm hg range, with no increase in coronary heart disease events. recently, there was a retrospective or post hoc analysis of the international Verapamil-trandolapril study (iNVest), which was a secondary prevention trial in patients with coronary disease. the achieved levels of on-treatment blood pressure were lower by about 5/10 mm hg than in many of the other hypertension trials. the analysis suggested a J-curve relationship such that with diastolic levels below the 70 to 80 mm hg range there appeared to be an upturn in the risk of myocardial infarction death. there wasn’t an increase in risk of stroke death. the acceptability in any one interpretation of these data has to be tempered by the fact that the confidence intervals widened greatly at the critically interesting levels of lower diastolic blood pressure because of sample size. On-treatment dia-stolic blood pressure below the 60 to 70 mm hg range was reached in too few patients in this study, or other published studies, to draw firm conclu-sions. An alternative interpretation of the data are that the J-curve patients were generally sicker: they were older and more likely to have diabetes, heart failure, or cancer. so, the J-curve hypothesis is still an open question, and the AhA guideline com-mittee tried to walk a fine line with the available data. for secondary prevention, <130/80 mm hg is a reasonable target, but go slowly. We don’t have enough data on diastolic values <60 mm hg to know what happens below that level, if you really do see this J-curve phenomenon.

Dr MOser: You’re not convinced that there is a J curve. to define this, risk is very much higher with diastolic blood pressure levels >100 mm hg, but it decreases dramatically at diastolic levels of 80 mm hg or so, and then at <70 mm hg there appears to be a possible increase in risk in patients with ischemic heart disease. that’s what the J curve is, if there is one.


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Dr ViCtOr: Yes.Dr MOser: But you’re not convinced this is real.Dr ViCtOr: At least 3 hypotheses have been

proposed to explain the J curve in cardiovascular mortality observed in retrospective analyses of some hypertension treatment trials. first, the only true J-curve hypothesis is that fatal ischemic events are precipitated when diastolic coronary perfusion falls below the limits of coronary autoregulation. there is no question that this occurs if blood pressure is lowered precipitously during an acute coronary syndrome (ie, when the myocardium is already ischemic). the question is whether this is a real issue in the outpatient management of blood pressure in patients with stable coronary disease.

the second hypothesis is that the upturn in cardiovascular deaths seen with low diastolic blood pressure is merely a reflection of isolated systolic hypertension—the real hemodynamic risk factor being the wide pulse pressure and high sys-tolic pressure, not the low diastolic pressure. the third hypothesis, as i mentioned earlier, is that the patients have low diastolic blood pressure because they’re sick, not because they have a type A doctor who lowered their blood pressure too much. in the outpatient setting, i think the real risk is not lower-ing the blood pressure enough, rather than the risk of overtreating.

Dr MOser: in people with ischemic heart dis-ease in whom coronary arteries fill during diastole, the blood vessels dilate to accommodate more flow when blood pressure is lowered, but eventually if you lower pressure too much they are unable to dilate anymore and ischemia results.

Dr ViCtOr: it’s below the autoregulation level. We don’t know what that is in human beings. in some animal models, it seems to be very low, around 30 mm hg.

Dr MOser: Do we have any clues from trials? the data from the original J curve paper were cer-tainly not convincing; there were only a few cases and the cutpoint for an increase in risk was about 80 mm hg.

Dr ViCtOr: A study that was published in 2006 also suggested that optimal diastolic pressure was in the low 80s.

Dr MOser: But shep, which was a placebo-controlled trial in the elderly, reported that there were no deleterious effects on coronary heart disease until diastolic blood pressure values were <55 to 60 mm hg. Actually, in shep the baseline diastolic blood pressure values were about 77 or 78 mm hg.

Dr ViCtOr: Yes.

Dr MOser: so there is a difference.Dr ViCtOr: the framingham data would

conclude that we needn’t worry until diastolic blood pressure levels are <70 mm hg. the key point is that we don’t have a large enough sample size below this level to have tested the question.

Dr MOser: there was a major meta-analysis that tried to address this. they used all the trials, even though some of them were poorly controlled. i believe that they identified a J curve under about a diastolic blood pressure of 60 mm hg, but there also was a J curve in patients who weren’t receiving treatment and in noncardiovascular deaths. they concluded, therefore, that it wasn’t the drug treat-ment, it was probably the sickness of the patient, as you pointed out. this discussion isn’t just an academic one. if we are going to attempt to reduce blood pressure in patients with coronary heart disease to <130/80 mm hg, we are going to see some patients with diastolic blood pressure values <70 mm hg; do we or do we not have to worry about this?

