The effects of medications on the outcome of aortic dissection remain poorly understood. We sought to address this by analyzing the International Registry of Acute Aortic Dissection (IRAD) global registry database. A total of 1,301 patients with acute aortic dissection (722 with type A and 579 with type B) with information on their medications at discharge and followed for ≤5 years were analyzed for the effects of the medications on mortality. The initial univariate analysis showed that use of β blockers was associated with improved survival in all patients (p = 0.03), in patients with type A overall (p = 0.02), and in patients with type A who received surgery (p = 0.006). The analysis also showed that use of calcium channel blockers was associated with improved survival in patients with type B overall (p = 0.02) and in patients with type B receiving medical management (p = 0.03). Multivariate models also showed that the use of β blockers was associated with improved survival in those with type A undergoing surgery (odds ratio 0.47, 95% confidence interval 0.25 to 0.90, p = 0.02) and the use of calcium channel blockers was associated with improved survival in patients with type B medically treated patients (odds ratio 0.55, 95% confidence interval 0.35 to 0.88, p = 0.01). In conclusion, the present study showed that use of β blockers was associated with improved outcome in all patients and in type A patients (overall as well as in those managed surgically). In contrast, use of calcium channel blockers was associated with improved survival selectively in those with type B (overall and in those treated medically). The use of angiotensin-converting enzyme inhibitors did not show association with mortality.
Medical management of aortic dissection is still mainly determined from personal experience, expert opinion, and historical observational studies. β Blockers are thought to be the first-line medication, and recent studies have suggested the benefit of inhibitors of the renin-angiotensin system, although the effect of calcium channel blockers is poorly understood. Guidelines from the European Society of Cardiology, Japanese Circulation Society, and American College of Cardiology/American Heart Association societies in the past decade have reaffirmed the lack of evidence for therapeutic approaches and targeted medical management. We, therefore, sought to understand the current approaches to medical management and the effects of medications on the outcomes by analyzing the International Registry of Acute Aortic Dissection (IRAD) database.
Methods
IRAD is a multinational registry of 24 referral centers in 12 countries. The details of the IRAD structure and methods used have been previously published.
Data from all patients with aortic dissection enrolled in IRAD from December 26, 1995 with follow-up to 5 years was examined, with a focus on patients discharged alive with medication and follow-up data that included the use of medications. The collected data included variables on clinical, imaging, and mortality data. Follow-up was monitored at each of the sites. Mortality data were obtained through the Social Security Death Index for American subjects when this information was missing. At each enrolling hospital, the study investigators worked with their ethics or institutional review board to obtain appropriate approval for participation.
The summary statistics between groups are presented as frequencies for categorical variables and the mean ± SD for continuous variables. Missing data were not defaulted to negative, and denominators reflected only the cases reported. The relations with follow-up outcome were investigated using univariate Cox regression analysis. Multivariate analysis was used to identify the independent predictors of outcome using models previously determined to be predictive of follow-up mortality. All-cause mortality was the examined end point. The variables tested for type A included history of atherosclerosis and previous cardiac surgery. For type B, female gender, a history of previous aortic aneurysm, a history of atherosclerosis, in-hospital renal failure, pleural effusion on chest radiograph, and in-hospital hypotension/shock were included. Stepwise selection of variables was performed sequentially with a default value for inclusion set at p < 0.05. SAS, version 8.2 (SAS Institute, Cary, North Carolina), was used for statistical analyses.
Results
For the 1,301 patients with acute aortic dissection who survived to discharge and had information on the medications at discharge and during follow-up (median 26.0 months, interquartile range 12.0 to 48.0), the blood pressure status on admission showed that a little >1/2 (50.2%) of all patients were hypertensive. Most of the patients with type B (70.1%) were hypertensive. In contrast, more of the patients with type A were normotensive (43.9%) than hypertensive (33.7%), with a significantly greater number of patients presenting with hypotension/shock than did those with type B (19.6% for type A vs 2.9% for type B), as would be expected for a typical patient population with aortic dissection. The mortality rate for all patients at 1 year was 6.1% and was 4.7% for those with type A and 7.9% for those with type B.
