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Does intensive medical treatment improve outcomes in aortic dissection?

BMJ 2014; 349 doi: (Published 09 September 2014) Cite this as: BMJ 2014;349:g5288
  1. Frank A Lederle, professor of medicine1,
  2. Janet T Powell, professor of vascular biology and medicine2,
  3. Christoph A Nienaber, professor of internal medicine/cardiology3
  1. 1Center for Chronic Disease Outcomes Research, VA Health Care System (111-O), Minneapolis, MN 55417, USA
  2. 2Vascular Surgery Research Group, Imperial College, London W6 8RP, UK
  3. 3Heart Center Rostock, University of Rostock, 18055 Rostock, Germany
  1. Correspondence to: F A Lederle frank.lederle{at}
  • Accepted 29 July 2014

Each year, aortic dissection affects one in 20 000 people,1 2 resulting in 3000 deaths in the United States. Men are affected twice as often as women, and most people affected are over the age of 65 years.1 2 Two thirds of dissections involve the ascending aorta (type A), and many of these patients die before reaching hospital.1 The survivors, who are usually treated with immediate surgery (open or endovascular) unless contraindicated, have a 30 day mortality of 20-50%.1 2 3 Dissections confined to the descending aorta (type B) are usually managed without repair unless complications develop,2 4 and with this approach they have a 30 day mortality of about 12%.1 3

For nearly half a century, the recommended initial medical management of acute aortic dissection of both types has been “aggressive” lowering of systolic blood pressure to below 100 or 120 mm Hg and heart rate to below 60 beats per minute, with first line use of intravenous β blockers.4 5

These recommendations for aortic dissection are notable in light of the increasing awareness in other areas of medicine of the risks of intensive treatment in general and regarding blood pressure in particular.6 7 After a series of reports of adverse events following rapid blood pressure lowering in hypertensive emergencies,7 the sixth and seventh reports of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommended lowering mean arterial blood pressure by no more than 25% within minutes to one hour, then to 160/100 mm Hg within the next two to six hours, noting that “excessive falls in pressure that may precipitate renal, cerebral, or coronary ischemia should be avoided.”8 However, an exception was made for “patients with aortic dissection who should have their [systolic blood pressure] lowered to <100 mmHg if tolerated.” The first line use of β blockers also differs from recommendations for patients without aortic dissection who have hypertension or are undergoing surgery, for whom this practice is discouraged because of evidence of increased cardiovascular morbidity and mortality.9 10 11

Long term control of systolic blood pressure to below 120 mm Hg after aortic dissection (with or without surgery) is also widely recommended,5 often requires five or more drugs,12 and contrasts with recommendations for patients over age 60 without aortic dissection, for whom the systolic blood pressure goal has recently been raised to 150 mm Hg.9

What is the evidence of uncertainty?

We sought evidence in Medline (Aneurysm, Dissecting), in the Cochrane Library, and in the reference lists of pertinent articles. Neither we nor a recent Cochrane review found any randomised trials on the medical management of aortic dissection.13

The first reported use of intensive medical treatment was by Wheat and Palmer in 1965.14 All six of their medically treated patients survived, contrary to their previous experience of no survivors among six patients treated with surgery. Their medical regimen was directed at limiting extension of the dissection by reducing the force of the cardiac impulse and involved lowering systolic blood pressure to about 100 mm Hg by using drugs with a negative inotropic effect. They were influenced by a report of aortic dissection occurring in nine of 44 patients with severe hypertension treated with hexamethonium, an antihypertensive drug with a positive inotropic effect, and by reports that aortic dissection could be prevented in susceptible turkeys by chronic treatment with the negative inotropes reserpine and later propranolol, although this occurred even at doses that did not affect blood pressure or heart rate.15

Acceptable outcomes in patients with dissection managed with intensive medical treatment were subsequently reported in series of a few dozen patients by the original authors and by others.14 15 However, type A and B dissections were not often distinguished before 1970, so comparisons of surgical and medical treatment in these early series are problematic. Further support for intensive medical treatment came from laboratory studies in which “intimal tears” made in synthetic “aortas” were shown to extend when the intensity of pulsatile (but not laminar) flow exceeded a threshold value.15 Later studies in dogs showed that extension of an introduced intimal tear was minimised by drugs that reduced both blood pressure and inotropic force.16

These laboratory studies suggested a beneficial effect of intensive treatment on the dissecting aorta but could not assess its overall effect on the patient. As early as 1967, clinicians were reporting that “the complications due to hypotensive therapy were significant.”17 Whether intensive medical treatment saved more lives by preventing extension of the dissection than were lost to the adverse consequences of hypotension was rarely considered. In the only direct comparison we identified, eight patients who received no treatment for type B dissection and nine patients treated with intensive medical treatment had equivalent survival rates.18 Many patients with dissection present with severe hypertension (three of Wheat’s original six patients had blood pressures above 200/140 mm Hg), so although blood pressure reduction is often clearly needed, little consideration seems to have been given to more moderate regimens.