Dr ViCtOr: the AhA guideline committee advised caution in lowering diastolic blood pres-sure to <60 mm hg in this setting, and that’s a reasonable interpretation of the available data. A recent retrospective analysis of the iNVest data clearly influenced this prudent cautionary note.

Dr MOser: Dr Wright, you have a patient who comes in with a blood pressure of 170/80 mm hg, not an unusual reading in a 78-year-old person. You would like to get the systolic pressure down to below 140 mm hg basal. systolic blood pressure is decreased to 150 mm hg, but the dia-stolic pressure varies between 60 and 55 mm hg. this patient probably has some coronary artery disease, even if he hasn’t been symptomatic. Do you stop, or do you continue to titrate medications to decrease the systolic pressure still further?

Dr WriGht: unfortunately, the data are certainly limited. As you know, we have clinical trial data documenting the benefit of lowering systolic blood pressures, but only to levels that would still be considered stage 1 hypertension. the Action to Control Cardiovascular risk in Diabetes (ACCOrD) trial, comparing outcomes in diabetic patients randomized to treatment to reach systolic blood pressure <120 mm hg compared with those treated to <140 mm hg, should report its findings in the next 1 or 2 years. the National institutes of health have only just indicated plans to fund a study to evaluate the benefit of lower systolic blood pressures in nondiabetics.

Dr MOser: so, what do you do?


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Dr WriGht: ideally, you’re dealing on a case-by-case basis. typically, i would still try to achieve a systolic pressure <140 mm hg but would certainly be quick to back off if, in fact, there is any evidence of adverse symptoms. One comment: i believe that there is a J curve. We assume that a blood pressure of zero is not that healthy.

Dr MOser: something we all can agree with.Dr WriGht: the question is where above zero

we are apt to run into problems. that is still very unclear. But i am more convinced about the harm of an elevated systolic blood pressure than i am about low diastolic blood pressure.

Dr MOser: so you would continue to attempt to lower the blood pressure in this patient to below a systolic level of 140 mm hg. Do you have a point where you really would say “enough”? if the patient’s diastolic pressure goes down to 50 mm hg, for example, would you stop? Or if the patient’s doing fine and the electrocardiogram hasn’t changed, would you want to go further?

Dr WriGht: As you know, it is rare to see diastolic blood pressure values <50 mm hg, even in shep, in which the baseline diastolic blood pressure was in the 70s [mm hg]. if there are no symptoms, i would attempt to go further if needed to achieve a systolic pressure less than the recom-mended 140 mm hg. this is a very subjective call and is based upon clinical judgment and not yet on data.

Dr MOser: right, but as you note, it is rare to see a diastolic pressure of 50 or 55 mm hg.

Dr WriGht: Yes.Dr MOser: ron, you had a comment?Dr ViCtOr: Yes, i think it’s important

in this context to talk about the intravascular Atherosclerotic plaque ultrasound study (iVus) substudy of the Comparison of Amlodipine and enalapril to Limit Occurrences of thrombosis (CAMeLOt) trial, in which patients with angio-graphically proven coronary disease received anti-hypertensive medications with baseline levels of blood pressure about 130/77 mm hg. there was an additional decrease of about 5/3 mm hg and reduced progression, even possible regression, of atherosclerotic plaque by iVus. these are small numbers because of the invasive nature of the study, but this clearly impacted the recommenda-tions and the guidelines.

Dr MOser: so you’re in favor of the AhA recommendations?

Dr ViCtOr: Yes.Dr MOser: Okay. And, of course, in shep, the

baseline diastolic pressures were about 77 or 78 mm

hg. Joel, we seem to approve the recommendations that in people with coronary artery disease or the equivalent (peripheral vascular disease plus diabe-tes, aortic aneurysm, etc), we should probably try to lower blood pressure to below 130/80 mm hg. the consensus appears to be that we’re not too worried about decreasing the diastolic pressure too much and making coronary artery disease worse. is there any caution for very elderly people because these are the people who start out with diastolic pressures of 70 or 75 mm hg and most or many of them have either overt or hidden coronary artery disease? Any recent data in the very elderly?

