Jianming Fang

Impact of Combination Evidence-Based Medical Therapy on Mortality in Patients With Acute Coronary Syndromes

Background—Several individual pharmacological agents, such as antiplatelet drugs, &bgr;-blockers, ACE inhibitors, and lipid-lowering agents, have proven efficacy in reducing mortality in patients with acute coronary syndromes. However, the impact of the combination of these agents on clinical outcomes has not been studied before. Methods and Results—A total of 1358 consecutive patients presenting with acute coronary syndromes between January 1999 and March 2002 were identified, and data on baseline demographics, comorbidities, and in-hospital management were collected. On the basis of discharge use of evidence-based therapies, we created a composite appropriateness score depending on the number of the drugs used divided by the number of the drugs potentially indicated for each patient. The impact of the composite score on 6-month mortality was analyzed using a risk-adjusted logistic regression model. The odds ratio for death for all indicated medications used (appropriateness level IV) versus none of the indicated medications used (appropriateness level 0) was 0.10 (95% CI, 0.03 to 0.42; P <0.0001); similarly, odds ratio for appropriateness level III versus level 0 was 0.17 (95% CI, 0.04 to 0.75; P =0.0018), odds ratio for appropriateness level II versus level 0 was 0.18 (95% CI, 0.04 to 0.77; P =0.01), and odds ratio for appropriateness level I versus level 0 was 0.36 (95% CI, 0.08 to 1.75; P =0.20). Conclusions—Use of combination evidence-based medical therapies was independently and strongly associated with lower 6-month mortality in patients with acute coronary syndromes. Such therapies, most of which are generic and inexpensive today, seem to offer a marked survival advantage compared with patients in whom such therapies are omitted.

Role and Results of Surgery in Acute Type B Aortic Dissection Insights From the International Registry of Acute Aortic Dissection (IRAD)

Background— The clinical profiles and outcomes of patients treated surgically for acute type B aortic dissection (ABAD) are often reported for those in small series or for those cared for at a single institution over a long time period, during which a continuous evolution in techniques has occurred. Accordingly, we sought to evaluate the clinical features and surgical results of patients enrolled in the International Registry of Acute Aortic Dissection by identifying primary factors that influenced surgical outcome and estimating average surgical mortality for ABAD in the current era. Methods and Results— A comprehensive analysis of 290 clinical variables and their relation to surgical outcomes for 82 patients who required surgery for ABAD (from a population of 1256 patients; mean±SD age, 60.6±15.0 years; 82.9% male) and who were enrolled in the International Registry of Acute Aortic Dissection was performed. The overall in-hospital mortality was 29.3%. Factors associated with increased surgical mortality based on univariate analysis were preoperative coma or altered consciousness, partial thrombosis of the false lumen, evidence of periaortic hematoma on diagnostic imaging, descending aortic diameter >6 cm, right ventricle dysfunction at surgery, and shorter time from the onset of symptoms to surgery. Factors associated with favorable outcomes included radiating pain, normotension at surgery (systolic blood pressure 100 to 149 mm Hg), and reduced hypothermic circulatory arrest time. The 2 independent predictors of surgical mortality were age >70 years (odds ratio, 4.32; 95% confidence interval, 1.30 to 14.34) and preoperative shock/hypotension (odds ratio, 6.05; 95% confidence interval, 1.12 to 32.49). Conclusions— The present study provides insights into current-day clinical profiles and surgical outcomes of ABAD. Knowledge about different preoperative clinical conditions may help surgeons in making treatment decisions among these high-risk patients.

Gender-Related Differences in Acute Aortic Dissection

Background—Few data exist on gender-related differences in clinical presentation, diagnostic findings, management, and outcomes in acute aortic dissection (AAD). Methods and Results—Accordingly, we evaluated 1078 patients enrolled in the International Registry of Acute Aortic Dissection (IRAD) to assess differences in clinical features, management, and in-hospital outcomes between men and women. Of the patients enrolled in IRAD (32.1%) with AAD, 346 were women. Although less frequently affected by AAD (32.1% of AAD), women were significantly older and had more often presented later than men (P =0.008); symptoms of coma/altered mental status were more common, whereas pulse deficit was less common. Diagnostic imaging suggestive of rupture, ie, periaortic hematoma, and pleural or pericardial effusion were more commonly observed in women. In-hospital complications of hypotension and tamponade occurred with greater frequency in women, resulting in higher in-hospital mortality compared with men. After adjustment for age and hypertension, women with aortic dissection die more frequently than men (OR, 1.4, P =0.04), predominantly in the 66- to 75-year age group. Moreover, surgical outcome was worse in women than men (P =0.013); type A dissection in women was associated with a higher surgical mortality of 32% versus 22% in men despite similar delay, surgical technique, and hemodynamics. Conclusions—Our analysis provides insights into gender-related differences in AAD with regard to clinical characteristics, management, and outcomes; important diagnostic and therapeutic implications may help shed light on aortic dissection in women to improve their outcomes.