Since the early reports, investigation of intensive medical treatment has been limited to a handful of case series. In these series, patients who successfully met some specified goal of intensive treatment during or after the initial hospital admission for acute aortic dissection were found to have fewer adverse outcomes over the next few years. For example, an international registry reported associations between drugs prescribed at discharge from hospital and improved long term survival, although the seemingly beneficial drug differed by location of the dissection (β blockers for type A dissection and calcium channel blockers for type B dissection).19 Concerns regarding these studies include small sample sizes (20-54 adverse outcomes per study), the possibility of post hoc selection of predictors and outcome measures, missing data (especially in the registry), and, most importantly, the possibility that worse outcomes were due to the reasons that patients failed to achieve goals of intensive treatment rather than to lack of the treatment itself, as intensive therapy seems to have been the intention for all patients.

Given the burgeoning of high quality evidence in cardiovascular medicine over recent decades, how did intensive medical treatment for aortic dissection escape the scrutiny of a randomised trial? Wheat and colleagues stated in 1969 that: “We have been reluctant to carry out such a test in the human patient. We believe the evidence from the experimental model in turkeys is overwhelmingly convincing in this regard.”14 Modern experience of the many reversals of accepted doctrines by later evidence makes this kind of conviction less tenable today.6 Additional statements by the proponents such as, “Usually, when the blood pressure is appropriately lowered, the patient’s pain is dramatically relieved”20 and “A sudden resurgence of cardiac impulse and blood pressure after they have been initially decreased can be disastrous”15 probably further discouraged investigation and fostered a more dogmatic adherence to the regimen.

The cardiology societies’ recommendation to use intensive medical treatment for dissection is rated class I level C—the strongest of recommendations based on the weakest of evidence.4 Is intensive treatment for dissection a “parachute,” a treatment of such obvious benefit that a randomised trial is unnecessary? For this to be the case, the apparent benefit of the treatment should outweigh the combined effect of plausible confounders.21 We believe that this condition has not been met for intensive medical treatment for aortic dissection. Neither the size nor even the direction of the effect of induced hypotension can be estimated from the data available. As for the preferential use of β blockers, the recent Cochrane review found “no strong source of evidence that one type of medication is superior to another.”13

Is ongoing research likely to provide the relevant evidence?

We searched for ongoing randomised trials in, the World Health Organization’s master registry, and a recent Cochrane review,13 and we found none. Observational studies do not provide sufficient evidence because they are confounded by the reasons that patients fail to achieve goals of intensive treatment, as noted above.

What should we do in the light of the uncertainty?

The time has come for a randomised trial of intensive medical treatment in patients with acute aortic dissection. Meanwhile, we suggest that clinicians who continue to use intensive treatment should consider moderating it when complications such as oliguria arise. Others, who are not persuaded of its benefits and share our concern about its risks, might choose to use less intensive treatment such as that described above from the Joint Commission regarding other hypertensive emergencies, with further blood pressure lowering only as needed to control pain and without attempting to slow sinus rhythm.

Recommendation for further research

  • Study question: would less intensive medical management improve outcomes in acute aortic dissection?

  • Study design: randomised trial

  • Population: patients with acute aortic dissection

  • Intervention: medical management as recommended for hypertensive emergencies (lowering systolic blood pressure by ≤25% within minutes to one hour, then to 160/100 mm Hg within the next two to six hours, with continuous blood pressure monitoring and parenteral drug treatment), plus any treatment considered necessary for pain control

  • Comparison: intensive medical treatment as currently recommended for aortic dissection (rapid lowering of systolic blood pressure to <120 mm Hg and heart rate to <60 beats per minute, with first line use of intravenous β blockers)

  • Outcome: survival and complications of both dissection and hypotension

  • This study could incorporate a factorial design with a second randomisation to evaluate endovascular repair versus no repair for uncomplicated type B dissection or versus open repair for type A dissection


Cite this as: BMJ 2014;349:g5288


  • This is one of a series of occasional articles that highlight areas of practice where management lacks convincing supporting evidence. The series adviser is David Tovey, editor in chief, the Cochrane Library. To suggest a topic for this series, please email us at uncertainties{at}

  • Contributors: All authors made substantial contributions to the conception or design of the paper and to revising it critically for important intellectual content. All authors had final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. FAL drafted the manuscript and is the guarantor.

  • Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: none.

  • Provenance and peer review: Not commissioned; externally peer reviewed


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