Dr hANDLer: Well, i think that was the ques-tion that preceded the hypertension in the Very elderly trial (hYVet). there had been a preceding meta-analysis and a hYVet pilot study suggesting that mortality is elevated nonsignificantly in patients aged 80 and older, although even those data showed a significant reduction in stroke and heart failure. What the updated hYVet results have told us is that treating patients aged 80 and older reduces mortality significantly. You have to be a little slow in titrating medications in these patients and giv-ing them time for their baroreceptors to adjust to a lower blood pressure, but the study objective in hYVet was to get the systolic pressure to <150 mm hg, and the investigators were able to do that and significantly reduce mortality.

Dr MOser: so that particular study seems to confirm the fact that even in the very elderly, in whom coronary heart disease is extremely prevalent, lowering the systolic blood pressure and reducing the diastolic is not going to be deleterious but beneficial.

Dr hANDLer: patients with high pulse pres-sures who are receiving treatment can get a signifi-cant decrease in systolic pressure without much of a change in the diastolic pressure. if, for example, a patient has a blood pressure of 160/60 mm hg, additional treatment is reasonable at least to get their systolic pressure to <150 mm hg, and that can often be accomplished with a marginal, if any, decrease in the diastolic pressure.

Dr MOser: that’s an important point, because in the patient with isolated systolic hypertension, you decrease the systolic pressure much more. ron, the other thing i believe this report dealt with, and it’s a hot subject that’s very important especially with modern therapy, is the patient with cerebrovascular disease in whom you want to use fibrinolytic therapy, or patients with coronary dis-ease who are receiving anticoagulants. they make a point of saying that you certainly want to get


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their blood pressure down. Maybe these are the people in whom 130/80 mm hg should be your goal. Do you agree with that?

Dr ViCtOr: Certainly. it is clear that elevated blood pressure, especially systolic, increases bleed-ing complications with acute thrombolytic therapy.

Dr MOser: Okay. Jackson, do you agree with that?

Dr WriGht: Yes, clearly.Dr MOser: Okay, because i think it’s a big

mistake to ignore an elevated blood pressure in someone with an ischemic stroke in whom fibrin-olytic therapy is indicated; many neurologists tell us to not attempt to lower blood pressure unless it is quite high—about 180 mm hg or so. Do you adhere to that?

Dr ViCtOr: they have relaxed the latest guidelines. if a patient is a candidate for acute thrombolytic therapy in the setting of an acute stroke, blood pressure should be lowered. And that’s a big concession from neurologists over the years. the benefits of acute thrombolytic therapy in that early window of the stroke are fantastic, so it’s very important. this treatment shouldn’t be used with markedly elevated blood pressure.

Dr MOser: Okay. so, how do we treat the patient with coronary heart disease and hyperten-sion? Jackson, do we approach him or her differ-ently than we would a 58-year-old person with no evidence of coronary heart disease, no peripheral vascular disease, and only 1 or 2 cardiovascular risk factors? A summary of the AhA recommenda-tions is in the table.

Dr WriGht: You’re dealing with secondary prevention in a patient population with compel-ling indications for specific agents. in addition, generally the patient with coronary disease and hypertension has other risk factors in addition to hypertension, so the goal is to achieve goal blood pressure as well as the goals for each of their risk factors. the patient clearly should be treated much more aggressively. i think the recommended goals are reasonable even if some of the goals represent extrapolation of existing data. My goal would be <140 mm hg for systolic blood pressure, but i would try for 130 mm hg. the more you try to lower blood pressure to 130 mm hg, the more you reach levels <140 mm hg on a population basis.

Dr MOser: Other than implementing lifestyle changes, we all agree with using statins, if neces-sary, weight loss, aspirin, and smoking cessation in any patient, especially those with coronary heart disease. But which antihypertensive medication would you use?

Dr WriGht: in terms of which antihyperten-sives should be used in the patient population with lower goals, we’re going to use essentially all the drugs that are out there. i’m going to use the anti-anginals, b-blockers and calcium channel blockers, and diuretics as well as angiotensin-converting enzyme (ACe) inhibitors and angiotensin ii recep-tor blockers (ArBs).

Dr MOser: Alright, let’s be specific. A 50-year-old man who is already receiving treatment for his dyslipidemia is 2 months post–myocardial infarc-tion and comes in with a blood pressure value of 150/90 mm hg. he exercises regularly and is not obese. Which drugs would you use?

