Practice guidelines, combination therapy

Either UFH or LMWH should be administered to patients with NSTE ACS. Therapy should be continued for up to 48 hours or until the end of the angiography or PCI procedure. In patients initiating warfarin therapy, UFH or LMWHs should be continued until the International Normalized Ratio (INR) with warfarin is in the therapeutic range for 2 consecutive days. The addition of UFH to aspirin reduces the rate of death or MI in patients with NSTE ACS.47 Enoxaparin was mentioned as preferred over UFH in the 2002 ACC/AHA clinical practice guidelines, as two large clinical trials found a reduction in the combined endpoint of death, MI, or need for PCI in patients... 

The combination of nitrates and hydralazine improves the composite endpoint of mortality, hospitalizations for HF, and quality of life in African Americans who receive standard therapy. A fixed-dose combination product is available that contains ISDN 20 mg and hydralazine 37.5 mg (BiDil). Practice guidelines recommend adding ISDN and hydralazine as part of standard therapy in African Americans with moderately severe to severe HF. The combination may also be reasonable for patients of other ethnicities with persistent symptoms despite optimized therapy with an ACE inhibitor (or ARB) and /Tblocker. The combination is also appropriate as first-line therapy in patients unable to tolerate ACE inhibitors or ARBs because of renal insufficiency, hyperkalemia, or possibly hypotension. 

Bell DS. Practical considerations and guidelines for dosing sulfonylureas as monotherapy or combination therapy. Clin Ther. 2004 26 1714-1727. 

The AASLD practice guidelines recommend that diuretic therapy be initiated with the combination of spironolactone and furosemide. Spironolactone alone was commonly recommended for initial therapy, but clinical trials have demonstrated a 14-day delay in the onset of action, as well as the development hyperkalemia when spironolactone is used alone. Administering spironolactone in single daily doses is justified based on its pharmacokinetics and helps to improve patient compliance. If tense ascites is present, paracentesis... 

Thalidomide (thalomid) is used to treat patients with relapsed and refractory MM, as well as early stage disease. The National Comprehensive Cancer Network (NCCN www.nccn.org) Clinical Practice Guidelines for Multiple Myeloma includes thalidomide as an option for salvage therapy in patients with relapsed or refractory MM, or as initial therapy in combination with dexamethasone for patients with advanced myeloma. Thalidomide is also in clinical trials for use in treating a variety of solid tumors and myelodysplasias. 

A series of studies demonstrates a synergistic effect between drug therapies and psychodynamic talk therapies. The effectiveness of each form of therapy used independently is less than their combined use in the case of major depression. See A. Solomon, The Noonday Demon An Atlas of Depression (New York Scribner s, 2001) E. Good, Chronic Depression Study Backs the Pairing of Therapy and Drugs, New York Times (May 18, 2000) L. Altshuler et al., Treatment of Depression in Women A Summary of the Expert Consensus Guidelines, of Psychiatric Practice 7 (May 2001) 185-208. Kleinman, Rethinking Psychiatry p. ii. 

The numerous clinical trials that have been widely published and that are summarized in other chapters of this textbook attest to the need for combination drug therapy in the ACS, It is to be expected that results obtained in clinical practice will vary somewhat from those found in clinical trials but on balance it is important to treat patients in accordance with guidelines derived from clinical trials unless there are contraindications or relative risks, It is not possible to state that a given drug is more effective or safer than another drug without a head-to-head clinical trial of the drug in question. 

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