Atorvastatin and quinapril inhibit blood coagulation in patients with coronary artery disease following 28 days of therapy.

BACKGROUND: We evaluated the antithrombotic effects of statins and angiotensin-converting enzyme inhibitor (ACEI) drugs in patients with coronary artery disease (CAD). METHODS AND RESULTS: Blood coagulation at the site of microvascular injury was assessed in 26 males with CAD before and after treatment with quinapril (10 mg day-1; n=13) or atorvastatin (40 mg day-1; n=13) for 4 weeks and an additional 4 weeks of combined therapy (quinapril+atorvastatin). Rates of prothrombin and factor V activation (FVa), fibrinogen (Fbg) cleavage and FVa inactivation showed that both quinapril and atorvastatin decreased the rates of: formation of thrombin B-chain (by 30.6%, P=0.007; and by 34.3%, P=0.003), formation of thrombin-antithrombin complexes (by 30.4%, P=0.0002; and by 40%, P=0.001), FV activation (by 19.1%, P=0.03; and by 21.8%, P=0.005) and Fbg depletion (by 29.2%, P=0.004; and by 32.7%, P=0.001). Atorvastatin alone accelerated FVa inactivation (P=0.005). A further 4 weeks of combined therapy enhanced most anticoagulant effects only when atorvastatin was added to quinapril. CONCLUSIONS: In CAD patients, atorvastatin and quinapril slowed blood clotting at the site of microvascular injury after 28 days of therapy. Addition of atorvastatin to quinapril, but not quinapril to the statin, enhanced the anticoagulant effects. Our findings might help explain the reduced risk of myocardial infarction or stroke in patients treated with statins and/or ACEIs and the lack of clinical benefits from ACEI added to prior statin therapy in patients at cardiovascular risk.

The evolving management of acute right-sided heart failure in cardiac transplant recipients.

Avoidance of the clinical syndrome of acute right-sided heart failure after heart transplantation is, unfortunately, not possible. Clinical experience and the literature certainly suggest that a significant factor in the successful management of right ventricular (RV) failure is recipient selection. Moreover, threshold hemodynamic values beyond which RV failure is certain to occur and heart transplantation is contraindicated do not exist. Nor are there values below which RV failure is always avoidable. Acute RV failure will remain a difficult and ever-present clinical syndrome in the transplant recipient. Goals in the treatment of this clinical problem include: 1. Preserving coronary perfusion through maintenance of systemic blood pressure. 2. Optimizing RV preload. 3. Reducing RV afterload by decreasing pulmonary vascular resistance (PVR). 4. Limiting pulmonary vasoconstriction through ventilation with high inspired oxygen concentrations (100% FiO(2)), increased tidal volume and optimal positive end expiratory pressure ventilation. Inhaled nitric oxide is recommended before leaving the operating room in cases where the initial therapies have had little impact. Intra-aortic balloon counterpulsation is employed in patients with impaired left ventricular (LV) function and may be of benefit in patients with RV dysfunction resulting from ischemia, preservation injury or reperfusion injury. Optimal LV function reduces RV afterload and PVR. A proactive decision regarding RV assist device implantation is made before leaving the operating room and is highly dependent upon overall hemodynamics, size and function of the ventricles as seen on transesophageal echocardiography, renal function and surgical bleeding. Only through careful preoperative planning can this life-threatening condition be managed in the postoperative period.

Evaluation of plasma cyclic GMP assay as a screening test for detection of acute cardiac allograft rejection.

Our aim was to assess the value of a single determination of plasma cyclic guanosine 3',5'-monophosphate (cGMP) in noninvasive screening for acute cardiac allograft rejection warranting augmentation of immunosuppression. Plasma cGMP levels were measured in 26 patients 1 to 13 months after heart transplantation on the same day the endomyocardial biopsies were performed. Acute moderate rejection (ISHLT 3A or 3B) was found in 10 out of 17 subjects (59%) with plasma cGMP >5 nmol/L, whereas there was mild or no rejection (ISHLT 0 to 1) in 8 from among 9 subjects (89%) with cGMP <5 nmol/L. Because cGMP levels <5 nmol/L appear to argue against the presence of acute rejection requiring therapy modification, our preliminary results suggest that a single plasma cGMP assay might be helpful in establishing indications for endomyocardial biopsy in heart transplant recipients.