Dr WriGht: is there any evidence of myocar-dial dysfunction?

Dr MOser: No.Dr WriGht: the b-blockers and calcium

channel blockers would be drugs of choice.Dr MOser: What would you start with?Dr WriGht: i’d probably start with a

b-blocker.Dr MOser: Would you start with a b-blocker,

which is indicated post–myocardial infarction with good data, by itself or with a diuretic or an ACe inhibitor?

Dr WriGht: At the first visit, i’d probably start with a b-blocker. then i guess the question relates to whether the b-blockers are the most protective against hypertensive complications. Are they sufficient in and of themselves as monother-apy, or should they be relegated to a lesser prior-ity in terms of selecting antihypertensive agents? While many (including myself) would relegate b-blockers to a secondary role behind diuretics, calcium channel blockers, and renin-angiotensin system inhibitors in the patient with uncompli-cated hypertension, they are still first-choice initial therapy in the patient with coronary disease.

Dr MOser: What is your expectation of lowering the blood pressure to the new goal of 130/80 mm hg?

Dr WriGht: it’s unlikely.Dr MOser: i’d say 50% or 40%.Dr WriGht: probably more in the range of

30% to 40%.Dr MOser: so the patient comes back in 2 or 3

weeks. You are following him very carefully. What do you do next? his pressure is now 145/90 mm hg.

Dr WriGht: then you have a choice. You’re certainly not going to add another sympatholytic. in the absence of left ventricular dysfunction, i am not convinced by evidence of a benefit of an ACe inhibitor or an ArB aside from blood pres-sure lowering. for instance, neither CAMeLOt


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nor ALLhAt suggested benefit of ACe inhibitors over calcium channel blockers or diuretics. Adding another more specific renin-angiotensin system inhibitor (like an ACe inhibitor) to a b-blocker (which lowers blood pressure in part by inhibiting renin release) produces less than additive blood pressure lowering than adding either a diuretic or a calcium channel blocker.

Dr MOser: Which calcium channel blocker; is there any difference?

Dr WriGht: since the patient is already on a b-blocker, i would probably not use verapamil or diltiazem, so it would be a dihydropyridine cal-cium channel blocker.

Dr MOser: Why wouldn’t you use nondihy-dropyridines like verapamil?

Dr WriGht: these agents have negative chro-notropic as well as inotropic effects.

Dr MOser: Will diltiazem or verapamil decrease cardiac function?

Dr WriGht: i would probably be more con-cerned about the risk of heart block and exacerbat-ing bradycardia than that of heart failure.

Dr MOser: ron, is this approach the correct one in a post–myocardial infarction patient?

Dr ViCtOr: it is important to emphasize that b-blockers, while no longer first-step therapy for uncomplicated hypertension, are clearly indicated

Table. Treatment of Hypertension in the Prevention and Management of Ischemic Heart Disease: Summary of the AHA Main Recommendations

Area of Concern

BP Target, mm Hg

Lifestyle Modificationa

Specific Drug Indications Comments

General CAD prevention

<140/90 Yes Any effective antihypertensive drug or combinationb

If SBP >160 mm Hg or DBP >100 mm Hg, start with 2 drugs

High CAD riskc <130/80 Yes ACE inhibitor or ARB or CCB or thiazide diuretic or combination

If SBP >160 mm Hg or DBP >100 mm Hg, start with 2 drugs

Stable angina <130/80 Yes b-Blocker and ACE inhibitor or ARBd

If a b-blocker is contraindicated or if adverse effects occur, diltiazem or verapamil can be substituted (but not if bradycardia or LVD is present); dihydropyridine CCB (not diltiazem or verapamil) can be added to b-blocker; a thiazide diuretic can be added for BP control

UA/NSTEMI, STEMI

<130/80 Yes b-Blocker (if patient is hemodynamically stable) and ACE inhibitor or ARBd

If b-blocker is contraindicated or if adverse effects occur, diltiazem or verapamil can be substituted (but not if bradycardia or LVD is present); dihydropyridine CCB (not diltiazem or verapamil) can be added to b-blocker; a thiazide diuretic can be added for BP control

LVD <120/80 Yes ACE inhibitor or ARB and b-blocker and aldosterone antagoniste and thiazide or loop diuretic and hydralazine/isosorbide dinitrate