At discharge, most patients (89.8%) were normotensive and hemodynamically stable, with a blood pressure of 124.0 ± 17.9/71.0 ± 10.6 mm Hg and a heart rate of 72.5 ± 11.5 beats/min. Those with type A tended to have a greater heart rate than those with type B (type A, 75.0 beats/min vs type B, 69.4 beats/min). Almost all patients received antihypertensive medications at discharge in our study population (96%), with 88.6% taking β blockers, 46.7% angiotensin-converting enzyme inhibitors, 50.3% calcium channel blockers, 28.9% diuretics, and 22.0% vasodilators. The demographic data are listed in Table 1 .
| Variable | All Patients (n = 1301) | Type A (n = 722) | Type B (n = 579) |
|---|---|---|---|
| Gender | |||
| Male | 918 (70.6%) | 510 (70.6%) | 408 (70.5%) |
| Female | 383 (29.4%) | 212 (29.4%) | 171 (29.5%) |
| Admission status | |||
| Hypertensive | 622/1,240 (50.2%) | 229/679 (33.7%) | 393/561 (70.1%) |
| Normotensive | 450/1,240 (36.3%) | 298/679 (43.9%) | 152/561 (27.1%) |
| Hypotensive/shock | 149/1,240 (12.0%) | 133/679 (19.6%) | 16/561 (2.9%) |
| Medications | |||
| Angiotensin-converting enzyme inhibitor | 561/1,201 (46.7%) | 272/667 (40.8%) | 289/534 (54.1%) |
| Angiotensin receptor blocker | 14/198 (7.1%) | 8/93 (8.6%) | 6/105 (5.7%) |
| β Blockers | 1,100/1,242 (88.6%) | 586/683 (85.8%) | 514/559 (91.9%) |
| Calcium channel blocker | 609/1,211 (50.3%) | 258/670 (38.5%) | 351/541 (64.9%) |
| Diuretic | 58/201 (28.9%) | 23/91 (25.3%) | 35/110 (31.8%) |
| Vasodilator | 259/1,179 (22.0%) | 97/655 (14.8%) | 162/524 (30.9%) |
| Discharge status | |||
| Systolic blood pressure (mm Hg) | 124.0 ± 17.9 | 124.1 ± 19.1 | 123.8 ± 16.3 |
| Diastolic blood pressure (mm Hg) | 71.0 ± 10.6 | 71.5 ± 10.3 | 70.4 ± 11.1 |
| Heart rate (beats/min) | 72.5 ± 11.5 | 75.0 ± 11.6 | 69.4 ± 10.6 |
| Hypertensive | 28/1,176 (2.4%) | 13/651 (2.0%) | 15/525 (2.9%) |
| Normotensive | 1,056/1,176 (89.8%) | 585/651 (89.9%) | 471/525 (89.7%) |
| Data at 1-year follow-up | |||
| Systolic blood pressure (mm Hg) | 129.2 ± 20.0 | 129.6 ± 21.7 | 128.4 ± 17.0 |
| Diastolic blood pressure (mm Hg) | 76.4 ± 16.3 | 77.0 ± 19.1 | 75.4 ± 10.6 |
| Heart rate (beats/min) | 68.5 ± 12.4 | 69.0 ± 12.1 | 67.8 ± 12.9 |
| Highest systolic blood pressure (mm Hg) | 145.8 ± 27.7 | 146.2 ± 30.6 | 145.1 ± 22.0 |
| Highest diastolic blood pressure (mm Hg) | 85.6 ± 27.6 | 85.9 ± 28.0 | 85.0 ± 26.8 |
| Mortality | 78/1,274 (6.1%) | 33/704 (4.7%) | 45/570 (7.9%) |
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