Clinical and biochemical results of the metalloproteinase inhibition with subantimicrobial doses of doxycycline to prevent acute coronary syndromes (MIDAS) pilot trial.

BACKGROUND: Vulnerable plaque demonstrates intense inflammation in which macrophages secrete matrix metalloproteinases (MMPs) that degrade the fibrous cap, ultimately leading to rupture, in situ thrombosis, and an associated clinical event. Thus, inhibition of MMP activity or more general suppression of vascular inflammation are attractive targets for interventions intended to reduce plaque rupture. We hypothesized that subantimicrobial doses of doxycycline (SDD) (20 mg twice daily) would benefit patients with coronary artery disease by reducing inflammation and MMP activity and thus possibly prevent coronary plaque rupture events. METHODS AND RESULTS: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study of 6 months of SDD or placebo treatment to reduce inflammation and prevent plaque rupture events. A total of 50 patients were enrolled, of whom 24 were randomized to placebo and 26 to SDD. At 6 months, there was no difference in the composite endpoint of sudden death, fatal myocardial infarction (MI), non-fatal MI, or troponin-positive unstable angina in SDD compared with placebo-treated patients (8.4% versus 0%, P=0.491). Biochemical markers of inflammation were assessed in plasma at study entry and after 6 months of therapy in 30 patients. In SDD-treated patients, high-sensitivity C-reactive protein (CRP) was reduced by 46% from 4.8+/-0.6 microg/mL to 2.6+/-0.4 microg/mL (P=0.007), whereas CRP was not significantly reduced in placebo patients. Interleukin (IL)-6 decreased from 22.1+/-3.7 pg/mL at baseline to 14.7+/-1.8 pg/mL at 6 months in SDD-treated patients (P=0.025) but did not decrease significantly in placebo-treated patients. On zymography, pro-MMP-9 activity was reduced 50% by SDD therapy (P=0.011), whereas it was unchanged by placebo treatment. CONCLUSIONS: SDD appears to exert potentially beneficial effects on inflammation that could promote plaque stability. These findings should be investigated in a larger study.

Effect of diabetes on long-term mortality following contemporary percutaneous coronary intervention: analysis of 4,284 cases.

OBJECTIVE: Diabetic patients are known to have reduced long-term survival following percutaneous transluminal coronary angioplasty compared with nondiabetic patients. However, it is unknown whether this survival disadvantage has persisted in the era of contemporary percutaneous coronary intervention (PCI) techniques, which include the widespread use of stents and the availability of platelet glycoprotein (GP) IIb/IIIa inhibitors. RESEARCH DESIGN AND METHODS: Three hospitals in New York City contributed prospectively defined data on 4,284 patients undergoing PCI. The primary end point was all-cause mortality following hospital discharge for PCI. RESULTS: Hypertension, renal insufficiency, and renal failure requiring dialysis were all more common in diabetic patients, whereas active smoking was less frequent. Congestive heart failure on admission was more common in diabetic than nondiabetic patients (7.7 vs. 4.0%, P < 0.001). Stents were placed in 78% of nondiabetic patients and 75% of diabetic patients (P = 0.045). Platelet GP IIb/IIIa antagonists were administered to 23% of nondiabetic and 24% of diabetic patients (P = NS). At a mean follow-up of 3 years, mortality was 8% among nondiabetic patients and 13% for diabetic patients (P < 0.001). After adjustment for differences in baseline characteristics between nondiabetic and diabetic patients, diabetes remained a significant independent hazard for late mortality (hazard ratio 1.462, 95% CI 1.169-1.828; P = 0.001). CONCLUSIONS: Following contemporary PCI, diabetic patients continue to have worse survival than nondiabetic patients.

A propensity analysis of the impact of platelet glycoprotein IIb/IIIa inhibitor therapy on in-hospital outcomes after percutaneous coronary intervention.