Association of Painless Acute Aortic Dissection With Increased Mortality

OBJECTIVE To evaluate the clinical characteristics and outcomes of patients with painless acute aortic dissection (AAD). PATIENTS AND METHODS For this study conducted from 1997 to 2001, we searched the International Registry of Acute Aortic Dissection to identify patients with painless AAD (group 1). Their clinical features and in-hospital events were compared with patients who had painful AAD (group 2). RESULTS Of the 977 patients in the database, 63 (6.4%) had painless AAD, and 914 (93.6%) had painful AAD. Patients in group 1 were older than those in group 2 (mean +/- SD age, 66.6 +/- 13.3 vs 61.9 +/- 14.1 years; P = .01). Type A dissection (involving the ascendIng aorta or the arch) was more frequent in group 1 (74.6% vs 60.9%; P = .03). Syncope (33.9% vs 11.7%; P < .001), congestive heart failure (19.7% vs 3.9%; P < .001), and stroke (11.3% vs 4.7%; P = .03) were more frequent presenting signs in group 1. Diabetes (10.2% vs 4.0%; P = .04), aortic aneurysm (29.5% vs 13.1%; P < .001), and prior cardiovascular surgery (48.1% vs 19.7%; P < .001) were also more common in group 1. In-hospital mortality was higher in group 1 (33.3% vs 23.2%; P = .05), especially due to type B dissection (limited to the descending aorta) (43.8% vs 10.4%; P < .001), and the prevalence of aortic rupture was higher among patients with type B dissection in group 1 (18.8% vs 5.9%; P = .04). CONCLUSION Patients with painless AAD had syncope, congestive heart failure, or stroke. Compared with patients who have painful AAD, patients who have painless AAD have higher mortality, especially when AAD is type B.

Differences in Clinical Presentation, Management, and Outcomes of Acute Type A Aortic Dissection in Patients With and Without Previous Cardiac Surgery

Background—There are less data on the clinical and diagnostic imaging characteristics, management, and outcomes of patients with previous cardiac surgery (PCS) presenting with acute type A aortic dissection (AAD). Methods and Results—In 617 patients with AAD, we evaluated the differences in the clinical characteristics, management, and in-hospital outcomes of the cohorts with and without PCS. A history of PCS was present in 100 of 617 patients. Patients with PCS were more likely to be males (P=0.02), older (P=0.014), and to have a history of previous aortic dissection (P<0.001) or aneurysms (P<0.001). In contrast, PCS patients were less likely to have presenting chest pain (P<0.001). Cardiac tamponade was less common in PCS patients (P=0.007). Fewer AAD patients with PCS underwent surgical repair (P=0.001). Hospital mortality was not adversely influenced by PCS (odds ratio [OR], 1.46; 95% confidence interval [CI], 0.81 to 2.63), but a trend for increased death was seen in patients with previous aortic valve replacement (AVR) (OR, 2.31; 95% CI, 0.98 to 5.43). Age70 years or older, previous AVR, shock, and renal failure identified PCS patients at risk for death. Conclusions—Our study highlights differences in clinical characteristics, management, and outcomes of AAD patients with PCS. Importantly, PCS, with the exception of previous AVR, does not adversely influence early outcomes of AAD patients, including those undergoing surgical repair. However, because of otherwise dismal outcomes with medical management of AAD, our data indicate that a history of PCS (even that of previous AVR) should not preclude physicians from recommending surgical correction of type A aortic dissection in appropriate patients.

Adherence to Medications by Patients After Acute Coronary Syndromes

BACKGROUND Nonadherence to medication may lead to poor medical outcomes. OBJECTIVE To describe medication-taking behavior of patients with a history of acute coronary syndromes (ACS) for 4 classes of drugs and determine the relationship between self-reported adherence and patient characteristics. METHODS Consenting patients with the diagnosis of ACS were interviewed by telephone approximately 10 months after discharge. The survey elicited data characterizing the patient, current medication regimens, beliefs about drug therapy, reasons for discontinuing medications, and adherence. The survey included the Beliefs About Medicine Questionnaire providing 4 scales: Specific Necessity, Specific Concerns, General Harm, and General Overuse, and the Medication Adherence Scale (MAS). Multivariate regression was used to determine the independent variables with the strongest association to the MAS. A p value ≤0.05 was considered significant for all analyses. RESULTS Two hundred eight patients were interviewed. Mean ± SD age was 64.9 ± 13.0 years, with 60.6% male, 95.7% white, 57.3% with a college education, 87.9% living with ≥1 other person, and 42% indicating excellent or very good health. The percentage of patients continuing on medication at the time of the survey category ranged from 87.4% (aspirin) to 66.0% (angiotensin-converting enzyme inhibitors). Reasons for stopping medication included physician discontinuation or adverse effects. Of patients still on drug therapy, the mean MAS was 1.3 ± 0.4, with 53.8% indicating nonadherence (score >1). The final regression model showed R2 = 0.132 and included heart-related health status and Specific Necessity as significant predictor variables. CONCLUSIONS After ACS, not all patients continue their drugs or take them exactly as prescribed. Determining beliefs about illness and medication may be helpful in developing interventions aimed at improving adherence.