Contraindicated: verapamil, diltiazem, clonidine, moxonidine, a-blockers

Abbreviations: ACE inhibitor, angiotensin-converting enzyme inhibitor; AHA, American Heart Association; ARB, angiotensin II receptor blocker; BP, blood pressure; CAD, coronary artery disease; CCB, calcium channel blocker; DBP, diastolic blood pres-sure; LVD, left ventricular dysfunction; NSTEMI, non-ST-elevation myocardial infarction; SBP, systolic blood pressure; STEMI, ST-elevation myocardial infarction; UA, unstable angina. Adapted with permission from Rosendorff et al. aWeight loss if appropriate, healthy diet (including sodium restriction), exercise, smoking cessation, and alcohol moderation. bEvidence supports ACE inhibitor (or ARB), CCB, or thiazide diuretic as first-line therapy. cDiabetes mellitus, chronic kidney disease, known CAD or CAD equivalent (carotid artery disease, peripheral arterial disease, abdominal aortic aneurism), or 10-year Framingham risk score ≥10%. dIf anterior myocardial infarction is present, if hypertension persists, if LVD or heart failure (HF) is present, or if the patient has diabetes mellitus. eIf severe HF is present (New York Heart Association class III or IV, or left ventricular ejection fraction <40% and clinical HF). Before making any management decisions, clinicians are strongly urged to read the full text of the relevant section of the scientific statement.


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in the post–myocardial infarction patient.Dr MOser: Which one would you use, by the

way?Dr ViCtOr: if blood pressure is not at goal,

i’d choose carvedilol because it is a more powerful antihypertensive.

Dr MOser: You don’t worry about orthostatic dizziness?

Dr ViCtOr: No.Dr MOser: it’s long-acting.Dr ViCtOr: Brand-name extended-release

carvedilol phosphate is long-acting. Generic carve-dilol needs to be dosed twice daily and now costs only $4 per month at Wal-Mart. its unfortunate that we do not have extensive outcome data with carvedilol, but my impression—and i think oth-ers agree—is that it is a stronger blood pressure–lowering agent than metoprolol. the patient you described is likely going to require 3 drugs to reach a blood pressure goal of <130/80 mm hg. A rea-sonable combination regimen would be carvedilol plus an ACe inhibitor or an ArB plus a long-act-ing dihydropyridine calcium channel blocker—and a touch of hydrochlorothiazide if needed.

Dr MOser: You may not need 3 different drugs. Why wouldn’t you just add a diuretic to the b-blocker as initial therapy?

Dr ViCtOr: the dihydropyridine calcium channel blocker is antianginal, so is the b-blocker, and the combination often produces a favorable reduction in double product.

Dr MOser: so your preference would be a b-blocker plus a calcium channel blocker?

Dr ViCtOr: Yes.Dr MOser: then add an ACe inhibitor or

an ArB and then a diuretic if necessary. A renin-angiotensin-aldosterone system inhibitor plus a diuretic has been shown to be effective. But you like an a-/b-blocker as part of the therapy, so it might get quite complicated.

Dr ViCtOr: Yes, and at present we just don’t have the outcome data we’d like with the com-bined a-/b-blockers.

Dr MOser: these agents are primarily b-blockers but have a different effect on vascular resistance. Joel, we all seem to agree that in a post–myocardial infarction patient with hyperten-sion, the first drug of choice would probably be a b-blocker. i would tend to agree with ron, and i’d probably start therapy with a b-blocker plus something else because i would not expect to lower the pressure to the new lower goals with just the b-blocker. What would be your sequence of medi-cation? A little different than ron’s?

Dr hANDLer: iNVest is the one trial we have treating hypertension limited to patients with known coronary artery disease. Most of the patients in this study required 3 drugs. As my next drug, i might prescribe an ACe inhibitor/thiazide combination pill, then titrate it. studies show that in these high-risk patients, earlier control is needed. if you step up with a combination tablet, in addition to the b-blocker, you get control sooner and you get closer to target.

Dr MOser: sounds reasonable, and i guess an ArB/diuretic, a calcium channel blocker/ACe inhibitor, or an ArB/calcium channel blocker combination might also be possible choices. ron, you’re a cardiologist—on another topic, what do you do in a patient with either a non-st segment depression infarction or an st segment depression infarction with hypertension? they come into the emergency department, and blood pressures fluctu-ate around 160/100 mm hg.