It is unknown whether the benefits of parenteral platelet glycoprotein (GP) IIb/IIIa inhibitors as an adjunct to percutaneous coronary intervention (PCI) demonstrated in randomized clinical trials extend to patients treated outside the setting of clinical trials. A contemporary registry of 10,847 consecutive PCI procedures was analyzed to determine the effect of GP IIb/IIIa inhibitor treatment on in-hospital major adverse coronary events ([MACEs] composite of death, urgent coronary artery bypass surgery, periprocedural myocardial infarction, abrupt closure, and stent thrombosis). In this registry, GP IIb/IIIa inhibitors were administered to 20.1% of patients. These patients were younger, more often men, and less often hypertensive than untreated patients. GP IIb/IIIa inhibitor-treated patients were more likely to present with acute myocardial infarction or unstable angina. Stents were placed in 79% of patients treated with GP IIb/IIIa inhibitors. MACEs occurred in 7.8% of GP IIb/IIIa inhibitor-treated patients compared with 3.8% of untreated patients (p <0.001). After multivariable adjustment for the propensity of GP IIb/IIIa inhibitor treatment as well as other possible confounders and interactions known to influence MACEs, GP IIb/IIIa inhibitor treatment was associated with a 57% increase in the risk of a MACE (odds ratio 1.57, 95% confidence interval 1.22 to 2.03; p = 0.0004). In a data set consisting of patients with a high degree of acuity predominantly treated with stent placement, GP IIb/IIIa inhibitor treatment is associated with an increase in thrombotic complications of PCI.

Comparison of in-hospital outcomes following early or delayed angioplasty for acute myocardial infarction.

BACKGROUND: Studies of primary angioplasty for treatment of acute myocardial infarction (AMI) have not appeared to demonstrate a reduction in efficacy as a function of time to treatment. We sought to compare the outcomes of patients treated in New York State with primary angioplasty within 6 hours of symptom onset to those treated between 6 and 23 hours after the onset of AMI. METHODS: We used data from the 1995 Coronary Angioplasty Reporting System of the New York State Department of Health to compare the in-hospital outcomes of patients treated with early (within 6 hours) or delayed angioplasty (6 23 hours) for AMI. RESULTS: Early angioplasty (within 6 hours after onset of chest pain) was attempted in 957 patients (71.3%), while 385 patients (28.7%) had a delayed procedure (6 23 hours after the onset of chest pain). Patients who underwent delayed angioplasty were older (mean age, 62.6 years versus 60.4 years in the early group; p < 0.01) and more often female (36% vs. 28% in the early treatment group; p < 0.001). Patients treated early more frequently demonstrated hemodynamic instability (13.6% versus 9.1% in the late treatment group; p = 0.02), malignant ventricular arrhythmia (8.5% versus 2.9% in the late treatment group; p < 0.001) and cardiogenic shock (6.6% versus 1.8% in the late treatment group; p < 0.001). Overall in-hospital mortality was 63/1,342 (4.7%) with no difference based on early or delayed angioplasty (5.2% versus 3.4%, respectively; p = NS). The composite of the major adverse cardiac events including in-hospital death, reinfarction and emergency bypass surgery did not differ significantly between the early and delayed groups (7.7% versus 5.5%, respectively; p = NS). In multivariable models, delayed angioplasty was not an independent predictor of either in-hospital mortality or major adverse cardiac events. CONCLUSION: Delayed reperfusion does not influence in-hospital clinical outcomes following PTCA for acute myocardial infarction.

In-hospital outcomes of contemporary percutaneous coronary interventions in the very elderly.

Coronary heart disease is the leading cause of death among the elderly (> 65 years) and the very elderly (> 85 years). Little information is available regarding the outcome of very elderly patients referred for PCI in the current era of improved techniques, devices, and pharmacotherapy. The objective of the current study was to evaluate the clinical characteristics and outcomes of very elderly patients > or = 85 years of age in a large, contemporary, multi-institutional PCI database. Five hospitals in the New York City metropolitan area contributed these prospectively defined data elements on consecutive patients undergoing PCI from 1 January 1998 to 1 October 1999. Of 10,847 patients, 5,341 (49%) were younger than 65 years, 3,342 (31%) were 65-74 years, 1,885 (17%) were 75-84 years, and 279 (2.6%) were at least 85 years of age. Following PCI, the very elderly developed stroke (P < 0.001) and renal failure requiring dialysis (P = 0.002) more commonly than younger patients following PCI. The very elderly had a significantly increased in-hospital mortality rate at 2.5% (P < 0.001). However, on multivariate analysis, age > or = 85 years was not an independent predictor of in-hospital mortality (OR = 1.22; 95% CI = 0.37-4.07). The very elderly should not be refused PCI on the basis of advanced age alone.