Lack of clopidogrel–CYP3A4 statin interaction in patients with acute coronary syndrome

Objective: To assess a clinically significant interaction between cytochrome P450 3A4 (CYP3A4) metabolised statin and clopidogrel. Design: Prospective single centre cohort study. Setting: Academic teaching hospital in the USA. Patients: 1651 patients presenting with acute coronary syndromes between January 1999 and February 2003 were studied. Data on baseline demographics, co-morbidities, and in-hospital management were collected. Main outcome measure: Association of CYP3A4 metabolised statin and clopidogrel use with in-hospital and six month mortality. The impact of the combined use of a CYP3A4 statin and clopidogrel on six month mortality and major adverse cardiac events was analysed by a risk adjusted logistic regression model. Results: The odds ratios for six month mortality were: for CYP3A4 statin, 0.43 (95% confidence interval (CI) 0.27 to 0.71, p  =  0.0009); for CYP3A4 statin plus clopidogrel, 0.36 (95% CI 0.23 to 0.60, p < 0.001); for non-CYP3A4 statin, 0.22 (95% CI 0.08 to 0.59, p  =  0.002); and for non-CYP3A4 statin plus clopidogrel, 0.22 (95% CI 0.06 to 0.75, p  =  0.016). Conclusions: Use of a combination of a CYP3A4 statin plus clopidogrel was associated with lower six month mortality and morbidity in patients with acute coronary syndromes. There was no significant difference in clinical benefit between a CYP3A4 statin and a non-CYP3A4 statin when used in conjunction with clopidogrel. This suggests that the proposed interaction is probably an ex vivo phenomenon and may not be clinically relevant.

Characteristics and In-Hospital Outcomes of Patients With Cardiac Tamponade Complicating Type A Acute Aortic Dissection

Cardiac tamponade (TMP) is a life-threatening complication of acute type A aortic dissection (AAD). The purpose of this study was to assess the clinical characteristics and in-hospital outcomes of TMP in the setting of AAD on the basis of the findings in the large cohort of the International Registry of Acute Aortic Dissection (IRAD). Six hundred seventy-four patients (mean age 61.8 +/- 14.2 years) with AAD in IRAD were studied. TMP was suspected on clinical grounds and confirmed by diagnostic imaging. Univariate testing was followed by multivariate logistic regression analysis to determine the association of TMP. TMP was detected in 126 patients with AAD (18.7%). Age did not differ between patients with and without TMP. Those with TMP less often had previous cardiac surgery (7.0% vs 17.1%, p = 0.007). Syncope (37.8% vs 13.7%, p <0.0001) and altered mental status (31.2% vs 10.6%, p <0.0001) were more common in patients with AAD with TMP than without TMP. Patients with TMP were more likely to have widened mediastina on chest x-ray (72.6% vs 60.3%, p = 0.02) and to have periaortic hematomas (44.7% vs 21.2%, p <0.0001). In-hospital outcomes were significantly worse in patients with TMP. The mortality of patients with TMP remained significantly higher, even after adjustment for baseline clinical characteristics (p <0.001). On logistic regression, altered mental status, hypotension, and early mortality were identified as independent correlates of TMP. In conclusion, TMP is not uncommon in patients with AAD. Syncope, altered mental status, and a widened mediastinum on chest x-ray on presentation suggest TMP, the presence of which warrants urgent operative therapy to improve outcome.

Impact of pre-diabetic state on clinical outcomes in patients with acute coronary syndrome

Diabetes mellitus is a well recognised risk factor for cardiovascular disease and diabetic individuals with acute coronary syndrome (ACS) have a two- to fourfold increased risk of adverse cardiovascular events compared to non-diabetic individuals.1 It is becoming increasingly clear that impaired glucose metabolism and the pre-diabetic state are also associated with adverse clinical outcomes. A retrospective study of 197 patients by Norhammar et al 2 showed that among non-diabetic patients with acute myocardial infarction, those with higher admission blood glucose had higher rates of death, rehospitalisation for heart failure, and rehospitalisation for non-fatal reinfarction. In this study, admission plasma glucose was an independent predictor of non-fatal reinfarction, hospitalisation for heart failure, and a major adverse cardiovascular event (MACE).2 Another study by Norhammar et al revealed that 35% of patients admitted to the coronary care unit with a myocardial infarction and no prior diagnosis of diabetes may have an abnormal glucose tolerance test at discharge.3 The American Diabetes Association (ADA) recently redefined the cut off point for normal fasting blood glucose concentrations from 110 mg/dl to 100 mg/dl, meaning that a value of 100 mg/dl or above would lead to a diagnosis of impaired fasting glucose, which is included in the term pre-diabetes.4 The impact of the new guideline is immense. Health and human services estimate that …

A Prior Myocardial Infarction: How Does it Affect Management and Outcomes in Recurrent Acute Coronary Syndromes?

Despite improved secondary prevention efforts, acute coronary syndrome (ACS) recurrence among patients with prior history of coronary events remains high. The differences in presentation, management, and subsequent clinical outcomes in patients with and without a prior myocardial infarction (MI) and presenting with another episode of ACS remain unexplored.