Dr ViCtOr: in unstable angina or non-st-elevation myocardial infarction, the initial therapy for hypertension should include a short-acting b-blocker (typically intravenous metoprolol) plus nitrates for chest pain. the goal is to reduce Bp in a controlled fashion to <130/80 mmhg. if blood pressure remains above this goal with b-blocker therapy alone, then a long-acting dihydropyridine calcium channel blocker should be added. if the patient is b-blocker–intolerant, treatment should be instituted with a nondihydropyridine calcium channel blocker in the absence of heart failure.

Dr MOser: how about an ACe inhibitor or ArB acutely or a nitrate? What do you think?

Dr ViCtOr: fine, so long as the patient is hemodynamically stable.

Dr MOser: Jackson, do you agree with that?Dr WriGht: i do.Dr ViCtOr: As emphasized by the guidelines,

it is important not to overshoot and cause hypoten-sion, which can extend the infarct.

Dr MOser: Most of the poor results occur because blood pressure is reduced quickly from levels of 160 mm hg or so to 110/80 mm hg.

Dr ViCtOr: particularly if someone is vol-ume-depleted because they’ve been vomiting or diaphoretic.

Dr MOser: Joel, do you agree with that?Dr hANDLer: i think that a short-acting b-block-

er is the way to go, using metoprolol as an example. You can get control of a potentially rapidly changing situation. the heart rate is reduced, which is very important acutely. i would then add a short-acting ACe inhibitor as tolerated, after about 24 hours.


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Dr MOser: Alright, what about the patient who comes in with a massive anterior wall infarc-tion and evidence of left ventricular dysfunction? Do we have indications for any specific drugs in that situation?

Dr ViCtOr: the recommendations in st-segment elevation myocardial infarction are similar to those in non-st-elevation myocardial infarction, except that an ACe inhibitor should be administered early, particularly if there is left ventricular dysfunction.

Dr MOser: so if someone comes in with a massive anterior wall infarction, is it reason-able to assume that they have left ventricular dysfunction?

Dr ViCtOr: Yes, but fortunately massive ante-rior wall infarcts are becoming as rare as hyperten-sive crisis. they are mainly seen now in people with drug-eluting stents in whom antiplatelet therapy is discontinued by mistake. We barely have enough large anterior myocardial infarctions to train the cardiology fellows how to take care of them—a good problem to have. With more aggressive preventive care and treatment of risk factors with antihypertensive and lipid-lowering therapy, pump failure fortunately is much less common now.

Dr MOser: Well, let me summarize. recent recommendations suggest that in people with either very high cardiovascular risk, whether you use the framingham risk calculator or not, or people who have vascular disease, aneurysms, or any clinical evidence of coronary heart disease, the goal blood pressure should be lower than in people at lower risk. it should be 130/80 mm hg, just as it is in dia-betics. in patients with left ventricular dysfunction,

it should even be lower if achievable, at around the ideal or optimal blood pressure of 120/80 mm hg. Most of us agree with that. We are not too wor-ried about the J curve, although i guess there might be a point where you’d say maybe we’re treating too aggressively if the diastolic blood pressure gets down to 50 or 55 mm hg. fortunately, we rarely see that. so we would continue to treat blood pres-sure if we can, absent adverse effects, and try to get the systolic blood pressure down to those new goal levels.

We would favor the use of a b-blocker in any-one post–myocardial infarction based on good trial data, with the addition of an ACe inhibi-tor, ArB, diuretic, or calcium channel blocker to achieve goal pressures. in the majority of cases, this requires at least 2 drugs. We would stay away from a-blockade acutely, and we would be cautious to make sure that we had a b-blocker component on board if we decide to use one.

so all in all, we generally agree with the recom-mendation of the AhA with one caveat. it always is nice to set these low blood pressure goals, but we must recognize that there may be difficulty in even achieving the 140/90 mm hg level. the lower goal pressures, however, should be our objective. hopefully these can be achieved without produc-ing significant side effects.

Disclosure: This expert panel discussion was supported by Daiichi-Sankyo, and each author received an honorarium from Daiichi-Sankyo for time and effort spent participating in the discussion and reviewing the transcript for important intellectual content before publication . The authors maintained full control of the discussion and the resulting content of this article; Daiichi-Sankyo had no input in the choice of topic, speakers, or content .


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how to treat hypertension in patients with coronary heart disease disease

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